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Annals of Clinical and Translational... Jun 2024To evaluate the intrinsic and extrinsic microstructural factors contributing to atrophy within individual thalamic subregions in multiple sclerosis using in vivo...
OBJECTIVE
To evaluate the intrinsic and extrinsic microstructural factors contributing to atrophy within individual thalamic subregions in multiple sclerosis using in vivo high-gradient diffusion MRI.
METHODS
In this cross-sectional study, 41 people with multiple sclerosis and 34 age and sex-matched healthy controls underwent 3T MRI with up to 300 mT/m gradients using a multi-shell diffusion protocol consisting of eight b-values and diffusion time of 19 ms. Each thalamus was parcellated into 25 subregions for volume determination and diffusion metric estimation. The soma and neurite density imaging model was applied to obtain estimates of intra-neurite, intra-soma, and extra-cellular signal fractions for each subregion and within structurally connected white matter trajectories and cortex.
RESULTS
Multiple sclerosis-related volume loss was more pronounced in posterior/medial subregions than anterior/ventral subregions. Intra-soma signal fraction was lower in multiple sclerosis, reflecting reduced cell body density, while the extra-cellular signal fraction was higher, reflecting greater extra-cellular space, both of which were observed more in posterior/medial subregions than anterior/ventral subregions. Lower intra-neurite signal fraction in connected normal-appearing white matter and lower intra-soma signal fraction of structurally connected cortex were associated with reduced subregional thalamic volumes. Intrinsic and extrinsic microstructural measures independently related to subregional volume with heterogeneity across atrophy-prone thalamic nuclei. Extrinsic microstructural alterations predicted left anteroventral, intrinsic microstructural alterations predicted bilateral medial pulvinar, and both intrinsic and extrinsic factors predicted lateral geniculate and medial mediodorsal volumes.
INTERPRETATION
Our results might be reflective of the involvement of anterograde and retrograde degeneration from white matter demyelination and cerebrospinal fluid-mediated damage in subregional thalamic volume loss.
Topics: Humans; Female; Male; Adult; Thalamus; Cross-Sectional Studies; Middle Aged; Multiple Sclerosis; Atrophy; White Matter; Diffusion Magnetic Resonance Imaging
PubMed: 38725151
DOI: 10.1002/acn3.52026 -
Neuron Jul 2023Cortical responses to visual stimuli are believed to rely on the geniculo-striate pathway. However, recent work has challenged this notion by showing that responses in...
Cortical responses to visual stimuli are believed to rely on the geniculo-striate pathway. However, recent work has challenged this notion by showing that responses in the postrhinal cortex (POR), a visual cortical area, instead depend on the tecto-thalamic pathway, which conveys visual information to the cortex via the superior colliculus (SC). Does POR's SC-dependence point to a wider system of tecto-thalamic cortical visual areas? What information might this system extract from the visual world? We discovered multiple mouse cortical areas whose visual responses rely on SC, with the most lateral showing the strongest SC-dependence. This system is driven by a genetically defined cell type that connects the SC to the pulvinar thalamic nucleus. Finally, we show that SC-dependent cortices distinguish self-generated from externally generated visual motion. Hence, lateral visual areas comprise a system that relies on the tecto-thalamic pathway and contributes to processing visual motion as animals move through the environment.
Topics: Mice; Animals; Superior Colliculi; Visual Pathways; Thalamus; Thalamic Nuclei; Pulvinar; Geniculate Bodies
PubMed: 37172584
DOI: 10.1016/j.neuron.2023.04.022 -
MedRxiv : the Preprint Server For... Jul 2023Motion processing deficits in schizophrenia have been linked to impairments in higher-order social-cognitive processes. The neural underpinnings are not fully understood...
BACKGROUND AND HYPOTHESIS
Motion processing deficits in schizophrenia have been linked to impairments in higher-order social-cognitive processes. The neural underpinnings are not fully understood but it has been hypothesized that middle temporal area (MT+) may serve as a bridge between purely sensory and more cognitive proceseses. We investigated the interrelationship between MT+ sensory processing deficits and impairments in higher-order processing using naturalistic videos with explicit motion and static images with implied-motion cues.
STUDY DESIGN
Functional magnetic resonance imaging was used to evaluate cortical and subcortical brain regions associated with real- and implied-motion processing in 28 individuals with schizophrenia and 20 neurotypical controls. These measures were related to face emotion recognition and motion-perception deficits, as measured behaviorally.
STUDY RESULTS
Activation of MT+ was abnormal in schizophrenia during both real- and implied-motion processing. Dysfunction of early visual cortex and pulvinar were also associated with impaired real-motion processing. During implied-motion-perception, MT+ participated in a wider network involving sensorimotor and prefrontal nodes of the human mirror neuron system, known to play a role in social-cognitive processes. Perception of both real- and implied-motion engaged the posterior superior temporal sulcus, a key node of the social brain network.
CONCLUSIONS
The findings support concepts of MT+ as a bridge between visual sensory areas and higher-order brain regions especially in relationship to face emotion recognition and social cognition. Our data argue for greater focus on MT+ contributions to social-cognitive processing, in addition to its well-documented role in visual motion processing.
PubMed: 37461678
DOI: 10.1101/2023.07.07.23292259 -
Frontiers in Neuroscience 2023In most neuroscience textbooks, the thalamus is presented as a structure that relays sensory signals from visual, auditory, somatosensory, and gustatory receptors to the... (Review)
Review
In most neuroscience textbooks, the thalamus is presented as a structure that relays sensory signals from visual, auditory, somatosensory, and gustatory receptors to the cerebral cortex. But the function of the thalamic nuclei goes beyond the simple transfer of information. This is especially true for the second-order nuclei, but also applies to first-order nuclei. First order thalamic nuclei receive information from the periphery, like the dorsal lateral geniculate nucleus (dLGN), which receives a direct input from the retina. In contrast, second order thalamic nuclei, like the pulvinar, receive minor or no input from the periphery, with the bulk of their input derived from cortical areas. The dLGN refines the information received from the retina by temporal decorrelation, thereby transmitting the most "relevant" signals to the visual cortex. The pulvinar is closely linked to virtually all visual cortical areas, and there is growing evidence that it is necessary for normal cortical processing and for aspects of visual cognition. In this article, we will discuss what we know and do not know about these structures and propose some thoughts based on the knowledge gained during the course of our careers. We hope that these thoughts will arouse curiosity about the visual thalamus and its important role, especially for the next generation of neuroscientists.
PubMed: 37712093
DOI: 10.3389/fnins.2023.1258393 -
Brain Communications 2024The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding...
The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. Herein, we aimed to examine (i) whether grey matter volume differs across thalamic subregions/nuclei in patients with blepharospasm and blepharospasm-oromandibular dystonia; (ii) causal relationships among abnormal thalamic nuclei; and (iii) whether these abnormal features can be used as neuroimaging biomarkers to distinguish patients with blepharospasm from blepharospasm-oromandibular dystonia and those with dystonia from healthy controls. Structural MRI data were collected from 56 patients with blepharospasm, 20 with blepharospasm-oromandibular dystonia and 58 healthy controls. Differences in thalamic nuclei volumes between groups and their relationships to clinical information were analysed in patients with dystonia. Granger causality analysis was employed to explore the causal effects among abnormal thalamic nuclei. Support vector machines were used to test whether these abnormal features could distinguish patients with different forms of dystonia and those with dystonia from healthy controls. Compared with healthy controls, patients with blepharospasm exhibited reduced grey matter volume in the lateral geniculate and pulvinar inferior nuclei, whereas those with blepharospasm-oromandibular dystonia showed decreased grey matter volume in the ventral anterior and ventral lateral anterior nuclei. Atrophy in the pulvinar inferior nucleus in blepharospasm patients and in the ventral lateral anterior nucleus in blepharospasm-oromandibular dystonia patients was negatively correlated with clinical severity and disease duration, respectively. The proposed machine learning scheme yielded a high accuracy in distinguishing blepharospasm patients from healthy controls (accuracy: 0.89), blepharospasm-oromandibular dystonia patients from healthy controls (accuracy: 0.82) and blepharospasm from blepharospasm-oromandibular dystonia patients (accuracy: 0.94). Most importantly, Granger causality analysis revealed that a progressive driving pathway from pulvinar inferior nuclear atrophy extends to lateral geniculate nuclear atrophy and then to ventral lateral anterior nuclear atrophy with increasing clinical severity in patients with blepharospasm. These findings suggest that the pulvinar inferior nucleus in the thalamus is the focal origin of blepharospasm, extending to pulvinar inferior nuclear atrophy and subsequently extending to the ventral lateral anterior nucleus causing involuntary lower facial and masticatory movements known as blepharospasm-oromandibular dystonia. Moreover, our results also provide potential targets for neuromodulation especially deep brain stimulation in patients with blepharospasm and blepharospasm-oromandibular dystonia.
PubMed: 38638150
DOI: 10.1093/braincomms/fcae117 -
Frontiers in Computational Neuroscience 2023Convolutional Neural Networks (CNN) are a class of machine learning models predominately used in computer vision tasks and can achieve human-like performance through... (Review)
Review
Convolutional Neural Networks (CNN) are a class of machine learning models predominately used in computer vision tasks and can achieve human-like performance through learning from experience. Their striking similarities to the structural and functional principles of the primate visual system allow for comparisons between these artificial networks and their biological counterparts, enabling exploration of how visual functions and neural representations may emerge in the real brain from a limited set of computational principles. After considering the basic features of CNNs, we discuss the opportunities and challenges of endorsing CNNs as models of the primate visual system. Specifically, we highlight several emerging notions about the anatomical and physiological properties of the visual system that still need to be systematically integrated into current CNN models. These tenets include the implementation of parallel processing pathways from the early stages of retinal input and the reconsideration of several assumptions concerning the serial progression of information flow. We suggest design choices and architectural constraints that could facilitate a closer alignment with biology provide causal evidence of the predictive link between the artificial and biological visual systems. Adopting this principled perspective could potentially lead to new research questions and applications of CNNs beyond modeling object recognition.
PubMed: 37485400
DOI: 10.3389/fncom.2023.1153572 -
Journal of Neurology Jan 2024To investigate brain MRI abnormalities in a cohort of patients with rapidly progressive dementia (RPD) with and without a diagnosis of Creutzfeldt-Jakob disease (CJD).
OBJECTIVE
To investigate brain MRI abnormalities in a cohort of patients with rapidly progressive dementia (RPD) with and without a diagnosis of Creutzfeldt-Jakob disease (CJD).
METHODS
One hundred and seven patients with diagnosis of prion disease (60 with definite sCJD, 33 with probable sCJD and 14 with genetic prion disease) and 40 non-prion related RPD patients (npRPD) underwent brain MRI including DWI and FLAIR. MRIs were evaluated with a semiquantitative rating score, which separately considered abnormal signal extent and intensity in 22 brain regions. Clinical findings at onset, disease duration, cerebrospinal-fluid 14-3-3 and t-tau protein levels, and EEG data were recorded.
RESULTS
Among patients with definite/probable diagnosis of CJD or genetic prion disease, 2/107 had normal DWI-MRI: in one patient a 2-months follow-up DWI-MRI showed CJD-related changes while the other had autopsy-proven CJD despite no DWI abnormalities 282 days after clinical onset. CJD-related cortical changes were detected in all lobes and involvement of thalamus was common. In the npRPD groups, 6/40 patients showed DWI alterations that clustered in three different patterns: (1) minimal/doubtful signal alterations (limbic encephalitis, dementia with Lewy bodies); (2) clearly suggestive of alternative diagnoses (status epilepticus, Wernicke or metabolic encephalopathy); (3) highly suggestive of CJD (mitochondrial disease), though cortical swelling let exclude CJD.
CONCLUSIONS
In the diagnostic work-up of RPD, negative/doubtful DWI makes CJD diagnosis rather unlikely, while specific DWI patterns help differentiating CJD from alternative diagnoses. The pulvinar sign is not exclusive of the variant form.
Topics: Humans; Creutzfeldt-Jakob Syndrome; Magnetic Resonance Imaging; Brain; Prion Diseases; Thalamus
PubMed: 37698615
DOI: 10.1007/s00415-023-11962-1 -
Communications Biology Sep 2023Exposure to blue wavelength light stimulates alertness and performance by modulating a widespread set of task-dependent cortical and subcortical areas. How light affects...
Exposure to blue wavelength light stimulates alertness and performance by modulating a widespread set of task-dependent cortical and subcortical areas. How light affects the crosstalk between brain areas to trigger this stimulating effect is not established. Here we record the brain activity of 19 healthy young participants (24.05±2.63; 12 women) while they complete an auditory attentional task in darkness or under an active (blue-enriched) or a control (orange) light, in an ultra-high-field 7 Tesla MRI scanner. We test if light modulates the effective connectivity between an area of the posterior associative thalamus, encompassing the pulvinar, and the intraparietal sulcus (IPS), key areas in the regulation of attention. We find that only the blue-enriched light strengthens the connection from the posterior thalamus to the IPS. To the best of our knowledge, our results provide the first empirical data supporting that blue wavelength light affects ongoing non-visual cognitive activity by modulating task-dependent information flow from subcortical to cortical areas.
Topics: Humans; Female; Thalamus; Cross Reactions; Healthy Volunteers; Light
PubMed: 37714936
DOI: 10.1038/s42003-023-05337-5 -
JAMA Psychiatry May 2024Posttraumatic stress disorder (PTSD) is a common psychiatric disorder that is particularly difficult to treat in military veterans. Noninvasive brain stimulation has... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Posttraumatic stress disorder (PTSD) is a common psychiatric disorder that is particularly difficult to treat in military veterans. Noninvasive brain stimulation has significant potential as a novel treatment to reduce PTSD symptoms.
OBJECTIVE
To test whether active transcranial direct current stimulation (tDCS) plus virtual reality (VR) is superior to sham tDCS plus VR for warzone-related PTSD.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind randomized clinical trial was conducted among US military veterans enrolled from April 2018 to May 2023 at a secondary care Department of Veterans Affairs hospital and included 1- and 3-month follow-up visits. Participants included US military veterans with chronic PTSD and warzone-related exposure, recruited via referral and advertisement. Patients in psychiatric treatment had to be on a stable regimen for at least 6 weeks to be eligible for enrollment. Data were analyzed from May to September 2023.
INTERVENTION
Participants were randomly assigned to receive 2-mA anodal tDCS or sham tDCS targeted to the ventromedial prefrontal cortex, during six 25-minute sessions of standardized warzone VR exposure, delivered over 2 to 3 weeks.
MAIN OUTCOMES AND MEASURES
The co-primary outcomes were self-reported PTSD symptoms, measured via the PTSD checklist for DSM-5 (PCL-5), alongside quality of life. Other outcomes included psychophysiological arousal, clinician-assessed PTSD, depression, and social/occupational function.
RESULTS
A total of 54 participants (mean [SD] age, 45.7 [10.5] years; 51 [94%] males) were assessed, including 26 in the active tDCS group and 28 in the sham tDCS group. Participants in the active tDCS group reported a superior reduction in self-reported PTSD symptom severity at 1 month (t = -2.27, P = .02; Cohen d = -0.82). There were no significant differences in quality of life between active and sham tDCS groups. Active tDCS significantly accelerated psychophysiological habituation to VR events between sessions compared with sham tDCS (F5,7689.8 = 4.65; P < .001). Adverse effects were consistent with the known safety profile of the corresponding interventions.
CONCLUSIONS AND RELEVANCE
These findings suggest that combined tDCS plus VR may be a promising strategy for PTSD reduction and underscore the innovative potential of these combined technologies.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03372460.
Topics: Humans; Stress Disorders, Post-Traumatic; Transcranial Direct Current Stimulation; Male; Female; Double-Blind Method; Adult; Veterans; Middle Aged; Prefrontal Cortex; Virtual Reality Exposure Therapy; Virtual Reality
PubMed: 38446471
DOI: 10.1001/jamapsychiatry.2023.5661 -
Scientific Reports Jun 2024The dorsal pulvinar has been implicated in visuospatial attentional and perceptual confidence processing. Pulvinar lesions in humans and monkeys lead to spatial neglect...
The dorsal pulvinar has been implicated in visuospatial attentional and perceptual confidence processing. Pulvinar lesions in humans and monkeys lead to spatial neglect symptoms, including an overt spatial saccade bias during free choices. However, it remains unclear whether disrupting the dorsal pulvinar during target selection that relies on a perceptual decision leads to a perceptual impairment or a more general spatial orienting and choice deficit. To address this question, we reversibly inactivated the unilateral dorsal pulvinar by injecting GABA-A agonist THIP while two macaque monkeys performed a color discrimination saccade task with varying perceptual difficulty. We used Signal Detection Theory and simulations to dissociate perceptual sensitivity (d-prime) and spatial selection bias (response criterion) effects. We expected a decrease in d-prime if dorsal pulvinar affects perceptual discrimination and a shift in response criterion if dorsal pulvinar is mainly involved in spatial orienting. After the inactivation, we observed response criterion shifts away from contralesional stimuli, especially when two competing stimuli in opposite hemifields were present. Notably, the d-prime and overall accuracy remained largely unaffected. Our results underline the critical contribution of the dorsal pulvinar to spatial orienting and action selection while showing it to be less important for visual perceptual discrimination.
Topics: Animals; Pulvinar; Saccades; Male; Space Perception; Visual Perception; Photic Stimulation; Macaca mulatta; Attention
PubMed: 38834578
DOI: 10.1038/s41598-024-62056-5