Subcortical Structures Research Articles

Altered Iron and Microstructure in Huntington's Disease Subcortical Nuclei: Insight From 7T MRI.

Pathophysiological changes of Huntington's disease (HD) can precede symptom onset by decades. Robust imaging biomarkers are needed to monitor HD progression, especially before the clinical onset. To investigate iron dysregulation and microstructure alterations in subcortical regions as HD imaging biomarkers, and to associate such alterations with motor and cognitive impairments. Prospective. Fourteen individuals with premanifest HD (38.0 ± 11.0 years, 9 females; far-from-onset N = 6, near-onset N = 8), 21 manifest HD patients (49.1 ± 12.1 years, 11 females), and 33 age-matched healthy controls (43.9 ± 12.2 years, 17 females). 7 T, T1 -weighted imaging, quantitative susceptibility mapping, and diffusion tensor imaging. Volume, susceptibility, fractional anisotropy (FA), and mean diffusivity (MD) within subcortical brain structures were compared across groups, used to establish HD classification models, and correlated to clinical measures and cognitive assessments. Generalized linear model, multivariate logistic regression, receiver operating characteristics with the area under the curve (AUC), and likelihood ratio test comparing a volumetric model to one that also includes susceptibility and diffusion metrics, Wilcoxon paired signed-rank test, and Pearson's correlation. A P-value <0.05 after Benjamini-Hochberg correction was considered statistically significant. Significantly higher striatal susceptibility and FA were found in premanifest and manifest HD preceding atrophy, even in far-from-onset premanifest HD compared to controls (putamen susceptibility: 0.027 ± 0.022 vs. 0.018 ± 0.013 ppm; FA: 0.358 ± 0.048 vs. 0.313 ± 0.039). The model with additional susceptibility, FA, and MD features showed higher AUC compared to volume features alone when differentiating premanifest HD from HC (0.83 vs. 0.66), and manifest from premanifest HD (0.94 vs. 0.83). Higher striatal susceptibility significantly correlated with cognitive deterioration in HD (executive function: r = -0.600; socioemotional function: r = -0.486). 7 T MRI revealed iron dysregulation and microstructure alterations with HD progression, which could precede volume loss, provide added value to HD differentiation, and might be associated with cognitive changes. 2 TECHNICAL EFFICACY: Stage 2.

Atypical case of glioblastoma localization: infratentorial localization (Clinical Case and the Review of the Literature)

Glioblastoma is the most common high-grade primary brain tumor, occurring primarily in adults. This infiltrating tumor locates deep in the white matter, subcortical structures and thalamus. The typical localization of glioblastoma is supratentorial, accounting for more than 99% of cases. Primary infratentorial growth of glioblastomas involving the cerebellum is a very rare condition, occurring in less than 1 % of cases reported in the literature. The differential diagnosis consists mainly of solitary metastatic lesions and medulloblastoma. The clinical manifestations of cerebellar lesions are similar, but the methods of surgical and chemoradiotherapy treatment, prognosis and outcome in cases with various histologic types of the tumors are different.Thus radiology, carried out using multiparametric MRI mapping, is an decision making procedure. In thus publication we present an atypical case of infratentorial glioblastoma in a 45-yearold patient.

Mapping Gilles de la Tourette syndrome through the distress and relief associated with tic-related behaviors: an fMRI study

Personal distress associated with tic urges or inhibition and relief associated with tic production are defining features of the personal experience in Gilles de la Tourette syndrome (GTS). These affective phenomena have not been studied using fMRI, hindering our understanding of GTS pathophysiology and possible treatments. Here, we present a novel cross-sectional fMRI study designed to map tic-related phenomenology using distress and relief as predicting variables. We adopted a mental imagery approach and dissected the brain activity associated with different phases of tic behaviors, premonitory urges, and the ensuing tic execution or inhibition: these were compared with the mental simulation of “relaxed situations” and pre-determined stereotyped motor behaviors. We then explored whether the ensuing brain patterns correlated with the distress or relief perceived for the different phases of the tasks. Patients experienced a higher level of distress during the imagery of tic-triggering scenarios and no relief during tic inhibition. On the other hand, patients experienced significant relief during tic imagery. Distress during tic-triggering scenarios and relief during tic imagery were significantly correlated. The distress perceived during urges correlated with increased activation in cortical sensorimotor areas, suggesting a motor alarm. Conversely, relief during tic execution was positively associated with the activity of a subcortical network. The activity of the putamen was associated with both distress during urges and relief during tic execution. These findings highlight the importance of assessing the affective component of tic-related phenomenology. Subcortical structures may be causally involved in the affective component of tic pathophysiology, with the putamen playing a central role in both tic urge and generation. We believe that our results can be readily translated into clinical practice for the development of personalized treatment plans tailored to each patient’s unique needs.

Direct comparison between 18F-Flortaucipir tau PET and quantitative susceptibility mapping in progressive supranuclear palsy

PurposeThe pattern of flortaucipir tau PET uptake is topographically similar to the pattern of magnetic susceptibility in progressive supranuclear palsy (PSP); both with increased signal in subcortical structures such as the basal ganglia and midbrain, suggesting that they may be closely related. However, their relationship remains unknown since no studies have directly compared these two modalities in the same PSP cohort. We hypothesized that some flortaucipir uptake in PSP is associated with magnetic susceptibility, and hence iron deposition. The aim of this study was to evaluate the regional relationship between flortaucipir uptake and magnetic susceptibility and to examine the effects of susceptibility on flortaucipir uptake in PSP. MethodsFifty PSP patients and 67 cognitively normal controls were prospectively recruited and underwent three Tesla MRI and flortaucipir tau PET scans. Quantitative susceptibility maps were reconstructed from multi-echo gradient-echo MRI images. Region of interest (ROI) analysis was performed to obtain flortaucipir and susceptibility values in the subcortical regions. Relationships between flortaucipir and susceptibility signals were evaluated using partial correlation analysis in the subcortical ROIs and voxel-based analysis in the whole brain. The effects of susceptibility on flortaucipir uptake were examined by using the framework of mediation analysis. ResultsBoth flortaucipir and susceptibility were greater in PSP compared to controls in the putamen, pallidum, subthalamic nucleus, red nucleus, and cerebellar dentate (p<0.05). The ROI-based and voxel-based analyses showed that these two signals were positively correlated in these five regions (r = 0.36–0.59, p<0.05). Mediation analysis showed that greater flortaucipir uptake was partially explained by susceptibility in the putamen, pallidum, subthalamic nucleus, and red nucleus, and fully explained in the cerebellar dentate. ConclusionsThese results suggest that some of the flortaucipir uptake in subcortical regions in PSP is related to iron deposition. These findings will contribute to our understanding of the mechanisms underlying flortaucipir tau PET findings in PSP and other neurodegenerative diseases.

The Neuroanatomy of the Habenular Complex and Its Role in the Regulation of Affective Behaviors.

The habenular complex is a diencephalic structure divided into the medial and lateral divisions that lie within the epithalamus of most vertebrates. This brain structure, whose activities are mainly regulated via inputs/outputs from and to the stria medullaris and the fasciculus retroflexus, plays a significant role in the modulation of anti-reward behaviors in both the rodent and human brain. Such anti-reward circuits are regulated by dopaminergic and serotonergic projections with several other subcortical and cortical regions; therefore, it is plausible that impairment to this key subcortical structure or its connections contributes to the pathogenesis of affective disorders. Current literature reveals the existence of structural changes in the habenula complex in individuals afflicted by such disorders; however, there is a need for more comprehensive investigations to elucidate the underlying neuroanatomical connections that underpin disease development. In this review article, we aim to provide a comprehensive view of the neuroanatomical differences between the rodent and human habenular complex, the main circuitries, and provide an update on the emerging roles of this understudied subcortical structure in the control of affective behaviors, with special emphasis to morbid conditions of the affective sphere.

Linking acetylated α-Tubulin redistribution to α-Synuclein pathology in brain of Parkinson's disease patients.

Highly specialized microtubules in neurons are crucial to both health and disease of the nervous system, and their properties are strictly regulated by different post-translational modifications, including α-Tubulin acetylation. An imbalance in the levels of acetylated α-Tubulin has been reported in experimental models of Parkinson's disease (PD) whereas pharmacological or genetic modulation that leads to increased acetylated α-Tubulin successfully rescues axonal transport defects and inhibits α-Synuclein aggregation. However, the role of acetylation of α-Tubulin in the human nervous system is largely unknown as most studies are based on in vitro evidence. To capture the complexity of the pathological processes in vivo, we analysed post-mortem human brain of PD patients and control subjects. In the brain of PD patients at Braak stage 6, we found a redistribution of acetylated α-Tubulin, which accumulates in the neuronal cell bodies in subcortical structures but not in the cerebral cortex, and decreases in the axonal compartment, both in putamen bundles of fibres and in sudomotor fibres. High-resolution and 3D reconstruction analysis linked acetylated α-Tubulin redistribution to α-Synuclein oligomerization and to phosphorylated Ser 129 α-Synuclein, leading us to propose a model for Lewy body (LB) formation. Finally, in post-mortem human brain, we observed threadlike structures, resembling tunnelling nanotubes that contain α-Synuclein oligomers and are associated with acetylated α-Tubulin enriched neurons. In conclusion, we support the role of acetylated α-Tubulin in PD pathogenesis and LB formation.

Structural volumetric and Periodic Table DTI patterns in Complex Normal Pressure Hydrocephalus-Toward the principles of a translational taxonomy.

We previously proposed a novel taxonomic framework to describe the diffusion tensor imaging (DTI) profiles of white matter tracts by their diffusivity and neural properties. We have shown the relevance of this strategy toward interpreting brain tissue signatures in Classic Normal Pressure Hydrocephalus vs. comparator cohorts of mild traumatic brain injury and Alzheimer's disease. In this iteration of the Periodic Table of DTI Elements, we examined patterns of tissue distortion in Complex NPH (CoNPH) and validated the methodology against an open-access dataset of healthy subjects, to expand its accessibility to a larger community. DTI measures for 12 patients with CoNPH with multiple comorbidities and 45 cognitively normal controls from the ADNI database were derived using the image processing pipeline on the brainlife.io open cloud computing platform. Using the Periodic Table algorithm, DTI profiles for CoNPH vs. controls were mapped according to injury patterns. Structural volumes in most structures tested were significantly lower and the lateral ventricles higher in CoNPH vs. controls. In CoNPH, significantly lower fractional anisotropy (FA) and higher mean, axial, and radial diffusivities (MD, L1, and L2 and 3, respectively) were observed in white matter related to the lateral ventricles. Most diffusivity measures across supratentorial and infratentorial structures were significantly higher in CoNPH, with the largest differences in the cerebellum cortex. In subcortical deep gray matter structures, CoNPH and controls differed most significantly in the hippocampus, with the CoNPH group having a significantly lower FA and higher MD, L1, and L2 and 3. Cerebral and cerebellar white matter demonstrated more potential reversibility of injury compared to cerebral and cerebellar cortices. The findings of widespread and significant reductions in subcortical deep gray matter structures, in comparison to healthy controls, support the hypothesis that Complex NPH cohorts retain imaging features associated with Classic NPH. The use of the algorithm of the Periodic Table allowed for greater consistency in the interpretation of DTI results by focusing on patterns of injury rather than an over-reliance on the interrogation of individual measures by statistical significance alone. Our aim is to provide a prototype that could be refined for an approach toward the concept of a "translational taxonomy."

The Interactions of Temporal and Sensory Representations in the Basal Ganglia.

In rodents and primates, interval estimation has been associated with a complex network of cortical and subcortical structures where the dorsal striatum plays a paramount role. Diverse evidence ranging from individual neurons to population activity has demonstrated that this area hosts temporal-related neural representations that may be instrumental for the perception and production of time intervals. However, little is known about how temporal representations interact with other well-known striatal representations, such as kinematic parameters of movements or somatosensory representations. An attractive hypothesis suggests that somatosensory representations may serve as the scaffold for complex representations such as elapsed time. Alternatively, these representations may coexist as independent streams of information that could be integrated into downstream nuclei, such as the substantia nigra or the globus pallidus. In this review, we will revise the available information suggesting an instrumental role of sensory representations in the construction of temporal representations at population and single-neuron levels throughout the basal ganglia.

Functional relationships of the cerebral cortex with subcortical structures in emotional stressful conditions

Studying central mechanisms of stress, which is assuming more an emotional aspect, is among the topical problems of modern neurophysiology and medicine. Having created complex conditions of adaptive behavior, rapid scientific and technological growth has required processing a huge flow of different information related to biological functions and social activity of human beings. According to WHO experts, in 70% of all cases emotional stress leads to various diseases including hypertension, myocardial infarction, stroke, atherosclerosis, as well as development of neurotic conditions, psychiatric disorders and disruption of normal adaptation of humans to social conditions of life. Many researchers have studied EEG and peripheral signals separately, but little attention has been paid to the correlation between these indicators. To date, issues related to the central mechanisms of stress and their relationship with autonomic functions have not been fully studied. The EEG cross-correlation analysis we have chosen is more advanced because, unlike conventional EEG analysis, it provides detailed information about the connections between brain structures in spatio-temporal relationships.

Exercise in the Treatment of Repetitive, Self-Injurious, and Aggressive Behavior in Adults with Autism Spectrum Disorder: A Neurobiological Analysis

Objective: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by markedly impaired social interaction and restricted/ repetitive patterns of behavior, interests, and activities. Maladaptive behaviors associated with ASD can include stereotyped, self-injurious, and aggressive behaviors. Current evidence-based interventions for ASD involve specialist availability, financial, time, and side effect constraints. Physical exercise has received increasing attention in the treatment of children with ASD, but research in adults is comparatively scarce. The purpose of this paper is to explore possible mechanisms by which exercise can reduce repetitive, self-injurious, and aggressive behaviors in adults with ASD. Methods: The literature on the neurobiology of exercise is reviewed and compared with the literature on the neurobiology of ASD. Information from this comparison is then used to formulate possible mechanisms by which exercise may reduce maladaptive behaviors in adults with ASD. Results: Plausible mechanisms for an exercise-induced beneficial effect on maladaptive behaviors in adults with ASD include modulation of neurotransmitter release and function, facilitation of endocannabinoid release, increased expression of neurotrophic factors, improved functional connectivity in higher-level cognitive networks, reduced oxidative stress, improved HPA axis function, treatment of comorbid depression, and reduction in amyloid beta deposition in cortical GABAergic neurons and subcortical structures. Conclusions: Future research should attempt to confirm the efficacy of exercise in reducing maladaptive behaviors in adults with ASD as well as the proposed mechanisms for such a relationship. Verification of these issues would have major implications in terms of supporting an evidence-based, inexpensive, widely available, and broadly beneficial treatment for adults with ASD.

Creutzfeldt-Jakob disease presenting as psychiatric disorder: case presentation and systematic review.

Creutzfeldt-Jakob disease (CJD) is a spongiform encephalopathy caused by misfolded human prion proteins (PrP)s. Due to variability in presentation, the diagnosis may be missed in lieu of various psychiatric disorders. Our study reports on a prototypical case and psychiatric mimic for CJD, and the workup used to establish the correct diagnosis. A 54-year-old male with a past medical history of traumatic brain injury and major depressive disorder presented with chest pain. During the hospital stay, he was found to be increasingly aggressive, and behaved out of character. Further review of clinical history revealed that the patient was diagnosed with cognitive impairment and depression one year prior. The patient was agitated, poorly redirectable, and had unstable gait on neurological examination. Magnetic resonance imaging (MRI) of the brain demonstrated restricted diffusion (DWI) along the parietooccipital and temporal regions (L > R) and in the subcortical structures, including the basal ganglia and thalami, with accompanying subtle fluid attenuation inversion recovery (FLAIR) hyperintense signal abnormality in these regions, deemed as artifactual at the time. Repeat MRI brain two months later demonstrated progression of the DWI signal with ADC correlate and FLAIR findings. Cerebrospinal fluid 14-3-3 and RT-QuIC samples were positive. Upon passing a few months later, brain autopsy and Western Blot confirmed the CJD diagnosis. Literature review was conducted on PubMed to identify CJD cases initially diagnosed as psychiatric disorder. Search terms included "CJD" or "Creutzfeldt-Jakob disease" with three common psychiatric diagnoses, "Depression," "Psychosis," and "Mania." Positive EEG, MRI, PET, and CSF (including protein 14-3-3 and tau) findings for CJD were found in 66.7, 81.1, 50, and 72.7% of cases, respectively. Overall, CJD can present as a psychiatric mimic. In suspicious cases, EEG, imaging, and CSF studies should be promptly utilized to arrive at the correct diagnosis. Repeated MRI imaging is often required to help in the diagnostic process. Brain biopsy should be considered in selected cases.

АКТИВНОСТЬ РЕГУЛЯТОРНЫХ СТРУКТУР МОЗГА ПРИ БОЕВОЙ ТРАВМЕ И ТРАВМЕ МИРНОГО ВРЕМЕНИ

Activation of the body’s regulatory systems provides adaptation to the impact of pathogenic factors. Prolonged exposure to extreme factors during combat operations can lead to the formation of a focus of pathologically increased exaltation in the central nervous system. The study aims to comparatively assess the tension of central regulatory structures in victims with battle and peacetime traumas in the acute period to develop criteria for indicating the severity of functional disorders of the central nervous system and pathogenetic treatment. Twenty servicemen who received mine-explosive trauma as a result of combat operations, twenty victims of domestic trauma, and twenty healthy males were examined. Neurophysiological and ultrasound methods of research were used to assess the functional state of the central nervous and cardiovascular systems: electroencephalography with quantitative analysis, transcranial Doppler with functional tests, electrocardiography with assessment of heart rate variability: The study assessed the index of spectral power of rhythms in alpha/theta ranges, indices of spectral power of heart rhythm (index of vagosympathetic balance; index of centralization; index of activation of subcortical structures), indices of vasodilatation/vasoconstriction reflecting reactivity of cerebral vessels to tests with hyper/hypocapnia. The following statistically significant differences were revealed between peacetime and wartime traumas: a decrease in vasodilation reserves for hypercapnia, and in some cases, their absence during battle trauma; increasing indices of centralization and activation of subcortical structures during battle trauma; decrease in the index of spectral power of rhythms in the alpha/theta ranges due to an increase in the power of the theta range during battle trauma. Based on this set of indicators, a scale of quantitative assessment of the degree of tension of regulatory subcortical structures in points was developed for early detection of patients with excessive activation of the central regulatory circuit leading to maladjustment and unfavorable course of the post-traumatic period.

Concurrent functional ultrasound imaging with graphene-based DC-coupled electrophysiology as a platform to study slow brain signals and cerebral blood flow under control and pathophysiological brain states.

Current methodology used to investigate how shifts in brain states associated with regional cerebral blood volume (CBV) change in deep brain areas, are limited by either the spatiotemporal resolution of the CBV techniques, and/or compatibility with electrophysiological recordings; particularly in relation to spontaneous brain activity and the study of individual events. Additionally, infraslow brain signals (<0.1 Hz), including spreading depolarisations, DC-shifts and infraslow oscillations (ISO), are poorly captured by traditional AC-coupled electrographic recordings; yet these very slow brain signals can profoundly change CBV. To gain an improved understanding of how infraslow brain signals couple to CBV we present a new method for concurrent CBV with wide bandwidth electrophysiological mapping using simultaneous functional ultrasound imaging (fUS) and graphene-based field effect transistor (gFET) DC-coupled electrophysiological acquisitions. To validate the feasibility of this methodology visually-evoked neurovascular coupling (NVC) responses were examined. gFET recordings are not affected by concurrent fUS imaging, and epidural placement of gFET arrays within the imaging window did not deteriorate fUS signal quality. To examine directly the impact of infra-slow potential shifts on CBV, cortical spreading depolarisations (CSDs) were induced. A biphasic pattern of decreased, followed by increased CBV, propagating throughout the ipsilateral cortex, and a delayed decrease in deeper subcortical brain regions was observed. In a model of acute seizures, CBV oscillations were observed prior to seizure initiation. Individual seizures occurred on the rising phase of both infraslow brain signal and CBV oscillations. When seizures co-occurred with CSDs, CBV responses were larger in amplitude, with delayed CBV decreases in subcortical structures. Overall, our data demonstrate that gFETs are highly compatible with fUS and allow concurrent examination of wide bandwidth electrophysiology and CBV. This graphene-enabled technological advance has the potential to improve our understanding of how infraslow brain signals relate to CBV changes in control and pathological brain states.

Is Quantifying Iron in the Putamen Important in Neurodegenerative Diseases?

Iron is crucial for the functioning of neurons. However, the accumulation of iron in subcortical structures, particularly in the putamen, has been linked to age-related decline in cognitive function and neurodegeneration. This accumulation leads to oxidative stress, which damages cellular components and contributes to the development of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Quantitative Susceptibility Mapping (QSM) has provided insights into the paramagnetic properties of iron, enabling the non-invasive measurement of iron deposits in brain structures. Studies have shown a significant correlation between increased iron levels in the putamen and the severity of neurodegenerative diseases, highlighting the vulnerability of the putamen to iron-induced toxicity. QSM holds promise as an imaging biomarker for understanding disease mechanisms, assessing disease severity, and monitoring treatment. However, further longitudinal studies are needed to evaluate the progression of iron deposition and its implications for disease pathology.

Experimental study of the influence of phenozanic acid and its combination with valproic acid on the development of the epileptic system

To study the effect of phenosanic acid (PA) and its combination with valproic acid (VA) on the development of the Epi system. A model of focal chronic epilepsy in rats was created by applying metallic cobalt to the surface of the sensorimotor area of the cortex. Long-term electrodes were implanted in the sensorimotor cortex of the left and right hemispheres, the hippocampus, and the hypothalamus. The effect of PA (80 mg/kg) and its combination with VA (200 mg/kg) on discharge activity was carried out on the 2nd day and at the stage of generalization of the Epi system - on the 6th day. The stability of the Epi system on day 10 was assessed by provoking the development of epileptic status (Epi status) in response to the administration of thiolactone homocysteine (HMC) at a dose of 5.5 mmol/kg. In rats treated with PA, low discharge activity is observed, which is confirmed by the absence of EEG and motor manifestations of status epilepticus caused by HMC. PA does not suppress paroxysmal activity at the stages of development of the Epi system. VA significantly suppresses paroxysmal activity, but does not affect the formation of new foci of Epi activity in subcortical structures and the contralateral cortex. The epi system of rats treated with VA is characterized by high discharge activity by the 10th day of the experiment and lability to provocation of epi status. The combination of drugs is more pronounced than PA, but less than VA, reduces the numerical characteristics of paroxysmal activity in the brain structures of rats. PA when administered alone, in combination with VA, causes a slowdown in the generalization of convulsive foci of Epi activity and prevents the formation of a stable Epi system. VA, having a pronounced anticonvulsant effect, does not weaken the development of the Epi system in the model of focal cobalt-induced epilepsy.

I like the way you move: how animate motion affects visual attention in early human infancy.

The ability to detect animates (as compared with inanimates) rapidly is advantageous for human survival. Due to its relevance, not only the adult human brain has evolved specific neural mechanisms to discriminate animates, but it has been proposed that selection finely tuned the human visual attention system to prioritize visual cues that signal the presence of living things. Among them, animate motion-i.e., the motion of animate entities -, is one of the most powerful cues that triggers humans' attention. From a developmental point of view, whether such specialization is inborn or acquired through experience is a fascinating research topic. This mini-review aims to summarize and discuss recent behavioral and electrophysiological research that suggests that animate motion has an attentional advantage in the first year of life starting from birth. Specifically, the rationale underlying this paper concerns how attention deployment is affected by animate motion conveyed both by the movement of a single dot and, also, when the single dot is embedded in a complex array, named biological motion. Overall, it will highlight the importance of both inborn predispositions to pay attention preferentially to animate motion, mainly supported by subcortical structures, and the exposure to certain experiences, shortly after birth, to drive the cortical attentional visual system to become the way it is in adults.

Behavioral disinhibition in stroke.

Post-stroke behavioral disinhibition (PSBD) is common in stroke survivors and often presents as impulsive, tactless or vulgar behavior. However, it often remains undiagnosed and thus untreated, even though it can lead to a longer length of stay in a rehabilitation facility. The proposed study will aim to evaluate the clinical, neuropsychological and magnetic resonance imaging (MRI) correlates of PSBD in a cohort of stroke survivors and describe its 12-month course. This prospective cohort study will recruit 237 patients and will be conducted at the Neurology Unit of the Prince of Wales Hospital. The project duration will be 24 months. The patients will be examined by multiple MRI methods, including diffusion-weighted imaging, within 1 week after stroke onset. The patients and their caregivers will receive a detailed assessment at a research clinic at 3, 9 and 15 months after stroke onset (T1, T2 and T3, respectively). The disinhibition subscale of the Frontal Systems Behavior Scale (FrSBe) will be completed by each subject and caregiver, and scores ≥65 will be considered to indicate PSBD.A stepwise logistic regression will be performed to assess the importance of lesions in the regions of interest (ROIs), together with other significant variables identified in the univariate analyses. For patients with PSBD at T1, the FrSBe disinhibition scores will be compared between the groups of patients with and without ROI infarcts, using covariance analysis. The demographic, clinical and MRI variables of remitters and non-remitters will be examined again at T2 and T3 by logistic regression. This project will be the first MRI study on PSBD in stroke survivors. The results will shed light on the associations of lesions in the orbitofrontal cortex, anterior temporal lobe and subcortical brain structures with the risk of PSBD. The obtained data will advance our understanding of the pathogenesis and clinical course of PSBD in stroke, as well as other neurological conditions. The findings are thus likely to be applicable to the large population of patients with neurological disorders at risk of PSBD and are expected to stimulate further research in this field.

Comparative characteristics of neuropsychological and neurometabolic changes in patients with Alzheimer's disease and vascular cognitive impairment

To investigate the pattern and connections of neuropsychological and metabolic indices in patients with cognitive disorders of Alzheimer's and vascular (subcortical-cortical) types of different severity. A total of 177 patients were examined, including 85 patients with Alzheimer's disease (AD) and 92 patients with vascular cognitive impairment (VCI). All patients underwent complex neuropsychological examination; 18F-FDG PET was performed in 17 patients with AD and 15 patients with VCI. The greatest changes in patients with AD were noted in the mnestic sphere, and the indicators significantly differed from the results of the study of patients with VCI already at the pre-dementia stage. Neurodynamic and dysregulatory disorders prevailed in patients with VCI. Patients with AD showed bilateral symmetrical reduction of metabolic activity in the cortex of parietal and temporal lobes, often in combination with marked hypometabolism in the hippocampal region. In patients with VCI, there were areas of decreased brain tissue metabolism of different localization and size, mainly in the projection of the basal ganglia and in the prefrontal and parietal cortex, as well as in the cingulate gyrus, which indirectly confirms the mechanism of disconnection of subcortical and cortical structures. In AD, impaired metabolic activity in the hippocampal region correlated with impaired temporal and spatial orientation (ρ=-0.54, p<0.05), memory impairment (ρ=-0.71, p<0.005). Hypometabolism of the parietal lobe cortex was associated with total MMSE score (ρ=-0.8, p<0.001), 10-word test (ρ=-0.89, p<0.001 and ρ=-0.82, p<0.001), visual-spatial impairment (ρ=-0.64, p<0.01), categorical association test (ρ=-0.73, p<0.005). In patients with VCI, dysregulatory disorders correlated with hypometabolism in the thalamic projection (ρ=-0.56, p<0.05), prefrontal cortex (ρ=-0.64, p<0.05) and in the cingulate gyrus (anterior regions) (ρ=-0.53, p<0.05). The results indicate the presence of differences in cognitive impairment and cerebral metabolism in patients with AD and VCI.

Brain Volumetric changes in patients with Spinocerebellar Ataxia Type 2

Aim: Spinocerebellar ataxia type 2 (SCA2) is a trinucleotide repeat disorder characterized by mutations in the ataxin-2 gene. Although the primary symptoms of this disease are related to cerebellar involvement, such as ataxia and dysarthria, cognitive disorders associated with supratentorial involvement, depression, and extrapyramidal symptoms are also common. The aim of this study was to investigate volumetric changes in patients with SCA2. Materials and Methods: Nine SCA2 patients and sixteen age and gender-matched healthy controls were included in the study. Voxel-based morphometry (VBM) was used to explore changes in whole brain gray and white matter, while surface-based morphometry (SBM) was employed to investigate changes in cortical thickness (CT), local gyrification index (LGI), sulcal depth (SD), and fractal dimension (FD). Deep learning methods were utilized for the automatic segmentation of subcortical gray matter structures and extrapyramidal system structures. Comparisons between groups were made using GLM, T-Test, and Mann-Whitney U test. Results: VBM results showed widespread gray matter loss in the cerebellum and widespread white matter loss in the brain stem (Cluster size: 25918 voxels for gray matter, 24557 voxels for white matter). SBM findings indicated a decrease in cortical thickness (Cluster size:19276 vertices for left hemisphere; 17276 vertices for right hemisphere), more pronounced in the supratentorial frontoparietal region, while FD, LGI, and SD did not differ between groups. Volume loss was observed in the subthalamic nucleus, globus pallidus internus and externus, and red nucleus in SCA2 patients. Conclusion: SCA2 patients exhibit white and gray matter volume loss in the infratentorial region. Additionally, they show a decrease in frontoparietal cortical thickness, while FD, LGI, and SD do not show any changes. Moreover, atrophy is also observed in the extrapyramidal system structures.

Pairing transcutaneous vagus nerve stimulation with an intensive bimanual training in children and adolescents with cerebral palsy: study protocol of a randomized sham-controlled trial.

Gross motor function impairments and manual dexterity deficits are frequently observed in children and adolescents with Cerebral Palsy (CP), having a major impact on their activity level and autonomy. Improving manual dexterity and activity level of patients with CP is often the focus of rehabilitation. Novel and adjuvant treatment methods that could support the standard training also in chronic conditions are a research priority. The transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive brain stimulation technique, which provides a bottom-up stimulation of subcortical and cortical brain structures, enhancing brain GABA and Noradrenaline levels. This technique may play a pivotal role in brain plasticity, which has not been tested in CP patients before. 44 children and adolescents with CP will be involved, treated in pairs in a randomized, double-blind, pre-post test study. The two groups will undergo the Hand-Arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) for 2 consecutive weeks, with 3 h daily sessions for 5 days per week, for an overall time interval of 30 h; the training will be combined with the application for 75 min/day of active or sham tVNS, in separate, randomly allocated groups. The primary outcome measure will include the scores at the Assisting Hand Assessment and Box and Block Test, and at an ad-hoc visuomotor task evaluating manual visuomotor control. Secondary outcomes will include the scores at the Children's Hand Experience Questionnaire, Canadian Occupational Performance Measure, Melbourne Assessment of Unilateral Upper Limb Function, Gross Motor Function Measure, Vineland, Pediatric quality of life inventory. The evaluation points will include pre (T0), post (T1) and 3-month follow up (T2) assessments. Safety and tolerability will also be assessed. The results of this trial will assess whether tVNS can effectively boost the effects of an intensive two-week bimanual training, in improving manual dexterity in children and adolescents with cerebral palsy, ensuring safety and tolerability throughout the intervention period.Clinical trial registration: ClinicalTrials.gov, NCT06372028.