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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 -
NeuroImage Oct 2023Spatial attention is often described as a mental spotlight that enhances information processing at the attended location. Using fMRI, we investigated background...
Spatial attention is often described as a mental spotlight that enhances information processing at the attended location. Using fMRI, we investigated background connectivity between the pulvinar and V1 in relation to focused versus diffused attention allocation, in weak and strong crowding contexts. Our findings revealed that focused attention led to enhanced correlations between the pulvinar and V1. Notably, this modulation was initiated by the pulvinar, and the strength of the modulation was dependent on the saliency of the target. These findings suggest that the pulvinar initiates information reweighting to V1, which underlies attentional selection in cluttered scenes.
Topics: Humans; Pulvinar; Cognition; Diffusion
PubMed: 37619793
DOI: 10.1016/j.neuroimage.2023.120341 -
Annals of Clinical and Translational... Jul 2023Deep brain stimulation (DBS) is a promising treatment for drug-refractory epilepsies (DRE) when targeting the anterior nuclei of thalamus (ANT). However, targeting other...
Deep brain stimulation (DBS) is a promising treatment for drug-refractory epilepsies (DRE) when targeting the anterior nuclei of thalamus (ANT). However, targeting other thalamic nuclei, such as the pulvinar, shows therapeutic promise. Our pioneering case study presents the application of ambulatory seizure monitoring using spectral fingerprinting (12.15-17.15 Hz) recorded through Medtronic Percept DBS implanted bilaterally in the medial pulvinar thalami. This technology offers unprecedented opportunities for real-time monitoring of seizure burden and thalamocortical network modulation for effective seizure reduction in patients with bilateral mesial temporal and temporal plus epilepsies that are not suitable for resection.
Topics: Humans; Pulvinar; Deep Brain Stimulation; Electrodes, Implanted; Epilepsy; Seizures
PubMed: 37231611
DOI: 10.1002/acn3.51815 -
Psychiatry Research Sep 2023Identifying objective biological subtypes that predict long-term functional outcomes is crucial for understanding neurobiological mechanisms and identifying potential...
Identifying objective biological subtypes that predict long-term functional outcomes is crucial for understanding neurobiological mechanisms and identifying potential targets. Using resting-state functional magnetic resonance imaging data from 178 patients and 70 controls, we explored social function patterns using latent profile analysis. Long-term outcomes were compared among the biological subtypes using K-means clustering. Partial least squares regression (PLSR) was used to identify gene expression profiles associated with alterations in activity by leveraging transcriptional data from the Allen Human Brain Atlas. In patients with more functional impairment, left medial pulvinar (PM) exhibited significantly lower regional homogeneity of brain activity (ReHo, [95% CI (0.06-0.27), P = 0.002), a finding validated in the independent cohort. Functional connectivity between PM and secondary visual cortex displayed a suggestive decrease. Patients belonging to "higher pulvinar ReHo - better information processing" demonstrated better long-term outcomes and acute treatment response [95% CI (11.2-34.4), P < 0.001]. The PLSR component of imaging-transcriptomic associations partly explained the ReHo differences among patients with varying levels of functional impairment. It revealed enrichment of genes in the synaptic signaling pathway. Pathological changes in the pulvinar may affect social functioning. Higher pulvinar ReHo and better information processing, two objective biomarkers, have a predictive value for better long-term functional outcomes.
Topics: Humans; Schizophrenia; Pulvinar; Brain; Cluster Analysis; Cognition
PubMed: 37598626
DOI: 10.1016/j.psychres.2023.115419 -
Journal of Neurosurgery Jan 2024Deep brain stimulation (DBS) is a rapidly growing surgical option for patients with drug-resistant epilepsy who are not candidates for resective/ablative surgery. Recent...
OBJECTIVE
Deep brain stimulation (DBS) is a rapidly growing surgical option for patients with drug-resistant epilepsy who are not candidates for resective/ablative surgery. Recent randomized controlled trials have demonstrated efficacy of DBS of the anterior nucleus of the thalamus (ANT), particularly in frontal or temporal epilepsy, whereas DBS of the centromedian (CM) nucleus appears to be most suitable in well-defined generalized epilepsy syndromes. At the authors' institution, DBS candidates who did not fit the populations represented in these trials were managed with DBS of multiple distinct targets, which included ANT, CM, and less-studied nuclei-i.e., mediodorsal nucleus, pulvinar, and subthalamic nucleus. The goal of this study was to present the authors' experience with these types of cases, and to motivate future investigations that can determine the long-term efficacy of multitarget DBS.
METHODS
This single-center retrospective study of adult patients with drug-resistant epilepsy who underwent multitarget DBS was performed to demonstrate the feasibility and safety of this approach, and to present seizure outcomes. Patients in this cohort had epilepsy with features that were difficult to treat with DBS of the ANT or CM nucleus alone, including multifocal/multilobar, diffuse-onset, and/or posterior-onset seizures; or both generalized and focal seizures.
RESULTS
Eight patients underwent DBS of 2-3 distinct thalamic/subthalamic nuclei. DBS was performed with 2 electrodes in each hemisphere. All leads in each patient were implanted with either frontal or parietal trajectories. There were no surgical complications. Among those with > 6 months of follow-up (n = 5; range 7-21 months), all patients were responders in terms of overall seizure frequency and/or convulsive seizure frequency (i.e., ≥ 50% reduction). Two patients had adverse stimulation effects, which resolved with further programming.
CONCLUSIONS
Multitarget DBS is a procedurally feasible and safe treatment strategy to maximize outcomes in patients with complex epilepsy. The authors highlight their approach to inform future studies that are sufficiently powered to assess its efficacy.
Topics: Adult; Humans; Deep Brain Stimulation; Retrospective Studies; Epilepsy; Drug Resistant Epilepsy; Seizures; Electrodes, Implanted
PubMed: 37486888
DOI: 10.3171/2023.5.JNS23982 -
NeuroImage Dec 2023The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging... (Randomized Controlled Trial)
Randomized Controlled Trial
The role of the thalamus in mediating the effects of lysergic acid diethylamide (LSD) was recently proposed in a model of communication and corroborated by imaging studies. However, a detailed analysis of LSD effects on nuclei-resolved thalamocortical connectivity is still missing. Here, in a group of healthy volunteers, we evaluated whether LSD intake alters the thalamocortical coupling in a nucleus-specific manner. Structural and resting-state functional Magnetic Resonance Imaging (MRI) data were acquired in a placebo-controlled study on subjects exposed to acute LSD administration. Structural MRI was used to parcel the thalamus into its constituent nuclei based on individual anatomy. Nucleus-specific changes of resting-state functional MRI (rs-fMRI) connectivity were mapped using a seed-based approach. LSD intake selectively increased the thalamocortical functional connectivity (FC) of the ventral complex, pulvinar, and non-specific nuclei. Functional coupling was increased between these nuclei and sensory cortices that include the somatosensory and auditory networks. The ventral and pulvinar nuclei also exhibited increased FC with parts of the associative cortex that are dense in serotonin type 2A receptors. These areas are hyperactive and hyper-connected upon LSD intake. At subcortical levels, LSD increased the functional coupling among the thalamus's ventral, pulvinar, and non-specific nuclei, but decreased the striatal-thalamic connectivity. These findings unravel some LSD effects on the modulation of subcortical-cortical circuits and associated behavioral outputs.
Topics: Humans; Thalamus; Pulvinar; Magnetic Resonance Imaging; Cerebral Cortex; Parietal Lobe; Neural Pathways
PubMed: 37858906
DOI: 10.1016/j.neuroimage.2023.120414 -
Trends in Neurosciences Feb 2024The pulvinar nucleus of the thalamus is a crucial component of the visual system and plays significant roles in sensory processing and cognitive integration. The... (Review)
Review
The pulvinar nucleus of the thalamus is a crucial component of the visual system and plays significant roles in sensory processing and cognitive integration. The pulvinar's extensive connectivity with cortical regions allows for bidirectional communication, contributing to the integration of sensory information across the visual hierarchy. Recent findings underscore the pulvinar's involvement in attentional modulation, feature binding, and predictive coding. In this review, we highlight recent advances in clarifying the pulvinar's circuitry and function. We discuss the contributions of the pulvinar to signal modulation across the global cortical network and place these findings within theoretical frameworks of cortical processing, particularly the global neuronal workspace (GNW) theory and predictive coding.
Topics: Humans; Pulvinar; Thalamus; Visual Perception; Attention; Sensation
PubMed: 38143202
DOI: 10.1016/j.tins.2023.11.008 -
Journal of Affective Disorders Nov 2023American youth are seriously impacted by depression and suicide. The Texas Youth Depression and Suicide Research Network (TX-YDSRN) Participant Registry Study was...
BACKGROUND
American youth are seriously impacted by depression and suicide. The Texas Youth Depression and Suicide Research Network (TX-YDSRN) Participant Registry Study was initiated in 2020 to develop predictive models for treatment outcomes in youth with depression and/or suicidality. This report presents the study rationale, design and baseline characteristics of the first 1000 participants.
METHODS
TX-YDSRN consists of the Network Hub (coordinating center), 12 medical school "Nodes" (manage/implement study), each with 1-5 primary care, inpatient, and/or outpatient Sub-Sites (recruitment, data collection). Participants are 8-20-year-olds who receive treatment or screen positive for depression and/or suicidality. Baseline data include mood and suicidality symptoms, associated comorbidities, treatment history, services used, and social determinants of health. Subsequent assessments occur every two months for 24 months.
RESULTS
Among 1000 participants, 68.7 % were 12-17 years, 24.6 % were ≥ 18 years, and 6.7 % were < 12. Overall, 36.8 % were non-Hispanic Caucasian, 73.4 % were female, and 79.9 % had a primary depressive disorder. Nearly half of the sample reported ≥1 suicide attempt, with rates similar in youth 12-17 years old (49.9 %) and those 18 years and older (45.5 %); 29.9 % of children <12 reported at least one suicide attempt. Depression and anxiety scores were in the moderate-severe range for all age groups (Patient Health Questionnaire for Adolescents [PHQ-A]: 12.9 ± 6.4; Generalized Anxiety Disorder [GAD-7]: 11.3 ± 5.9).
LIMITATIONS
The sample includes youth who are receiving depression care at enrollment and may not be representative of non-diagnosed, non-treatment seeking youth.
CONCLUSIONS
The TX-YDSRN is one of the largest prospective longitudinal cohort registries designed to develop predictive models for outcome trajectories based on disorder heterogeneity, social determinants of health, and treatment availability.
Topics: Child; Humans; Adolescent; Female; Male; Depression; Texas; Prospective Studies; Delivery of Health Care; Registries
PubMed: 37459975
DOI: 10.1016/j.jad.2023.07.035