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Visual pathways of the brain are organized into parallel channels that code different features of the external environment. In the current study, we investigated the anatomical organization of parallel pathways from the superior colliculus (SC) to the pulvinar nucleus in the mouse. Virus injections placed in the ipsilateral and contralateral SC to induce the expression of different fluorescent proteins defines two pulvinar zones. The lateral pulvinar (Pl) receives ipsilateral SC input and the caudal medial pulvinar (Pcm) receives bilateral SC input. To examine the ultrastructure of these projections using transmission electron microscopy, we injected the SC with viruses to induce peroxidase expression within synaptic vesicles or mitochondria. We quantitatively compared the sizes of ipsilateral and contralateral tectopulvinar terminals and their postsynaptic dendrites, as well as the sizes of the overall population of synaptic terminals and their postsynaptic dendrites in the Pl and Pcm. Our ultrastructural analysis revealed that ipsilateral tectopulvinar terminals are significantly larger than contralateral tectopulvinar terminals. In particular, the ipsilateral tectopulvinar projection includes a subset of large terminals (≥ 1 μm(2)) that envelop dendritic protrusions of postsynaptic dendrites. We also found that both ipsilateral and contralateral tectopulvinar terminals are significantly larger than the overall population of synaptic terminals in both the Pl and Pcm. Thus, the ipsilateral tectopulvinar projection is structurally distinct from the bilateral tectopulvinar pathway, but both tectopulvinar channels may be considered the primary or “driving” input to the Pl and Pcm.

Drug‐resistant focal epilepsy with regional neocortical seizure onsets originating from the posterior quadrant can be particularly difficult to treat with resective surgery due to the overlap with eloquent cortex. Published reports indicate that corticothalamic treatment targeting the anterior or centromedian nucleus of the thalamus with direct brain‐responsive stimulation may be an effective approach to treat regional neocortical epilepsy. The pulvinar has remained largely unstudied as a neurostimulation target to treat refractory epilepsy. Because the pulvinar has connections with the posterior quadrant, neurostimulation may be effective if applied to seizures originating in this area. We performed a retrospective chart review of patients with regional neocortical seizure onsets in the posterior quadrant treated with the RNS System. Demographics, epilepsy history, clinical seizure frequencies, and neuropsychological testing results were obtained from the chart. Electrocorticogram (ECoG) records stored by the RNS System were reviewed to evaluate electrographic seizure onset patterns. Our patients were followed for 10, 12.5, and 15 months. All patients were responders (≥50% seizure reduction), and two of the three patients experienced a ≥90% reduction in seizures at the last follow‐up. Pre‐ and postsurgical neuropsychological evaluations were compared for two of the patients, and there was no evidence of cognitive decline found in either patient. Interestingly, mild cognitive improvements were reported. The third patient had only postimplant neuropsychological testing data available. Findings for this patient suggested executive dysfunction that was present prior to the RNS System which did not worsen with surgery. A visual inspection of ECoGs revealed near‐simultaneous seizure onsets in neocortical and pulvinar leads in two patients. Seizure onsets in the third patient were more variable. This is the first published report of brain‐responsive neurostimulation targeting the pulvinar to treat refractory regional onset epilepsy of posterior quadrant origin.

Lesions in the primary visual cortex (V1) cause extensive retrograde degeneration in the lateral geniculate nucleus, but it remains unclear whether they also trigger any neuronal loss in other subcortical visual centers. The inferior (IPul) and lateral (LPul) pulvinar nuclei have been regarded as part of the pathways that convey visual information to both V1 and extrastriate cortex. Here, we apply stereological analysis techniques to NeuN-stained sections of marmoset brain, in order to investigate whether the volume of these nuclei, and the number of neurons they comprise, change following unilateral long-term V1 lesions. For comparison, the medial pulvinar nucleus (MPul), which has no connections with V1, was also studied. Compared to control animals, animals with lesions incurred either 6 weeks after birth or in adulthood showed significant LPul volume loss following long (> 11 months) survival times. However, no obvious areas of neuronal degeneration were observed. In addition, estimates of neuronal density in lesioned hemispheres were similar to those in the non-lesioned hemispheres of same animals. Our results support the view that, in marked contrast with the geniculocortical projection, the pulvinar pathway is largely spared from the most severe long-term effects of V1 lesions, whether incurred in early postnatal or adult life. This difference can be linked to the more divergent pattern of pulvinar connectivity to the visual cortex, including strong reciprocal connections with extrastriate areas. The results also caution against interpretation of volume loss in brain structures as a marker for neuronal degeneration.

Objectives To define both the severity and extent of structural alteration in certain thalamic nuclei by means of MR morphometry and to compare these findings with clinical performance in different phenotypes of multiple sclerosis (MS). Methods We comparatively measured the thalamus nuclei volumes of patients with remitting-relapsing (RRMS) and secondary-progressive (SPMS) phenotypes of multiple sclerosis and healthy control subjects (HC). The evaluation of neurological performance was based on the results of Expanded Disability Status Scale and Multiple Sclerosis Severity Scale. Cognitive and mental state was rated according to the results of Mini-Mental State Examination, Frontal Assessment Battery, Montreal Cognitive Assessment and Symbol Digit Modalities Test. Freesurfer 6.0 was used for thalamic nuclei volumes calculation. Results The median volume decline in thalamic pulvinar nuclei in RRMS group on the left side (anterior nucleus − 186,6 mm3, posterior nucleus – 149,4 mm3, medial nucleus 852,4 mm3) compared to HC (anterior nucleus – 229,2 mm3, posterior nucleus – 187,5 mm3, medical nucleus – 1081,3 mm3). Same group, right side – anterior nucleus – 219,5 mm3, posterior nucleus 187,1 mm3, medial nucleus – 989,6 mm3; HC group – anterior nucleus 261,1 mm3, posterior nucleus 240,5 mm3, medial nucleus – 1196,7 mm3 (p Conclusion These findings indicate the credible correlation between clinical progression of neurological and cognitive impairment in MS patients with asymmetry left-sided thalamic nuclei atrophy and may be considered a potential predicting tool of MS progression.

While research in previous decades demonstrated a link between the pulvinar nucleus of the thalamus and visual selective attention, the pulvinar’s specific functional role has remained elusive. However, methodological advances in electrophysiological recordings in non-human primates, including simultaneous recordings in multiple brain regions, have recently begun to reveal the pulvinar’s functional contributions to selective attention. These new findings suggest that the pulvinar is critical for the efficient transmission of sensory information within and between cortical regions, both synchronizing cortical activity across brain regions and controlling cortical excitability. These new findings further suggest that the pulvinar’s influence on cortical processing is embedded in a dynamic selection process that balances sensory and motor functions within the large-scale network that directs selective attention.

Introduction: Executive dysfunction is common in dementia with Lewy bodies (DLB). The pulvinar nucleus plays a role in executive control and synchronizes with cortical regions in the salience network that are vulnerable to Lewy pathology. Objective: We investigated the pulvinar subregions in patients with mild DLB and their associations with executive function. Methods: The sample consisted of 38 DLB patients and 38 age- and sex-matched normal controls. We evaluated cognitive function using the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet. We obtained four pulvinar nuclei using preprocessed T1-weighted magnetic resonance images. We compared volumes and textures of the DLB patients and the normal controls for each nucleus. We used a linear regression to determine the association of textures and neuropsychological test scores. Results: The DLB patients showed comparable volumes to the normal controls in all pulvinar nuclei. However, the DLB patients showed different texture of the left medial pulvinar (PuM) from the normal controls. The entropy, contrast, and cluster shade were lower but autocorrelation of left PuM was higher in the DLB patients compared to the normal controls. These texture features of the left PuM were associated with the set-shifting performance measured by the Trail Making Test. Conclusions: In DLB, the left PuM may be altered from early stage, which may contribute to the development of executive dysfunction.

Carpal Tunnel Syndrome (CTS) is a median nerve entrapment neuropathy that alters primary somatosensory cortex (S1) organization. While electro-acupuncture (EA), a form of peripheral neuromodulation, has been shown to improve clinical and neurophysiological CTS outcomes, the role of EA-evoked brain response during therapy (within and beyond S1) for improved outcomes is unknown. We investigated S1-associated whole brain fMRI connectivity during both a resting and sustained EA stimulation state in age-matched healthy controls (N = 28) and CTS patients (N = 64), at baseline and after 8 weeks of acupuncture therapy (local, distal, or sham EA). Compared to healthy controls, CTS patients at baseline showed decreased resting state functional connectivity between S1 and thalamic pulvinar nucleus. Increases in S1/pulvinar connectivity strength following verum EA therapy (combined local and distal) were correlated with improvements in median nerve velocity (r = 0.38, p = 0.035). During sustained local EA, compared to healthy controls, CTS patients demonstrated increased functional connectivity between S1 and anterior hippocampus (aHipp). Following 8 weeks of local EA therapy, S1/aHipp connectivity significantly decreased and greater decrease was associated with improvement in patients' functional status (r = 0.64, p = 0.01) and increased median nerve velocity (r = −0.62, p = 0.013). Thus, connectivity between S1 and other brain areas is also disrupted in CTS patients and may be improved following EA therapy. Furthermore, stimulus-evoked fMRI connectivity adds therapy-specific, mechanistic insight to more common resting state connectivity approaches. Specifically, local EA modulates S1 connectivity to sensory and affective processing regions, linked to patient function and median nerve health.

The importance of (inherited) genetic impact in reading development is well established. De novo mutation is another important contributor that is recently gathering interest as a major liability of neurodevelopmental disorders, but has been neglected in reading research to date. Paternal age at childbirth (PatAGE) is known as the most prominent risk factor for de novo mutation, which has been repeatedly shown by molecular genetic studies. As one of the first efforts, we performed a preliminary investigation of the relationship between PatAGE, offspring's reading, and brain structure in a longitudinal neuroimaging study following 51 children from kindergarten through third grade. The results showed that greater PatAGE was significantly associated with worse reading, explaining an additional 9.5% of the variance after controlling for a number of confounds—including familial factors and cognitive‐linguistic reading precursors. Moreover, this effect was mediated by volumetric maturation of the left posterior thalamus from ages 5 to 8. Complementary analyses indicated the PatAGE‐related thalamic region was most likely located in the pulvinar nuclei and related to the dorsal attention network by using brain atlases, public datasets, and offspring's diffusion imaging data. Altogether, these findings provide novel insights into neurocognitive mechanisms underlying the PatAGE effect on reading acquisition during its earliest phase and suggest promising areas of future research., In the present study, Xia et al. demonstrate that advanced paternal age at childbirth (PatAGE) is negatively associated with offspring's reading. Moreover, this association is mediated by neuroanatomical maturation in the left posterior thalamus, which is closely linked with the dorsal attention network. These findings suggest a novel pathway through which parents affects their offspring's reading ability and suggest future avenues of research on PatAGE‐related factors, such as de novo mutation, in reading.

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 terminals 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 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 cortico-thalamic loop. Taken together, results of our model suggest that the pulvnar 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.

Posterior thalamic pulvinar nuclei have been implicated in different aspects of spatial attention, but their exact role in humans remain unclear. Most neuropsychological studies of attention deficits after pulvinar lesion have concerned single patients or small samples. Here we examined a group of 13 patients with focal damage to posterior thalamus on a visual search task with faces, allowing us to test several hypotheses concerning pulvinar function in controlling attention to visually salient or emotionally significant stimuli. Our results identified two subgroups of thalamic patients with distinct patterns of attentional responsiveness to emotional and colour features in face targets. One group with lesions located in anterior and ventral portions of thalamus showed intact performance, with a normal facilitation of visual search for faces with emotional (fearful or happy) expressions on both side of space, similar to healthy controls. By contrast, a second group showed a slower and poorer detection of face targets, most severe for neutral faces, but with a paradoxically enhanced facilitation by both colour and emotional features. This second group had lesions centred on the pulvinar, involving mainly the dorso-medial sectors in patients showing enhanced effects of colour features, but extending to more dorso-lateral sectors in those with enhanced effects of emotional features. These findings reveal that pulvinar nuclei are not critical for orienting attention to emotionally or visually salient features, but instead provide new evidence in support of previous hypotheses suggesting an important role in controlling attention in visual scenes with distracting information.

ObjectiveTo investigate the dynamic functional connectivity of thalamocortical networks in interictal migraine patients and whether clinical features are associated with abnormal connectivity.MethodsWe investigated dynamic functional network connectivity (dFNC) of the migraine brain in 89 interictal migraine patients and 70 healthy controls. We focused on the temporal properties of thalamocortical connectivity using sliding window cross-correlation, clustering state analysis, and graph-theory methods. Relationships between clinical symptoms and abnormal dFNC were evaluated using a multivariate linear regression model.ResultsFive dFNC brain states were identified to characterize and compare dynamic functional connectivity patterns. We demonstrated that migraineurs spent more time in a strongly interconnected between-network state, but they spent less time in a sparsely connected state. Interestingly, we found that abnormal posterior thalamus (pulvinar nucleus) dFNC with the visual cortex and the precuneus were significantly correlated with headache frequency of migraine. Further topologic measures revealed that migraineurs had significantly lower efficiency of information transfer in both global and local dFNC.ConclusionOur results demonstrated a transient pathologic state with atypical thalamocortical connectivity in migraineurs and extended current findings regarding abnormal thalamocortical networks and dysrhythmia in migraine.

Dysfunctional thalamocortical interactions have been suggested as putative mechanisms of ineffective pain modulation and also suggested as possible pathophysiology of fibromyalgia (FM). However, it remains unclear which specific thalamocortical networks are altered and whether it is related to abnormal pain perception in people with FM. Here, we conducted combined vertex-wise subcortical shape, cortical thickness, structural covariance, and resting-state functional connectivity analyses to address these questions. FM group exhibited a regional shape deflation of the left posterior thalamus encompassing the ventral posterior lateral and pulvinar nuclei. The structural covariance analysis showed that the extent of regional deflation of the left posterior thalamus was negatively covaried with the left inferior parietal cortical thickness in the FM group, whereas those two regions were positively covaried in the healthy controls. In functional connectivity analysis with the left posterior thalamus as a seed, FM group had less connectivity with the periaqueductal gray compared with healthy controls, but enhanced connectivity between the posterior thalamus and bilateral inferior parietal regions, associated with a lower electrical pain threshold at the hand dorsum (pain-free point). Overall, our findings showed the structural thalamic alteration interacts with the cortical regions in a functionally maladaptive direction, leading the FM brain more responsive to external stimuli and potentially contributing to pain amplification.

One important aspect for managing social interactions is the ability to rapidly and accurately perceive and respond to facial expressions, which is highly dependent upon intact processing within both cortical and subcortical components of the early visual pathways. Social cognitive deficits, including face emotion recognition (FER) deficits, are characteristic of several neuropsychiatric disorders, including schizophrenia (Sz) and autism spectrum disorders (ASD). Here, we investigated potential visual sensory contributions to FER deficits in Sz (n=28) and adult ASD (n=20) participants compared to neurotypical (n=30) controls using task-based fMRI during an implicit static/dynamic FER task. Compared to neurotypical controls, both Sz and ASD participants had significantly lower FER scores which interrelated with diminished activation of the superior temporal sulcus (STS). In Sz, STS deficits were predicted by reduced activation of both early visual regions and the pulvinar nucleus of the thalamus, along with impaired cortico-pulvinar interaction. By contrast, ASD participants showed patterns of increased early visual cortical and pulvinar activation. Large effect-size structural and histological abnormalities of pulvinar have previously been documented in Sz. Moreover, we have recently demonstrated impaired pulvinar activation to simple visual stimuli in Sz. Here, we provide the first demonstration of a disease-specific contribution of impaired pulvinar activation to social cognitive impairment in Sz.

Tourette syndrome (TS) is a neurobehavioral disorder for which the neurological mechanism has not been elucidated. Voxel-based morphometry (VBM) studies have revealed abnormalities in gray matter volume (GMV) in patients with TS; however, consistent results have not been obtained. The current study attempted to provide a voxel wise meta-analysis of gray matter changes using seed-based d mapping (SDM). We identified ten relevant studies that investigated gray matter alterations in TS patients and performed a meta-analysis using the SDM method to quantitatively estimate regional gray matter abnormalities. Next, we examined the relationships between GMV abnormalities and demographic and clinical characteristics. Our results demonstrated that TS patients had smaller GMV in the bilateral inferior frontal gyri and greater GMV in the cerebellum, right striatum (putamen), and bilateral thalami (pulvinar nucleus) than healthy controls. A meta-regression analysis did not identify correlations between GMV changes and demographic or clinical variables. This meta-analysis confirmed significant and consistent GMV changes in several brain regions of TS patients, primarily in the cortico-striato-thalamo-cortical network.

How do humans learn from raw sensory experience? Throughout life, but most obviously in infancy, we learn without explicit instruction. We propose a detailed biological mechanism for the widely-embraced idea that learning is based on the differences between predictions and actual outcomes (i.e., predictive error-driven learning). Specifically, numerous weak projections into the pulvinar nucleus of the thalamus generate top-down predictions, and sparse, focal driver inputs from lower areas supply the actual outcome, originating in layer 5 intrinsic bursting (5IB) neurons. Thus, the outcome is only briefly activated, roughly every 100 msec (i.e., 10 Hz, alpha), resulting in a temporal difference error signal, which drives local synaptic changes throughout the neocortex, resulting in a biologically-plausible form of error backpropagation learning. We implemented these mechanisms in a large-scale model of the visual system, and found that the simulated inferotemporal (IT) pathway learns to systematically categorize 3D objects according to invariant shape properties, based solely on predictive learning from raw visual inputs. These categories match human judgments on the same stimuli, and are consistent with neural representations in IT cortex in primates., 56 pages, 22 figures

A prominent feature of sensory processing is the ability to distinguish whether the activation of the sensory periphery is caused by changes in the external world or by the animal’s own actions1. Saccades, rapid eye movements executed by animals across phyla2–4, cause the visual scene to momentarily shift on the retina. The mechanisms by which visual systems differentiate between motion of the visual scene induced by saccades from motion due to changes in the external world are not fully understood. Here, we discovered that in mouse primary visual cortex (V1), the two types of motion evoke distinct patterns of activity across the population of neurons. As a result, a decoder of motion direction trained on the response to motion in the external world fails to generalize when tested on the response to saccades that induce similar motion on the retina. This is because during saccades, V1 combines the visual input with a strong non-visual input arriving from the pulvinar nucleus of the thalamus. This non-visual input is an efference copy – a copy of the oculomotor command that differs depending on the direction of the saccades. Silencing the pulvinar prevented the non-visual input from reaching V1, such that the pattern of activity in V1 was now similar no matter whether the motion was generated in the external world or by saccades. Thus, the pulvinar input to V1 ensures differential responses to the external and self-generated motion and may prevent downstream areas from extracting motion information about visual stimulus shifts generated by saccades. Changing the pattern of evoked activity through an efference copy may be a general mechanism that enables sensory cortices in mammals to distinguish between external and self-generated stimuli.

Background Although a central role of the thalamus for sleep regulation is undisputed, the exact localization of the crucial structures within the thalamus remains controversial. Case presentation Here we report a 35 year old woman with no prior comorbidities who developed severe and persistent hypersomnia with long sleep time after a small right-sided MRI-verified thalamic stroke affecting the dorsal part of the pulvinar and the dorsolateral boarders of the dorsomedial nuclei. Conclusion The observed symptoms suggest a crucial role of posterior thalamus but not the midline parts of the thalamus in sleep-wake control.

The cortical processing of visual information is thought to follow a hierarchical framework. This framework of connections between visual areas is based on the laminar patterns of direct feedforward and feedback cortico-cortical projections. However, this view ignores the cortico-thalamo-cortical projections to the pulvinar nucleus in the thalamus, which provides an alternative transthalamic information transfer between cortical areas. It was proposed that corticothalamic (CT) pathways follow a similar hierarchical pattern as cortico-cortical connections. Two main types of CT projections have been recognized: drivers and modulators. Drivers originate mainly in Layer 5 whereas modulators are from Layer 6. Little is known about the laminar distribution of these projections to the pulvinar across visual cortical areas. Here, we analyzed the distribution of CT neurons projecting to the lateral posterior (LP) thalamus in two species: cats and mice. Injections of the retrograde tracer fragment B of cholera toxin (CTb) were performed in the LP. The morphology and cortical laminar distribution of CTb-labeled neurons was assessed. In cats, neurons were mostly found in Layer 6 except in Area 17, where they were mostly in Layer 5. In contrast, CT neurons in mice were mostly located in Layer 6 across all areas. Thus, our results demonstrate that CT projections in mice do not follow the same organization as cats suggesting that the transthalamic pathways play distinct roles in these species.

The extrageniculate visual pathway, which carries visual information from the retina through the superficial layers of the superior colliculus and the pulvinar nucleus, is poorly understood. The pulvinar is thought to modulate information flow between cortical areas, and has been implicated in cognitive tasks like directing visually guided actions. In order to better understand the underlying circuitry, we performed retrograde injections of modified rabies virus in the visual cortex and pulvinar of the Long-Evans rat. We found a relatively small population of cells projecting to primary visual cortex (V1), compared to a much larger population projecting to higher visual cortex. Reciprocal corticothalamic projections showed a similar result, implying that pulvinar does not play as big a role in directly modulating V1 activity as previously thought.

Background. Neuroimaging studies of spinal cord injury (SCI) have mostly examined the functional organization of the cortex, with only limited focus on the subcortical substrates of the injury. However, thalamus is an important modulator and sensory relay that requires investigation at a subnuclei level to gain insight into the neuroplasticity following SCI. Objective. To use resting-state functional magnetic resonance imaging to examine the functional connectivity (FC) of thalamic subnuclei in complete SCI patients. Methods. A seed-based connectivity analysis was applied for 3 thalamic subnuclei: pulvinar, mediodorsal, and ventrolateral nucleus in each hemisphere. A nonparametric 2-sample t test with permutations was applied for each of the 6 thalamic seeds to compute FC differences between 22 healthy controls and 19 complete SCI patients with paraplegia. Results. Connectivity analysis showed a decrease in the FC of the bilateral mediodorsal nucleus with right superior temporal gyrus and anterior cingulate cortex in the SCI group. Similarly, the left ventrolateral nucleus exhibited decreased FC with left superior temporal gyrus in SCI group. In contrast, left pulvinar nucleus demonstrated an increase in FC with left inferior frontal gyrus and left inferior parietal lobule in SCI group. Our findings also indicate a negative relationship between postinjury durations and thalamic FC to regions of sensorimotor and visual cortices, where longer postinjury durations (~12 months) is associated with higher negative connectivity between these regions. Conclusion. This study provides evidence for reorganization in the thalamocortical connections known to be involved in multisensory integration and affective processing, with possible implications in the generation of sensory abnormalities after SCI.

Введение. Таламус является «передающим органом», который участвует в широком спектре неврологических функций. Функциональная уникальность и высокая чувствительность к повреждению при рассеянном склерозе (РС) в самых ранних стадиях заболевания делают таламус барометром диффузного повреждения головного мозга при РС. Цель исследования — изучить структурные и функциональные изменения таламуса и его субрегионов методом магнитно-резонансной морфометрии и определить их клиническую значимость при различных типах течения РС. Материалы и методы. Обследовано 68 пациентов с ремиттирующим (n = 40) и вторично-прогрессирующим (n = 28) типами течения РС, контроль составили 10 здоровых человек соответствующего возраста и пола. Неврологическая оценка пациентов проведена по шкалам инвалидизации (EDSS) и агрессивности РС (MSSS). Когнитивную и психическую сферы тестировали с использованием MMSE, FAB, MoCA, SDMT, теста Бека и HADS. Всем пациентам были выполнены МРТ головного мозга и проведена морфометрическая оценка полученных данных с помощью программы «Freesurfer 6.0». Результаты. Объемы ядер подушки таламуса при ремиттирующем РС были снижены слева (М (переднее : заднее) = 186,6 : 149,4 мм3 ) в сравнении с контролем (229,5 : 187,5 мм3 ) и справа (219,5 : 187,1 мм3 ) в сравнении с контролем (261,6 : 240,5 мм3 ; p < 0,05). Размеры левых ядер таламуса были достоверно снижены при вторично прогрессирующем РС по сравнению с ремиттирующим РС и контролем. С EDSS коррелировали уменьшение объемов коленчатых тел слева (r = –0,48) и ядер подушки таламуса слева (r = 0,46–0,54). Стандартные нейропсихологические шкалы коррелировали с объемом медиадорсального медиального крупноклеточного ядра (r(MMSE : FAB : MoCA) = 0,51 : 0,45 : 0,59). Максимальная корреляция теста SDMT (письменный раздел) установлена с левым вентральным передним ядром (r = 0,71). Заключение. Полученные данные свидетельствуют о высокой значимости атрофии ядер таламуса в прогрессировании инвалидизации и когнитивных нарушений при РС. Магнитно-резонансная морфометрия ядер таламуса может рассматриваться как важный маркер и предиктор прогрессирования РС., Introduction. The thalamus is a 'transmitting organ' that is involved in a wide range of neurological functions. Its functional uniqueness and high sensitivity to damage during the earliest stages of multiple sclerosis (MS) make the thalamus a kind of barometer of diffuse brain damage in MS. The aim of the study was to examine the structural and functional changes in the thalamus and its subregions using magnetic resonance morphometry and to determine their clinical significance in different types of MS. Materials and methods. We examined 68 patients with relapsing-remitting (n = 40) and secondary progressive (n = 28) MS. The control group consisted of 10 healthy people matched for age and gender. The Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS) were used to assess the patients' neurological status. The cognitive and mental domains were tested using the MMSE, FAB, MoCA, SDMT, Beck's test, and HADS. All patients underwent a brain MRI and morphometric evaluation of the obtained data using the FreeSurfer 6.0 software. Results. The size of the thalamic pulvinar in relapsing-remitting MS was reduced on the left (M (anterior : posterior) = 186.6 : 149.4 mm3) compared with the controls (229.5 : 187.5 mm3) and on the right (219.5 : 187.1 mm3) compared with the controls (261.6 : 240.5 mm3; p < 0.05). The size of the left thalamic nuclei was significantly reduced in secondary progressive MS when compared with relapsing-remitting MS and the controls. EDSS was correlated with a decrease in the dimensions of the geniculate nucleus on the left (r = –0.48) and the pulvinar nuclei on the left (r = 0.46–0.54). Standard neuropsychological scales correlated with the size of the medial dorsal nucleus (r (MMSE:FAB:MoCA) = 0.51; 0.45; 0.59). The greatest correlation was between the SDMT test (written section) and the left ventral anterior nucleus (r = 0.71). Conclusion. The obtained data indicate that thalamic nuclei atrophy plays a significant role in the progression of disability and cognitive disorders in MS. Mag- netic resonance morphometry of the thalamic nuclei can be considered an important marker and predictor of MS progression., «ANNALS OF CLINICAL AND EXPERIMENTAL NEUROLOGY», Том 14, № 3 (2020), Анналы клинической и экспериментальной неврологии, Выпуск 3 2020

The pulvinar is the largest thalamic nucleus in the brain and considered as a key structure in sensory processing and attention. Although its anatomy is well known, in particular thanks to studies in non-human primates, its role in perception and cognition remains poorly understood. Here, we used resting-state functional connectivity from a large sample of high-resolution data provided by the Human Connectome Project, combined with a large-scale meta-analysis approach to segregate and characterize the functional organization of the pulvinar nucleus. We identified five clusters per pulvinar with distinct connectivity profiles and determined their respective co-activation patterns. Using the Neurosynth database, we then investigated the functional significance of these co-activation networks. Our results confirm the functional heterogeneity of the pulvinar, revealing clearcut differences across clusters in terms of their connectivity patterns and associated cognitive domains. While the anterior and lateral clusters appear to be involved in action and attention domains, the ventromedial and dorsomedial clusters may preferentially subserve emotional processes and saliency detection. In contrast, the inferior cluster shows less specificity but correlates with perception and memory processes. Collectively, our results suggest that the pulvinar underwrites different components of cognition, supporting a central role in the coordination of cortico-subcortical processes mediated by distributed brain networks.

Recent evidence demonstrates that the pulvinar nuclei play a critical role in shaping the connectivity and function of the multiple cortical areas they connect. Surprisingly, however, little is known about the development of this area, the largest corpus of the thalamic nuclei, which go on to occupy 40% of the adult thalamus in the human. It was proposed that the nonhuman primate and the human pulvinar develop according to very different processes, with a greatly reduced neurogenic period in nonhuman primate compared to human and divergent origins. In the marmoset monkey, we demonstrate that neurons populating the pulvinar are generated throughout gestation, suggesting that this aspect of development is more similar to the human than first predicted. While we were able to confirm the diencephalic source of pulvinar neurons, we provide new evidence contesting the presence of an additional niche in the telencephalon. Finally, our study defines new molecular markers that will simplify future investigations in the development and evolution of the pulvinar.

The cortical visual hierarchy communicates in different oscillatory ranges. While gamma waves influence the feedforward processing, alpha oscillations travel in the feedback direction. Little is known how this oscillatory cortical communication depends on an alternative route that involves the pulvinar nucleus of the thalamus. We investigated whether the oscillatory coupling between the primary visual cortex (area 17) and area 21a depends on the transthalamic pathway involving the pulvinar in cats. To that end, visual evoked responses were recorded in areas 17 and 21a before, during and after inactivation of the pulvinar. Local field potentials were analyzed with Wavelet and Granger causality tools to determine the oscillatory coupling between layers. The results indicate that cortical oscillatory activity was enhanced during pulvinar inactivation, in particular for area 21a. In area 17, alpha band responses were represented in layers II/III. In area 21a, gamma oscillations, except for layer I, were significantly increased, especially in layer IV. Granger causality showed that the pulvinar modulated the oscillatory information between areas 17 and 21a in gamma and alpha bands for the feedforward and feedback processing, respectively. Together, these findings indicate that the pulvinar is involved in the mechanisms underlying oscillatory communication along the visual cortex.

Background Dementia with Lewy bodies is characterized by transient clinical features, including fluctuating cognition and visual hallucinations, implicating dysfunction of cerebral hub regions, such as the pulvinar nuclei of the thalamus. However, the pulvinar is typically only mildly affected by Lewy body pathology in dementia with Lewy bodies, suggesting additional factors may account for its proposed dysfunction. Methods We conducted a comprehensive analysis of postmortem pulvinar tissue using whole-transcriptome RNA sequencing, protein expression analysis, and histological evaluation. Results We identified 321 transcripts as significantly different between dementia with Lewy bodies cases and neurologically normal controls, with gene ontology pathway analysis suggesting the enrichment of transcripts related to synapses and positive regulation of immune functioning. At the protein level, proteins related to synaptic efficiency were decreased, and general synaptic markers remained intact. Analysis of glial subpopulations revealed astrogliosis without activated microglia, which was associated with synaptic changes but not neurodegenerative pathology. Discussion These results indicate that the pulvinar, a region with relatively low Lewy body pathological burden, manifests changes at the molecular level that differ from previous reports in a more severely affected region. We speculate that these alterations result from neurodegenerative changes in regions connected to the pulvinar and likely contribute to a variety of cognitive changes resulting from decreased cortical synchrony in dementia with Lewy bodies. © 2018 International Parkinson and Movement Disorder Society.

Recent advances in susceptibility MRI have dramatically improved the visualization of deep gray matter brain regions and the quantification of their magnetic properties in vivo, providing a novel tool to study the poorly understood iron homeostasis in the human brain. In this study, we used an advanced combination of the recent quantitative susceptibility mapping technique with dedicated analysis methods to study intra-thalamic tissue alterations in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS). Thalamic pathology is one of the earliest hallmarks of MS and has been shown to correlate with cognitive dysfunction and fatigue, but the mechanisms underlying the thalamic pathology are poorly understood. We enrolled a total of 120 patients, 40 with CIS, 40 with Relapsing Remitting MS (RRMS), and 40 with Secondary Progressive MS (SPMS). For each of the three patient groups, we recruited 40 controls, group matched for age- and sex (120 total). We acquired quantitative susceptibility maps using a single-echo gradient echo MRI pulse sequence at 3 T. Group differences were studied by voxel-based analysis as well as with a custom thalamus atlas. We used threshold-free cluster enhancement (TFCE) and multiple regression analyses, respectively. We found significantly reduced magnetic susceptibility compared to controls in focal thalamic subregions of patients with RRMS (whole thalamus excluding the pulvinar nucleus) and SPMS (primarily pulvinar nucleus), but not in patients with CIS. Susceptibility reduction was significantly associated with disease duration in the pulvinar, the left lateral nuclear region, and the global thalamus. Susceptibility reduction indicates a decrease in tissue iron concentration suggesting an involvement of chronic microglia activation in the depletion of iron from oligodendrocytes in this central and integrative brain region. Not necessarily specific to MS, inflammation-mediated iron release may lead to a vicious circle that reduces the protection of axons and neuronal repair.

Dysarthria is a frequent symptom in patients with stroke. The anatomical structures responsible for dysarthria have been reported in patients with lacunar infarcts, but the related lesions in patients with basal ganglia hemorrhage (BGH) have not been investigated. The aim of this study was to identify associations between the lesion location and the presence/absence of dysarthria in patients with BGH using voxel-based lesion symptom mapping (VLSM) analyses. A retrospective analysis was conducted on 26 patients with acute BGH (mean age, 54.0 years; men:women, 14:12) who underwent conservative management. The patients were classified into groups based on the presence or absence of dysarthria at the time of admission, which was determined by reviewing the patients' medical records. Brain lesions were traced on magnetic resonance images that were acquired within the first 3 weeks after BGH onset, and then separate high-resolution region-of-interest images were generated. Associations between dysarthria and the lesion location were determined with the VLSM analyses. The average volume of the delimited lesions was 7.38±5.75cm3. The VLSM analyses identified several voxel clusters, mainly in the pulvinar nucleus of the left thalamus, that were significantly related to the presence of dysarthria at admission. These findings suggest that patients with BGH extending into the left pulvinar nucleus should be monitored for dysarthria.

In this review, we outline the history of our current understanding of the organization of the pulvinar complex of mammals. We include more recent evidence from our own studies of both New and Old World monkeys, prosimian galagos, and close relatives of primates, including tree shrews and rodents. Based on cumulative evidence, we provide insights into the possible evolution of the visual pulvinar complex, as well as the possible co-evolution of the inferior pulvinar nuclei and temporal cortical visual areas within the MT complex.

See Duering and Schmidt (doi:10.1093/awx135) for a scientific commentary on this article.Thalamic alterations have been observed in infarcts initially sparing the thalamus but interrupting thalamo-cortical or cortico-thalamic projections. We aimed at extending this knowledge by demonstrating with in vivo imaging sensitive to iron accumulation, one marker of neurodegeneration, that (i) secondary thalamic alterations are focally located in specific thalamic nuclei depending on the initial infarct location; and (ii) such secondary alterations can contribute independently to the long-term outcome. To tackle this issue, 172 patients with an infarct initially sparing the thalamus were prospectively evaluated clinically and with magnetic resonance imaging to quantify iron through R2* map at 24-72 h and at 1-year follow-up. An asymmetry index was used to compare R2* within the thalamus ipsilateral versus contralateral to infarct and we focused on the 95th percentile of R2* as a metric of high iron content. Spatial distribution within the thalamus was analysed on an average R2* map from the entire cohort. The asymmetry index of the 95th percentile within individual nuclei (medio-dorsal, pulvinar, lateral group) were compared according to the initial infarct location in simple and multiple regression analyses and using voxel-based lesion-symptom mapping. Associations between the asymmetry index of the 95th percentile and functional, cognitive and emotional outcome were calculated in multiple regression models. We showed that R2* was not modified at 24-72 h but showed heterogeneous increase at 1 year mainly within the medio-dorsal and pulvinar nuclei. The asymmetry index of the 95th percentile within the medio-dorsal nucleus was significantly associated with infarcts involving anterior areas (frontal P = 0.05, temporal P = 0.02, lenticular P = 0.01) while the asymmetry index of the 95th percentile within the pulvinar nucleus was significantly associated with infarcts involving posterior areas (parietal P = 0.046, temporal P < 0.001) independently of age, gender and infarct volume, which was confirmed by voxel-based lesion-symptom mapping. The asymmetry index of the 95th percentile within the entire thalamus at 1 year was independently associated with poor functional outcome (P = 0.04), poor cognitive outcome (P = 0.03), post-stroke anxiety (P = 0.04) and post-stroke depression (P = 0.02). We have therefore identified that iron accumulates within the thalamus ipsilateral to infarct after a delay with a focal distribution that is strongly linked to the initial infarct location (in relation with the pattern of connectivity between thalamic nuclei and cortical areas or deep nuclei), which independently contributes to functional, cognitive and emotional outcome.

BACKGROUND AND PURPOSE: Aspartylglucosaminuria is a rare lysosomal storage disorder that causes slowly progressive, childhood-onset intellectual disability and motor deterioration. Previous studies have shown, for example, hypointensity in the thalami in patients with aspartylglucosaminuria on T2WI, especially in the pulvinar nuclei. Susceptibility-weighted imaging is a neuroimaging technique that uses tissue magnetic susceptibility to generate contrast and is able to visualize iron and other mineral deposits in the brain. SWI findings in aspartylglucosaminuria have not been reported previously. MATERIALS AND METHODS: Twenty-one patients with aspartylglucosaminuria (10 girls; 7.4–15.0 years of age) underwent 3T MR imaging. The protocol included an SWI sequence, and the images were visually evaluated. Thirteen patients (6 girls, 7.4–15.0 years of age) had good-quality SWI. Eight patients had motion artifacts and were excluded from the visual analysis. Thirteen healthy children (8 girls, 7.3–14.1 years of age) were imaged as controls. RESULTS: We found a considerably uniform distribution of decreased signal intensity in SWI in the thalamic nuclei in 13 patients with aspartylglucosaminuria. The most evident hypointensity was found in the pulvinar nuclei. Patchy hypointensities were also found especially in the medial and anterior thalamic nuclei. Moreover, some hypointensity was noted in globi pallidi and substantia nigra in older patients. The filtered-phase images indicated accumulation of paramagnetic compounds in these areas. No abnormal findings were seen in the SWI of the healthy controls. CONCLUSIONS: SWI indicates accumulation of paramagnetic compounds in the thalamic nuclei in patients with aspartylglucosaminuria. The finding may raise the suspicion of this rare disease in clinical practice.

OBJECTIVE Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thalamic demyelinated lesions, thalamic neuronal loss, and cerebral white matter (WM) lesions to thalamic volume. METHODS We used postmortem in situ magnetic resonance imaging (MRI) scans of 95 subjects with MS to correlate thalamic lesion volumes with global MRI metrics. We histologically characterized thalamic demyelination patterns and compared neuronal loss and neuritic pathology in the thalami with the extremes of volume. RESULTS Grossly apparent thalamic discolorations in cm-thick brain slices were T2/fluid-attenuated inversion recovery (FLAIR) hyperintense, T1-hypointense, and appeared as perivascular demyelinated lesions with dystrophic neurons/axons. Subependymal demyelinated lesions with axonal loss and microglial/macrophage activation were also observed. The 12 subjects with the least thalamic volume had a 17.6% reduction of median neuronal density in the dorsomedial/ventrolateral and pulvinar nuclei compared with the 14 subjects with the greatest thalamic volume (p = 0.03). After correcting for age, disease duration, sex, and T2 lesion volume, the total (p = 0.20), ovoid (p = 0.31), or subependymal (p = 0.44) MRI thalamic lesion volumes correlated with thalamic volume. Thalamic volume correlated with cerebral T2 lesion volume (Spearman's rho = -0.65, p

Highlights • Increased fMRI activation of bilateral pulvinar nuclei with symptomatic light. • Pulvinar nuclei are associated with melanopsin visual pathway and migraine. • First demonstration of fMRI activation of melanopsin pathway during photophobia., Numerous pathologies can contribute to photophobia. When considering light transduction alone, photophobia may be triggered through melanopsin pathways (non-image forming), rod and cone pathways (image-forming), or some combination of the two. We evaluated a 39 year old female patient with longstanding idiopathic photophobia that was exacerbated by blue light, and tested her by presenting visual stimuli in an event-related fMRI experiment. Analysis showed significantly greater activation in bilateral pulvinar nuclei, associated with the melanopsin intrinsically photosensitive retinal ganglion cell (ipRGC) visual pathway, and their activation is consistent with the patient's report that blue light differentially evoked photophobia. This appears to be the first demonstration of functional activation of the ipRGC pathway during photophobia in a patient.

Verticality misperception after stroke is a frequent neurological deficit that leads to postural imbalance and a higher risk of falls. The posterior thalamic nuclei are described to be involved with verticality perception, but it is unknown if extra-thalamic lesions can have the same effect via diaschisis and degeneration of thalamic nuclei. We investigated the relationship between thalamic fractional anisotropy (FA, a proxy of structural integrity), and verticality perception, in patients after stroke with diverse encephalic extra-thalamic lesions. We included 11 first time post-stroke patients with extra-thalamic primary lesions, and compared their region-based FA to a group of 25 age-matched healthy controls. For the patient sample, correlation and regression analyses evaluated the relationship between thalamic nuclei FA and error of postural vertical (PV) and haptic vertical (HV) in the roll (PVroll/HVroll) and pitch planes (PVpitch/HVpitch). Relative to controls, patients showed decreased FA of anterior, ventral anterior, ventral posterior lateral, dorsal, and pulvinar thalamic nuclei, despite the primary lesions being extra-thalamic. We found a significant correlation between HVroll, and FA in the anterior and dorsal nuclei, and PVroll with FA in the anterior nucleus. FA in the anterior, ventral anterior, ventral posterior lateral, dorsal and pulvinar nuclei predicted PV, and FA in the ventral anterior, ventral posterior lateral and dorsal nuclei predicted HV. While prior studies indicate that primary lesions of the thalamus can result in verticality misperception, here we present evidence supporting that secondary degeneration of thalamic nuclei via diaschisis can also be associated with verticality misperception after stroke.

Background and objectives We assessed correlations between the resting state functional connectivity (RSFC) of different thalamic nuclei and seizure frequency in patients with drug-resistant medial temporal lobe epilepsy (mTLE). Methods Seventeen patients with mTLE and 17 sex-/age-/handedness-matched controls participated. A seed-based correlation method for the resting-state FMRI data was implemented to get RSFC maps of 70 thalamic nuclei seed masks. Group statistics for individual RSFC for subjects and seed masks were performed to obtain within-group characteristics and between-group differences with age covariates. A linear regression was applied to test whether seizure frequency correlated with thalamic nuclear RSFC with the whole brain in mTLE patients. Results RSFC of thalamic nuclei showed spatially distinguishable connectivity patterns that reflected principal inputs and outputs that were derived from priori anatomical knowledge. We found group differences between normal control and mTLE groups in RSFC for nuclei seeds located in various subdivisions of thalamus. The RSFCs in some of those nuclei were strongly correlated with seizure frequency. Conclusions Mediodorsal thalamic nuclei may play important roles in seizure activity or in the regulation of neuronal activity in the limbic system. The RSFC of motor- and sensory-relay nuclei may help elucidate sensory-motor deficits associated with chronic seizure activity. RSFC of the pulvinar nuclei of the thalamus could also be a key reflection of symptom-related functional deficits in mTLE., Highlights • We assessed the functional connectivity for 70 thalamic nuclei of temporal lobe epilepsy subjects. • Each nucleus showed distinguishable connectivity along its known pathological preference. • Especially, the mediodorsal thalamic nuclei may play important roles in seizure frequency.

Functional magnetic resonance imaging (fMRI) successfully disentangled neuronal pathophysiology of major depression (MD), but only a few fMRI studies have investigated correlates and predictors of remission. Moreover, most studies have used clinical outcome parameters from two time points, which do not optimally depict differential response times. Therefore, we aimed to detect neuronal correlates of response and remission in an antidepressant treatment study with 7 T fMRI, potentially harnessing advances in detection power and spatial specificity. Moreover, we modeled outcome parameters from multiple study visits during a 12-week antidepressant fMRI study in 26 acute (aMD) patients compared to 36 stable remitted (rMD) patients and 33 healthy control subjects (HC). During an electrical painful stimulation task, significantly higher baseline activity in aMD compared to HC and rMD in the medial thalamic nuclei of the pulvinar was detected (p = 0.004, FWE-corrected), which was reduced by treatment. Moreover, clinical response followed a sigmoid function with a plateau phase in the beginning, a rapid decline and a further plateau at treatment end. By modeling the dynamic speed of response with fMRI-data, perigenual anterior cingulate activity after treatment was significantly associated with antidepressant response (p

Background: Posterior cortical atrophy (PCA) is a clinical variant of Alzheimer's disease (AD) that presents with progressive visuospatial symptoms. While amnestic AD is characterized by disrupted default mode network (DMN) connectivity with corresponding increases in salience network (SN) connectivity, a visuospatial network appears to be disrupted early in PCA. Based on PCA patients' clinical features, we hypothesized that, in addition to early decreased integrity within the visuospatial network, patients with PCA would show increases in SN connectivity despite relative preservation of DMN. As the lateral pulvinar nucleus of the thalamus has direct anatomical connections with striate and extrastriate cortex and DMN, and the medial pulvinar is anatomically interconnected with SN, we further hypothesized that lateral and medial pulvinar nuclei might be implicated in intrinsic connectivity changes in PCA. Methods: 26 patients with PCA and 64 matched controls were recruited through UCSF Memory and Aging Center research programs. Each completed a standardized neuropsychological battery, structural MRI, and task-free fMRI. Seed-based functional correlations were used to probe networks of interest, including those seeded by the medial and lateral pulvinar thalamic nuclei, across the whole brain, and functional data analyses were adjusted for brain atrophy. Results: Patients with PCA showed disproportionate deficits in the visuospatial domain; they also showed preserved social sensitivity and endorsed more depressive symptoms than HCs. PCA patients had significant parietooccipital atrophy accompanied by widespread connectivity decreases within the visuospatial network, enhanced connectivity between some structures in SN, and enhanced connectivity between key nodes of the DMN compared to controls. Increased SN connectivity correlated with a measure of social sensitivity, and increased DMN connectivity correlated with short-term memory performance. Medial pulvinar connectivity increases in PCA were topographically similar to SN (anterior insula) connectivity increases, while lateral pulvinar connectivity increases were similar to DMN (posterior cingulate) connectivity increases. Conclusions: PCA is characterized by preserved to heightened connectivity in the SN and DMN despite decreased visuospatial network connectivity. The spatial similarity of medial and lateral pulvinar connectivity changes to those seen in the SN and DMN suggests a role for the pulvinar in intrinsic connectivity network changes in PCA. Keywords: Posterior cortical atrophy, Pulvinar, Alzheimer's disease, Functional connectivity, Default mode network, Salience network

Recent evidence for abnormal thalamic connectivity in autism spectrum disorders (ASD) and sensory processing disorders suggests the thalamus may play a role in sensory over-responsivity (SOR), an extreme negative response to sensory stimuli, which is common in ASD. However, there is yet little understanding of changes in thalamic connectivity during exposure to aversive sensory inputs in individuals with ASD. In particular, the pulvinar nucleus of the thalamus is implicated in atypical sensory processing given its role in selective attention, regulation, and sensory integration. This study aimed to examine the role of pulvinar connectivity in ASD during mildly aversive sensory input. Functional magnetic resonance imaging was used to examine connectivity with the pulvinar during exposure to mildly aversive auditory and tactile stimuli in 38 youth (age 9-17; 19 ASD, 19 IQ-matched typically developing (TD)). Parents rated children's SOR severity on two standard scales. Compared to TD, ASD participants displayed aberrant modulation of connectivity between pulvinar and cortex (including sensory-motor and prefrontal regions) during sensory stimulation. In ASD participants, pulvinar-amygdala connectivity was correlated with severity of SOR symptoms. Deficits in modulation of thalamocortical connectivity in youth with ASD may reflect reduced thalamo-cortical inhibition in response to sensory stimulation, which could lead to difficulty filtering out and/or integrating sensory information. An increase in amygdala connectivity with the pulvinar might be partially responsible for deficits in selective attention as the amygdala signals the brain to attend to distracting sensory stimuli. Autism Res 2017, 10: 801-809. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with cognitive, motor, and emotional symptoms. The thalamus and basal ganglia form circuits with the cortex supporting all three of these behavioral domains. Abnormalities in the structure of subcortical regions may suggest atypical development of these networks, with implications for understanding the neural basis of ASD symptoms. Findings from previous volumetric studies have been inconsistent. Here, using advanced surface-based methodology, we investigated localized differences in shape and surface area in the basal ganglia and thalamus in ASD, using T1-weighted anatomical images from the Autism Brain Imaging Data Exchange (373 male participants aged 7-35 years with ASD and 384 typically developing). We modeled effects of diagnosis, age, and their interaction on volume, shape, and surface area. In participants with ASD, we found expanded surface area in the right posterior thalamus corresponding to the pulvinar nucleus, and a more concave shape in the left mediodorsal nucleus. The shape of both caudal putamen and pallidum showed a relatively steeper increase in concavity with age in ASD. Within ASD participants, restricted, repetitive behaviors were positively associated with surface area in bilateral globus pallidus. We found no differences in overall volume, suggesting that surface-based approaches have greater sensitivity to detect localized differences in subcortical structure. This work adds to a growing body of literature implicating corticobasal ganglia-thalamic circuits in the pathophysiology of ASD. These circuits subserve a range of cognitive, emotional, and motor functions, and may have a broad role in the complex symptom profile in ASD.

It has been hypothesized that fatigue sensation impairs the ability and efficiency to perform activities and can be a cause of fatigue itself. As such, it is important to clarify the neural mechanisms of fatigue sensation. The re-experiencing of mental fatigue sensation involves brain regions including Brodmann's area (BA) 40, BA 39, and the pulvinar nucleus. In the present study, we examined neural activity caused by re-experiencing a physical fatigue sensation that had been experienced. Fifteen healthy male volunteers participated in fatigue and control experiments in a crossover fashion. In the fatigue experiment, participants performed a handgrip task for 10 min to induce a physical fatigue sensation and then re-experienced the physical fatigue sensation during magnetoencephalography (MEG) session. In the control experiment, they did not perform the handgrip task but re-experienced the sensation without physical fatigue in an MEG session. Neural activity related to re-experiencing physical fatigue sensations of the right hand (right condition), left hand (left condition), and related to listening to the auditory cues (sound condition) was assessed using spatial filtering analyses of the MEG data. Changes in oscillatory band power in some brain regions, including BA 40, were common between the right and left conditions. A part of the neural activity related to the re-experiencing physical fatigue sensation, such as the decrease in alpha (8-13 Hz) band power in the BA 40, was also observed in the sound condition. These findings may help to understand the neural mechanisms related to intentionally and unintentionally re-experiencing physical fatigue sensation.

The tree shrew (Tupaia belangeri) striate cortex is reciprocally connected with the dorsal lateral geniculate nucleus (dLGN), the ventral pulvinar nucleus (Pv), and the claustrum. In the Pv or the dLGN, striate cortex projections are thought to either strongly "drive", or more subtly "modulate" activity patterns respectively. To provide clues to the function of the claustrum, we compare the synaptic arrangements of striate cortex projections to the dLGN, Pv, and claustrum, using anterograde tracing and electron microscopy. Tissue was additionally stained with antibodies against γ-aminobutyric acid (GABA) to identify GABAergic interneurons and non-GABAergic projection cells. The striate cortex terminals were largest in the Pv (0.94 ± 0.08 μm2 ), intermediate in the claustrum (0.34 ± 0.02 μm2 ), and smallest in the dLGN (0.24 ± 0.01 μm2 ). Contacts on interneurons were most common in the Pv (39%), intermediate in the claustrum (15%), and least common in the dLGN (12%). In the claustrum, non-GABAergic terminals (0.34 ± 0.01 μm2 ) and striate cortex terminals were not significantly different in size. The largest terminals in the claustrum were GABAergic (0.51 ± 0.02 μm2 ), and these terminals contacted dendrites and somata that were significantly larger (1.90 ± 0.30 μm2 ) than those contacted by cortex or non-GABAergic terminals (0.28 ± 0.02 μm2 and 0.25 ± 0.02 μm2 , respectively). Our results indicate that the synaptic organization of the claustrum does not correspond to a driver/modulator framework. Instead, the circuitry of the claustrum suggests an integration of convergent cortical inputs, gated by GABAergic circuits. J. Comp. Neurol. 525:1403-1420, 2017. © 2016 Wiley Periodicals, Inc.

Objective To investigate brain volumes in patients with well-characterized juvenile myoclonic epilepsy (JME). Materials and methods We studied the MRI images of seventeen subjects with EEG and clinically defined JME and seventeen age- and sex-matched controls using voxel-based morphometry (VBM) and automated and manual volumetry. Results We found no significant group differences in the cortical volumes by automated techniques for all regions or for the whole brain. However, we found a larger pulvinar nucleus in JME using VBM with small volume correction and a larger thalamus with manual volumetry (P = 0.001; corrected two-tailed t-test). By analysing the individual subjects, we determined that considerable heterogeneity exists even in this highly selected group. Histograms of all JME and matched control regions' volumes showed more subjects with JME had smaller hippocampi and larger thalami (P < 0.05; chi-square). Subjects in whom the first seizure was absence were more likely to have smaller hippocampi than their matched control, while those without absences showed no differences (P < 0.05, chi-square). Conclusions There is ample evidence for frontal cortical thalamic network changes in JME, but subcortical structural differences were more distinct in this group. Given the heterogeneity of brain volumes in the clinical population, further advancement in the field will require the examination of stringent genetically controlled populations.

Parasympathetic arousal is associated with states of heightened attention and well-being. Arousal may affect widespread cortical and subcortical systems across the brain, however, little is known about its influence on cognitive task processing and performance. In the current study, healthy adult participants (n ​= ​20) underwent multi-band echo-planar imaging (TR ​= ​0.72 ​s) with simultaneous pulse oximetry recordings during performance of the Multi Source Interference Task (MSIT), the Oddball Task (OBT), and during rest. Processing speed on both tasks was robustly related to heart rate (HR). Participants with slower HR responded faster on both the MSIT (33% variance explained) and the OBT (25% variance explained). Within all participants, trial-to-trial fluctuations in processing speed were robustly related to the heartbeat-stimulus interval, a metric that is dependent both on the concurrent HR and the stimulus timing with respect to the heartbeat. Models examining the cardiac-BOLD response revealed that a distributed set of regions showed arousal-related activity that was distinct for different task conditions. Across these cortical regions, activity increased with slower HR. Arousal-related activity was distinct from task-evoked activity and it was robust to the inclusion of additional physiological nuisance regressors into the models. For the MSIT, such arousal-related activity occurred across visual and dorsal attention network regions. For the OBT, this activity occurred within fronto-parietal regions. For rest, arousal-related activity also occurred, but was confined to visual regions. The pulvinar nucleus of the thalamus showed arousal-related activity during all three task conditions. Widespread cortical activity, associated with increased parasympathetic arousal, may be propagated by thalamic circuits and contributes to improved attention. This activity is distinct from task-evoked activity, but affects cognitive performance and therefore should be incorporated into neurobiological models of cognition and clinical disorders.