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PLoS Biology Mar 2023Experience and training are known to boost our skills and mold the brain's organization and function. Yet, structural plasticity and functional neurotransmission are...
Experience and training are known to boost our skills and mold the brain's organization and function. Yet, structural plasticity and functional neurotransmission are typically studied at different scales (large-scale networks, local circuits), limiting our understanding of the adaptive interactions that support learning of complex cognitive skills in the adult brain. Here, we employ multimodal brain imaging to investigate the link between microstructural (myelination) and neurochemical (GABAergic) plasticity for decision-making. We test (in males, due to potential confounding menstrual cycle effects on GABA measurements in females) for changes in MRI-measured myelin, GABA, and functional connectivity before versus after training on a perceptual decision task that involves identifying targets in clutter. We demonstrate that training alters subcortical (pulvinar, hippocampus) myelination and its functional connectivity to visual cortex and relates to decreased visual cortex GABAergic inhibition. Modeling interactions between MRI measures of myelin, GABA, and functional connectivity indicates that pulvinar myelin plasticity interacts-through thalamocortical connectivity-with GABAergic inhibition in visual cortex to support learning. Our findings propose a dynamic interplay of adaptive microstructural and neurochemical plasticity in subcortico-cortical circuits that supports learning for optimized decision-making in the adult human brain.
Topics: Adult; Male; Female; Humans; Learning; Brain; Magnetic Resonance Imaging; Brain Mapping; gamma-Aminobutyric Acid; Neuronal Plasticity
PubMed: 36897881
DOI: 10.1371/journal.pbio.3002029 -
Human Brain Mapping Apr 2023Cross-modal plasticity in blind individuals has been reported over the past decades showing that nonvisual information is carried and processed by "visual" brain...
Cross-modal plasticity in blind individuals has been reported over the past decades showing that nonvisual information is carried and processed by "visual" brain structures. However, despite multiple efforts, the structural underpinnings of cross-modal plasticity in congenitally blind individuals remain unclear. We mapped thalamocortical connectivity and assessed the integrity of white matter of 10 congenitally blind individuals and 10 sighted controls. We hypothesized an aberrant thalamocortical pattern of connectivity taking place in the absence of visual stimuli from birth as a potential mechanism of cross-modal plasticity. In addition to the impaired microstructure of visual white matter bundles, we observed structural connectivity changes between the thalamus and occipital and temporal cortices. Specifically, the thalamic territory dedicated to connections with the occipital cortex was smaller and displayed weaker connectivity in congenitally blind individuals, whereas those connecting with the temporal cortex showed greater volume and increased connectivity. The abnormal pattern of thalamocortical connectivity included the lateral and medial geniculate nuclei and the pulvinar nucleus. For the first time in humans, a remapping of structural thalamocortical connections involving both unimodal and multimodal thalamic nuclei has been demonstrated, shedding light on the possible mechanisms of cross-modal plasticity in humans. The present findings may help understand the functional adaptations commonly observed in congenitally blind individuals.
Topics: Humans; Blindness; Occipital Lobe; Thalamus; Temporal Lobe; Geniculate Bodies
PubMed: 36661404
DOI: 10.1002/hbm.26192 -
European Journal of Neurology Jan 2022Magnetic resonance imaging (MRI) is commonly used in the diagnostic work-up for status epilepticus (SE). The purpose of this study was to characterize MRI features in SE...
BACKGROUND AND PURPOSE
Magnetic resonance imaging (MRI) is commonly used in the diagnostic work-up for status epilepticus (SE). The purpose of this study was to characterize MRI features in SE patients and determine their association with clinical and electroencephalography (EEG) findings. The mid-term consequences of baseline MRI features were also analysed.
METHODS
This is a prospective study including consecutive patients with SE who underwent brain MRI within 240 h after SE onset. The MRI protocol included T1-weighted (T1WI), T2-weighted (T2W), fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) sequences. Follow-up MRI was performed after SE resolution in some patients.
RESULTS
Sixty patients (56.7% men, mean age 58.3 years) were included. SE-related MRI abnormalities were seen in 31 (51.7%), manifesting as hyperintensities on T2W/FLAIR imaging (58.1%) and DWI (74.2%) sequences. Hippocampal and pulvinar involvement was seen in 58.0% and 25.8% of patients, respectively. MRI abnormalities were associated with a longer SE duration (p = 0.013) and the presence of lateralized periodic discharges (LPDs) on EEG (p < 0.001). Amongst the 33 follow-up MRIs, nine (27.3%) showed mesial temporal sclerosis (MTS), which was associated with severe clinical status (p = 0.031), hippocampal oedema (p = 0.001) and LPDs (p = 0.001) at baseline. A poorer clinical outcome was associated with baseline T2W/FLAIR imaging hyperintensities (p = 0.003).
CONCLUSION
MRI showed abnormalities in more than half of SE patients. A longer SE duration and LPDs on EEG were associated with SE-related MRI abnormalities and the development of MTS.
Topics: Diffusion Magnetic Resonance Imaging; Electroencephalography; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Status Epilepticus
PubMed: 34390102
DOI: 10.1111/ene.15065 -
Proceedings of the National Academy of... May 2022Higher-order thalamic nuclei contribute to sensory processing via projections to primary and higher cerebral cortical areas, but it is unknown which of their cortical...
Higher-order thalamic nuclei contribute to sensory processing via projections to primary and higher cerebral cortical areas, but it is unknown which of their cortical and subcortical inputs contribute to their distinct output pathways. We used subpopulation specific viral strategies in mice to anatomically and physiologically dissect pathways of the higher-order thalamic nuclei of the somatosensory and visual systems (the posterior medial nucleus and pulvinar). Employing a complementary optogenetics and electrical stimulation strategy, we show that synapses in cortex from higher-order thalamus have functionally divergent properties in primary vs. higher cortical areas. Higher-order thalamic projections onto excitatory targets in S1 and V1 were weakly modulatory, while projections to S2 and higher visual areas were strong drivers of postsynaptic targets. Then, using transsynaptic tracing verified by optogenetics to map inputs to higher-order thalamus, we show that posterior medial nucleus cells projecting to S1 are driven by neurons in layer 5 of S1, S2, and M1 and that pulvinar cells projecting to V1 are driven by neurons in layer 5 of V1 and higher visual areas. Therefore, in both systems, layer 5 of primary and higher cortical areas drives transthalamic feedback modulation of primary sensory cortex through higher-order thalamus. These results highlight conserved organization that may be shared by other thalamocortical circuitry. They also support the hypothesis that direct corticocortical projections in the brain are paralleled by transthalamic pathways, even in the feedback direction, with feedforward transthalamic pathways acting as drivers, while feedback through thalamus is modulatory.
Topics: Animals; Mice; Neural Pathways; Neuroanatomical Tract-Tracing Techniques; Somatosensory Cortex; Synapses; Thalamic Nuclei
PubMed: 35588455
DOI: 10.1073/pnas.2201481119 -
NeuroImage Feb 2023Selective attention mechanisms operate across large-scale cortical networks by amplifying behaviorally relevant sensory information while suppressing interference from...
Selective attention mechanisms operate across large-scale cortical networks by amplifying behaviorally relevant sensory information while suppressing interference from distractors. Although it is known that fronto-parietal regions convey information about attentional priorities, it is unclear how such cortical communication is orchestrated. Based on its unique connectivity pattern with the cortex, we hypothesized that the pulvinar, a nucleus of the thalamus, may play a key role in coordinating and modulating remote cortical activity during selective attention. By using a visual task that orthogonally manipulated top-down selection and bottom-up competition during functional MRI, we investigated the modulations induced by task-relevant (spatial cue) and task-irrelevant but salient (distractor) stimuli on functional interactions between the pulvinar, occipito-temporal cortex, and frontoparietal areas involved in selective attention. Pulvinar activity and connectivity were distinctively modulated during the co-occurrence of the cue and salient distractor stimuli, as opposed to the presence of one of these factors alone. Causal modelling analysis further indicated that the pulvinar acted by weighting excitatory signals to cortical areas, predominantly in the presence of both the cue and the distractor. These results converge to support a pivotal role of the pulvinar in integrating top-down and bottom-up signals among distributed networks when confronted with conflicting visual stimuli, and thus contributing to shape priority maps for the guidance of attention.
Topics: Humans; Pulvinar; Thalamus; Parietal Lobe; Frontal Lobe; Magnetic Resonance Imaging
PubMed: 36572132
DOI: 10.1016/j.neuroimage.2022.119832 -
Neuroreport May 2020Evidence from cognitive neuroscience indicates that subcortical regions, especially the pulvinar region of the thalamus, are involved in semantic processing. In the...
Evidence from cognitive neuroscience indicates that subcortical regions, especially the pulvinar region of the thalamus, are involved in semantic processing. In the current study, graph-based methods were used to investigate whether a cortical-subcortical network is involved in vocabulary processing. In addition to traditional resting-state functional connectivity (rsFC) analysis between local brain areas, we applied a novel method to validate the interaction between semantic network hubs and the pulvinar. Unlike the traditional rsFC, the new metrics assessed rsFC pattern similarity (rsFCS), which was calculated with a cosine similarity algorithm based on whole-network topological information. We also applied a support vector regression program based on left pulvinar connectivity patterns. A brain-behavior analysis was conducted based on 100 randomly selected unrelated participants from the Human Connectome Project S1200 database. After controlling for the visuospatial and attention test scores, the rsFC between the left middle temporal gyrus, left inferior parietal lobule, and left pulvinar was significantly positively correlated with age-adjusted picture vocabulary scores. Similar results were confirmed based on the new rsFCS analysis. The support vector regression procedures also showed a clearly relationship between picture vocabulary scores and left pulvinar-related rsFCs. Our study verified a role for a subcortical-cortical network in vocabulary processing that is based on local and whole-network topologies.
Topics: Adult; Brain; Connectome; Female; Humans; Magnetic Resonance Imaging; Male; Neural Pathways; Pulvinar; Semantics; Vocabulary; Young Adult
PubMed: 32366811
DOI: 10.1097/WNR.0000000000001444 -
Vision (Basel, Switzerland) Mar 2020The pulvinar, also called the lateral posterior nucleus of the thalamus in rodents, is one of the higher-order thalamic relays and the main visual extrageniculate...
The pulvinar, also called the lateral posterior nucleus of the thalamus in rodents, is one of the higher-order thalamic relays and the main visual extrageniculate thalamic nucleus in rodents and primates. Although primate studies report the pulvinar is engaged under attentional demands, there are open questions about the detailed role of the pulvinar in visuospatial attention. The pulvinar provides the primary thalamic input to the posterior parietal cortex (PPC). Both the pulvinar and the PPC are known to be important for visuospatial attention. Our previous work showed that neuronal activity in the PPC correlated with multiple phases of a visuospatial attention (VSA) task, including onset of the visual stimuli, decision-making, task-relevant locations, and behavioral outcomes. Here, we hypothesized that the pulvinar, as the major thalamic input to the PPC, is involved in visuospatial attention as well as in other cognitive functions related to the processing of visual information. We recorded the neuronal activity of the pulvinar in rats during their performance on the VSA task. The task was designed to engage goal-directed, top-down attention as well as stimulus-driven, bottom-up attention. Rats monitored three possible locations for the brief appearance of a target stimulus. An approach to the correct target location was followed by a liquid reward. For analysis, each trial was divided into behavioral epochs demarcated by stimulus onset, selection behavior, and approach to reward. We found that neurons in the pulvinar signaled stimulus onset and selection behavior consistent with the interpretation that the pulvinar is engaged in both bottom-up and top-down visuospatial attention. Our results also suggested that pulvinar cells responded to allocentric and egocentric task-relevant locations.
PubMed: 32121530
DOI: 10.3390/vision4010015 -
Neuropsychopharmacology : Official... Jan 2024Accelerated TMS is an emerging application of Transcranial Magnetic Stimulation (TMS) aimed to reduce treatment length and improve response time. Extant literature... (Review)
Review
Accelerated TMS is an emerging application of Transcranial Magnetic Stimulation (TMS) aimed to reduce treatment length and improve response time. Extant literature generally shows similar efficacy and safety profiles compared to the FDA-cleared protocols for TMS to treat major depressive disorder (MDD), yet accelerated TMS research remains at a very early stage in development. The few applied protocols have not been standardized and vary significantly across a set of core elements. In this review, we consider nine elements that include treatment parameters (i.e., frequency and inter-stimulation interval), cumulative exposure (i.e., number of treatment days, sessions per day, and pulses per session), individualized parameters (i.e., treatment target and dose), and brain state (i.e., context and concurrent treatments). Precisely which of these elements is critical and what parameters are most optimal for the treatment of MDD remains unclear. Other important considerations for accelerated TMS include durability of effect, safety profiles as doses increase over time, the possibility and advantage of individualized functional neuronavigation, use of biological readouts, and accessibility for patients most in need of the treatment. Overall, accelerated TMS appears to hold promise to reduce treatment time and achieve rapid reduction in depressive symptoms, but at this time significant work remains to be done. Rigorous clinical trials combining clinical outcomes and neuroscientific measures such as electroencephalogram, magnetic resonance imaging and e-field modeling are needed to define the future of accelerated TMS for MDD.
Topics: Humans; Depressive Disorder, Major; Transcranial Magnetic Stimulation; Depression; Electroencephalography; Prefrontal Cortex; Treatment Outcome
PubMed: 37217771
DOI: 10.1038/s41386-023-01599-z -
Current Biology : CB Dec 2022Eye movements cause rapid motion of the retinal image, potentially confusable with external motion. A recent study shows that neurons in mouse primary visual cortex...
Eye movements cause rapid motion of the retinal image, potentially confusable with external motion. A recent study shows that neurons in mouse primary visual cortex distinguish self-generated from external motion by combining sensory input with saccade-related signals from the thalamic pulvinar nucleus.
Topics: Animals; Mice; Eye Movements; Saccades; Neurons; Perception; Motion Perception; Photic Stimulation; Visual Perception
PubMed: 36538882
DOI: 10.1016/j.cub.2022.11.003 -
BioRxiv : the Preprint Server For... Dec 2023Recent investigations of cell type changes in Multiple Sclerosis (MS) using single-cell profiling methods have focused on active lesional and peri-lesional brain tissue,...
Recent investigations of cell type changes in Multiple Sclerosis (MS) using single-cell profiling methods have focused on active lesional and peri-lesional brain tissue, and have implicated a number of peripheral and central nervous system cell types. However, an important question is the extent to which so-called "normal-appearing" non-lesional tissue in individuals with MS accumulate changes over the lifespan. Here, we compared post-mortem non-lesional brain tissue from donors with a pathological or clinical diagnosis of MS from the Religious Orders Study or Rush Memory and Aging Project (ROSMAP) cohorts to age- and sex-matched brains from persons without MS (controls). We profiled three brain regions using single-nucleus RNA-seq: dorsolateral prefrontal cortex (DLPFC), normal appearing white matter (NAWM) and the pulvinar in thalamus (PULV), from 15 control individuals, 8 individuals with MS, and 5 individuals with other detrimental pathologies accompanied by demyelination, resulting in a total of 78 samples. We identified region- and cell type-specific differences in non-lesional samples from individuals diagnosed with MS and/or exhibiting secondary demyelination with other neurological conditions, as compared to control donors. These differences included lower proportions of oligodendrocytes with expression of myelination related genes MOBP, MBP, PLP1, as well as higher proportions of CRYAB+ oligodendrocytes in all three brain regions. Among microglial signatures, we identified subgroups that were higher in both demyelination (TMEM163+/ERC2+), as well as those that were specifically higher in MS donors (HIF1A+/SPP1+) and specifically in donors with secondary demyelination (SOCS6+/MYO1E+), in both white and grey matter. To validate our findings, we generated Visium spatial transcriptomics data on matched tissue from 13 donors, and recapitulated our observations of gene expression differences in oligodendrocytes and microglia. Finally, we show that some of the differences observed between control and MS donors in NAWM mirror those previously reported between control WM and active lesions in MS donors. Overall, our investigation sheds additional light on cell type- and disease-specific differences present even in non-lesional white and grey matter tissue, highlighting widespread cellular signatures that may be associated with downstream pathological changes.
PubMed: 38187779
DOI: 10.1101/2023.12.20.572491