-
Brain : a Journal of Neurology Jul 2023Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in a subset of patients with refractory focal epilepsy. One important...
Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in a subset of patients with refractory focal epilepsy. One important uncertainty is to what extent thalamic subregions other than the ANT could be recruited more prominently in the propagation of focal onset seizures. We designed the current study to simultaneously monitor the engagement of the ANT, mediodorsal (MD) and pulvinar (PUL) nuclei during seizures in patients who could be candidates for thalamic neuromodulation. We studied 11 patients with clinical manifestations of presumed temporal lobe epilepsy (TLE) undergoing invasive stereo-encephalography (sEEG) monitoring to confirm the source of their seizures. We extended cortical electrodes to reach the ANT, MD and PUL nuclei of the thalamus. More than one thalamic subdivision was simultaneously interrogated in nine patients. We recorded seizures with implanted electrodes across various regions of the brain and documented seizure onset zones (SOZ) in each recorded seizure. We visually identified the first thalamic subregion to be involved in seizure propagation. Additionally, in eight patients, we applied repeated single pulse electrical stimulation in each SOZ and recorded the time and prominence of evoked responses across the implanted thalamic regions. Our approach for multisite thalamic sampling was safe and caused no adverse events. Intracranial EEG recordings confirmed SOZ in medial temporal lobe, insula, orbitofrontal and temporal neocortical sites, highlighting the importance of invasive monitoring for accurate localization of SOZs. In all patients, seizures with the same propagation network and originating from the same SOZ involved the same thalamic subregion, with a stereotyped thalamic EEG signature. Qualitative visual reviews of ictal EEGs were largely consistent with the quantitative analysis of the corticothalamic evoked potentials, and both documented that thalamic nuclei other than ANT could have the earliest participation in seizure propagation. Specifically, pulvinar nuclei were involved earlier and more prominently than ANT in more than half of the patients. However, which specific thalamic subregion first demonstrated ictal activity could not be reliably predicted based on clinical semiology or lobar localization of SOZs. Our findings document the feasibility and safety of bilateral multisite sampling from the human thalamus. This may allow more personalized thalamic targets to be identified for neuromodulation. Future studies are needed to determine if a personalized thalamic neuromodulation leads to greater improvements in clinical outcome.
Topics: Humans; Seizures; Brain; Epilepsy, Temporal Lobe; Electroencephalography; Drug Resistant Epilepsy; Anterior Thalamic Nuclei; Electrodes, Implanted
PubMed: 37137813
DOI: 10.1093/brain/awad121 -
Schizophrenia Research Jun 2023The thalamus is central to brain functions ranging from primary sensory processing to higher-order cognition. Structural deficits in thalamic association nuclei such as...
BACKGROUND
The thalamus is central to brain functions ranging from primary sensory processing to higher-order cognition. Structural deficits in thalamic association nuclei such as the pulvinar and mediodorsal nuclei have previously been reported in schizophrenia. However, the specificity with regards to clinical presentation, and whether or not bipolar disorder (BD) is associated with similar alterations is unclear.
METHODS
We investigated thalamic nuclei volumes in 334 patients with schizophrenia spectrum disorders (SSD) (median age 29 years, 59 % male), 322 patients with BD (30 years, 40 % male), and 826 healthy controls (HC) (34 years, 54 % male). Volumes of 25 thalamic nuclei were extracted from T1-weighted magnetic resonance imaging using an automated Bayesian segmentation method and compared between groups. Furthermore, we explored associations with clinical characteristics across diagnostic groups, including psychotic and mood symptoms and medication use, as well as diagnostic subtype in BD.
RESULTS
Significantly smaller volumes were found in the mediodorsal, pulvinar, and lateral and medial geniculate thalamic nuclei in SSD. Similarly, smaller volumes were found in BD in the same four regions, but mediodorsal nucleus volume alterations were limited to its lateral part and pulvinar alterations to its anterior region. Smaller volumes in BD compared to HC were seen only in BD type I, not BD type II. Across diagnoses, having more negative symptoms was associated with smaller pulvinar volumes.
CONCLUSIONS
Structural alterations were found in both SSD and BD, mainly in the thalamic association nuclei. Structural deficits in the pulvinar may be of relevance for negative symptoms.
Topics: Humans; Male; Adult; Female; Schizophrenia; Bayes Theorem; Thalamic Nuclei; Thalamus; Mediodorsal Thalamic Nucleus; Magnetic Resonance Imaging
PubMed: 37126979
DOI: 10.1016/j.schres.2023.04.008 -
NeuroImage. Clinical 2023C9orf72 mutation carriers with different neurological phenotypes show cortical and subcortical atrophy in multiple different brain regions, even in pre-symptomatic...
OBJECTIVE
C9orf72 mutation carriers with different neurological phenotypes show cortical and subcortical atrophy in multiple different brain regions, even in pre-symptomatic phases. Despite there is a substantial amount of knowledge, small sample sizes, clinical heterogeneity, as well as different choices of image analysis may hide anatomical abnormalities that are unique to amyotrophic lateral sclerosis (ALS) patients with this genotype or that are indicative of the C9orf72-specific trait overlain in fronto-temporal dementia patients.
METHODS
Brain structural and resting state functional magnetic imaging was obtained in 24 C9orf72 positive (ALSC9+) ALS patients paired for burden disease with 24 C9orf72 negative (ALSC9-) ALS patients. A comprehensive structural evaluation of cortical thickness and subcortical volumes between ALSC9+ and ALSC9- patients was performed while a region of interest (ROI)-ROI analysis of functional connectivity was implemented to assess functional alterations among abnormal cortical and subcortical regions. Results were corrected for multiple comparisons.
RESULTS
Compared to ALSC9- patients, ALSC9+ patients exhibited extensive disease-specific patterns of thalamo-cortico-striatal atrophy, supported by functional alterations of the identified abnormal regions. Cortical thinning was most pronounced in posterior areas and extended to frontal regions. Bilateral atrophy of the mediodorsal and pulvinar nuclei was observed, emphasizing a focal rather than global thalamus atrophy. Volume loss in a large portion of bilateral caudate and left putamen was reported. The marked reduction of functional connectivity observed between the left posterior thalamus and almost all the atrophic cortical regions support the central role of the thalamus in the pathogenic mechanism of C9orf72-mediated disease.
CONCLUSIONS
These findings constitute a coherent and robust picture of ALS patients with C9orf72-mediated disease, unveiling a specific structural and functional characterization of thalamo-cortico-striatal circuit alteration. Our study introduces new evidence in the characterization of the pathogenic mechanisms of C9orf72 mutation.
Topics: Humans; Amyotrophic Lateral Sclerosis; C9orf72 Protein; Magnetic Resonance Imaging; Mutation; Atrophy
PubMed: 37068310
DOI: 10.1016/j.nicl.2023.103400 -
Cureus Mar 2023While bilateral stimulation of the anterior thalamic nuclei remains the only approved deep brain stimulation (DBS) option for focal epilepsy, two additional thalamic... (Review)
Review
While bilateral stimulation of the anterior thalamic nuclei remains the only approved deep brain stimulation (DBS) option for focal epilepsy, two additional thalamic targets have been proposed. Earlier work indicated the potential of centromedian thalamic nucleus stimulation with recent findings highlighting the medial pulvinar nucleus. The latter has been shown to exhibit electrophysiological and imaging alterations in patients with partial status epilepticus and temporal lobe epilepsy. On this basis, recent studies have begun assessing the feasibility and efficacy of pulvinar stimulation, with encouraging results on the reduction of seizure frequency and severity. Building on existing neuroanatomical knowledge, indicating that the medial pulvinar is connected to the temporal lobe via the temporopulvinar bundle of Arnold, we hypothesize that this is one of the routes through which medial pulvinar stimulation affects temporal lobe structures. We suggest that further anatomic, imaging, and electrophysiologic studies are warranted to deepen our understanding of the subject and guide future clinical applications.
PubMed: 37025746
DOI: 10.7759/cureus.35772 -
Brain Imaging and Behavior Aug 2023Little information is available on the magnetic resonance imaging (MRI) determination of the hippocampal formation (HF) during the perinatal period. However, this...
Little information is available on the magnetic resonance imaging (MRI) determination of the hippocampal formation (HF) during the perinatal period. However, this exploration is increasingly used, which requires defining visible HF landmarks on MRI images, validated through histological analysis. This study aims to provide a protocol to identify HF landmarks on MRI images, followed by histological validation through serial sections of the temporal lobe of the samples examined, to assess the longitudinal extent of the hippocampus during the perinatal period. We examined ex vivo MRI images from nine infant control brain samples. Histological validation of the hippocampal formation MRI images was obtained through serial sectioning and examination of Nissl-stained sections at 250 μm intervals along the entire length of the hippocampal formation. Up to six landmarks were identified both in MRI images and the serial histological sections. Proceeding in an anterior to posterior (rostrocaudal) direction, these were as follows: 1) the limen insulae (fronto-temporal junction); 2) the beginning of the amygdaloid complex; 3) the beginning of the lateral ventricle; 4) the caudal limit of the uncus, indicated by the start of the lateral geniculate nucleus (at the level of the gyrus intralimbicus); 5) the end of the lateral geniculate nucleus (beginning of the pulvinar); and 6) the beginning of the fornix. After histological validation of each of these landmarks, the full longitudinal length of the hippocampal formation and distances between landmarks were calculated. No statistically significant differences were found in total length or between landmarks. While the HF is anatomically organized at birth, its annotation is particularly challenging to perform. The histological validation of HF landmarks allows a better understanding of MRI images. The proposed protocol could be useful to assess MRI hippocampal quantification in children and possible variations due to different neurological diseases.
Topics: Infant; Child; Infant, Newborn; Humans; Magnetic Resonance Imaging; Hippocampus; Temporal Lobe; Brain; Magnetic Resonance Spectroscopy
PubMed: 37024762
DOI: 10.1007/s11682-023-00768-4 -
Frontiers in Neuroscience 2023Although the thalamus is perceived as a passive relay station for almost all sensory signals, the function of individual thalamic nuclei remains unresolved. In the...
Although the thalamus is perceived as a passive relay station for almost all sensory signals, the function of individual thalamic nuclei remains unresolved. In the present study, we aimed to identify the sensorimotor nuclei of the thalamus in humans using task-based fMRI at a field strength of 9.4T by assessing the individual subject-specific sensorimotor BOLD response during a combined active motor (finger-tapping) and passive sensory (tactile-finger) stimulation. We demonstrate that both tasks increase BOLD signal response in the lateral nuclei group (VPL, VA, VLa, and VLp), and in the pulvinar nuclei group (PuA, PuM, and PuL). Finger-tapping stimuli evokes a stronger BOLD response compared to the tactile stimuli, and additionally engages the intralaminar nuclei group (CM and Pf). In addition, our results demonstrate reproducible thalamic nuclei activation during motor and tactile stimuli. This work provides important insight into understanding the function of individual thalamic nuclei in processing various input signals and corroborates the benefits of using ultra-high-field MR scanners for functional imaging of fine-scale deeply located brain structures.
PubMed: 37008235
DOI: 10.3389/fnins.2023.1116002 -
Plant Physiology May 2023
Topics: Pulvinar; Plant Leaves; Cell Wall
PubMed: 36932717
DOI: 10.1093/plphys/kiad166 -
Scientific Reports Mar 2023We aimed to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with primary restless legs syndrome (RLS) compared to...
We aimed to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with primary restless legs syndrome (RLS) compared to healthy controls. Seventy-one patients with primary RLS and 55 healthy controls were recruited. They underwent brain MRI using a three-tesla MRI scanner, including three-dimensional T1-weighted images. The intrinsic thalamic network was determined using graph theoretical analysis. The right and left whole thalamic volumes, and the right pulvinar inferior, left ventral posterolateral, left medial ventral, and left pulvinar inferior nuclei volumes in the patients with RLS were lower than those in healthy controls (0.433 vs. 0.447%, p = 0.034; 0.482 vs. 0.502%, p = 0.016; 0.013 vs. 0.015%, p = 0.031; 0.062 vs. 0.065%, p = 0.035; 0.001 vs. 0.001%, p = 0.034; 0.018 vs. 0.020%, p = 0.043; respectively). There was also a difference in the intrinsic thalamic network between the groups. The assortative coefficient in patients with RLS was higher than that in healthy controls (0.0318 vs. - 0.0358, p = 0.048). We demonstrated the alterations of thalamic nuclei volumes and intrinsic thalamic network in patients with RLS compared to healthy controls. These changes might be related to RLS pathophysiology and suggest the pivotal role of the thalamus in RLS symptoms.
Topics: Humans; Restless Legs Syndrome; Thalamus; Thalamic Nuclei; Magnetic Resonance Imaging; Pulvinar
PubMed: 36932255
DOI: 10.1038/s41598-023-31606-8 -
BioRxiv : the Preprint Server For... Feb 2023Microsaccades (MSs) are commonly associated with spatially directed attention, but how they affect visual processing is still not clear. We studied MSs in a task in...
Microsaccades (MSs) are commonly associated with spatially directed attention, but how they affect visual processing is still not clear. We studied MSs in a task in which the animal was randomly cued to attend to a target stimulus and ignore distractors, and it was rewarded for detecting a color change in the target. We found that the enhancement of firing rates normally found with attention to a cued stimulus was delayed until the first MS directed towards that stimulus. Once that MS occurred, attention to the target was engaged and there were persistent effects of attention on firing rates for the remainder of the trial. These effects were found in the superficial and deep layers of V4 as well as the lateral pulvinar and IT cortex. Although the tuning curves of V4 cells do not change depending on the locus of spatial attention, we found pronounced effects of MS direction on stimulus representations that persisted for the length of the trial in V4. In intervals following a MS towards the target in the RF, stimulus decoding from population activity was substantially better than in intervals following a MS away from the target. Likewise, turning curves of cells were substantially sharper following a MS towards the target in the RF. This sharpening appeared to result from both a "refreshing" of the initial transient sensory response to stimulus onset, and a magnification of the effects of attention in this condition. MSs to the target also enhanced the neuronal response to the behaviorally relevant target color change and led to faster reaction times. These results thus reveal a major link between spatial attention, object processing and its coordination with eye movements.
PubMed: 36909549
DOI: 10.1101/2023.02.25.529300 -
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