Carlos R. Hernandez-Castillo

Functional connectivity changes related to cognitive and motor performance in spinocerebellar ataxia type 2

Several neuropathological studies in spinocerebellar ataxia type 2 (SCA2) have revealed significant atrophy of the cerebellum, brainstem, sensorimotor cortex, and several regions in the frontal lobe. However, the impact of the neurodegeneration on the functional integration of the remaining tissue is unknown. To analyze the clinical impact of these functional changes, we correlated the abnormal functional connectivity found in SCA2 patients with their scores in clinical scales. To obtain the functional connectivity changes, we followed two approaches. In one we used areas with significant cerebellar gray matter atrophy as anchor seeds, and in the other we performed a whole‐brain data‐driven analysis.

Extensive White Matter Alterations and Its Correlations with Ataxia Severity in SCA 2 Patients

Background Previous studies of SCA2 have revealed significant degeneration of white matter tracts in cerebellar and cerebral regions. The motor deficit in these patients may be attributable to the degradation of projection fibers associated with the underlying neurodegenerative process. However, this relationship remains unclear. Statistical analysis of diffusion tensor imaging enables an unbiased whole-brain quantitative comparison of the diffusion proprieties of white matter tracts in vivo. Methods Fourteen genetically confirmed SCA2 patients and aged-matched healthy controls participated in the study. Tract-based spatial statistics were performed to analyze structural white matter damage using two different measurements: fractional anisotropy (FA) and mean diffusivity (MD). Significant diffusion differences were correlated with the patients ataxia impairment. Results Our analysis revealed decreased FA mainly in the inferior/middle/superior cerebellar peduncles, the bilateral posterior limb of the internal capsule and the bilateral superior corona radiata. Increases in MD were found mainly in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Clinical impairment measured with the SARA score correlated with FA in superior parietal white matter and bilateral anterior corona radiata. Correlations with MD were found in cerebellar white matter and the middle cerebellar peduncle. Conclusion Our findings show significant correlations between diffusion measurements in key areas affected in SCA2 and measures of motor impairment, suggesting a disruption of information flow between motor and sensory-integration areas. These findings result in a more comprehensive view of the clinical impact of the white matter degeneration in SCA2.

Motor and sensory cortical reorganization after bilateral forearm transplantation: Four-year follow-up fMRI case study

The objective of this study was to characterize the cortical activity pattern of one patient who received bilateral forearm transplants. Using fMRI we acquired motor and sensory brain activity every year after surgery and during three consecutive years while the patient underwent physical rehabilitation. The motor related cortical activity evaluated during the first year showed a sparse pattern involving several brain regions. Over time, the analysis showed a progressive delimitation of the motor-related areas that had significant activity. The results also showed continuous size reductions of the activated cluster in the motor cortex. The activation in the sensory cortex showed significant increases in cluster size over time. The intensity of both motor and sensory cortical activations correlated with the Disabilities of the Arm, Shoulder and Hand questionnaire. Our results show significant cortical reorganization of motor and sensory cortices after transplantation of bilateral forearm transplantation over a four-year period.

Cognitive Deficits Correlate with White Matter Deterioration in Spinocerebellar Ataxia Type 2

OBJECTIVES The aim of this study was to explore the relationship between cognitive and white matter deterioration in a group of participants with spinocerebellar ataxia type 2 (SCA2). METHODS Fourteen genetically confirmed participants with SCA2 and 14 aged-matched controls participated in the study. Diffusion tensor imaging tract-based spatial statistics were performed to analyze structural white matter integrity. Significant group differences in the mean diffusivity were correlated with SCA2 cognitive deficits. RESULTS Our analysis revealed higher mean diffusivity in the SCA2 group in cerebellar white matter, medial lemniscus, and middle cerebellar peduncle, among other regions. Cognitive scores correlated with white matter mean diffusivity in the parahippocampal area, inferior frontal and supramarginal gyri and the stria terminalis. CONCLUSIONS Our findings show significant correlations between white matter microstructural damage in key areas affected in SCA2 and cognitive deficits. These findings result in a more comprehensive understanding of the effect of the neurodegenerative process in people with SCA2.

Social and Cultural Elements Associated with Neurocognitive Dysfunctions in Spinocerebellar Ataxia Type 2 Patients.

Spinocerebellar Ataxia Type 2 (SCA2) is a rare genetic disorder producing cerebellar degeneration and affecting motor abilities. Neuroimaging studies also show neurodegeneration in subcortical and cortical regions related to emotional and social processes. From social neuroscience, it is suggested that motor and social abilities can be influenced by particular cultural dynamics so, culture is fundamental to understand the effect of brain-related alterations. Here, we present the first analysis about the cultural elements related to the SCA2 disorder in 15 patients previously evaluated with neuroimaging and psychometric instruments, and their nuclear relationships distributed in six geographical and cultural regions in Mexico. Ethnographic records and photographic and video archives about the quotidian participant’s routine were obtained from the patients, their relatives and their caregivers. The information was categorized and interpreted taking into consideration cultural issues and patients’ medical files. Our analyses suggest that most of the participants do not understand the nature of the disease and this misunderstanding favors magic and non-medical explanations. Patients’ testimonies suggest a decrease in pain perception as well as motor alterations that may be related to interoceptive dysfunctions. Relatives’ testimonies indicate patients’ lack of social and emotional interests that may be related to frontal, temporal, and cerebellar degeneration. In general, participants use their religious beliefs to deal with the disease and only a few of them trust the health system. Patients and their families are either openly rejected and ignored, tolerated or even helped by their community accordingly to different regional traits. We propose that ethnography can provide social representations to understand the patients’ alterations, to formulate neurobiological hypotheses, to develop neurocognitive interventions, and to improve the medical approach to the disease.

A representative template of the neonatal cerebellum

&NA; The cerebellum plays an important role in human brain development. To improve the spatial specificity of the analysis of human cerebellar magnetic resonance imaging (MRI) data, we present a new template of the neonatal human cerebellum and brainstem based on the anatomy of 20 full‐term healthy neonates. The template is spatially unbiased, which means that the location of each structure is not biased by the anatomy of the individuals used to create the template. In comparison to current whole‐brain templates, it allows for an improved voxel‐by‐voxel normalization for MRI analysis. To align the cerebellum to the template, it needs to be isolated from the surrounding tissue, a process for which an automated algorithm has been developed. Our methodology outperforms normalization to a whole‐brain neonatal template, using either linear or nonlinear transformations. Our algorithm reduces the spatial variability of the infratentorial area, while simultaneously increasing the overlap of the cerebellum. The template and the related software are freely available as part of SUIT v3.3 SPM toolbox.

Unique degeneration signatures in the cerebellar cortex for spinocerebellar ataxias 2, 3, and 7

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative diseases that selectively affect vulnerable neuronal populations in the cerebellum and other subcortical regions. While previous studies have reported subtype differences in the absolute amount of degeneration in specific regions of interest, they failed to account for two important factors. First, they did not control for overall differences in the severity of the degeneration pattern, and second, they did not fully characterize the spatial pattern of degeneration for each SCA subtype. Here, we provide a systematic characterization of the spatial degeneration patterns for three polyQ SCAs (55 patients, either SCA2, SCA3, or SCA7) while controlling for the severity of the degeneration pattern. After this correction, the cerebellar degeneration pattern can successfully classify between the three different SCA subtypes with high cross-validated accuracy. Specifically, degeneration in SCA3 disproportionally affects motor regions of the cerebellar cortex, which explains the relatively severe motor symptoms observed in this subtype. Our results demonstrate that each of the three studied SCA subtypes has a unique cerebellar degeneration signature, hinting at differences in the disease process. Clinically, these differentiable patterns of cerebellar degeneration can be used to reliably discern subtypes, even at relatively early stages of the disease.

Comparing fully automated state-of-the-art cerebellum parcellation from magnetic resonance images

&NA; The human cerebellum plays an essential role in motor control, is involved in cognitive function (i.e., attention, working memory, and language), and helps to regulate emotional responses. Quantitative in‐vivo assessment of the cerebellum is important in the study of several neurological diseases including cerebellar ataxia, autism, and schizophrenia. Different structural subdivisions of the cerebellum have been shown to correlate with differing pathologies. To further understand these pathologies, it is helpful to automatically parcellate the cerebellum at the highest fidelity possible. In this paper, we coordinated with colleagues around the world to evaluate automated cerebellum parcellation algorithms on two clinical cohorts showing that the cerebellum can be parcellated to a high accuracy by newer methods. We characterize these various methods at four hierarchical levels: coarse (i.e., whole cerebellum and gross structures), lobe, subdivisions of the vermis, and the lobules. Due to the number of labels, the hierarchy of labels, the number of algorithms, and the two cohorts, we have restricted our analyses to the Dice measure of overlap. Under these conditions, machine learning based methods provide a collection of strategies that are efficient and deliver parcellations of a high standard across both cohorts, surpassing previous work in the area. In conjunction with the rank‐sum computation, we identified an overall winning method.

Early Huntington’s Disease: Impulse Control Deficits but Correct Judgment Regarding Risky Situations

BACKGROUND Huntingtons disease (HD) patients show alterations in decision making tasks. However, it is still uncertain if these deficits are due to poor judgment regarding risky situations, or to impulse control deficits. OBJECTIVE To elucidate whether decision-making in patients is related to genuine risk behavior or to impulse control deficits. METHODS To test between these two alternative possibilities, we evaluated the performance of 19 prodromal HD patients and 19 matched healthy controls in the Cambridge Gambling Task (CGT). This task assesses decision-making while dissociating between genuine risk-taking behaviors (ascending condition) from impulsive behavior (descending condition). RESULTS The results showed that patients and controls had the same performance during all trials in the ascending condition, reflecting a correct judgment regarding risky situations; however, during the descending condition, patients responded before the controls in all trials, making a significantly larger number of higher bets. Unlike the control group, they did not wait for more optimal subsequent options. CONCLUSION These results suggest impulse control deficits in HD gene carriers, but unimpaired risk-taking judgment.

Neural correlates of spatial working memory manipulation in a sequential Vernier discrimination task.

Visuospatial working memory refers to the short-term storage and manipulation of visuospatial information. To study the neural bases of these processes, 17 participants took part in a modified sequential Vernier task while they were being scanned using an event-related functional MRI protocol. During each trial, participants retained the spatial position of a line during a delay period to later evaluate if it was presented aligned to a second line. This design allowed testing the manipulation of the spatial information from memory. During encoding, there was a larger parietal and cingulate activation under the experimental condition, whereas the opposite was true for the occipital cortex. Throughout the delay period of the experimental condition there was significant bilateral activation in the caudal superior frontal sulcus/middle frontal gyrus, as well as the insular and superior parietal lobes, which confirms the findings from previous studies. During manipulation of spatial memory, the analysis showed higher activation in the lingual gyrus. This increase of activity in visual areas during the manipulation phase fits with the hypothesis that information stored in sensory cortices becomes reactivated once the information is needed to be utilized.