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NeuroImage. Clinical 2022Dysfunction of the thalamus has been proposed as a core mechanism of fatal familial insomnia. However, detailed metabolic and structural alterations in thalamic...
BACKGROUND
Dysfunction of the thalamus has been proposed as a core mechanism of fatal familial insomnia. However, detailed metabolic and structural alterations in thalamic subnuclei are not well documented. We aimed to address the multimodal structuro-metabolic pattern at the level of the thalamic nuclei in fatal familial insomnia patients, and investigated the clinical presentation of primary thalamic alterations.
MATERIALS AND METHODS
Five fatal familial insomnia patients and 10 healthy controls were enrolled in this study. All participants underwent neuropsychological assessments, polysomnography, electroencephalogram, and cerebrospinal fluid tests. MRI and fluorodeoxyglucose PET were acquired on a hybrid PET/MRI system. Structural and metabolic changes were compared using voxel-based morphometry analyses and standardized uptake value ratio analyses, focusing on thalamic subnuclei region of interest analyses. Correlation analysis was conducted between gray matter volume and metabolic decrease ratios, and clinical features.
RESULTS
The whole-brain analysis showed that gray matter volume decline was confined to the bilateral thalamus and right middle temporal pole in fatal familial insomnia patients, whereas hypometabolism was observed in the bilateral thalamus, basal ganglia, and widespread cortices, mainly in the forebrain. In the regions of interest analysis, gray matter volume and metabolism decreases were prominent in bilateral medial dorsal nuclei, anterior nuclei, and the pulvinar, which is consistent with neuropathological and clinical findings. A positive correlation was found between gray matter volume and metabolic decrease ratios.
CONCLUSIONS
Our study revealed specific structuro-metabolic pattern of fatal familial insomnia that demonstrated the essential roles of medial dorsal nuclei, anterior nuclei, and pulvinar, which may be a potential biomarker in diagnosis. Also, primary thalamic subnuclei alterations may be correlated with insomnia, neuropsychiatric, and autonomic symptoms sparing primary cortical involvement.
Topics: Case-Control Studies; Humans; Insomnia, Fatal Familial; Magnetic Resonance Imaging; Positron-Emission Tomography; Thalamus
PubMed: 35504222
DOI: 10.1016/j.nicl.2022.103026 -
The European Journal of Neuroscience Jan 2016The role of higher-order thalamic structures in sensory processing remains poorly understood. Here, we used the ferret (Mustela putorius furo) as a novel model species...
The role of higher-order thalamic structures in sensory processing remains poorly understood. Here, we used the ferret (Mustela putorius furo) as a novel model species for the study of the lateral posterior (LP)-pulvinar complex and its structural and functional connectivity with area 17 [primary visual cortex (V1)]. We found reciprocal anatomical connections between the lateral part of the LP nucleus of the LP-pulvinar complex (LPl) and V1. In order to investigate the role of this feedback loop between LPl and V1 in shaping network activity, we determined the functional interactions between LPl and the supragranular, granular and infragranular layers of V1 by recording multiunit activity and local field potentials. Coherence was strongest between LPl and the supragranular V1, with the most distinct peaks in the delta and alpha frequency bands. Inter-area interaction measured by spike-phase coupling identified the delta frequency band being dominated by the infragranular V1 and multiple frequency bands that were most pronounced in the supragranular V1. This inter-area coupling was differentially modulated by full-field synthetic and naturalistic visual stimulation. We also found that visual responses in LPl were distinct from those in V1 in terms of their reliability. Together, our data support a model of multiple communication channels between LPl and the layers of V1 that are enabled by oscillations in different frequency bands. This demonstration of anatomical and functional connectivity between LPl and V1 in ferrets provides a roadmap for studying the interaction dynamics during behaviour, and a template for identifying the activity dynamics of other thalamo-cortical feedback loops.
Topics: Action Potentials; Animals; Brain Waves; Female; Ferrets; Neural Pathways; Neurons; Photic Stimulation; Pulvinar; Visual Cortex
PubMed: 26505737
DOI: 10.1111/ejn.13116 -
Frontiers in Cellular Neuroscience 2021Two types of corticothalamic (CT) terminals reach the pulvinar nucleus of the thalamus, and their distribution varies according to the hierarchical level of the cortical...
Two types of corticothalamic (CT) terminals reach the pulvinar nucleus of the thalamus, and their distribution varies according to the hierarchical level of the cortical area they originate from. While type 2 terminals are more abundant at lower hierarchical levels, terminals from higher cortical areas mostly exhibit type 1 axons. Such terminals also evoke different excitatory postsynaptic potential dynamic profiles, presenting facilitation for type 1 and depression for type 2. As the pulvinar is involved in the oscillatory regulation between intercortical areas, fundamental questions about the role of these different terminal types in the neuronal communication throughout the cortical hierarchy are yielded. Our theoretical results support that the co-action of the two types of terminals produces different oscillatory rhythms in pulvinar neurons. More precisely, terminal types 1 and 2 produce alpha-band oscillations at a specific range of connectivity weights. Such oscillatory activity is generated by an unstable transition of the balanced state network's properties that it is found between the quiescent state and the stable asynchronous spike response state. While CT projections from areas 17 and 21a are arranged in the model as the empirical proportion of terminal types 1 and 2, the actions of these two cortical connections are antagonistic. As area 17 generates low-band oscillatory activity, cortical area 21a shifts pulvinar responses to stable asynchronous spiking activity and vice versa when area 17 produces an asynchronous state. To further investigate such oscillatory effects through corticothalamo-cortical projections, the transthalamic pathway, we created a cortical feedforward network of two cortical areas, 17 and 21a, with CT connections to a pulvinar-like network with two cortico-recipient compartments. With this model, the transthalamic pathway propagates alpha waves from the pulvinar to area 21a. This oscillatory transfer ceases when reciprocal connections from area 21a reach the pulvinar, closing the CT loop. Taken together, results of our model suggest that the pulvinar shows a bi-stable spiking activity, oscillatory or regular asynchronous spiking, whose responses are gated by the different activation of cortico-pulvinar projections from lower to higher-order areas such as areas 17 and 21a.
PubMed: 34938163
DOI: 10.3389/fncel.2021.787170 -
AJNR. American Journal of Neuroradiology Jun 2021Gadolinium complexes have paramagnetic properties; thus, we aimed to determine the susceptibility changes in the globus pallidus and dentate nucleus following...
BACKGROUND AND PURPOSE
Gadolinium complexes have paramagnetic properties; thus, we aimed to determine the susceptibility changes in the globus pallidus and dentate nucleus following administration of linear or macrocyclic gadolinium-based contrast agents in children.
MATERIALS AND METHODS
Thirty-three patients with linear gadolinium-based contrast agent gadopentetate dimeglumine administration, 33 age- and sex-matched patients with macrocyclic gadolinium-based contrast agent gadobutrol administration, and 33 age- and sex-matched control subjects without gadolinium exposure were enrolled in this retrospective study. The signal intensity on SWI and T1WI was determined in the dentate nucleus, middle cerebellar peduncle, globus pallidus, and pulvinar of the thalamus in an ROI-based analysis to calculate dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios. A repeated measures ANOVA was performed to compare SWI, SWI, and T1WI signal intensity ratios between gadolinium-based contrast agent groups and control subjects. Pearson correlation analysis was performed to determine any correlation between signal intensity ratios and variables.
RESULTS
Dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios for both SWI and SWI were lower for the linear gadolinium-based contrast agent group compared with macrocyclic gadolinium-based contrast agent and control groups ( < .05). No significant difference of the SWI and SWI ratios were noted between the macrocyclic gadolinium-based contrast agent group and the control group ( > .05). Both dentate nucleus-to-middle cerebellar peduncle and globus pallidus-to-thalamus ratios on T1WI in the linear gadolinium-based contrast agent group were higher than in the control group and the macrocyclic gadolinium-based contrast agent group ( < .05). A negative correlation was identified between SWI and SWI ratios and the number of linear gadolinium-based contrast agent administrations (dentate nucleus-to-middle cerebellar peduncle ratio: SWI, = -0.43, = .005; SWI, = -0.38, = .011; globus pallidus-to-thalamus ratio: SWI, = -0.39, = .009; SWI, = -0.33, = .017).
CONCLUSIONS
SWI analysis of the pediatric brain demonstrated a statistically significant decrease in SWI and SWI values for the dentate nucleus and globus pallidus after administration of linear gadolinium-based contrast agents but not macrocyclic gadolinium-based contrast agents.
Topics: Adolescent; Cerebellar Nuclei; Child; Child, Preschool; Contrast Media; Female; Gadolinium; Gadolinium DTPA; Globus Pallidus; Humans; Magnetic Resonance Imaging; Male; Organometallic Compounds; Retrospective Studies
PubMed: 33888459
DOI: 10.3174/ajnr.A7143 -
Bone & Joint Research Dec 2020As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the...
As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the acetabulum's surface area and showing the first signs of degeneration. The fossa's function is expected to be more than augmenting static stability with the ligamentum teres and being a templating landmark in arthroplasty. Indeed, the fossa, which is almost mature at 16 weeks of intrauterine development, plays a key role in hip development, enabling its nutrition through vascularization and synovial fluid, as well as the influx of chondrogenic stem/progenitor cells that build articular cartilage. The pulvinar, a fibrofatty tissue in the fossa, has the same developmental origin as the synovium and articular cartilage and is a biologically active area. Its unique anatomy allows for homogeneous distribution of the axial loads into the joint. It is composed of intra-articular adipose tissue (IAAT), which has adipocytes, fibroblasts, leucocytes, and abundant mast cells, which participate in the inflammatory cascade after an insult to the joint. Hence, the fossa and pulvinar should be considered in decision-making and surgical outcomes in hip preservation surgery, not only for their size, shape, and extent, but also for their biological capacity as a source of cytokines, immune cells, and chondrogenic stem cells. Cite this article: 2020;9(12):857-869.
PubMed: 33275027
DOI: 10.1302/2046-3758.912.BJR-2020-0254.R1 -
Frontiers in Human Neuroscience 2022Responsive neurostimulation is an evolving therapeutic option for patients with treatment-refractory epilepsy. Open-loop, continuous stimulation of the anterior thalamic... (Review)
Review
INTRODUCTION
Responsive neurostimulation is an evolving therapeutic option for patients with treatment-refractory epilepsy. Open-loop, continuous stimulation of the anterior thalamic nuclei is the only approved modality, yet chronic stimulation rarely induces complete seizure remission and is associated with neuropsychiatric adverse effects. Accounts of off-label responsive stimulation in thalamic nuclei describe significant improvements in patients who have failed multiple drug regimens, vagal nerve stimulation, and other invasive measures. This systematic review surveys the currently available data supporting the use of responsive thalamic neurostimulation in primary and secondary generalized, treatment-refractory epilepsy.
MATERIALS AND METHODS
A systematic review was performed using the following combination of keywords and controlled vocabulary: ("Seizures"[Mesh] AND "Thalamus"[Mesh] AND "Deep Brain Stimulation"[Mesh]) OR (responsive neurostim* AND (thalamus[MeSH])) OR [responsive neurostimulation AND thalamus AND (epilepsy OR seizures)]. In addition, a search of the publications listed under the PubMed "cited by" tab was performed for all publications that passed title/abstract screening in addition to manually searching their reference lists.
RESULTS
Ten publications were identified describing a total of 29 subjects with a broad range of epilepsy disorders treated with closed-loop thalamic neurostimulation. The median age of subjects was 31 years old (range 10-65 years). Of the 29 subjects, 15 were stimulated in the anterior, 11 in the centromedian, and 3 in the pulvinar nuclei. Excluding 5 subjects who were treated for 1 month or less, median time on stimulation was 19 months (range 2.4-54 months). Of these subjects, 17/24 experienced greater than or equal to 50%, 11/24 least 75%, and 9/24 at least 90% reduction in seizures. Although a minority of patients did not exhibit significant clinical improvement by follow-up, there was a general trend of increasing treatment efficacy with longer periods on closed-loop thalamic stimulation.
CONCLUSION
The data supporting off-label closed-loop thalamic stimulation for refractory epilepsy is limited to 29 adult and pediatric patients, many of whom experienced significant improvement in seizure duration and frequency. This encouraging progress must be verified in larger studies.
PubMed: 35865353
DOI: 10.3389/fnhum.2022.910345 -
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 -
Frontiers in Neural Circuits 2015The idea that dorsal thalamic inputs can be divided into "drivers", which provide the primary excitatory drive for the relay of information to cortex, and "modulators",... (Review)
Review
The idea that dorsal thalamic inputs can be divided into "drivers", which provide the primary excitatory drive for the relay of information to cortex, and "modulators", which alter the gain of signal transmission, has provided a valuable organizing principle for the study of thalamic function. This view further promoted the identification of "first order" and "higher order" thalamic nuclei, based on the origin of their driving inputs. Since the introduction of this influential terminology, a number of studies have revealed the existence of a wide variety of thalamic organizational schemes. For example, some thalamic nuclei are not innervated by typical driver inputs, but instead receive input from terminals which exhibit features distinct from those of either classic drivers or modulators. In addition, many thalamic nuclei contain unique combinations of convergent first order, higher order, and/or other "driver-like" inputs that do not conform with the driver/modulator framework. The assortment of synaptic arrangements identified in the thalamus are reviewed and discussed from the perspective that this organizational diversity can dramatically increase the computational capabilities of the thalamus, reflecting its essential roles in sensory, motor, and sensory-motor circuits.
Topics: Animals; Neural Pathways; Neurons; Perception; Thalamus
PubMed: 26793068
DOI: 10.3389/fncir.2015.00086 -
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 -
NeuroImage. Clinical 2017Hexanucleotide repeat expansions in are the most common known genetic cause of familial and sporadic frontotemporal dementia and amyotrophic lateral sclerosis. Previous...
Hexanucleotide repeat expansions in are the most common known genetic cause of familial and sporadic frontotemporal dementia and amyotrophic lateral sclerosis. Previous work has shown that patients with behavioral variant frontotemporal dementia due to show salience and sensorimotor network disruptions comparable to those seen in sporadic behavioral variant frontotemporal dementia, but it remains unknown how early in the lifespan these and other changes in brain structure and function arise. To gain insights into this question, we compared 15 presymptomatic carriers (age 43.7 ± 10.2 years, nine females) to matched healthy controls. We used voxel-based morphometry to assess gray matter, diffusion tensor imaging to interrogate white matter tracts, and task-free functional MRI to probe the salience, sensorimotor, default mode, and medial pulvinar thalamus-seeded networks. We further used a retrospective chart review to ascertain psychiatric histories in carriers and their non-carrier family members. Carriers showed normal cognition and behavior despite gray matter volume and brain connectivity deficits that were apparent as early as the fourth decade of life. Gray matter volume deficits were topographically similar though less severe than those in patients with behavioral variant frontotemporal dementia due to , with major foci in cingulate, insula, thalamus, and striatum. Reduced white matter integrity was found in the corpus callosum, cingulum bundles, corticospinal tracts, uncinate fasciculi and inferior longitudinal fasciculi. Intrinsic connectivity deficits were detected in all four networks but most prominent in salience and medial pulvinar thalamus-seeded networks. Carrier and control groups showed comparable relationships between imaging metrics and age, suggesting that deficits emerge during early adulthood. Carriers and non-carrier family members had comparable lifetime histories of psychiatric symptoms. Taken together, the findings suggest that presymptomatic expansion carriers exhibit functionally compensated brain volume and connectivity deficits that are similar, though less severe, to those reported during the symptomatic phase. The early adulthood emergence of these deficits suggests that they represent aberrant network patterning during development, an early neurodegeneration prodrome, or both.
Topics: Adult; Amyotrophic Lateral Sclerosis; Asymptomatic Diseases; Brain; C9orf72 Protein; DNA Repeat Expansion; Diffusion Tensor Imaging; Female; Frontotemporal Dementia; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net; Neuropsychological Tests; Oxygen; Proteins
PubMed: 28337409
DOI: 10.1016/j.nicl.2016.12.006