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Frontiers in Systems Neuroscience 2017The pulvinar is the largest of the thalamic nuclei in the primates, including humans. In the primates, two of the three major subdivisions, the lateral and inferior... (Review)
Review
The pulvinar is the largest of the thalamic nuclei in the primates, including humans. In the primates, two of the three major subdivisions, the lateral and inferior pulvinar, are heavily interconnected with a significant proportion of the visual association cortex. However, while we now have a better understanding of the bidirectional connectivity of these pulvinar subdivisions, its functions remain somewhat of an enigma. Over the past few years, researchers have started to tackle this problem by addressing it from the angle of development and visual cortical lesions. In this review, we will draw together literature from the realms of studies in nonhuman primates and humans that have informed much of the current understanding. This literature has been responsible for changing many long-held opinions on the development of the visual cortex and how the pulvinar interacts dynamically with cortices during early life to ensure rapid development and functional capacity Furthermore, there is evidence to suggest involvement of the pulvinar following lesions of the primary visual cortex (V1) and geniculostriate pathway in early life which have far better functional outcomes than identical lesions obtained in adulthood. Shedding new light on the pulvinar and its role following lesions of the visual brain has implications for our understanding of visual brain disorders and the potential for recovery.
PubMed: 28228719
DOI: 10.3389/fnsys.2017.00003 -
JIMD Reports Sep 2022Aspartylglucosaminuria (AGU) is a rare lysosomal storage disorder that causes stagnation of development in adolescence and neurodegeneration in early adulthood....
Aspartylglucosaminuria (AGU) is a rare lysosomal storage disorder that causes stagnation of development in adolescence and neurodegeneration in early adulthood. Precision therapies, including gene transfer therapy, are in development with a goal of taking advantage of the slow clinical course. Understanding of disease natural history and identification of disease-relevant biomarkers are important steps in clinical trial readiness. We describe the clinical features of a diverse population of patients with AGU, including potential imaging and electrophysiological biomarkers. This is a single-center, cross-sectional study of the clinical, neuropsychological, electrophysiological, and imaging characteristics of AGU. A comprehensive assessment of eight participants (5 Non-Finnish) revealed a mean non-verbal IQ (NVIQ) of 70.25 ± 10.33 which decreased with age (rs = -0.85, = 0.008). All participants demonstrated deficits in communication and gross/fine motor dysfunction. Auditory and visual evoked potentials demonstrated abnormalities in one or both modalities in 7 of 8 subjects, suggesting sensory pathway dysfunction. Brain imaging demonstrated T2 FLAIR hypointensity in the pulvinar nuclei and cerebral atrophy, as previously shown in the Finnish AGU population. Magnetic resonance spectroscopy (MRS) showed a 5.1 ppm peak corresponding to the toxic substrate (GlcNAc-Asn), which accumulates in AGU. Our results showed there was no significant difference between Finnish and Non-Finnish patients, and performance on standardized cognitive and motor testing was similar to prior studies. Age-related changes on functional assessments and disease-relevant abnormalities on surrogate biomarkers, such as MRS, could be used as outcome measures in a clinical trial.
PubMed: 36101820
DOI: 10.1002/jmd2.12294 -
Schizophrenia Research Dec 2020Identification of reliable biomarkers of prognosis in subjects with high risk to psychosis is an essential step to improve care and treatment of this population of... (Review)
Review
Identification of reliable biomarkers of prognosis in subjects with high risk to psychosis is an essential step to improve care and treatment of this population of help-seekers. Longitudinal studies highlight some clinical criteria, cognitive deficits, patterns of gray matter alterations and profiles of blood metabolites that provide some levels of prediction regarding the conversion to psychosis. Further effort is warranted to validate these results and implement these types of approaches in clinical settings. Such biomarkers may however fall short in entangling the biological mechanisms underlying the disease progression, an essential step in the development of novel therapies. Circuit-based approaches, which map on well-identified cerebral functions, could meet these needs. Converging evidence indicates that thalamus abnormalities are central to schizophrenia pathophysiology, contributing to clinical symptoms, cognitive and sensory deficits. This review highlights the various thalamus-related anomalies reported in individuals with genetic risks and in the different phases of the disorder, from prodromal to chronic stages. Several anomalies are potent endophenotypes, while others exist in clinical high-risk subjects and worsen in those who convert to full psychosis. Aberrant functional coupling between thalamus and cortex, low glutamate content and readouts from resting EEG carry predictive values for transition to psychosis or functional outcome. In this context, thalamus-related anomalies represent a valuable entry point to tackle circuit-based alterations associated with the emergence of psychosis. This review also proposes that longitudinal surveys of neuroimaging, EEG readouts associated with circuits encompassing the mediodorsal, pulvinar in high-risk individuals could unveil biological mechanisms contributing to this psychiatric disorder.
Topics: Biomarkers; Humans; Magnetic Resonance Imaging; Psychotic Disorders; Schizophrenia; Thalamus
PubMed: 31147286
DOI: 10.1016/j.schres.2019.05.027 -
Current Research in Neurobiology 2023The role of thalamocortical circuits in memory has driven a recent burst of scholarship, especially in animal models. Investigating this circuitry in humans is more... (Review)
Review
The role of thalamocortical circuits in memory has driven a recent burst of scholarship, especially in animal models. Investigating this circuitry in humans is more challenging. And yet, the development of new recording and stimulation technologies deployed for clinical indications has created novel opportunities for data collection to elucidate the cognitive roles of thalamic structures. These technologies include stereoelectroencephalography (SEEG), deep brain stimulation (DBS), and responsive neurostimulation (RNS), all of which have been applied to memory-related thalamic regions, specifically for seizure localization and treatment. This review seeks to summarize the existing applications of neuromodulation of the anterior thalamic nuclei (ANT) and highlight several devices and their capabilities that can allow cognitive researchers to design experiments to assay its functionality. Our goal is to introduce to investigators, who may not be familiar with these clinical devices, the capabilities, and limitations of these tools for understanding the neurophysiology of the ANT as it pertains to memory and other behaviors. We also briefly cover the targeting of other thalamic regions including the centromedian (CM) nucleus, dorsomedial (DM) nucleus, and pulvinar, with associated potential avenues of experimentation.
PubMed: 38020810
DOI: 10.1016/j.crneur.2023.100109 -
Epilepsy & Behavior : E&B Feb 2021While temporal lobe epilepsy (TLE) is a focal epilepsy, previous work demonstrates that TLE causes widespread brain-network disruptions. Impaired visuospatial attention...
While temporal lobe epilepsy (TLE) is a focal epilepsy, previous work demonstrates that TLE causes widespread brain-network disruptions. Impaired visuospatial attention and learning in TLE may be related to thalamic arousal nuclei connectivity. Our prior preliminary work in a smaller patient cohort suggests that patients with TLE demonstrate abnormal functional connectivity between central lateral (CL) thalamic nucleus and medial occipital lobe. Others have shown pulvinar connectivity disturbances in TLE, but it is incompletely understood how TLE affects pulvinar subnuclei. Also, the effects of epilepsy surgery on thalamic functional connectivity remains poorly understood. In this study, we examine the effects of TLE on functional connectivity of two key thalamic arousal-nuclei: lateral pulvinar (PuL) and CL. We evaluate resting-state functional connectivity of the PuL and CL in 40 patients with TLE and 40 controls using fMRI. In 25 patients, postoperative images (>1 year) were also compared with preoperative images. Compared to controls, patients with TLE exhibit loss of normal positive connectivity between PuL and lateral occipital lobe (p < 0.05), and a loss of normal negative connectivity between CL and medial occipital lobe (p < 0.01, paired t-tests). FMRI amplitude of low-frequency fluctuation (ALFF) in TLE trended higher in ipsilateral PuL (p = 0.06), but was lower in the lateral occipital (p < 0.01) and medial occipital lobe in patients versus controls (p < 0.05, paired t-tests). More abnormal ALFF in the ipsilateral lateral occipital lobe is associated with worse preoperative performance on Rey Complex Figure Test Immediate (p < 0.05, r = 0.381) and Delayed scores (p < 0.05, r = 0.413, Pearson's Correlations). After surgery, connectivity between PuL and lateral occipital lobe remains abnormal in patients (p < 0.01), but connectivity between CL and medial occipital lobe improves and is no longer different from control values (p > 0.05, ANOVA, post hoc Fischer's LSD). In conclusion, thalamic arousal nuclei exhibit abnormal connectivity with occipital lobe in TLE, and some connections may improve after surgery. Studying thalamic arousal centers may help explain distal network disturbances in TLE.
Topics: Arousal; Brain; Epilepsy, Temporal Lobe; Humans; Magnetic Resonance Imaging; Thalamus
PubMed: 33334720
DOI: 10.1016/j.yebeh.2020.107645 -
Human Brain Mapping Jul 2015The human pulvinar is the largest thalamic area in terms of size and cortical connectivity. Although much is known about regional pulvinar structural anatomy, relatively... (Meta-Analysis)
Meta-Analysis
The human pulvinar is the largest thalamic area in terms of size and cortical connectivity. Although much is known about regional pulvinar structural anatomy, relatively little is known about pulvinar functional anatomy in humans. Cooccurrence of experimentally induced brain activity is a traditional metric used to establish interregional brain connectivity and forms the foundation of functional neuroimaging connectivity analyses. Because functional neuroimaging studies report task-related coactivations within a standardized space, meta-analysis of many whole-brain studies can define the brain's interregional coactivation across many tasks. Such an analysis can also detect and define variations in functional coactivations within a particular region. Here we use coactivation profiles reported in ∼ 7,700 functional neuroimaging studies to parcellate and define the pulvinar's functional anatomy. Parcellation of the pulvinar's coactivation profile identified five clusters per pulvinar of distinct functional coactivation. These clusters showed a high degree of symmetry across hemispheres and correspondence with the human pulvinar's cytoarchitecture. We investigated the functional coactivation profiles of each resultant pulvinar cluster with meta-analytic methods. By referencing existent neuroimaging and lesion-deficit literature, these profiles make a case for regional pulvinar specialization within the larger human attention-controlling network. Reference to this literature also informs specific hypotheses that can be tested in subsequent studies in healthy and clinical populations.
Topics: Brain Mapping; Humans; Nerve Net; Pulvinar
PubMed: 25821061
DOI: 10.1002/hbm.22781 -
Nature Communications Dec 2018The pulvinar influences communication between cortical areas. We use fMRI to characterize the functional organization of the human pulvinar and its coupling with cortex....
The pulvinar influences communication between cortical areas. We use fMRI to characterize the functional organization of the human pulvinar and its coupling with cortex. The ventral pulvinar is sensitive to spatial position and moment-to-moment transitions in visual statistics, but also differentiates visual categories such as faces and scenes. The dorsal pulvinar is modulated by spatial attention and is sensitive to the temporal structure of visual input. Cortical areas are functionally coupled with discrete pulvinar regions. The spatial organization of this coupling reflects the functional specializations and anatomical distances between cortical areas. The ventral pulvinar is functionally coupled with occipital-temporal cortices. The dorsal pulvinar is functionally coupled with frontal, parietal, and cingulate cortices, including the attention, default mode, and human-specific tool networks. These differences mirror the principles governing cortical organization of dorsal and ventral cortical visual streams. These results provide a functional framework for how the pulvinar facilitates and regulates cortical processing.
Topics: Adult; Cerebral Cortex; Female; Humans; Magnetic Resonance Imaging; Male; Pulvinar; Young Adult
PubMed: 30568159
DOI: 10.1038/s41467-018-07725-6 -
Frontiers in Systems Neuroscience 2015
PubMed: 25852498
DOI: 10.3389/fnsys.2015.00039 -
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 -
NeuroImage Nov 2022Brain iron homeostasis is necessary for healthy brain function. MRI and histological studies have shown altered brain iron levels in the brains of patients with multiple...
Brain iron homeostasis is necessary for healthy brain function. MRI and histological studies have shown altered brain iron levels in the brains of patients with multiple sclerosis (MS), particularly in the deep gray matter (DGM). Previous studies were able to only partially separate iron-modifying effects because of incomplete knowledge of iron-modifying processes and influencing factors. It is therefore unclear to what extent and at which stages of the disease different processes contribute to brain iron changes. We postulate that spatially covarying magnetic susceptibility networks determined with Independent Component Analysis (ICA) reflect, and allow for the study of, independent processes regulating iron levels. We applied ICA to quantitative susceptibility maps for 170 individuals aged 9-81 years without neurological disease ("Healthy Aging" (HA) cohort), and for a cohort of 120 patients with MS and 120 age- and sex-matched healthy controls (HC; together the "MS/HC" cohort). Two DGM-associated "susceptibility networks" identified in the HA cohort (the Dorsal Striatum and Globus Pallidus Interna Networks) were highly internally reproducible (i.e. "robust") across multiple ICA repetitions on cohort subsets. DGM areas overlapping both robust networks had higher susceptibility levels than DGM areas overlapping only a single robust network, suggesting that these networks were caused by independent processes of increasing iron concentration. Because MS is thought to accelerate brain aging, we hypothesized that associations between age and the two robust DGM-associated networks would be enhanced in patients with MS. However, only one of these networks was altered in patients with MS, and it had a null age association in patients with MS rather than a stronger association. Further analysis of the MS/HC cohort revealed three additional disease-related networks (the Pulvinar, Mesencephalon, and Caudate Networks) that were differentially altered between patients with MS and HCs and between MS subtypes. Exploratory regression analyses of the disease-related networks revealed differential associations with disease duration and T2 lesion volume. Finally, analysis of ROI-based disease effects in the MS/HC cohort revealed an effect of disease status only in the putamen ROI and exploratory regression analysis did not show associations between the caudate and pulvinar ROIs and disease duration or T2 lesion volume, showing the ICA-based approach was more sensitive to disease effects. These results suggest that the ICA network framework increases sensitivity for studying patterns of brain iron change, opening a new avenue for understanding brain iron physiology under normal and disease conditions.
Topics: Brain; Brain Diseases; Gray Matter; Humans; Iron; Magnetic Resonance Imaging; Multiple Sclerosis
PubMed: 35878723
DOI: 10.1016/j.neuroimage.2022.119503