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Vasilkovska T, Salajeghe S, Vanreusel V, Van Audekerke J, Verschuuren M, Hirschler L, Warnking J, Pintelon I, Pustina D, Cachope R, Mrzljak L, Muñoz-Sanjuan I, Barbier EL, De Vos WH, Van der Linden A, Verhoye M. Longitudinal alterations in brain perfusion and vascular reactivity in the zQ175DN mouse model of Huntington's disease. J Biomed Sci 2024; 31:37. [PMID: 38627751 PMCID: PMC11022401 DOI: 10.1186/s12929-024-01028-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 04/08/2024] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND Huntington's disease (HD) is marked by a CAG-repeat expansion in the huntingtin gene that causes neuronal dysfunction and loss, affecting mainly the striatum and the cortex. Alterations in the neurovascular coupling system have been shown to lead to dysregulated energy supply to brain regions in several neurological diseases, including HD, which could potentially trigger the process of neurodegeneration. In particular, it has been observed in cross-sectional human HD studies that vascular alterations are associated to impaired cerebral blood flow (CBF). To assess whether whole-brain changes in CBF are present and follow a pattern of progression, we investigated both resting-state brain perfusion and vascular reactivity longitudinally in the zQ175DN mouse model of HD. METHODS Using pseudo-continuous arterial spin labelling (pCASL) MRI in the zQ175DN model of HD and age-matched wild-type (WT) mice, we assessed whole-brain, resting-state perfusion at 3, 6 and 9 and 13 months of age, and assessed hypercapnia-induced cerebrovascular reactivity (CVR), at 4.5, 6, 9 and 15 months of age. RESULTS We found increased perfusion in cortical regions of zQ175DN HET mice at 3 months of age, and a reduction of this anomaly at 6 and 9 months, ages at which behavioural deficits have been reported. On the other hand, under hypercapnia, CBF was reduced in zQ175DN HET mice as compared to the WT: for multiple brain regions at 6 months of age, for only somatosensory and retrosplenial cortices at 9 months of age, and brain-wide by 15 months. CVR impairments in cortical regions, the thalamus and globus pallidus were observed in zQ175DN HET mice at 9 months, with whole brain reactivity diminished at 15 months of age. Interestingly, blood vessel density was increased in the motor cortex at 3 months, while average vessel length was reduced in the lateral portion of the caudate putamen at 6 months of age. CONCLUSION Our findings reveal early cortical resting-state hyperperfusion and impaired CVR at ages that present motor anomalies in this HD model, suggesting that further characterization of brain perfusion alterations in animal models is warranted as a potential therapeutic target in HD.
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Affiliation(s)
- Tamara Vasilkovska
- Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium.
- µNEURO Research Centre of Excellence, University of Antwerp, Antwerp, Belgium.
| | - Somaie Salajeghe
- Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
| | - Verdi Vanreusel
- Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
| | - Johan Van Audekerke
- Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
- µNEURO Research Centre of Excellence, University of Antwerp, Antwerp, Belgium
| | - Marlies Verschuuren
- µNEURO Research Centre of Excellence, University of Antwerp, Antwerp, Belgium
- Laboratory of Cell Biology and Histology, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
- Antwerp Centre for Advanced Microscopy, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
| | - Lydiane Hirschler
- C.J. Gorter MRI Center, Leiden University Medical Center, Leiden, the Netherlands
| | - Jan Warnking
- Univ. Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences, Grenoble, France
| | - Isabel Pintelon
- µNEURO Research Centre of Excellence, University of Antwerp, Antwerp, Belgium
- Laboratory of Cell Biology and Histology, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
- Antwerp Centre for Advanced Microscopy, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
| | - Dorian Pustina
- CHDI Management, Inc., the company that manages the scientific activities of CHDI Foundation, Inc, Princeton, NJ, USA
| | - Roger Cachope
- CHDI Management, Inc., the company that manages the scientific activities of CHDI Foundation, Inc, Princeton, NJ, USA
| | - Ladislav Mrzljak
- CHDI Management, Inc., the company that manages the scientific activities of CHDI Foundation, Inc, Princeton, NJ, USA
- Present Address: Takeda Pharmaceuticals, Cambridge, MA, USA
| | - Ignacio Muñoz-Sanjuan
- CHDI Management, Inc., the company that manages the scientific activities of CHDI Foundation, Inc, Princeton, NJ, USA
- Present Address: Cajal Neuroscience Inc, Seattle, WA, USA
| | - Emmanuel L Barbier
- Univ. Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences, Grenoble, France
| | - Winnok H De Vos
- µNEURO Research Centre of Excellence, University of Antwerp, Antwerp, Belgium
- Laboratory of Cell Biology and Histology, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
- Antwerp Centre for Advanced Microscopy, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
| | - Annemie Van der Linden
- Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
- µNEURO Research Centre of Excellence, University of Antwerp, Antwerp, Belgium
| | - Marleen Verhoye
- Bio-Imaging Lab, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
- µNEURO Research Centre of Excellence, University of Antwerp, Antwerp, Belgium
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Nuttall R, El Mir A, Jäger C, Letz S, Wohlschläger A, Schneider G. Broadly applicable methods for the detection of artefacts in electroencephalography acquired simultaneously with hemodynamic recordings. MethodsX 2023; 11:102376. [PMID: 37767154 PMCID: PMC10520509 DOI: 10.1016/j.mex.2023.102376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
Electroencephalography (EEG) data, acquired simultaneously with magnetic resonance imaging (MRI), must be corrected for artefacts related to MR gradient switches (GS) and the cardioballistic (CB) effect. Canonical approaches require additional signal acquisition for artefact detection (e.g., MR volume onsets, ECG), without which the EEG data would be rendered uncleanable from these artefacts.•We present two broadly applicable methods for artefact detection based on peak detection combined with temporal constraints with respect to periodicity directly from the EEG data itself; no additional signals are required. We validated the performance of our methods versus the two canonical approaches for detection of GS/CB artefact, respectively, on 26 healthy human EEG-functional MRI resting-state datasets. Utilising various performance metrics, we found our methods to perform as well as - and sometimes better than - the canonical standard approaches. With as little as one EEG channel recording, our methods can be applied to detect GS/CB artefacts in EEG data acquired simultaneously with MRI in the absence of MR volume onsets and/or an ECG recording. The detected artefact onsets can then be fed into the standard artefact correction software.
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Affiliation(s)
- Rachel Nuttall
- Department of Anesthesiology and Intensive Care, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich 81675, Germany
| | - Aya El Mir
- Department of Anesthesiology and Intensive Care, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich 81675, Germany
- New York University Abu Dhabi, Engineering Division, Saadiyat Marina District, Abu Dhabi, United Arab Emirates
| | - Cilia Jäger
- Department of Neuroradiology, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich 81675, Germany
| | - Svenja Letz
- Department of Anesthesiology and Intensive Care, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich 81675, Germany
| | - Afra Wohlschläger
- Department of Neuroradiology, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich 81675, Germany
| | - Gerhard Schneider
- Department of Anesthesiology and Intensive Care, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich 81675, Germany
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Tesler F, Linne ML, Destexhe A. Modeling the relationship between neuronal activity and the BOLD signal: contributions from astrocyte calcium dynamics. Sci Rep 2023; 13:6451. [PMID: 37081004 PMCID: PMC10119111 DOI: 10.1038/s41598-023-32618-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 03/30/2023] [Indexed: 04/22/2023] Open
Abstract
Functional magnetic resonance imaging relies on the coupling between neuronal and vascular activity, but the mechanisms behind this coupling are still under discussion. Recent experimental evidence suggests that calcium signaling may play a significant role in neurovascular coupling. However, it is still controversial where this calcium signal is located (in neurons or elsewhere), how it operates and how relevant is its role. In this paper we introduce a biologically plausible model of the neurovascular coupling and we show that calcium signaling in astrocytes can explain main aspects of the dynamics of the coupling. We find that calcium signaling can explain so-far unrelated features such as the linear and non-linear regimes, the negative vascular response (undershoot) and the emergence of a (calcium-driven) Hemodynamic Response Function. These features are reproduced here for the first time by a single model of the detailed neuronal-astrocyte-vascular pathway. Furthermore, we analyze how information is coded and transmitted from the neuronal to the vascular system and we predict that frequency modulation of astrocytic calcium dynamics plays a key role in this process. Finally, our work provides a framework to link neuronal activity to the BOLD signal, and vice-versa, where neuronal activity can be inferred from the BOLD signal. This opens new ways to link known alterations of astrocytic calcium signaling in neurodegenerative diseases (e.g. Alzheimer's and Parkinson's diseases) with detectable changes in the neurovascular coupling.
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Affiliation(s)
- Federico Tesler
- CNRS, Paris-Saclay Institute of Neuroscience (NeuroPSI), Paris-Saclay University, 91400, Saclay, France.
| | - Marja-Leena Linne
- Faculty of Medicine and Health Technology, Tampere University, 33720, Tampere, Finland
| | - Alain Destexhe
- CNRS, Paris-Saclay Institute of Neuroscience (NeuroPSI), Paris-Saclay University, 91400, Saclay, France
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Neuronal nitric oxide synthase positive neurons in the human corpus callosum: a possible link with the callosal blood-oxygen-level dependent (BOLD) effect. Brain Struct Funct 2023; 228:511-523. [PMID: 36460768 DOI: 10.1007/s00429-022-02599-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 11/18/2022] [Indexed: 12/04/2022]
Abstract
Brain functions have been investigated in the past decades via the blood-oxygen-level dependent (BOLD) effect using functional magnetic resonance imaging. One hypothesis explaining the BOLD effect involves the Nitric Oxide (NO) gaseous neurotransmitter, possibly released also by cells in the corpus callosum (CC). The eventual presence of NO releasing neurons and/or glial cells in the CC can be assessed by immunohistochemistry. Serial sections both from paraffin-embedded and frozen samples of CC obtained from adult human brains autopsy were studied with immunohistochemistry and immunofluorescence analysis, using an antibody against the neuronal isoform of Nitric Oxide Synthase (nNOS), the enzyme synthetizing the NO. The staining revealed the presence of many nNOS-immunopositive cells in the CC, shown to be neurons with immunofluorescence. Neuronal NOS-positive neurons presented different morphologies, were more numerous 4 mm apart from the midline, and displayed a peak in the body of the CC. In some cases, they were located at the upper boundary of the CC, more densely packed in the proximity of the callosal arterioles. The significant presence of nNOS-immunopositive neurons within the commissure suggests their probable role in the CC neurovascular regulation in the adult brain and could explain the BOLD effect detected in human CC.
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Nag S, Uludag K. Dynamic Effective Connectivity using Physiologically informed Dynamic Causal Model with Recurrent Units: A functional Magnetic Resonance Imaging simulation study. Front Hum Neurosci 2023; 17:1001848. [PMID: 36936613 PMCID: PMC10014816 DOI: 10.3389/fnhum.2023.1001848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Accepted: 01/25/2023] [Indexed: 03/05/2023] Open
Abstract
Functional MRI (fMRI) is an indirect reflection of neuronal activity. Using generative biophysical model of fMRI data such as Dynamic Causal Model (DCM), the underlying neuronal activities of different brain areas and their causal interactions (i.e., effective connectivity) can be calculated. Most DCM studies typically consider the effective connectivity to be static for a cognitive task within an experimental run. However, changes in experimental conditions during complex tasks such as movie-watching might result in temporal variations in the connectivity strengths. In this fMRI simulation study, we leverage state-of-the-art Physiologically informed DCM (P-DCM) along with a recurrent window approach and discretization of the equations to infer the underlying neuronal dynamics and concurrently the dynamic (time-varying) effective connectivities between various brain regions for task-based fMRI. Results from simulation studies on 3- and 10-region models showed that functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) responses and effective connectivity time-courses can be accurately predicted and distinguished from faulty graphical connectivity models representing cognitive hypotheses. In summary, we propose and validate a novel approach to determine dynamic effective connectivity between brain areas during complex cognitive tasks by combining P-DCM with recurrent units.
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Affiliation(s)
- Sayan Nag
- Techna Institute & Koerner Scientist in MR Imaging, University Health Network, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- *Correspondence: Sayan Nag,
| | - Kamil Uludag
- Techna Institute & Koerner Scientist in MR Imaging, University Health Network, Toronto, ON, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada
- Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon, Republic of Korea
- Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Republic of Korea
- Kamil Uludag,
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Bach P, Schuster R, Koopmann A, Vollstaedt-Klein S, Spanagel R, Kiefer F. Plasma calcium concentration during detoxification predicts neural cue-reactivity and craving during early abstinence in alcohol-dependent patients. Eur Arch Psychiatry Clin Neurosci 2022; 272:341-348. [PMID: 33630132 PMCID: PMC8866328 DOI: 10.1007/s00406-021-01240-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 02/12/2021] [Indexed: 11/26/2022]
Abstract
Recent studies on the pathophysiology of alcohol dependence suggest a link between peripheral calcium concentrations and alcohol craving. Here, we investigated the association between plasma calcium concentration, cue-induced brain activation, and alcohol craving. Plasma calcium concentrations were measured at the onset of inpatient detoxification in a sample of N = 115 alcohol-dependent patients. Alcohol cue-reactivity was assessed during early abstinence (mean 11.1 days) using a functional magnetic resonance imaging (fMRI) alcohol cue-reactivity task. Multiple regression analyses and bivariate correlations between plasma calcium concentrations, clinical craving measures and neural alcohol cue-reactivity (CR) were tested. Results show a significant negative correlation between plasma calcium concentrations and compulsive alcohol craving. Higher calcium levels predicted higher alcohol cue-induced brain response in a cluster of frontal brain areas, including the dorsolateral prefrontal cortex (dlPFC), the anterior prefrontal cortex (alPFC), and the inferior (IFG) and middle frontal gyri (MFG). In addition, functional brain activation in those areas correlated negatively with craving for alcohol during fMRI. Higher peripheral calcium concentrations during withdrawal predicted increased alcohol cue-induced brain activation in frontal brain areas, which are associated with craving inhibition and cognitive control functions. This might indicate that higher plasma calcium concentrations at onset of detoxification could modulate craving inhibition during early abstinence.Trial registration number: DRKS00003388; date of registration: 14.12.2011.
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Affiliation(s)
- Patrick Bach
- Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Heidelberg University, Central Institute of Mental Health, Square J5, 68159, Mannheim, Germany
- Feuerlein Center on Translational Addiction Medicine, Heidelberg University, Heidelberg, Germany
| | - Rilana Schuster
- Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Heidelberg University, Central Institute of Mental Health, Square J5, 68159, Mannheim, Germany.
- Feuerlein Center on Translational Addiction Medicine, Heidelberg University, Heidelberg, Germany.
- Spinal Cord Injury Center, Heidelberg University Hospital, Schlierbacher Landstraße 200 a, 69118, Heidelberg, Germany.
| | - Anne Koopmann
- Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Heidelberg University, Central Institute of Mental Health, Square J5, 68159, Mannheim, Germany
- Feuerlein Center on Translational Addiction Medicine, Heidelberg University, Heidelberg, Germany
| | - Sabine Vollstaedt-Klein
- Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Heidelberg University, Central Institute of Mental Health, Square J5, 68159, Mannheim, Germany
- Feuerlein Center on Translational Addiction Medicine, Heidelberg University, Heidelberg, Germany
| | - Rainer Spanagel
- Medical Faculty Mannheim, Heidelberg University, Institute of Psychopharmacology, Central Institute of Mental Health, Heidelberg, Germany
| | - Falk Kiefer
- Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Heidelberg University, Central Institute of Mental Health, Square J5, 68159, Mannheim, Germany
- Feuerlein Center on Translational Addiction Medicine, Heidelberg University, Heidelberg, Germany
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Hidalgo-Lopez E, Zeidman P, Harris T, Razi A, Pletzer B. Spectral dynamic causal modelling in healthy women reveals brain connectivity changes along the menstrual cycle. Commun Biol 2021; 4:954. [PMID: 34376799 PMCID: PMC8355156 DOI: 10.1038/s42003-021-02447-w] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 07/01/2021] [Indexed: 01/01/2023] Open
Abstract
Longitudinal menstrual cycle studies allow to investigate the effects of ovarian hormones on brain organization. Here, we use spectral dynamic causal modelling (spDCM) in a triple network model to assess effective connectivity changes along the menstrual cycle within and between the default mode, salience and executive control networks (DMN, SN, and ECN). Sixty healthy young women were scanned three times along their menstrual cycle, during early follicular, pre-ovulatory and mid-luteal phase. Related to estradiol, right before ovulation the left insula recruits the ECN, while the right middle frontal gyrus decreases its connectivity to the precuneus and the DMN decouples into anterior/posterior parts. Related to progesterone during the mid-luteal phase, the insulae (SN) engage to each other, while decreasing their connectivity to parietal ECN, which in turn engages the posterior DMN. When including the most confident connections in a leave-one out cross-validation, we find an above-chance prediction of the left-out subjects' cycle phase. These findings corroborate the plasticity of the female brain in response to acute hormone fluctuations and may help to further understand the neuroendocrine interactions underlying cognitive changes along the menstrual cycle.
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Affiliation(s)
- Esmeralda Hidalgo-Lopez
- Department of Psychology and Centre for Cognitive Neuroscience, University of Salzburg, Salzburg, Austria.
| | - Peter Zeidman
- The Wellcome Centre for Human Neuroimaging, University College London, London, UK
| | - TiAnni Harris
- Department of Psychology and Centre for Cognitive Neuroscience, University of Salzburg, Salzburg, Austria
| | - Adeel Razi
- The Wellcome Centre for Human Neuroimaging, University College London, London, UK
- Turner Institute for Brain and Mental Health, Monash University, Clayton, VIC, Australia
| | - Belinda Pletzer
- Department of Psychology and Centre for Cognitive Neuroscience, University of Salzburg, Salzburg, Austria.
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Yabluchanskiy A, Nyul-Toth A, Csiszar A, Gulej R, Saunders D, Towner R, Turner M, Zhao Y, Abdelkari D, Rypma B, Tarantini S. Age-related alterations in the cerebrovasculature affect neurovascular coupling and BOLD fMRI responses: Insights from animal models of aging. Psychophysiology 2021; 58:e13718. [PMID: 33141436 PMCID: PMC9166153 DOI: 10.1111/psyp.13718] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 08/10/2020] [Accepted: 09/28/2020] [Indexed: 12/11/2022]
Abstract
The present and future research efforts in cognitive neuroscience and psychophysiology rely on the measurement, understanding, and interpretation of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to effectively investigate brain function. Aging and age-associated pathophysiological processes change the structural and functional integrity of the cerebrovasculature which can significantly alter how the BOLD signal is recorded and interpreted. In order to gain an improved understanding of the benefits, drawbacks, and methodological implications for BOLD fMRI in the context of cognitive neuroscience, it is crucial to understand the cellular and molecular mechanism of age-related vascular pathologies. This review discusses the multifaceted effects of aging and the contributions of age-related pathologies on structural and functional integrity of the cerebral microcirculation as they has been investigated in animal models of aging, including age-related alterations in neurovascular coupling responses, cellular and molecular mechanisms involved in microvascular damage, vascular rarefaction, blood-brain barrier disruption, senescence, humoral deficiencies as they relate to, and potentially introduce confounding factors in the interpretation of BOLD fMRI.
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Affiliation(s)
- Andriy Yabluchanskiy
- Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Adam Nyul-Toth
- Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- Institute of Biophysics, Biological Research Centre, Szeged, Hungary
| | - Anna Csiszar
- Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Rafal Gulej
- Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma, OK, USA
| | - Debra Saunders
- Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma, OK, USA
| | - Rheal Towner
- Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma, OK, USA
| | - Monroe Turner
- School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA
| | - Yuguang Zhao
- School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA
| | - Dema Abdelkari
- School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA
| | - Bart Rypma
- School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA
- Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Stefano Tarantini
- Vascular Cognitive Impairment and Neurodegeneration Program, Oklahoma Center for Geroscience and Healthy Brain Aging, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
- International Training Program in Geroscience, Doctoral School of Basic and Translational Medicine/Department of Public Health, Semmelweis University, Budapest, Hungary
- Department of Health Promotion Sciences, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
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Grubb S, Lauritzen M, Aalkjær C. Brain capillary pericytes and neurovascular coupling. Comp Biochem Physiol A Mol Integr Physiol 2021; 254:110893. [DOI: 10.1016/j.cbpa.2020.110893] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Revised: 12/28/2020] [Accepted: 12/28/2020] [Indexed: 12/23/2022]
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de la Rosa N, Ress D, Taylor AJ, Kim JH. Retinotopic variations of the negative blood-oxygen-level dependent hemodynamic response function in human primary visual cortex. J Neurophysiol 2021; 125:1045-1057. [PMID: 33625949 DOI: 10.1152/jn.00676.2020] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Functional magnetic resonance imaging (fMRI) measures blood-oxygen-level-dependent (BOLD) contrast that is generally assumed to be linearly related to excitatory neural activity. The positive hemodynamic response function (pHRF) is the positive BOLD response (PBR) evoked by a brief neural stimulation; the pHRF is often used as the impulse response for linear analysis of neural excitation. Many fMRI studies have observed a negative BOLD response (NBR) that is often associated with neural suppression. However, the temporal dynamics of the NBR evoked by a brief stimulus, the negative HRF (nHRF), remains unclear. Here, a unilateral visual stimulus was presented in a slow event-related design to elicit both pHRFs in the stimulus representation (SR), and nHRFs elsewhere. The observed nHRFs were not inverted versions of the pHRF previously reported. They were characterized by a stronger initial negative response followed by a significantly later positive peak. In contralateral primary visual cortex (V1), these differences varied with eccentricity from the SR. Similar nHRFs were observed in ipsilateral V1 with less eccentricity variation. Experiments with the blocked version of the same stimulus confirmed that brain regions presenting the unexpected nHRF dynamics correspond to those presenting a strong NBR. These data demonstrated that shift-invariant temporal linearity did not hold for the NBR while confirming that the PBR maintained rough linearity. Modeling indicated that the observed nHRFs can be created by suppression of both blood flow and oxygen metabolism. Critically, the nHRF can be misinterpreted as a pHRF due to their similarity, which could confound linear analysis for event-related fMRI experiments.NEW & NOTEWORTHY We investigate dynamics of the negative hemodynamic response function (nHRF), the negative blood-oxygen-level-dependent (BOLD) response (NBR) evoked by a brief stimulus, in human early visual cortex. Here, we show that the nHRFs are not inverted versions of the corresponding pHRFs. The nHRF has complex dynamics that varied significantly with eccentricity. The results also show shift-invariant temporal linearity does not hold for the NBR.
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Poplawsky AJ, Iordanova B, Vazquez AL, Kim SG, Fukuda M. Postsynaptic activity of inhibitory neurons evokes hemodynamic fMRI responses. Neuroimage 2021; 225:117457. [PMID: 33069862 PMCID: PMC7818351 DOI: 10.1016/j.neuroimage.2020.117457] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 09/15/2020] [Accepted: 10/12/2020] [Indexed: 02/08/2023] Open
Abstract
Functional MRI responses are localized to the synaptic sites of evoked inhibitory neurons, but it is unknown whether, or by what mechanisms, these neurons initiate functional hyperemia. Here, the neuronal origins of these hemodynamic responses were investigated by fMRI or local field potential and blood flow measurements during topical application of pharmacological agents when GABAergic granule cells in the rat olfactory bulb were synaptically targeted. First, to examine if postsynaptic activation of these inhibitory neurons was required for neurovascular coupling, we applied an NMDA receptor antagonist during cerebral blood volume-weighted fMRI acquisition and found that responses below the drug application site (up to ~1.5 mm) significantly decreased within ~30 min. Similarly, large decreases in granule cell postsynaptic activities and blood flow responses were observed when AMPA or NMDA receptor antagonists were applied. Second, inhibition of nitric oxide synthase preferentially decreased the initial, fast component of the blood flow response, while inhibitors of astrocyte-specific glutamate transporters and vasoactive intestinal peptide receptors did not decrease blood flow responses. Third, inhibition of GABA release with a presynaptic GABAB receptor agonist caused less reduction of neuronal and blood flow responses compared to the postsynaptic glutamate receptor antagonists. In conclusion, local hyperemia by synaptically-evoked inhibitory neurons was primarily driven by their postsynaptic activities, possibly through NMDA receptor-dependent calcium signaling that was not wholly dependent on nitric oxide.
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Affiliation(s)
| | - Bistra Iordanova
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15203, United States
| | - Alberto L Vazquez
- Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15203, United States; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15203, United States
| | - Seong-Gi Kim
- Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon 440-330, Korea; Department of Biomedical Engineering, Sungkyunkwan University, Suwon, 440-330, Korea
| | - Mitsuhiro Fukuda
- Department of Radiology, University of Pittsburgh, Pittsburgh, PA 15203, United States.
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12
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Excitation-Inhibition Imbalance Leads to Alteration of Neuronal Coherence and Neurovascular Coupling under Acute Stress. J Neurosci 2020; 40:9148-9162. [PMID: 33087471 PMCID: PMC7673010 DOI: 10.1523/jneurosci.1553-20.2020] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 10/08/2020] [Accepted: 10/13/2020] [Indexed: 01/08/2023] Open
Abstract
A single stressful event can cause morphologic and functional changes in neurons and even malfunction of vascular systems, which can lead to acute stress disorder or post-traumatic stress disorder. However, there is a lack of evidence regarding how acute stress impacts neuronal activity, the concurrent vascular response, and the relationship between these two factors, which is defined as neurovascular coupling. Here, using in vivo two-photon imaging, we found that NMDA-evoked calcium transients of excitatory neurons were impaired and that vasodilation of penetrating arterioles was concomitantly disrupted in acutely stressed male mice. Furthermore, acute stress altered the relationship between excitatory neuronal calcium coherence and vascular responses. By measuring NMDA-evoked excitatory and inhibitory neuronal calcium activity in acute brain slices, we confirmed that neuronal coherence both between excitatory neurons and between excitatory and inhibitory neurons was reduced by acute stress but restored by blockade of glucocorticoid receptor signaling. Furthermore, the ratio of sEPSCs to sIPSCs was altered by acute stress, suggesting that the excitation-inhibition balance was disrupted by acute stress. In summary, in vivo, ex vivo, and whole-cell recording studies demonstrate that acute stress modifies excitatory-inhibitory neuronal coherence, disrupts the excitation-inhibition balance, and causes consequent neurovascular coupling changes, providing critical insights into the neural mechanism of stress-induced disorders. SIGNIFICANCE STATEMENT Acute stress can cause pathologic conditions, such as acute stress disorder and post-traumatic stress disorder, by affecting the functions of neurons and blood vessels. However, investigations into the impacts of acute stress on neurovascular coupling, the tight connection between local neural activity and subsequent blood flow changes, are lacking. Through investigations at the in vivo, ex vivo, and whole-cell recording levels, we found that acute stress alters the NMDA-evoked vascular response, impairs the function and coherence of excitatory and inhibitory neurons, and disrupts the excitatory and inhibitory balance. These novel findings provide insights into the relevance of the excitatory-inhibitory balance, neuronal coherence, and neurovascular coupling to stress-induced disorders.
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13
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Do CT, Manjaly ZM, Heinzle J, Schöbi D, Kasper L, Pruessmann KP, Stephan KE, Frässle S. Hemodynamic modeling of long-term aspirin effects on blood oxygenated level dependent responses at 7 Tesla in patients at cardiovascular risk. Eur J Neurosci 2020; 53:1262-1278. [PMID: 32936980 DOI: 10.1111/ejn.14970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 08/06/2020] [Accepted: 09/02/2020] [Indexed: 11/29/2022]
Abstract
Aspirin is considered a potential confound for functional magnetic resonance imaging (fMRI) studies. This is because aspirin affects the synthesis of prostaglandin, a vasoactive mediator centrally involved in neurovascular coupling, a process underlying blood oxygenated level dependent (BOLD) responses. Aspirin-induced changes in BOLD signal are a potential confound for fMRI studies of at-risk individuals or patients (e.g. with cardiovascular conditions or stroke) who receive low-dose aspirin prophylactically and are compared to healthy controls without aspirin. To examine the severity of this potential confound, we combined high field (7 Tesla) MRI during a simple hand movement task with a biophysically informed hemodynamic model. We compared elderly individuals receiving aspirin for primary or secondary prophylactic purposes versus age-matched volunteers without aspirin medication, testing for putative differences in BOLD responses. Specifically, we fitted hemodynamic models to BOLD responses from 14 regions activated by the task and examined whether model parameter estimates were significantly altered by aspirin. While our analyses indicate that hemodynamics differed across regions, consistent with the known regional variability of BOLD responses, we neither found a significant main effect of aspirin (i.e., an average effect across brain regions) nor an expected drug × region interaction. While our sample size is not sufficiently large to rule out small-to-medium global effects of aspirin, we had adequate statistical power for detecting the expected interaction. Altogether, our analysis suggests that patients with cardiovascular risk receiving low-dose aspirin for primary or secondary prophylactic purposes do not show strongly altered BOLD signals when compared to healthy controls without aspirin.
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Affiliation(s)
- Cao-Tri Do
- Translational Neuromodeling Unit, Institute of Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland
| | - Zina-Mary Manjaly
- Department of Neurology, Schulthess Clinic, Zurich, Switzerland.,Department of Health Science and Technology (D-HEST), ETH Zurich, Zurich, Switzerland
| | - Jakob Heinzle
- Translational Neuromodeling Unit, Institute of Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland
| | - Dario Schöbi
- Translational Neuromodeling Unit, Institute of Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland
| | - Lars Kasper
- Translational Neuromodeling Unit, Institute of Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland.,MR Technology Group, Institute of Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland
| | - Klaas P Pruessmann
- MR Technology Group, Institute of Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland
| | - Klaas Enno Stephan
- Translational Neuromodeling Unit, Institute of Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland.,Wellcome Centre for Human Neuroimaging, University College London, London, UK.,Max Planck Institute for Metabolism Research, Cologne, Germany
| | - Stefan Frässle
- Translational Neuromodeling Unit, Institute of Biomedical Engineering, University of Zurich & ETH Zurich, Zurich, Switzerland
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14
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Examining fMRI time-series entropy as a marker for brain E/I balance with pharmacological neuromodulation in a non-human primate translational model. Neurosci Lett 2020; 728:134984. [PMID: 32315710 DOI: 10.1016/j.neulet.2020.134984] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Revised: 04/02/2020] [Accepted: 04/13/2020] [Indexed: 11/23/2022]
Abstract
Recently, there has been a lot of interest in the neuroimaging community in exploring fMRI time-series measures of local neuronal activity and excitation/inhibition (E/I) balance in the brain. In this preliminary study we probed the sensitivity of widely used sample entropy (SE) measure at multiple scales to controlled alteration of the brain's E/I balance in non-human primates (NHPs) with a well-characterized sub-anesthetic ketamine infusion fMRI model. We found that SE failed to detect the expected changes in E/I balance induced by ketamine. Subsequently, noticing that the complexity in the time series contributing SE could be dominated by non-neuronal noise in this experimental setting, we developed a new time-series measure called restricted sample entropy (RSE) by restricting SE estimations to regular portions of the fMRI time-series. RSE was able to adequately reflect the increased excitatory activity engendered by disinhibition of glutamergic neurons, through sub-anesthetic ketamine infusion. These results show that RSE is potentially a powerful tool for examining local neural activity, E/I balance, and alterations in brain state.
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15
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Vanderweyen DC, Theaud G, Sidhu J, Rheault F, Sarubbo S, Descoteaux M, Fortin D. The role of diffusion tractography in refining glial tumor resection. Brain Struct Funct 2020; 225:1413-1436. [PMID: 32180019 DOI: 10.1007/s00429-020-02056-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2019] [Accepted: 02/28/2020] [Indexed: 12/14/2022]
Abstract
Primary brain tumors are notoriously hard to resect surgically. Due to their infiltrative nature, finding the optimal resection boundary without damaging healthy tissue can be challenging. One potential tool to help make this decision is diffusion-weighted magnetic resonance imaging (dMRI) tractography. dMRI exploits the diffusion of water molecule along axons to generate a 3D modelization of the white matter bundles in the brain. This feature is particularly useful to visualize how a tumor affects its surrounding white matter and plan a surgical path. This paper reviews the different ways in which dMRI can be used to improve brain tumor resection, its benefits and also its limitations. We expose surgical tools that can be paired with dMRI to improve its impact on surgical outcome, such as loading the 3D tractography in the neuronavigation system and direct electrical stimulation to validate the position of the white matter bundles of interest. We also review articles validating dMRI findings using other anatomical investigation techniques, such as postmortem dissections, manganese-enhanced MRI, electrophysiological stimulations, and phantom studies with known ground truth. We will be discussing the areas of the brain where dMRI performs well and where the future challenges are. We will conclude this review with suggestions and take home messages for neurosurgeons, tractographers, and vendors for advancing the field and on how to benefit from tractography's use in clinical practice.
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Affiliation(s)
- Davy Charles Vanderweyen
- Department of Surgery, Division of Neurosurgery, Faculty of Medicine, University of Sherbrooke, 3001 12 Ave N, Sherbrooke, QC, J1H 5H3, Canada.
| | - Guillaume Theaud
- Sherbrooke Connectivity Imaging Lab (SCIL), Computer Science Department, University of Sherbrooke, 2500 Boulevard Université, Sherbrooke, QC, J1K2R1, Canada
| | - Jasmeen Sidhu
- Sherbrooke Connectivity Imaging Lab (SCIL), Computer Science Department, University of Sherbrooke, 2500 Boulevard Université, Sherbrooke, QC, J1K2R1, Canada
| | - François Rheault
- Sherbrooke Connectivity Imaging Lab (SCIL), Computer Science Department, University of Sherbrooke, 2500 Boulevard Université, Sherbrooke, QC, J1K2R1, Canada
| | - Silvio Sarubbo
- Division of Neurosurgery, Emergency Area, Structural and Functional Connectivity Lab Project, "S. Chiara" Hospital, Azienda Provinciale Per I Servizi Sanitari (APSS), Trento, Italy
| | - Maxime Descoteaux
- Sherbrooke Connectivity Imaging Lab (SCIL), Computer Science Department, University of Sherbrooke, 2500 Boulevard Université, Sherbrooke, QC, J1K2R1, Canada
| | - David Fortin
- Department of Surgery, Division of Neurosurgery, Faculty of Medicine, University of Sherbrooke, 3001 12 Ave N, Sherbrooke, QC, J1H 5H3, Canada
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16
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Self MW, van Kerkoerle T, Goebel R, Roelfsema PR. Benchmarking laminar fMRI: Neuronal spiking and synaptic activity during top-down and bottom-up processing in the different layers of cortex. Neuroimage 2019. [DOI: 10.1016/j.neuroimage.2017.06.045] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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17
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Chong TTJ. Voodoo surgery? The distinct challenges of functional neuroimaging in clinical neurology. Brain 2019; 140:e76. [PMID: 29053789 DOI: 10.1093/brain/awx283] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Trevor T-J Chong
- Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Victoria 3800, Australia.,Department of Clinical Neurosciences, St Vincent's Hospital, Melbourne, Victoria 3065, Australia.,Cognitive Decline and Memory Service, Alfred Health, Melbourne, Victoria 3004, Australia
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18
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Dhakal K, Norgaard M, Adhikari BM, Yun KS, Dhamala M. Higher Node Activity with Less Functional Connectivity During Musical Improvisation. Brain Connect 2019; 9:296-309. [DOI: 10.1089/brain.2017.0566] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Affiliation(s)
- Kiran Dhakal
- Department of Physics and Astronomy, Georgia State University, Atlanta, Georgia
| | | | - Bhim M. Adhikari
- Department of Physics and Astronomy, Georgia State University, Atlanta, Georgia
- Department of Psychiatry, Maryland Psychiatry Research Center, University of Maryland School of Medicine, Baltimore, Maryland
| | - Kristy S. Yun
- Department of Physics and Astronomy, Georgia State University, Atlanta, Georgia
| | - Mukesh Dhamala
- Department of Physics and Astronomy, Georgia State University, Atlanta, Georgia
- Neuroscience Institute, Georgia State University, Atlanta, Georgia
- Center for Behavioral Neuroscience, Georgia State University, Atlanta, Georgia
- Center for Nano-Optics, Georgia State University, Atlanta, Georgia
- Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia
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19
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Liu X, Pu Y, Wu D, Zhang Z, Hu X, Liu L. Cross-Frequency Coupling Between Cerebral Blood Flow Velocity and EEG in Ischemic Stroke Patients With Large Vessel Occlusion. Front Neurol 2019; 10:194. [PMID: 30915019 PMCID: PMC6422917 DOI: 10.3389/fneur.2019.00194] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 02/14/2019] [Indexed: 01/18/2023] Open
Abstract
Background: Neurovascular coupling enables a rapid adaptation of cerebral blood flow (CBF) to support neuronal activities. Whether this mechanism is compromised during the acute phase after ischemic stroke remains unknown. In this study, we applied a phase-amplitude cross-frequency coupling (PAC) algorithm to investigate multimodal neuro signals including CBF velocity (CBFV), and electroencephalography (EEG). Methods: Acute ischemic stroke patients admitted to the Neurointensive Care Unit, Tiantan Hospital, Capital Medical University (Beijing, China) with continuous monitoring of 8-lead EEG (F3-C3, T3-P3, P3-O1, F4-C4, T4-P4, P4-O2), non-invasive arterial blood pressure (ABP), and bilateral CBFV of the middle cerebral arteries or posterior cerebral arteries were retrospectively analyzed. PAC was calculated between the phase of CBFV in frequency bands (0-0.05 and 0.05-0.15 Hz) and the EEG amplitude in five bands (δ, θ, α, β, γ). The global PAC was calculated as the sum of all PACs across the six EEG channels and five EEG bands for each patient. The hemispherical asymmetry of cross-frequency coupling (CFC) was calculated as the difference between left and right PAC. Results: Sixteen patients (3 males) met our inclusion criteria. Their age was 60.9 ± 7.9 years old. The mean ABP, mean left CBFV, and mean right CBFV were 90.2 ± 31.2 mmHg, 57.3 ± 20.6 cm/s, and 68.4 ± 20.9 cm/s, respectively. The PAC between CBFV and EEG was significantly higher in β and γ bands than in the other three bands. Occipital region (P3-O1 and P4-O2 channels) showed stronger PAC than the other regions. The deceased group tended to have smaller global PAC than the survival group (the area under the receiver operating characteristic curve [AUROC] was 0.81, p = 0.57). The unfavorable outcome group showed smaller global PAC than the favorable group (AUROC = 0.65, p = 0.23). The PAC asymmetry between the two brain hemispheres correlates with the degree of stenosis in stroke patients (p = 0.01). Conclusion: We showed that CBFV interacts with EEG in β and γ bands through a phase-amplitude CFC relationship, with the strongest PAC found in the occipital region and that the degree of hemispherical asymmetry of CFC correlates with the degree of stenosis.
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Affiliation(s)
- Xiuyun Liu
- Department of Physiological Nursing, University of California, San Francisco, San Francisco, CA, United States
| | - Yuehua Pu
- Neurointensive Care Unit, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Dan Wu
- Department of Physiological Nursing, University of California, San Francisco, San Francisco, CA, United States
- School of Computer and Information Technology, Beijing Jiaotong University, Beijing, China
| | - Zhe Zhang
- Neurointensive Care Unit, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Xiao Hu
- Department of Physiological Nursing, University of California, San Francisco, San Francisco, CA, United States
- Department of Neurosurgery, School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
- Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States
- Institute of Computational Health Sciences, University of California, San Francisco, San Francisco, CA, United States
| | - Liping Liu
- Neurointensive Care Unit, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
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20
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Cellular and Ionic Mechanisms of Arterial Vasomotion. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1124:297-312. [DOI: 10.1007/978-981-13-5895-1_12] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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21
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Kovács R, Gerevich Z, Friedman A, Otáhal J, Prager O, Gabriel S, Berndt N. Bioenergetic Mechanisms of Seizure Control. Front Cell Neurosci 2018; 12:335. [PMID: 30349461 PMCID: PMC6187982 DOI: 10.3389/fncel.2018.00335] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Accepted: 09/12/2018] [Indexed: 12/14/2022] Open
Abstract
Epilepsy is characterized by the regular occurrence of seizures, which follow a stereotypical sequence of alterations in the electroencephalogram. Seizures are typically a self limiting phenomenon, concluding finally in the cessation of hypersynchronous activity and followed by a state of decreased neuronal excitability which might underlie the cognitive and psychological symptoms the patients experience in the wake of seizures. Many efforts have been devoted to understand how seizures spontaneously stop in hope to exploit this knowledge in anticonvulsant or neuroprotective therapies. Besides the alterations in ion-channels, transmitters and neuromodulators, the successive build up of disturbances in energy metabolism have been suggested as a mechanism for seizure termination. Energy metabolism and substrate supply of the brain are tightly regulated by different mechanisms called neurometabolic and neurovascular coupling. Here we summarize the current knowledge whether these mechanisms are sufficient to cover the energy demand of hypersynchronous activity and whether a mismatch between energy need and supply could contribute to seizure control.
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Affiliation(s)
- Richard Kovács
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Neurophysiologie, Berlin, Germany
| | - Zoltan Gerevich
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Neurophysiologie, Berlin, Germany
| | - Alon Friedman
- Departments of Physiology and Cell Biology, Cognitive and Brain Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beersheba, Israel.,Department of Medical Neuroscience, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada
| | - Jakub Otáhal
- Institute of Physiology, Czech Academy of Sciences, Prague, Czechia
| | - Ofer Prager
- Departments of Physiology and Cell Biology, Cognitive and Brain Sciences, The Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beersheba, Israel
| | - Siegrun Gabriel
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Neurophysiologie, Berlin, Germany
| | - Nikolaus Berndt
- Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Biochemie, Berlin, Germany.,Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Computational and Imaging Science in Cardiovascular Medicine, Berlin, Germany
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22
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Köhler S, Wagner G, Bär KJ. Activation of brainstem and midbrain nuclei during cognitive control in medicated patients with schizophrenia. Hum Brain Mapp 2018; 40:202-213. [PMID: 30184301 DOI: 10.1002/hbm.24365] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 07/27/2018] [Accepted: 08/07/2018] [Indexed: 12/12/2022] Open
Abstract
Evidence suggests that cognitive control functions as well as the underlying brain network, anchored by the prefrontal cortex (PFC) and the dorsal anterior cingulate cortex (dACC), are dysfunctional in schizophrenia. Catecholamine producing midbrain and brainstem nuclei are densely connected with the PFC and dACC and exert profound contributions to cognitive control processes. Dysfunctions within the underlying neurotransmitter systems are considered to play a central role in the occurrence of various symptoms of schizophrenia. We sought to investigate the putatively abnormal activation pattern of the dopaminergic midbrain nuclei, that is, ventral tegmental area (VTA) and substantia nigra as well as that of the noradrenergic locus coeruleus (LC) in patients with schizophrenia during cognitive control. A total of 28 medicated patients and 27 healthy controls were investigated with the manual version of the Stroop task using event-related fMRI. The main finding was a reduced BOLD activation in the VTA during both Stroop task conditions in patients in comparison to controls, which correlated significantly with the degree of negative symptoms. We further detected a comparable LC activation in in patients and healthy controls. However, in controls LC activation was significantly correlated with the Stroop interference time, which was not observed in patients. The finding of reduced VTA activation in schizophrenia patients lends further support to the assumed dysfunction of the DA system in schizophrenia. In addition, despite comparable LC activation, the nonsignificant correlation with the Stroop interference time might indicate altered LC functioning in schizophrenia and, thus, needs further investigations.
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Affiliation(s)
- Stefanie Köhler
- Psychiatric Brain and Body Research Group Jena, Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany
| | - Gerd Wagner
- Psychiatric Brain and Body Research Group Jena, Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany
| | - Karl-Jürgen Bär
- Psychiatric Brain and Body Research Group Jena, Department of Psychiatry and Psychotherapy, University Hospital Jena, Jena, Germany
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23
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Zhao X, Liu J, Yang S, Song D, Wang C, Chen C, Wang C, Pu F, Yang R, Li X, Wang Q, Ge S, Lin Y, Liu X, Cai D. A novel pharmacodynamic model in rats for preventing vascular dementia from maintaining neurovascular coupling sensitivity. Eur J Pharmacol 2018. [PMID: 29526715 DOI: 10.1016/j.ejphar.2018.03.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Vascular dementia (VaD) is the common cognitive disorder derived mainly from lacunar stroke. The neurovascular coupling (NVC) dysfunction involves in its pathogenesis. VaD lacks suitable animal models for developing preventive therapies. This study aimed to confirm a model for preventing VaD via maintaining NVC sensitivity in rats. The model was replicated with autologous microthrombi against the background of hypercholesterolemia. A phosphodiesterase inhibitor (pentoxyfylline) was preventively administrated to confirm the role of NVC sensitivity. Cognitive function was evaluated as exploratory, learning and memorizing abilities. NVC sensitivity was defined as the ratio of microcirculative cerebral blood flow (∆CBF) to the quantitative electroencephalograph (∆qEEG) before and after penicillin stimulation. The pathogenesis of NVC dysfunction was explored as expressions of neuronal (nNOS), inducible (iNOS) and endothelial nitric oxide synthase (eNOS) in cerebral cortex. The model rats showed cognitive impairment, microvascular edema (2.54 ± 0.30%, P < 0.01), neuronal edema (1.24 ± 0.48%, P < 0.01) and nissl body loss (0.03 ± 0.003%, P < 0.01) in cerebral cortex, and neuronal necrosis in hippocampal CA1 region (neuronal cell number 41.76 ± 10.04 cells, P < 0.01) compared with sham group. The NVC dullness in model rats was confirmed as significantly decreased ratio of ∆CBF/∆qEEG (0.05 ± 0.02%, P < 0.01) compared with sham group (0.20 ± 0.06%). The underlying mechanism of NVC dysfunction was found as imbalanced NOS expressions (decreased nNOS and eNOS, while increased iNOS levels in cerebral cortex). The NVC dullness was significantly relieved in pentoxyfylline administrated rats (0.12 ± 0.06%, P < 0.01). It indicated that this model was suitable to evaluate candidates for preventing VaD via maintaining NVC sensitivity.
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Affiliation(s)
- Xin Zhao
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
| | - Jinyu Liu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
| | - Shijun Yang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
| | - Dandan Song
- Department of Pathophysiology, Chinese PLA General Hospital, Beijing 10853, China
| | - Chen Wang
- Department of Pathophysiology, Chinese PLA General Hospital, Beijing 10853, China
| | - Chen Chen
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
| | - Chengcheng Wang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
| | - Feifei Pu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
| | - Runmei Yang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
| | - Xiaoya Li
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
| | - Qiuting Wang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
| | - Shasha Ge
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
| | - Yulin Lin
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China
| | - Xiuhua Liu
- Department of Pathophysiology, Chinese PLA General Hospital, Beijing 10853, China.
| | - Dayong Cai
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
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24
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Guerra G, Lucariello A, Perna A, Botta L, De Luca A, Moccia F. The Role of Endothelial Ca 2+ Signaling in Neurovascular Coupling: A View from the Lumen. Int J Mol Sci 2018; 19:E938. [PMID: 29561829 PMCID: PMC5979341 DOI: 10.3390/ijms19040938] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Revised: 03/16/2018] [Accepted: 03/17/2018] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca2+-dependent manner throughout peripheral vasculature. METHODS We analyzed the literature in search of the most recent updates on the potential role of endothelial Ca2+ signaling in NVC. RESULTS We found that several neurotransmitters (i.e., glutamate and acetylcholine) and neuromodulators (e.g., ATP) can induce dilation of cerebral vessels by inducing an increase in endothelial Ca2+ concentration. This, in turn, results in nitric oxide or prostaglandin E2 release or activate intermediate and small-conductance Ca2+-activated K⁺ channels, which are responsible for endothelial-dependent hyperpolarization (EDH). In addition, brain endothelial cells express multiple transient receptor potential (TRP) channels (i.e., TRPC3, TRPV3, TRPV4, TRPA1), which induce vasodilation by activating EDH. CONCLUSIONS It is possible to conclude that endothelial Ca2+ signaling is an emerging pathway in the control of NVC.
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Affiliation(s)
- Germano Guerra
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, via F. De Santis, 86100 Campobasso, Italy.
| | - Angela Lucariello
- Department of Mental Health and Preventive Medicine, Section of Human Anatomy, University of Campania "L. Vanvitelli", 81100 Naples, Italy.
| | - Angelica Perna
- Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, via F. De Santis, 86100 Campobasso, Italy.
| | - Laura Botta
- Laboratory of General Physiology, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, via Forlanini 6, 27100 Pavia, Italy.
| | - Antonio De Luca
- Department of Mental Health and Preventive Medicine, Section of Human Anatomy, University of Campania "L. Vanvitelli", 81100 Naples, Italy.
| | - Francesco Moccia
- Laboratory of General Physiology, Department of Biology and Biotechnology "L. Spallanzani", University of Pavia, via Forlanini 6, 27100 Pavia, Italy.
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How to choose the right MR sequence for your research question at 7 T and above? Neuroimage 2018; 168:119-140. [DOI: 10.1016/j.neuroimage.2017.04.044] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 04/18/2017] [Accepted: 04/19/2017] [Indexed: 12/29/2022] Open
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Brain activity for tactile allodynia: a longitudinal awake rat functional magnetic resonance imaging study tracking emergence of neuropathic pain. Pain 2017; 158:488-497. [PMID: 28135213 DOI: 10.1097/j.pain.0000000000000788] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Tactile allodynia, a condition in which innocuous mechanical stimuli are perceived as painful, is a common feature of chronic pain. However, how the brain reorganizes in relation to the emergence of tactile allodynia is still largely unknown. This may stem from the fact that experiments in humans are cross-sectional in nature, whereas animal brain imaging studies typically require anaesthesia rendering the brain incapable of consciously sensing or responding to pain. In this longitudinal functional magnetic resonance imaging study in awake rats, we tracked brain activity with the development of tactile allodynia. Before injury, innocuous air-puff stimuli evoked a distributed sensory network of activations, including contralateral somatosensory cortices, thalamus, insula, and cingulate cortex. Moreover, the primary somatosensory cortex displayed a graded response tracking air-puff stimulus intensities. After neuropathic injury, and for stimuli in which the intensity exceeded the paw withdrawal threshold (evoking tactile allodynia), the blood oxygenation level-dependent response in the primary somatosensory cortex was equivalent to that evoked by the identical stimulus before injury. In contrast, nucleus accumbens and prefrontal brain areas displayed abnormal activity to normally innocuous stimuli when such stimuli induced tactile allodynia at 28 days after peripheral nerve injury, which had not been the case at 5 days after injury. Our data indicate that tactile allodynia-related nociceptive inputs are not observable in the primary somatosensory cortex BOLD response. Instead, our data suggest that, in time, tactile allodynia differentially engages neural circuits that regulate the affective and motivational components of pain.
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Havlicek M, Ivanov D, Roebroeck A, Uludağ K. Determining Excitatory and Inhibitory Neuronal Activity from Multimodal fMRI Data Using a Generative Hemodynamic Model. Front Neurosci 2017; 11:616. [PMID: 29249925 PMCID: PMC5715391 DOI: 10.3389/fnins.2017.00616] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 10/23/2017] [Indexed: 12/12/2022] Open
Abstract
Hemodynamic responses, in general, and the blood oxygenation level-dependent (BOLD) fMRI signal, in particular, provide an indirect measure of neuronal activity. There is strong evidence that the BOLD response correlates well with post-synaptic changes, induced by changes in the excitatory and inhibitory (E-I) balance between active neuronal populations. Typical BOLD responses exhibit transients, such as the early-overshoot and post-stimulus undershoot, that can be linked to transients in neuronal activity, but they can also result from vascular uncoupling between cerebral blood flow (CBF) and venous cerebral blood volume (venous CBV). Recently, we have proposed a novel generative hemodynamic model of the BOLD signal within the dynamic causal modeling framework, inspired by physiological observations, called P-DCM (Havlicek et al., 2015). We demonstrated the generative model's ability to more accurately model commonly observed neuronal and vascular transients in single regions but also effective connectivity between multiple brain areas (Havlicek et al., 2017b). In this paper, we additionally demonstrate the versatility of the generative model to jointly explain dynamic relationships between neuronal and hemodynamic physiological variables underlying the BOLD signal using multi-modal data. For this purpose, we utilized three distinct data-sets of experimentally induced responses in the primary visual areas measured in human, cat, and monkey brain, respectively: (1) CBF and BOLD responses; (2) CBF, total CBV, and BOLD responses (Jin and Kim, 2008); and (3) positive and negative neuronal and BOLD responses (Shmuel et al., 2006). By fitting the generative model to the three multi-modal experimental data-sets, we showed that the presence or absence of dynamic features in the BOLD signal is not an unambiguous indication of presence or absence of those features on the neuronal level. Nevertheless, the generative model that takes into account the dynamics of the physiological mechanisms underlying the BOLD response allowed dissociating neuronal from vascular transients and deducing excitatory and inhibitory neuronal activity time-courses from BOLD data alone and from multi-modal data.
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Affiliation(s)
- Martin Havlicek
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
| | - Dimo Ivanov
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
| | - Alard Roebroeck
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
| | - Kamil Uludağ
- Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
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Wright PW, Brier LM, Bauer AQ, Baxter GA, Kraft AW, Reisman MD, Bice AR, Snyder AZ, Lee JM, Culver JP. Functional connectivity structure of cortical calcium dynamics in anesthetized and awake mice. PLoS One 2017; 12:e0185759. [PMID: 29049297 PMCID: PMC5648115 DOI: 10.1371/journal.pone.0185759] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 09/19/2017] [Indexed: 11/30/2022] Open
Abstract
The interplay between hemodynamic-based markers of cortical activity (e.g. fMRI and optical intrinsic signal imaging), which are an indirect and relatively slow report of neural activity, and underlying synaptic electrical and metabolic activity through neurovascular coupling is a topic of ongoing research and debate. As application of resting state functional connectivity measures is extended further into topics such as brain development, aging and disease, the importance of understanding the fundamental physiological basis for functional connectivity will grow. Here we extend functional connectivity analysis from hemodynamic- to calcium-based imaging. Transgenic mice (n = 7) expressing a fluorescent calcium indicator (GCaMP6) driven by the Thy1 promoter in glutamatergic neurons were imaged transcranially in both anesthetized (using ketamine/xylazine) and awake states. Sequential LED illumination (λ = 454, 523, 595, 640nm) enabled concurrent imaging of both GCaMP6 fluorescence emission (corrected for hemoglobin absorption) and hemodynamics. Functional connectivity network maps were constructed for infraslow (0.009–0.08Hz), intermediate (0.08–0.4Hz), and high (0.4–4.0Hz) frequency bands. At infraslow and intermediate frequencies, commonly used in BOLD fMRI and fcOIS studies of functional connectivity and implicated in neurovascular coupling mechanisms, GCaMP6 and HbO2 functional connectivity structures were in high agreement, both qualitatively and also quantitatively through a measure of spatial similarity. The spontaneous dynamics of both contrasts had the highest correlation when the GCaMP6 signal was delayed with a ~0.6–1.5s temporal offset. Within the higher-frequency delta band, sensitive to slow wave sleep oscillations in non-REM sleep and anesthesia, we evaluate the speed with which the connectivity analysis stabilized and found that the functional connectivity maps captured putative network structure within time window lengths as short as 30 seconds. Homotopic GCaMP6 functional connectivity maps at 0.4–4.0Hz in the anesthetized states show a striking correlated and anti-correlated structure along the anterior to posterior axis. This structure is potentially explained in part by observed propagation of delta-band activity from frontal somatomotor regions to visuoparietal areas. During awake imaging, this spatio-temporal quality is altered, and a more complex and detailed functional connectivity structure is observed. The combined calcium/hemoglobin imaging technique described here will enable the dissociation of changes in ionic and hemodynamic functional structure and neurovascular coupling and provide a framework for subsequent studies of neurological disease such as stroke.
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Affiliation(s)
- Patrick W. Wright
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, United States of America
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Lindsey M. Brier
- Department of Neuroscience, Washington University in St. Louis, St. Louis, Missouri, United States of America
| | - Adam Q. Bauer
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Grant A. Baxter
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Andrew W. Kraft
- Department of Neuroscience, Washington University in St. Louis, St. Louis, Missouri, United States of America
| | - Matthew D. Reisman
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Department of Physics, Washington University in St. Louis, St. Louis, Missouri, United States of America
| | - Annie R. Bice
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Abraham Z. Snyder
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Jin-Moo Lee
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, United States of America
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Department Neurology, Washington University School of Medicine, St. Louis, Missouri, United States of America
| | - Joseph P. Culver
- Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, United States of America
- Department of Radiology, Washington University School of Medicine, St. Louis, Missouri, United States of America
- Department of Neuroscience, Washington University in St. Louis, St. Louis, Missouri, United States of America
- * E-mail:
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Cacioppo S. Neuroimaging of Female Sexual Desire and Hypoactive Sexual Desire Disorder. Sex Med Rev 2017; 5:434-444. [DOI: 10.1016/j.sxmr.2017.07.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Revised: 07/13/2017] [Accepted: 07/15/2017] [Indexed: 10/18/2022]
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Sten S, Lundengård K, Witt S, Cedersund G, Elinder F, Engström M. Neural inhibition can explain negative BOLD responses: A mechanistic modelling and fMRI study. Neuroimage 2017; 158:219-231. [DOI: 10.1016/j.neuroimage.2017.07.002] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 06/03/2017] [Accepted: 07/02/2017] [Indexed: 12/13/2022] Open
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Hinojosa-Rodríguez M, Harmony T, Carrillo-Prado C, Van Horn JD, Irimia A, Torgerson C, Jacokes Z. Clinical neuroimaging in the preterm infant: Diagnosis and prognosis. Neuroimage Clin 2017; 16:355-368. [PMID: 28861337 PMCID: PMC5568883 DOI: 10.1016/j.nicl.2017.08.015] [Citation(s) in RCA: 82] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2017] [Revised: 08/11/2017] [Accepted: 08/12/2017] [Indexed: 01/30/2023]
Abstract
Perinatal care advances emerging over the past twenty years have helped to diminish the mortality and severe neurological morbidity of extremely and very preterm neonates (e.g., cystic Periventricular Leukomalacia [c-PVL] and Germinal Matrix Hemorrhage - Intraventricular Hemorrhage [GMH-IVH grade 3-4/4]; 22 to < 32 weeks of gestational age, GA). However, motor and/or cognitive disabilities associated with mild-to-moderate white and gray matter injury are frequently present in this population (e.g., non-cystic Periventricular Leukomalacia [non-cystic PVL], neuronal-axonal injury and GMH-IVH grade 1-2/4). Brain research studies using magnetic resonance imaging (MRI) report that 50% to 80% of extremely and very preterm neonates have diffuse white matter abnormalities (WMA) which correspond to only the minimum grade of severity. Nevertheless, mild-to-moderate diffuse WMA has also been associated with significant affectations of motor and cognitive activities. Due to increased neonatal survival and the intrinsic characteristics of diffuse WMA, there is a growing need to study the brain of the premature infant using non-invasive neuroimaging techniques sensitive to microscopic and/or diffuse lesions. This emerging need has led the scientific community to try to bridge the gap between concepts or ideas from different methodologies and approaches; for instance, neuropathology, neuroimaging and clinical findings. This is evident from the combination of intense pre-clinical and clinicopathologic research along with neonatal neurology and quantitative neuroimaging research. In the following review, we explore literature relating the most frequently observed neuropathological patterns with the recent neuroimaging findings in preterm newborns and infants with perinatal brain injury. Specifically, we focus our discussions on the use of neuroimaging to aid diagnosis, measure morphometric brain damage, and track long-term neurodevelopmental outcomes.
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Affiliation(s)
- Manuel Hinojosa-Rodríguez
- Unidad de Investigación en Neurodesarrollo, Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus Juriquilla, Mexico
| | - Thalía Harmony
- Unidad de Investigación en Neurodesarrollo, Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus Juriquilla, Mexico
| | - Cristina Carrillo-Prado
- Unidad de Investigación en Neurodesarrollo, Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Campus Juriquilla, Mexico
| | - John Darrell Van Horn
- USC Mark and Mary Stevens Neuroimaging and Informatics Institute, 2025 Zonal Avenue, SHN, Los Angeles, California 90033, USA
| | - Andrei Irimia
- USC Mark and Mary Stevens Neuroimaging and Informatics Institute, 2025 Zonal Avenue, SHN, Los Angeles, California 90033, USA
| | - Carinna Torgerson
- USC Mark and Mary Stevens Neuroimaging and Informatics Institute, 2025 Zonal Avenue, SHN, Los Angeles, California 90033, USA
| | - Zachary Jacokes
- USC Mark and Mary Stevens Neuroimaging and Informatics Institute, 2025 Zonal Avenue, SHN, Los Angeles, California 90033, USA
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Changes in Hemodynamic Response Patterns in Motor Cortices Measured by Task-Based Functional Magnetic Resonance Imaging in Patients With Moyamoya Disease. J Comput Assist Tomogr 2017; 41:461-466. [PMID: 27801696 DOI: 10.1097/rct.0000000000000542] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVE We aimed to study the value of blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) in assessing cerebral hemodynamic changes for moyamoya disease (MMD). METHODS We recruited 15 healthy volunteers, 15 patients with MMD without dyskinesia, and 30 patients with MMD who experienced paroxysmal limb dyskinesia. The BOLD-fMRI scans were obtained during grasping motions of the left or right hand. Hemodynamic response curves in the primary motor cortices were generated. Six response parameters including negative response time (Tnr), maximum signal intensity of negative response, time to peak, maximum peak arrival time, maximum signal intensity of positive response, and positive response time were measured. RESULTS The hemodynamic response curve in the primary motor cortices of MMD patients showed extended Tnr, prolonged positive response time, and delayed time to peak than those of the controls. The response curve showed longer Tnr and maximum peak arrival time in the primary motor cortices on the affected side of the dyskinesia group. CONCLUSIONS Blood oxygen level-dependent fMRI is an effective technique to assess hemodynamic changes in patients with MMD.
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Unexpected global impact of VTA dopamine neuron activation as measured by opto-fMRI. Mol Psychiatry 2017; 22:585-594. [PMID: 27457809 PMCID: PMC5269559 DOI: 10.1038/mp.2016.102] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Revised: 04/27/2016] [Accepted: 05/02/2016] [Indexed: 12/17/2022]
Abstract
Dopamine neurons in the ventral tegmental area (VTA) are strongly implicated in cognitive and affective processing as well as in psychiatric disorders, including schizophrenia, depression, attention-deficit hyperactivity disorder and substance abuse disorders. In human studies, dopamine-related functions are routinely assessed using functional magnetic resonance imaging (fMRI) measures of blood oxygenation-level-dependent (BOLD) signals during the performance of dopamine-dependent tasks. There is, however, a critical void in our knowledge about whether and how activation of VTA dopamine neurons specifically influences regional or global fMRI signals. Here, we used optogenetics in Th::Cre rats to selectively stimulate VTA dopamine neurons while simultaneously measuring global hemodynamic changes using BOLD and cerebral blood volume-weighted (CBVw) fMRI. Phasic activation of VTA dopamine neurons increased BOLD and CBVw fMRI signals in VTA-innervated limbic regions, including the ventral striatum (nucleus accumbens). Surprisingly, basal ganglia regions that receive sparse or no VTA dopaminergic innervation, including the dorsal striatum and the globus pallidus, were also activated. In fact, the most prominent fMRI signal increase in the forebrain was observed in the dorsal striatum that is not traditionally associated with VTA dopamine neurotransmission. These data establish causation between phasic activation of VTA dopamine neurons and global fMRI signals. They further suggest that mesolimbic and non-limbic basal ganglia dopamine circuits are functionally connected and thus provide a potential novel framework for understanding dopamine-dependent functions and interpreting data obtained from human fMRI studies.
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The relationship between oscillatory EEG activity and the laminar-specific BOLD signal. Proc Natl Acad Sci U S A 2016; 113:6761-6. [PMID: 27247416 DOI: 10.1073/pnas.1522577113] [Citation(s) in RCA: 126] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Electrophysiological recordings in animals have indicated that visual cortex γ-band oscillatory activity is predominantly observed in superficial cortical layers, whereas α- and β-band activity is stronger in deep layers. These rhythms, as well as the different cortical layers, have also been closely related to feedforward and feedback streams of information. Recently, it has become possible to measure laminar activity in humans with high-resolution functional MRI (fMRI). In this study, we investigated whether these different frequency bands show a differential relation with the laminar-resolved blood-oxygen level-dependent (BOLD) signal by combining data from simultaneously recorded EEG and fMRI from the early visual cortex. Our visual attention paradigm allowed us to investigate how variations in strength over trials and variations in the attention effect over subjects relate to each other in both modalities. We demonstrate that γ-band EEG power correlates positively with the superficial layers' BOLD signal and that β-power is negatively correlated to deep layer BOLD and α-power to both deep and superficial layer BOLD. These results provide a neurophysiological basis for human laminar fMRI and link human EEG and high-resolution fMRI to systems-level neuroscience in animals.
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35
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Domijan D, Šetić M. Resonant Dynamics of Grounded Cognition: Explanation of Behavioral and Neuroimaging Data Using the ART Neural Network. Front Psychol 2016; 7:139. [PMID: 26903933 PMCID: PMC4749698 DOI: 10.3389/fpsyg.2016.00139] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2015] [Accepted: 01/26/2016] [Indexed: 11/13/2022] Open
Abstract
Research on grounded cognition suggests that the processing of a word or concept reactivates the perceptual representations that are associated with the referent object. The objective of this work is to demonstrate how behavioral and functional neuroimaging data on grounded cognition can be understood as different manifestations of the same cortical circuit designed to achieve stable category learning, as proposed by the adaptive resonance theory (ART). We showed that the ART neural network provides a mechanistic explanation of why reaction times in behavioral studies depend on the expectation or attentional priming created by the word meaning (Richter and Zwaan, 2009). A mismatch between top-down expectation and bottom-up sensory data activates an orienting subsystem that slows execution of the current task. Furthermore, we simulated the data from functional neuroimaging studies of color knowledge retrieval that showed anterior shift (Chao and Martin, 1999; Thompson-Schill, 2003) and an overlap effect (Simmons et al., 2007; Hsu et al., 2011) in the left fusiform gyrus. We explain the anterior effect as a result of the partial activation of different components of the same ART circuit in the condition of passive viewing. Conversely, a demanding perceptual task requires activation of the whole ART circuit. This condition is reflected in the fMRI image as an overlap between cortical activation during perceptual and conceptual processing. We conclude that the ART neural network is able to explain how the brain grounds symbols in perception via perceptual simulation.
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Affiliation(s)
- Dražen Domijan
- Laboratory for Experimental Psychology, Department of Psychology, Faculty of Humanities and Social Sciences, University of Rijeka Rijeka, Croatia
| | - Mia Šetić
- Psychology Research Laboratory, Department of Psychology, Catholic University of Croatia Zagreb, Croatia
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Kazan SM, Mohammadi S, Callaghan MF, Flandin G, Huber L, Leech R, Kennerley A, Windischberger C, Weiskopf N. Vascular autorescaling of fMRI (VasA fMRI) improves sensitivity of population studies: A pilot study. Neuroimage 2016; 124:794-805. [PMID: 26416648 PMCID: PMC4655941 DOI: 10.1016/j.neuroimage.2015.09.033] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Revised: 09/11/2015] [Accepted: 09/17/2015] [Indexed: 11/04/2022] Open
Abstract
The blood oxygenation level-dependent (BOLD) signal is widely used for functional magnetic resonance imaging (fMRI) of brain function in health and disease. The statistical power of fMRI group studies is significantly hampered by high inter-subject variance due to differences in baseline vascular physiology. Several methods have been proposed to account for physiological vascularization differences between subjects and hence improve the sensitivity in group studies. However, these methods require the acquisition of additional reference scans (such as a full resting-state fMRI session or ASL-based calibrated BOLD). We present a vascular autorescaling (VasA) method, which does not require any additional reference scans. VasA is based on the observation that slow oscillations (<0.1Hz) in arterial blood CO2 levels occur naturally due to changes in respiration patterns. These oscillations yield fMRI signal changes whose amplitudes reflect the blood oxygenation levels and underlying local vascularization and vascular responsivity. VasA estimates proxies of the amplitude of these CO2-driven oscillations directly from the residuals of task-related fMRI data without the need for reference scans. The estimates are used to scale the amplitude of task-related fMRI responses, to account for vascular differences. The VasA maps compared well to cerebrovascular reactivity (CVR) maps and cerebral blood volume maps based on vascular space occupancy (VASO) measurements in four volunteers, speaking to the physiological vascular basis of VasA. VasA was validated in a wide variety of tasks in 138 volunteers. VasA increased t-scores by up to 30% in specific brain areas such as the visual cortex. The number of activated voxels was increased by up to 200% in brain areas such as the orbital frontal cortex while still controlling the nominal false-positive rate. VasA fMRI outperformed previously proposed rescaling approaches based on resting-state fMRI data and can be readily applied to any task-related fMRI data set, even retrospectively.
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Affiliation(s)
- Samira M Kazan
- Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, University College London, London WC1N 3BG, United Kingdom.
| | - Siawoosh Mohammadi
- Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, University College London, London WC1N 3BG, United Kingdom
| | - Martina F Callaghan
- Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, University College London, London WC1N 3BG, United Kingdom
| | - Guillaume Flandin
- Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, University College London, London WC1N 3BG, United Kingdom
| | - Laurentius Huber
- NMR-Unit, Max Planck Institute for Human Cognition and Brain Sciences, Leipzig, Germany
| | - Robert Leech
- Cognitive, Clinical and Computational Neuroimaging Lab, Imperial College, Hammersmith Hospital, University of London, London W12 0NN, United Kingdom
| | - Aneurin Kennerley
- Department of Psychology, University of Sheffield, Western Bank, Sheffield S10 2TN, United Kingdom
| | - Christian Windischberger
- MR Centre of Excellence, Centre for Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria
| | - Nikolaus Weiskopf
- Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, University College London, London WC1N 3BG, United Kingdom; Department of Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
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Zippo AG, Rinaldi S, Pellegata G, Caramenti GC, Valente M, Fontani V, Biella GEM. Electrophysiological effects of non-invasive Radio Electric Asymmetric Conveyor (REAC) on thalamocortical neural activities and perturbed experimental conditions. Sci Rep 2015; 5:18200. [PMID: 26658170 PMCID: PMC4676007 DOI: 10.1038/srep18200] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Accepted: 11/13/2015] [Indexed: 01/20/2023] Open
Abstract
The microwave emitting Radio Electric Asymmetric Conveyor (REAC) is a technology able to interact with biological tissues at low emission intensity (2 mW at the emitter and 2.4 or 5.8 GHz) by inducing radiofrequency generated microcurrents. It shows remarkable biological effects at many scales from gene modulations up to functional global remodeling even in human subjects. Previous REAC experiments by functional Magnetic Resonance Imaging (fMRI) on healthy human subjects have shown deep modulations of cortical BOLD signals. In this paper we studied the effects of REAC application on spontaneous and evoked neuronal activities simultaneously recorded by microelectrode matrices from the somatosensory thalamo-cortical axis in control and chronic pain experimental animal models. We analyzed the spontaneous spiking activity and the Local Field Potentials (LFPs) before and after REAC applied with a different protocol. The single neuron spiking activities, the neuronal responses to peripheral light mechanical stimuli, the population discharge synchronies as well as the correlations and the network dynamic connectivity characteristics have been analyzed. Modulations of the neuronal frequency associated with changes of functional correlations and significant LFP temporal realignments have been diffusely observed. Analyses by topological methods have shown changes in functional connectivity with significant modifications of the network features.
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Affiliation(s)
- Antonio G Zippo
- Institute of Molecular Bioimaging and Physiology, Dept. of Bio-Medicine, National Research Council (CNR), LITA Bldg., Via Fratelli Cervi, 93, 20090 Segrate (Milan), Italy
| | - Salvatore Rinaldi
- Department of Regenerative Medicine, Rinaldi Fontani Institute, Viale Belfiore 43, 50144 Florence, Italy.,Department of Neuro Psycho Physical Optimization, Rinaldi Fontani Institute, Viale Belfiore 43, 50144 Florence, Italy.,Research Department, Rinaldi Fontani Foundation - NPO, Viale Belfiore 43, 50144 Florence, Italy
| | - Giulio Pellegata
- Institute of Molecular Bioimaging and Physiology, Dept. of Bio-Medicine, National Research Council (CNR), LITA Bldg., Via Fratelli Cervi, 93, 20090 Segrate (Milan), Italy
| | - Gian Carlo Caramenti
- Institute of Biomedical Technology, National Research Council, (CNR), LITA Bldg., Via Fratelli Cervi, 93, 20090 Segrate (Milan), Italy
| | - Maurizio Valente
- Institute of Molecular Bioimaging and Physiology, Dept. of Bio-Medicine, National Research Council (CNR), LITA Bldg., Via Fratelli Cervi, 93, 20090 Segrate (Milan), Italy
| | - Vania Fontani
- Department of Regenerative Medicine, Rinaldi Fontani Institute, Viale Belfiore 43, 50144 Florence, Italy.,Department of Neuro Psycho Physical Optimization, Rinaldi Fontani Institute, Viale Belfiore 43, 50144 Florence, Italy.,Research Department, Rinaldi Fontani Foundation - NPO, Viale Belfiore 43, 50144 Florence, Italy
| | - Gabriele E M Biella
- Institute of Molecular Bioimaging and Physiology, Dept. of Bio-Medicine, National Research Council (CNR), LITA Bldg., Via Fratelli Cervi, 93, 20090 Segrate (Milan), Italy
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COX-2-Derived Prostaglandin E2 Produced by Pyramidal Neurons Contributes to Neurovascular Coupling in the Rodent Cerebral Cortex. J Neurosci 2015; 35:11791-810. [PMID: 26311764 DOI: 10.1523/jneurosci.0651-15.2015] [Citation(s) in RCA: 78] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
UNLABELLED Vasodilatory prostaglandins play a key role in neurovascular coupling (NVC), the tight link between neuronal activity and local cerebral blood flow, but their precise identity, cellular origin and the receptors involved remain unclear. Here we show in rats that NMDA-induced vasodilation and hemodynamic responses evoked by whisker stimulation involve cyclooxygenase-2 (COX-2) activity and activation of the prostaglandin E2 (PgE2) receptors EP2 and EP4. Using liquid chromatography-electrospray ionization-tandem mass spectrometry, we demonstrate that PgE2 is released by NMDA in cortical slices. The characterization of PgE2 producing cells by immunohistochemistry and single-cell reverse transcriptase-PCR revealed that pyramidal cells and not astrocytes are the main cell type equipped for PgE2 synthesis, one third expressing COX-2 systematically associated with a PgE2 synthase. Consistent with their central role in NVC, in vivo optogenetic stimulation of pyramidal cells evoked COX-2-dependent hyperemic responses in mice. These observations identify PgE2 as the main prostaglandin mediating sensory-evoked NVC, pyramidal cells as their principal source and vasodilatory EP2 and EP4 receptors as their targets. SIGNIFICANCE STATEMENT Brain function critically depends on a permanent spatiotemporal match between neuronal activity and blood supply, known as NVC. In the cerebral cortex, prostaglandins are major contributors to NVC. However, their biochemical identity remains elusive and their cellular origins are still under debate. Although astrocytes can induce vasodilations through the release of prostaglandins, the recruitment of this pathway during sensory stimulation is questioned. Using multidisciplinary approaches from single-cell reverse transcriptase-PCR, mass spectrometry, to ex vivo and in vivo pharmacology and optogenetics, we provide compelling evidence identifying PgE2 as the main prostaglandin in NVC, pyramidal neurons as their main cellular source and the vasodilatory EP2 and EP4 receptors as their main targets. These original findings will certainly change the current view of NVC.
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Sagari A, Iso N, Moriuchi T, Ogahara K, Kitajima E, Tanaka K, Tabira T, Higashi T. Changes in Cerebral Hemodynamics during Complex Motor Learning by Character Entry into Touch-Screen Terminals. PLoS One 2015; 10:e0140552. [PMID: 26485534 PMCID: PMC4618511 DOI: 10.1371/journal.pone.0140552] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Accepted: 09/28/2015] [Indexed: 11/18/2022] Open
Abstract
Introduction Studies of cerebral hemodynamics during motor learning have mostly focused on neurorehabilitation interventions and their effectiveness. However, only a few imaging studies of motor learning and the underlying complex cognitive processes have been performed. Methods We measured cerebral hemodynamics using near-infrared spectroscopy (NIRS) in relation to acquisition patterns of motor skills in healthy subjects using character entry into a touch-screen terminal. Twenty healthy, right-handed subjects who had no previous experience with character entry using a touch-screen terminal participated in this study. They were asked to enter the characters of a randomly formed Japanese syllabary into the touch-screen terminal. All subjects performed the task with their right thumb for 15 s alternating with 25 s of rest for 30 repetitions. Performance was calculated by subtracting the number of incorrect answers from the number of correct answers, and gains in motor skills were evaluated according to the changes in performance across cycles. Behavioral and oxygenated hemoglobin concentration changes across task cycles were analyzed using Spearman’s rank correlations. Results Performance correlated positively with task cycle, thus confirming motor learning. Hemodynamic activation over the left sensorimotor cortex (SMC) showed a positive correlation with task cycle, whereas activations over the right prefrontal cortex (PFC) and supplementary motor area (SMA) showed negative correlations. Conclusions We suggest that increases in finger momentum with motor learning are reflected in the activity of the left SMC. We further speculate that the right PFC and SMA were activated during the early phases of motor learning, and that this activity was attenuated with learning progress.
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Affiliation(s)
- Akira Sagari
- Unit of Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Japanese Red Cross Society Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Naoki Iso
- Unit of Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Medical Corporation Tojinkai Miharadai Hospital, Nagasaki, Japan
| | - Takefumi Moriuchi
- Unit of Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- Medical Corporation Tojinkai Miharadai Hospital, Nagasaki, Japan
| | - Kakuya Ogahara
- Faculty of Health and Social Work, School of Rehabilitation, Kanagawa University of Human Services, Kanagawa, Japan
| | - Eiji Kitajima
- Center for Industry, University and Government Cooperation, Nagasaki University, Nagasaki, Japan
| | - Koji Tanaka
- Unit of Physical and Occupational Therapy, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
| | - Takayuki Tabira
- Faculty of Rehabilitation Sciences, Nishikyushu University, Saga, Japan
| | - Toshio Higashi
- Unit of Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
- * E-mail:
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Resting-State fMRI in MS: General Concepts and Brief Overview of Its Application. BIOMED RESEARCH INTERNATIONAL 2015; 2015:212693. [PMID: 26413509 PMCID: PMC4564590 DOI: 10.1155/2015/212693] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Revised: 01/15/2015] [Accepted: 01/28/2015] [Indexed: 01/30/2023]
Abstract
Brain functional connectivity (FC) is defined as the coherence in the activity between cerebral areas under a task or in the resting-state (RS). By applying functional magnetic resonance imaging (fMRI), RS FC shows several patterns which define RS brain networks (RSNs) involved in specific functions, because brain function is known to depend not only on the activity within individual regions, but also on the functional interaction of different areas across the whole brain. Region-of-interest analysis and independent component analysis are the two most commonly applied methods for RS investigation. Multiple sclerosis (MS) is characterized by multiple lesions mainly affecting the white matter, determining both structural and functional disconnection between various areas of the central nervous system. The study of RS FC in MS is mainly aimed at understanding alterations in the intrinsic functional architecture of the brain and their role in disease progression and clinical impairment. In this paper, we will examine the results obtained by the application of RS fMRI in different multiple sclerosis (MS) phenotypes and the correlations of FC changes with clinical features in this pathology. The knowledge of RS FC changes may represent a substantial step forward in the MS research field, both for clinical and therapeutic purposes.
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COX-2-Derived Prostaglandin E2 Produced by Pyramidal Neurons Contributes to Neurovascular Coupling in the Rodent Cerebral Cortex. J Neurosci 2015. [PMID: 26311764 DOI: 10.1523/jneurosci.0651‐15.2015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
UNLABELLED Vasodilatory prostaglandins play a key role in neurovascular coupling (NVC), the tight link between neuronal activity and local cerebral blood flow, but their precise identity, cellular origin and the receptors involved remain unclear. Here we show in rats that NMDA-induced vasodilation and hemodynamic responses evoked by whisker stimulation involve cyclooxygenase-2 (COX-2) activity and activation of the prostaglandin E2 (PgE2) receptors EP2 and EP4. Using liquid chromatography-electrospray ionization-tandem mass spectrometry, we demonstrate that PgE2 is released by NMDA in cortical slices. The characterization of PgE2 producing cells by immunohistochemistry and single-cell reverse transcriptase-PCR revealed that pyramidal cells and not astrocytes are the main cell type equipped for PgE2 synthesis, one third expressing COX-2 systematically associated with a PgE2 synthase. Consistent with their central role in NVC, in vivo optogenetic stimulation of pyramidal cells evoked COX-2-dependent hyperemic responses in mice. These observations identify PgE2 as the main prostaglandin mediating sensory-evoked NVC, pyramidal cells as their principal source and vasodilatory EP2 and EP4 receptors as their targets. SIGNIFICANCE STATEMENT Brain function critically depends on a permanent spatiotemporal match between neuronal activity and blood supply, known as NVC. In the cerebral cortex, prostaglandins are major contributors to NVC. However, their biochemical identity remains elusive and their cellular origins are still under debate. Although astrocytes can induce vasodilations through the release of prostaglandins, the recruitment of this pathway during sensory stimulation is questioned. Using multidisciplinary approaches from single-cell reverse transcriptase-PCR, mass spectrometry, to ex vivo and in vivo pharmacology and optogenetics, we provide compelling evidence identifying PgE2 as the main prostaglandin in NVC, pyramidal neurons as their main cellular source and the vasodilatory EP2 and EP4 receptors as their main targets. These original findings will certainly change the current view of NVC.
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Drenckhahn C, Koch SP, Dümmler J, Kohl-Bareis M, Steinbrink J, Dreier JP. A validation study of the use of near-infrared spectroscopy imaging in primary and secondary motor areas of the human brain. Epilepsy Behav 2015; 49:118-25. [PMID: 25976181 DOI: 10.1016/j.yebeh.2015.04.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Accepted: 04/03/2015] [Indexed: 10/23/2022]
Abstract
The electroencephalographically measured Bereitschafts (readiness)-potential in the supplementary motor area (SMA) serves as a signature of the preparation of motor activity. Using a multichannel, noninvasive near-infrared spectroscopy (NIRS) imager, we studied the vascular correlate of the readiness potential. Sixteen healthy subjects performed a self-paced or externally triggered motor task in a single or repetitive pattern, while NIRS simultaneously recorded the task-related responses of deoxygenated hemoglobin (HbR) in the primary motor area (M1) and the SMA. Right-hand movements in the repetitive sequence trial elicited a significantly greater HbR response in both the SMA and the left M1 compared to left-hand movements. During the single sequence condition, the HbR response in the SMA, but not in the M1, was significantly greater for self-paced than for externally cued movements. Nonetheless, an unequivocal temporal delay was not found between the SMA and M1. Near-infrared spectroscopy is a promising, noninvasive bedside tool for the neuromonitoring of epileptic seizures or cortical spreading depolarizations (CSDs) in patients with epilepsy, stroke, or brain trauma because these pathological events are associated with typical spatial and temporal changes in HbR. Propagation is a characteristic feature of these events which importantly supports their identification and characterization in invasive recordings. Unfortunately, the present noninvasive study failed to show a temporal delay during self-paced movements between the SMA and M1 as a vascular correlate of the readiness potential. Although this result does not exclude, in principle, the possibility that scalp-NIRS can detect a temporal delay between different regions during epileptic seizures or CSDs, it strongly suggests that further technological development of NIRS should focus on both improved spatial and temporal resolution. This article is part of a Special Issue entitled Status Epilepticus.
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Affiliation(s)
- Christoph Drenckhahn
- Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany; Department of Neurology, Charité University Medicine Berlin, Berlin, Germany; Berlin Neuroimaging Center, Charité University Medicine Berlin, Berlin, Germany
| | - Stefan P Koch
- Berlin Neuroimaging Center, Charité University Medicine Berlin, Berlin, Germany
| | - Johannes Dümmler
- Department of Anaesthesiology and Intensive Care Medicine, Christian-Albrechts University, Kiel, Germany
| | | | - Jens Steinbrink
- Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany; Berlin Neuroimaging Center, Charité University Medicine Berlin, Berlin, Germany
| | - Jens P Dreier
- Center for Stroke Research Berlin, Charité University Medicine Berlin, Berlin, Germany; Department of Neurology, Charité University Medicine Berlin, Berlin, Germany; Department of Experimental Neurology, Charité University Medicine Berlin, Berlin, Germany; Berlin Neuroimaging Center, Charité University Medicine Berlin, Berlin, Germany.
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Van Den Berge N, Vanhove C, Descamps B, Dauwe I, van Mierlo P, Vonck K, Keereman V, Raedt R, Boon P, Van Holen R. Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain. PLoS One 2015; 10:e0133245. [PMID: 26193653 PMCID: PMC4508110 DOI: 10.1371/journal.pone.0133245] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2015] [Accepted: 06/24/2015] [Indexed: 01/12/2023] Open
Abstract
Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS.
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Affiliation(s)
- Nathalie Van Den Berge
- Medical Image and Signal Processing Group, Ghent University-iMinds Medical IT department, Ghent, Belgium
- * E-mail:
| | - Christian Vanhove
- Medical Image and Signal Processing Group, Ghent University-iMinds Medical IT department, Ghent, Belgium
| | - Benedicte Descamps
- Medical Image and Signal Processing Group, Ghent University-iMinds Medical IT department, Ghent, Belgium
| | - Ine Dauwe
- Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Ghent University Hospital, Ghent, Belgium
| | - Pieter van Mierlo
- Medical Image and Signal Processing Group, Ghent University-iMinds Medical IT department, Ghent, Belgium
| | - Kristl Vonck
- Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Ghent University Hospital, Ghent, Belgium
| | - Vincent Keereman
- Medical Image and Signal Processing Group, Ghent University-iMinds Medical IT department, Ghent, Belgium
| | - Robrecht Raedt
- Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Ghent University Hospital, Ghent, Belgium
| | - Paul Boon
- Laboratory for Clinical and Experimental Neurophysiology, Neurobiology and Neuropsychology, Ghent University Hospital, Ghent, Belgium
| | - Roel Van Holen
- Medical Image and Signal Processing Group, Ghent University-iMinds Medical IT department, Ghent, Belgium
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Hand use predicts the structure of representations in sensorimotor cortex. Nat Neurosci 2015; 18:1034-40. [PMID: 26030847 DOI: 10.1038/nn.4038] [Citation(s) in RCA: 144] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2015] [Accepted: 05/07/2015] [Indexed: 11/08/2022]
Abstract
Fine finger movements are controlled by the population activity of neurons in the hand area of primary motor cortex. Experiments using microstimulation and single-neuron electrophysiology suggest that this area represents coordinated multi-joint, rather than single-finger movements. However, the principle by which these representations are organized remains unclear. We analyzed activity patterns during individuated finger movements using functional magnetic resonance imaging (fMRI). Although the spatial layout of finger-specific activity patterns was variable across participants, the relative similarity between any pair of activity patterns was well preserved. This invariant organization was better explained by the correlation structure of everyday hand movements than by correlated muscle activity. This also generalized to an experiment using complex multi-finger movements. Finally, the organizational structure correlated with patterns of involuntary co-contracted finger movements for high-force presses. Together, our results suggest that hand use shapes the relative arrangement of finger-specific activity patterns in sensory-motor cortex.
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45
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Vanni S, Sharifian F, Heikkinen H, Vigário R. Modeling fMRI signals can provide insights into neural processing in the cerebral cortex. J Neurophysiol 2015; 114:768-80. [PMID: 25972586 DOI: 10.1152/jn.00332.2014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2014] [Accepted: 05/04/2015] [Indexed: 12/16/2022] Open
Abstract
Every stimulus or task activates multiple areas in the mammalian cortex. These distributed activations can be measured with functional magnetic resonance imaging (fMRI), which has the best spatial resolution among the noninvasive brain imaging methods. Unfortunately, the relationship between the fMRI activations and distributed cortical processing has remained unclear, both because the coupling between neural and fMRI activations has remained poorly understood and because fMRI voxels are too large to directly sense the local neural events. To get an idea of the local processing given the macroscopic data, we need models to simulate the neural activity and to provide output that can be compared with fMRI data. Such models can describe neural mechanisms as mathematical functions between input and output in a specific system, with little correspondence to physiological mechanisms. Alternatively, models can be biomimetic, including biological details with straightforward correspondence to experimental data. After careful balancing between complexity, computational efficiency, and realism, a biomimetic simulation should be able to provide insight into how biological structures or functions contribute to actual data processing as well as to promote theory-driven neuroscience experiments. This review analyzes the requirements for validating system-level computational models with fMRI. In particular, we study mesoscopic biomimetic models, which include a limited set of details from real-life networks and enable system-level simulations of neural mass action. In addition, we discuss how recent developments in neurophysiology and biophysics may significantly advance the modelling of fMRI signals.
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Affiliation(s)
- Simo Vanni
- Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland;
| | - Fariba Sharifian
- Clinical Neurosciences, Neurology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Neuroscience and Biomedical Engineering, School of Science, Aalto University, Espoo, Finland; Advanced Magnetic Imaging Centre, Aalto Neuroimaging, School of Science, Aalto University, Espoo, Finland; and
| | - Hanna Heikkinen
- Department of Neuroscience and Biomedical Engineering, School of Science, Aalto University, Espoo, Finland; Advanced Magnetic Imaging Centre, Aalto Neuroimaging, School of Science, Aalto University, Espoo, Finland; and
| | - Ricardo Vigário
- Department Computer Science, School of Science, Aalto University, Espoo, Finland
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Hakun JG, Zhu Z, Brown CA, Johnson NF, Gold BT. Longitudinal alterations to brain function, structure, and cognitive performance in healthy older adults: A fMRI-DTI study. Neuropsychologia 2015; 71:225-35. [PMID: 25862416 DOI: 10.1016/j.neuropsychologia.2015.04.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 04/06/2015] [Accepted: 04/07/2015] [Indexed: 10/23/2022]
Abstract
Cross-sectional research has shown that older adults tend to have different frontal cortex activation patterns, poorer brain structure, and lower task performance than younger adults. However, relationships between longitudinal changes in brain function, brain structure, and cognitive performance in older adults are less well understood. Here we present the results of a longitudinal, combined fMRI-DTI study in cognitive normal (CN) older adults. A two time-point study was conducted in which participants completed a task switching paradigm while fMRI data was collected and underwent the identical scanning protocol an average of 3.3 years later (SD=2 months). We observed longitudinal fMRI activation increases in bilateral regions of lateral frontal cortex at time point 2. These fMRI activation increases were associated with longitudinal declines in WM microstructure in a portion of the corpus callosum connecting the increasingly recruited frontal regions. In addition, the fMRI activation increase in the left VLPFC was associated with longitudinal increases in response latencies. Taken together, our results suggest that local frontal activation increases in CN older adults may in part reflect a response to reduced inter-hemispheric signaling mechanisms.
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Affiliation(s)
| | - Zude Zhu
- Department of Anatomy and Neurobiology, USA
| | | | | | - Brian T Gold
- Department of Anatomy and Neurobiology, USA; Magnetic Resonance Imaging and Spectroscopy Center, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
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47
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Smoking normalizes cerebral blood flow and oxygen consumption after 12-hour abstention. J Cereb Blood Flow Metab 2015; 35:699-705. [PMID: 25605288 PMCID: PMC4420887 DOI: 10.1038/jcbfm.2014.246] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Revised: 11/12/2014] [Accepted: 12/05/2014] [Indexed: 02/07/2023]
Abstract
Acute nicotine administration stimulates [(14)C]deoxyglucose trapping in thalamus and other regions of rat brain, but acute effects of nicotine and smoking on energy metabolism have rarely been investigated in human brain by positron emission tomography (PET). We obtained quantitative PET measurements of cerebral blood flow (CBF) and metabolic rate of oxygen (CMRO2) in 12 smokers who had refrained from smoking overnight, and in a historical group of nonsmokers, testing the prediction that overnight abstinence results in widespread, coupled reductions of CBF and CMRO2. At the end of the abstention period, global grey-matter CBF and CMRO2 were both reduced by 17% relative to nonsmokers. At 15 minutes after renewed smoking, global CBF had increased insignificantly, while global CMRO2 had increased by 11%. Regional analysis showed that CMRO2 had increased in the left putamen and thalamus, and in right posterior cortical regions at this time. At 60 and 105 minutes after smoking resumption, CBF had increased by 8% and CMRO2 had increased by 11-12%. Thus, we find substantial and global impairment of CBF/CMRO2 in abstaining smokers, and acute restoration by resumption of smoking. The reduced CBF and CMRO2 during acute abstention may mediate the cognitive changes described in chronic smokers.
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Gold BT. Lifelong bilingualism and neural reserve against Alzheimer's disease: a review of findings and potential mechanisms. Behav Brain Res 2015; 281:9-15. [PMID: 25496781 PMCID: PMC4305453 DOI: 10.1016/j.bbr.2014.12.006] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Revised: 11/30/2014] [Accepted: 12/01/2014] [Indexed: 12/01/2022]
Abstract
Alzheimer's disease (AD) is a progressive brain disorder that initially affects medial temporal lobe circuitry and memory functions. Current drug treatments have only modest effects on the symptomatic course of the disease. In contrast, a growing body of evidence suggests that lifelong bilingualism may delay the onset of clinical AD symptoms by several years. The purpose of the present review is to summarize evidence for bilingualism as a reserve variable against AD and discuss potential underlying neurocognitive mechanisms. Evidence is reviewed suggesting that bilingualism may delay clinical AD symptoms by protecting frontostriatal and frontoparietal executive control circuitry rather than medial temporal lobe memory circuitry. Cellular and molecular mechanisms that may contribute to bilingual cognitive reserve effects are discussed, including those that may affect neuronal metabolic functions, dynamic neuronal-glial interactions, vascular factors, myelin structure and neurochemical signaling. Future studies that may test some of these potential mechanisms of bilingual CR effects are proposed.
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Affiliation(s)
- Brian T Gold
- Department of Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA; Magnetic Resonance Imaging and Spectroscopy Center, University of Kentucky, Lexington, KY 40536, USA; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536, USA.
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49
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Bengson JJ, Kelley TA, Mangun GR. The neural correlates of volitional attention: A combined fMRI and ERP study. Hum Brain Mapp 2015; 36:2443-54. [PMID: 25731128 DOI: 10.1002/hbm.22783] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2014] [Revised: 01/30/2015] [Accepted: 02/24/2015] [Indexed: 11/11/2022] Open
Abstract
Studies of visual-spatial attention typically use instructional cues to direct attention to a relevant location, but in everyday vision, attention is often focused volitionally, in the absence of external signals. Although investigations of cued attention comprise hundreds of behavioral and physiological studies, remarkably few studies of voluntary attention have addressed the challenging question of how spatial attention is initiated and controlled in the absence of external instructions, which we refer to as willed attention. To explore this question, we employed a trial-by-trial spatial attention task using electroencephalography and functional magnetic resonance imaging (fMRI). The fMRI results reveal a unique network of brain regions for willed attention that includes the anterior cingulate cortex, left middle frontal gyrus (MFG), and the left and right anterior insula (AI). We also observed two event-related potentials (ERPs) associated with willed attention; one with a frontal distribution occurring 250-350 ms postdecision cue onset (EWAC: Early Willed Attention Component), and another occurring between 400 and 800 ms postdecision-cue onset (WAC: Willed Attention Component). In addition, each ERP component uniquely correlated across subjects with different willed attention-specific sites of BOLD activation. The EWAC was correlated with the willed attention-specific left AI and left MFG activations and the later WAC was correlated only with left AI. These results offer a comprehensive and novel view of the electrophysiological and anatomical profile of willed attention and further illustrate the relationship between scalp-recorded ERPs and the BOLD response.
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Affiliation(s)
- Jesse J Bengson
- Center for Mind and Brain, UC Davis, Davis, California, 95618.,Department of Psychology UC Davis, 267 Cousteau Place, Davis, California
| | - Todd A Kelley
- Center for Mind and Brain, UC Davis, Davis, California, 95618.,Microsoft Corporation, Studio Users Research, Redmond, Washington
| | - George R Mangun
- Center for Mind and Brain, UC Davis, Davis, California, 95618.,Department of Psychology UC Davis, 267 Cousteau Place, Davis, California.,Department of Neurology UC Davis, Davis, California
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50
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Passow S, Specht K, Adamsen TC, Biermann M, Brekke N, Craven AR, Ersland L, Grüner R, Kleven-Madsen N, Kvernenes OH, Schwarzlmüller T, Olesen RA, Hugdahl K. Default-mode network functional connectivity is closely related to metabolic activity. Hum Brain Mapp 2015; 36:2027-38. [PMID: 25644693 PMCID: PMC5006878 DOI: 10.1002/hbm.22753] [Citation(s) in RCA: 110] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 01/14/2015] [Accepted: 01/20/2015] [Indexed: 11/15/2022] Open
Abstract
Over the last decade, the brain's default‐mode network (DMN) and its function has attracted a lot of attention in the field of neuroscience. However, the exact underlying mechanisms of DMN functional connectivity, or more specifically, the blood‐oxygen level‐dependent (BOLD) signal, are still incompletely understood. In the present study, we combined 2‐deoxy‐2‐[18F]fluoroglucose positron emission tomography (FDG‐PET), proton magnetic resonance spectroscopy (1H‐MRS), and resting‐state functional magnetic resonance imaging (rs‐fMRI) to investigate more directly the association between local glucose consumption, local glutamatergic neurotransmission and DMN functional connectivity during rest. The results of the correlation analyzes using the dorsal posterior cingulate cortex (dPCC) as seed region showed spatial similarities between fluctuations in FDG‐uptake and fluctuations in BOLD signal. More specifically, in both modalities the same DMN areas in the inferior parietal lobe, angular gyrus, precuneus, middle, and medial frontal gyrus were positively correlated with the dPCC. Furthermore, we could demonstrate that local glucose consumption in the medial frontal gyrus, PCC and left angular gyrus was associated with functional connectivity within the DMN. We did not, however, find a relationship between glutamatergic neurotransmission and functional connectivity. In line with very recent findings, our results lend further support for a close association between local metabolic activity and functional connectivity and provide further insights towards a better understanding of the underlying mechanism of the BOLD signal. Hum Brain Mapp 36:2027–2038, 2015. © 2015 Wiley Periodicals, Inc.
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Affiliation(s)
- Susanne Passow
- Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway; NORMENT Center of Excellence, University of Oslo, Norway
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