Methods for quantitative susceptibility and R2* mapping in whole post-mortem brains at 7T

AbstractSusceptibility weighted magnetic resonance imaging (MRI) is sensitive to the local concentration of iron and myelin. Here, we describe a robust image processing pipeline for quantitative susceptibility mapping (QSM) and R2* mapping of fixed post-mortem, whole-brain data. Using this pipeline, we compare the resulting quantitative maps in brains from patients with amyotrophic lateral sclerosis (ALS) and controls, with validation against iron and myelin histology.Twelve post-mortem brains were scanned with a multi-echo gradient echo sequence at 7T, from which susceptibility and R2* maps were generated. Semi-quantitative histological analysis for ferritin (the principal iron storage protein) and myelin proteolipid protein was performed in the primary motor, anterior cingulate and visual cortices.Magnetic susceptibility and R2* values in primary motor cortex were higher in ALS compared to control brains. Magnetic susceptibility and R2* showed positive correlations with both myelin and ferritin estimates from histology. Four out of nine ALS brains exhibited clearly visible hyperintense susceptibility and R2* values in the primary motor cortex.Our results demonstrate the potential for MRI-histology studies in whole, fixed post-mortem brains to investigate the biophysical source of susceptibility weighted MRI signals in neurodegenerative diseases like ALS.

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What drives MRI-measured cortical atrophy in multiple sclerosis?

Multiple Sclerosis Journal ◽

10.1177/1352458514562440 ◽

2015 ◽

Vol 21 (10) ◽

pp. 1280-1290 ◽

Cited By ~ 49

Author(s):

V Popescu ◽

R Klaver ◽

P Voorn ◽

Y Galis-de Graaf ◽

DL Knol ◽

...

Keyword(s):

Multiple Sclerosis ◽

Inferior Frontal Gyrus ◽

Superior Temporal Gyrus ◽

Anterior Cingulate ◽

Cortical Atrophy ◽

Post Mortem ◽

Mri Imaging ◽

Cortical Volume ◽

Axonal Pathology ◽

Magnetic Resonance Imaging Mri

Background: Cortical atrophy, assessed with magnetic resonance imaging (MRI), is an important outcome measure in multiple sclerosis (MS) studies. However, the underlying histopathology of cortical volume measures is unknown. Objective: We investigated the histopathological substrate of MRI-measured cortical volume in MS using combined post-mortem imaging and histopathology. Methods: MS brain donors underwent post-mortem whole-brain in-situ MRI imaging. After MRI, tissue blocks were systematically sampled from the superior and inferior frontal gyrus, anterior cingulate gyrus, inferior parietal lobule, and superior temporal gyrus. Histopathological markers included neuronal, axonal, synapse, astrocyte, dendrite, myelin, and oligodendrocyte densities. Matched cortical volumes from the aforementioned anatomical regions were measured on the MRI, and used as outcomes in a nested prediction model. Results: Forty-five tissue blocks were sampled from 11 MS brain donors. Mean age at death was 68±12 years, post-mortem interval 4±1 hours, and disease duration 35±15 years. MRI-measured regional cortical volumes varied depending on anatomical region. Neuronal density, neuronal size, and axonal density were significant predictors of GM volume. Conclusions: In patients with long-standing disease, neuronal and axonal pathology are the predominant pathological substrates of MRI-measured cortical volume in chronic MS.

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Parallel Information Processing in Motor Systems: Intracerebral Recordings of Readiness Potential and CNV in Human Subjects

Neural Plasticity ◽

10.1155/np.2000.65 ◽

2000 ◽

Vol 7 (1-2) ◽

pp. 65-72 ◽

Cited By ~ 14

Author(s):

Ivan Rektor

Keyword(s):

Basal Ganglia ◽

Motor Cortex ◽

Primary Motor Cortex ◽

Human Subjects ◽

Anterior Cingulate ◽

Readiness Potential ◽

Task Context ◽

Subcortical Structures ◽

Depth Electrodes ◽

Simultaneous Activation

We performed intracerebral recordings of Readiness Potential (RP) and Contingent Negative Variation (CNV) with simple repetitive distal limb movement in candidates for epilepsy surgery. In 26 patients (in Paris), depth electrodes were located in various cortical structures; in eight patients (in Brno), in the basal ganglia and the cortex. RPs were displayed in the conteral primary motor cortex, conteral somato-sensory cortex, and bilaterally in the SMA and the caudal part of the anterior cingulate cortices. CNVs were recorded in the same cortical regiom as the RP, as well as in the ipsilateral primary motor cortex, and bilaterally in the premotor fronto-lateral, parietal superior, and middle temporal regions. In the basal ganglia, the RP was recorded in the putamen in six of seven patients, and in the head of the caudate nucleus and the pallidum in the only patient with electrodes in these recording sites. We suggest that our results are consistent with a long-lasting, simultaneous activation of cortical and subcortical structures, before and during self-paced and stimulus-triggered movements. The particular regiom that are simultaneously active may be determined by the task context.

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Magnetic susceptibility in the deep layers of the primary motor cortex in Amyotrophic Lateral Sclerosis

NeuroImage Clinical ◽

10.1016/j.nicl.2016.04.011 ◽

2016 ◽

Vol 12 ◽

pp. 965-969 ◽

Cited By ~ 37

Author(s):

M. Costagli ◽

G. Donatelli ◽

L. Biagi ◽

E. Caldarazzo Ienco ◽

G. Siciliano ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Magnetic Susceptibility ◽

Motor Cortex ◽

Primary Motor Cortex ◽

Deep Layers ◽

Lateral Sclerosis

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Two Neural Networks for Laughter: A Tractography Study

Cerebral Cortex ◽

10.1093/cercor/bhaa264 ◽

2020 ◽

Author(s):

M Gerbella ◽

C Pinardi ◽

G Di Cesare ◽

G Rizzolatti ◽

F Caruana

Keyword(s):

Motor Cortex ◽

Primary Motor Cortex ◽

Motor Behavior ◽

Internal Capsule ◽

Anterior Cingulate ◽

Neural Basis ◽

Temporal Pole ◽

Complex Motor ◽

Frontal Operculum ◽

Descending Projections

Abstract Laughter is a complex motor behavior occurring in both emotional and nonemotional contexts. Here, we investigated whether the different functions of laughter are mediated by distinct networks and, if this is the case, which are the white matter tracts sustaining them. We performed a multifiber tractography investigation placing seeds in regions involved in laughter production, as identified by previous intracerebral electrical stimulation studies in humans: the pregenual anterior cingulate (pACC), ventral temporal pole (TPv), frontal operculum (FO), presupplementary motor cortex, and ventral striatum/nucleus accumbens (VS/NAcc). The primary motor cortex (M1) and two subcortical territories were also studied to trace the descending projections. Results provided evidence for the existence of two relatively distinct networks. A first network, including pACC, TPv, and VS/NAcc, is interconnected through the anterior cingulate bundle, the accumbofrontal tract, and the uncinate fasciculus, reaching the brainstem throughout the mamillo-tegmental tract. This network is likely involved in the production of emotional laughter. A second network, anchored to FO and M1, projects to the brainstem motor nuclei through the internal capsule. It is most likely the neural basis of nonemotional and conversational laughter. The two networks interact throughout the pre-SMA that is connected to both pACC and FO.

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Brain Data Standards Ontology: A data-driven ontology of transcriptomically defined cell types in the primary motor cortex

10.1101/2021.10.10.463703 ◽

2021 ◽

Author(s):

Shawn Zheng Kai Tan ◽

Huseyin Kir ◽

Brian Aevermann ◽

Tom Gillespie ◽

Michael Hawrylycz ◽

...

Keyword(s):

Motor Cortex ◽

Single Cell ◽

Primary Motor Cortex ◽

Cell Types ◽

Use Cases ◽

Data Driven ◽

Cell Type ◽

Data Standards ◽

Brain Data ◽

The Brain

Large scale single cell omics profiling is revolutionising our understanding of cell types, especially in complex organs like the brain. This presents both an opportunity and a challenge for cell ontologies. Annotation of cell types in single cell 'omics data typically uses unstructured free text, making comparison and mapping of annotation between datasets challenging. Annotation with cell ontologies is key to overcoming this challenge, but this will require meeting the challenge of extending cell ontologies representing classically defined cell types by defining and classifying cell types directly from data. Here we present the Brain Data Standards Ontology (BDSO), a data driven ontology that is built as an extension to the Cell Ontology (CL). It supports two major use cases: cell type annotation, and navigation, search, and organisation of a web application integrating single cell omics datasets for the mammalian primary motor cortex. The ontology is built using a semi-automated pipeline that interlinks cell type taxonomies and necessary and sufficient marker genes, and imports relevant ontology modules derived from external ontologies. Overall, the BDS ontology provides an underlying structure that supports these use cases, while remaining sustainable and extensible through automation as our knowledge of brain cell type expands.

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Post-Stroke Intractable Pain

Pain Neurosurgery ◽

10.1093/med/9780190887674.003.0022 ◽

2019 ◽

pp. 173-178

Author(s):

Innocent Njoku ◽

Julie G. Pilitsis

Keyword(s):

Electrical Stimulation ◽

Motor Cortex ◽

Primary Motor Cortex ◽

Pain Syndrome ◽

Underlying Mechanism ◽

Anterior Cingulate ◽

Intractable Pain ◽

Analgesic Effects ◽

Diagnostic Work ◽

Stimulation Of

Deep brain stimulation (DBS) has been used as a mode to treat chronic intractable pain by targeting the ventroposterior (VP) thalamus, the periaqueductal gray (PAG), or the anterior cingulate cortex (ACC). The exact underlying mechanism by which these targets produce an analgesic effect remains unclear, but stimulation of the thalamocortical pathways, alteration of thalamic activity, and interference of the pain relay pathway have been postulated as plausible mechanisms. Motor cortex stimulation (MCS) has also been used for the treatment of intractable pain through stimulation of the primary motor cortex. Intermittent electrical stimulation is delivered at thresholds lower than evoking a motor response but adequate enough to provide variable analgesic effects. We present a case to illustrate the diagnostic work-up, surgical technique, complications, and outcomes of (sub)cortical electrical stimulation for central pain syndrome.

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Operculo-insular and anterior cingulate plasticity induced by transcranial magnetic stimulation in the human motor cortex: a dynamic casual modeling study

Journal of Neurophysiology ◽

10.1152/jn.00670.2020 ◽

2021 ◽

Vol 125 (4) ◽

pp. 1180-1190

Author(s):

Duncan J. Hodkinson ◽

Andreas Bungert ◽

Richard Bowtell ◽

Stephen R. Jackson ◽

JeYoung Jung

Keyword(s):

Transcranial Magnetic Stimulation ◽

Motor Cortex ◽

Magnetic Stimulation ◽

Primary Motor Cortex ◽

Effective Connectivity ◽

Anterior Cingulate ◽

Human Motor Cortex ◽

Promising Treatment ◽

Human Motor ◽

Lateral Pain

Transcranial magnetic stimulation of the primary motor cortex (M1) is a promising treatment for chronic pain, but its mechanism of action remains unclear. Competing dynamic causal models of effective connectivity between M1 and medial and lateral pain systems suggest direct input into the insular, anterior cingulate cortex, and parietal operculum. This supports the hypothesis that analgesia produced from M1 stimulation most likely acts through the activation of top-down processes associated with intracortical modulation.

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Supplementary motor area structure and function: Review and hypotheses

Behavioral and Brain Sciences ◽

10.1017/s0140525x00045167 ◽

1985 ◽

Vol 8 (4) ◽

pp. 567-588 ◽

Cited By ~ 807

Author(s):

Gary Goldberg

Keyword(s):

Motor Cortex ◽

Primary Motor Cortex ◽

Supplementary Motor Area ◽

Motor Area ◽

Anterior Cingulate ◽

Current Evidence ◽

Limbic Cortex ◽

Extended Action ◽

Discrete Action ◽

And Function

AbstractThough its existence has been known for well over 30 years, only recently has the supplementary motor area (SMA) and its role in the cortical organization of movement come to be examined in detail by neuroscientists. Evidence from a wide variety of investigational perspectives is reviewed in an attempt to synthesize a conceptual framework for understanding SMA function. It is suggested that the SMA has an important role to play in the intentional process whereby internal context influences the elaboration of action. It may be viewed as phylogenetically older motor cortex, derived from anterior cingulate periarchicortical limbic cortex, which, as a key part of a medial premotor system, is crucial in the “programming” and fluent execution of extended action sequences which are “projectional” in that they rely on model-based prediction. This medial system can be distinguished from a lateral premotor system postulated to have evolved over phylogeny from a different neural source. An anatomico-physiologic model of the medial premotor system is proposed which embodies the principles of cyclicity and reentrance in the process of selecting those neural components to become active in conjunction with the performance of a particular action. The postulated dynamic action of this model in the microgenesis of a discrete action is outlined. It is concluded that although there is a great deal to be learned about the SMA, a convergence of current evidence can be identified. Such evidence suggests that the SMA plays an important role in the development of the intention-to-act and the specification and elaboration of action through its mediation between medial limbic cortex and primary motor cortex.

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Aging-related hypometabolism in the anterior cingulate cortex mediates the relationship between age vs. executive function but not vs. memory in cognitively intact elders

10.1101/635219 ◽

2019 ◽

Author(s):

José V. Pardo ◽

Shantal M. Nyabwari ◽

Joel T. Lee ◽

Keyword(s):

Executive Function ◽

Motor Cortex ◽

Cognitive Decline ◽

Anterior Cingulate Cortex ◽

Control Region ◽

Primary Motor Cortex ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Cognitively Intact ◽

The Relationship

ABSTRACTElucidating the pathophysiology of cognitive decline during aging in those without overt neurodegeneration is a prerequisite to improved diagnosis, prevention, and treatment of cognitive aging. We showed previously the anterior cingulate cortex (ACC) and adjacent medial prefrontal cortex (mPFC) are centers for aging-related metabolic dysfunction that correlate with age-associated cognitive decline in healthy volunteers. Here, we examine using the extensive and well-characterized ADNI dataset the hypothesis that ACC metabolism in healthy seniors functions as a mediator in the relationship between age and executive function. In agreement with our previous findings, highly significant correlations arose between age and metabolism; metabolism and fluency; and age and fluency. These observations motivated a mediation model in which ACC metabolism mediates the relationship between age and fluency score. Significance of the indirect effect was examined by Sobel testing and bootstrapping. In these cognitively intact seniors with “typical aging,” there was neither a correlation between age and memory scores nor between ACC metabolism and memory scores. The metabolism in a control region, the primary motor cortex, showed no correlation with age or ACC metabolism. These findings motivate further research into aging-related ACC dysfunction to prevent, diagnose, and treat the decline in executive function associated with aging in the absence of known neurodegenerative diseases.SIGNIFICANCE STATEMENTThe pathophysiology of aging-related cognitive decline remains unclear but the anterior cingulate cortex (ACC), a major component of the anterior human attention system, shows decreasing metabolism that correlates with declining executive function despite otherwise intact cognition. Here, the relationships between ACC metabolism, age, executive function, and memory were examined using the large, public, ADNI database. Earlier findings were confirmed. In addition, ACC metabolism was found a mediator between age and executive function. In contrast, no correlation arose between memory and age or between memory and ACC metabolism. No correlations surfaced when using the metabolism of the right primary motor cortex as a control region. Development of preventive medicine and novel treatments will require elucidation of aging-related ACC pathophysiology requiring further research.

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Perisomatic innervation and neurochemical features of giant pyramidal neurons in both hemispheres of the human primary motor cortex

Brain Structure and Function ◽

10.1007/s00429-020-02182-8 ◽

2020 ◽

Author(s):

Péter Szocsics ◽

Péter Papp ◽

László Havas ◽

Masahiko Watanabe ◽

Zsófia Maglóczky

Keyword(s):

Motor Cortex ◽

Calcium Binding ◽

Primary Motor Cortex ◽

Glutamate Transporter ◽

Morphological Properties ◽

Post Mortem ◽

Human Motor Cortex ◽

Post Mortem Interval ◽

Soma Size ◽

Betz Cells

AbstractBetz cells—the gigantopyramidal neurons found in high amount in the primary motor cortex—are among of the most characteristic neuronal cells. A part of them contains the calcium-binding protein parvalbumin (PV) in primates. However, less is known about these cells in the human motor cortex despite their important role in different neurological disorders. Therefore, the aim of our study was to investigate the neurochemical features and perisomatic input properties of Betz cells in control human samples with short post-mortem interval. We used different microscopic techniques to investigate the primary motor cortex of both hemispheres. The soma size and density, and expression of PV of the Betz cells were investigated. Furthermore, we used confocal fluorescent and electron microscopy to examine their perisomatic input. The soma size and density showed moderate variability among samples and hemispheres. Post-mortem interval and hemispherical localization did not influence these features. Around 70% of Betz cells expressed PV, but in less intensity than the cortical interneurons. Betz neurons receive dense perisomatic input, which are mostly VIAAT- (vesicular inhibitory amino acid transporter) and PV immunopositive. In the electron microscope, we found PV-immunolabelled terminals with asymmetric-like synaptic structure, too. Terminals with morphologically similar synaptic specialisation were also found among vGluT2- (vesicular glutamate transporter type 2) immunostained terminals contacting Betz cells. Our data suggest that Betz cells’ morphological properties showed less variability among subjects and hemispheres than the density of them. Their neurochemical and perisomatic input characteristics support their role in execution of fast and precise movements.

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