Genotype-specific spinal cord damage in spinocerebellar ataxias: an ENIGMA-Ataxia study.

BACKGROUND: Spinal cord damage is a feature of many spinocerebellar ataxias (SCAs), but well-powered in vivo studies are lacking and links with disease severity and progression remain unclear. Here we characterise cervical spinal cord morphometric abnormalities in SCA1, SCA2, SCA3 and SCA6 using a large multisite MRI dataset. METHODS: Upper spinal cord (vertebrae C1-C4) cross-sectional area (CSA) and eccentricity (flattening) were assessed using MRI data from nine sites within the ENIGMA-Ataxia consortium, including 364 people with ataxic SCA, 56 individuals with preataxic SCA and 394 nonataxic controls. Correlations and subgroup analyses within the SCA cohorts were undertaken based on disease duration and ataxia severity. RESULTS: Individuals in the ataxic stage of SCA1, SCA2 and SCA3, relative to non-ataxic controls, had significantly reduced CSA and increased eccentricity at all examined levels. CSA showed large effect sizes (d>2.0) and correlated with ataxia severity (r<-0.43) and disease duration (r<-0.21). Eccentricity correlated only with ataxia severity in SCA2 (r=0.28). No significant spinal cord differences were evident in SCA6. In preataxic individuals, CSA was significantly reduced in SCA2 (d=1.6) and SCA3 (d=1.7), and the SCA2 group also showed increased eccentricity (d=1.1) relative to nonataxic controls. Subgroup analyses confirmed that CSA and eccentricity are abnormal in early disease stages in SCA1, SCA2 and SCA3. CSA declined with disease progression in all, whereas eccentricity progressed only in SCA2. CONCLUSIONS: Spinal cord abnormalities are an early and progressive feature of SCA1, SCA2 and SCA3, but not SCA6, which can be captured using quantitative MRI.

The role of feedback in the production of skilled finger sequences.

Actions involving fine control of the hand, for example, grasping an object, rely heavily on sensory information from the fingertips. Although the integration of feedback during the execution of individual movements is well understood, less is known about the use of sensory feedback in the control of skilled movement sequences. To address this gap, we trained participants to produce sequences of finger movements on a keyboard-like device over a 4-day training period. Participants received haptic, visual, and auditory feedback indicating the occurrence of each finger press. We then either transiently delayed or advanced the feedback for a single press by a small amount of time (30 or 60 ms). We observed that participants rapidly adjusted their ongoing finger press by either accelerating or prolonging the ongoing press, in accordance with the direction of the perturbation. Furthermore, we could show that this rapid behavioral modulation was driven by haptic feedback. Although these feedback-driven adjustments reduced in size with practice, they were still clearly present at the end of training. In contrast to the directionally specific effect we observed on the perturbed press, a feedback perturbation resulted in a delayed onset of the subsequent presses irrespective of perturbation direction or feedback modality. This observation is consistent with a hierarchical organization of even very skilled and fast movement sequences, with different levels reacting distinctly to sensory perturbations.NEW & NOTEWORTHY Sensory feedback is important during the execution of a movement. However, little is known about how sensory feedback is used during the production of movement sequences. Here, we show two distinct feedback processes in the execution of fast finger movement sequences. By transiently delaying or advancing the feedback of a single press within a sequence, we observed a directionally specific effect on the perturbed press and a directionally non-specific effect on the subsequent presses.

Evaluating brain parcellations using the distance-controlled boundary coefficient.

One important approach to human brain mapping is to define a set of distinct regions that can be linked to unique functions. Numerous brain parcellations have been proposed, using cytoarchitectonic, structural, or functional magnetic resonance imaging (fMRI) data. The intrinsic smoothness of brain data, however, poses a problem for current methods seeking to compare different parcellations. For example, criteria that simply compare within-parcel to between-parcel similarity provide even random parcellations with a high value. Furthermore, the evaluation is biased by the spatial scale of the parcellation. To address this problem, we propose the distance-controlled boundary coefficient (DCBC), an unbiased criterion to evaluate discrete parcellations. We employ this new criterion to evaluate existing parcellations of the human neocortex in their power to predict functional boundaries for an fMRI data set with many different tasks, as well as for resting-state data. We find that common anatomical parcellations do not perform better than chance, suggesting that task-based functional boundaries do not align well with sulcal landmarks. Parcellations based on resting-state fMRI data perform well; in some cases, as well as a parcellation defined on the evaluation data itself. Finally, multi-modal parcellations that combine functional and anatomical criteria perform substantially worse than those based on functional data alone, indicating that functionally homogeneous regions often span major anatomical landmarks. Overall, the DCBC advances the field of functional brain mapping by providing an unbiased metric that compares the predictive ability of different brain parcellations to define brain regions that are functionally maximally distinct.

Brain Structure and Degeneration Staging in Friedreich Ataxia: Magnetic Resonance Imaging Volumetrics from the ENIGMA-Ataxia Working Group.

OBJECTIVE: Friedreich ataxia (FRDA) is an inherited neurological disease defined by progressive movement incoordination. We undertook a comprehensive characterization of the spatial profile and progressive evolution of structural brain abnormalities in people with FRDA. METHODS: A coordinated international analysis of regional brain volume using magnetic resonance imaging data charted the whole-brain profile, interindividual variability, and temporal staging of structural brain differences in 248 individuals with FRDA and 262 healthy controls. RESULTS: The brainstem, dentate nucleus region, and superior and inferior cerebellar peduncles showed the greatest reductions in volume relative to controls (Cohen d = 1.5-2.6). Cerebellar gray matter alterations were most pronounced in lobules I-VI (d = 0.8), whereas cerebral differences occurred most prominently in precentral gyri (d = 0.6) and corticospinal tracts (d = 1.4). Earlier onset age predicted less volume in the motor cerebellum (rmax  = 0.35) and peduncles (rmax  = 0.36). Disease duration and severity correlated with volume deficits in the dentate nucleus region, brainstem, and superior/inferior cerebellar peduncles (rmax  = -0.49); subgrouping showed these to be robust and early features of FRDA, and strong candidates for further biomarker validation. Cerebral white matter abnormalities, particularly in corticospinal pathways, emerge as intermediate disease features. Cerebellar and cerebral gray matter loss, principally targeting motor and sensory systems, preferentially manifests later in the disease course. INTERPRETATION: FRDA is defined by an evolving spatial profile of neuroanatomical changes beyond primary pathology in the cerebellum and spinal cord, in line with its progressive clinical course. The design, interpretation, and generalization of research studies and clinical trials must consider neuroanatomical staging and associated interindividual variability in brain measures. ANN NEUROL 2021;90:570-583.

Mapping the Cerebellar Cognitive Affective Syndrome in Patients with Chronic Cerebellar Strokes.

The cerebellar cognitive affective syndrome (CCAS) has been consistently described in patients with acute/subacute cerebellar injuries. However, studies with chronic patients have had controversial findings that have not been explored with new cerebellar-target tests, such as the CCAS scale (CCAS-S). The objective of this research is to prove and contrast the usefulness of the CCAS-S and the Montreal Cognitive Assessment (MoCA) test to evaluate cognitive/affective impairments in patients with chronic acquired cerebellar lesions, and to map the cerebellar areas whose lesions correlated with dysfunctions in these tests. CCAS-S and MoCA were administrated to 22 patients with isolated chronic cerebellar strokes and a matched comparison group. The neural bases underpinning both tests were explored with multivariate lesion-symptom mapping (LSM) methods. MoCA and CCAS-S had an adequate test performance with efficient discrimination between patients and healthy volunteers. However, only impairments determined by the CCAS-S resulted in significant regional localization within the cerebellum. Specifically, patients with chronic cerebellar lesions in right-lateralized posterolateral regions manifested cognitive impairments inherent to CCAS. These findings concurred with the anterior-sensorimotor/posterior-cognitive dichotomy in the human cerebellum and revealed clinically intra- and cross-lobular significant regions (portions of right lobule VI, VII, Crus I-II) for verbal tasks that overlap with the "language" functional boundaries in the cerebellum. Our findings prove the usefulness of MoCA and CCAS-S to reveal cognitive impairments in patients with chronic acquired cerebellar lesions. This study extends the understanding of long-term CCAS and introduces multivariate LSM methods to identify clinically intra- and cross-lobular significant regions underpinning chronic CCAS.

Cognitive Impairments in Spinocerebellar Ataxia Type 10 and Their Relation to Cortical Thickness.

BACKGROUND: Spinocerebellar ataxia type 10 is a neurodegenerative disorder caused by the expansion of an ATTCT pentanucleotide repeat. Its clinical features include ataxia and, in some cases, epileptic seizures. There is, however, a dearth of information about its cognitive deficits and the neural bases underpinning them. OBJECTIVES: The objectives of this study were to characterize the performance of spinocerebellar ataxia type 10 patients in 2 cognitive domains typically affected in spinocerebellar ataxias, memory and executive function, and to correlate the identified cognitive impairments with ataxia severity and cerebral/cerebellar cortical thickness, as quantified by MRI. METHODS: Memory and executive function tests were administered to 17 genetically confirmed Mexican spinocerebellar ataxia type 10 patients, and their results were compared with 17 healthy matched volunteers. MRI was performed in 16 patients. RESULTS: Patients showed deficits in visual and visuospatial short-term memory, reduced storage capacity for verbal memory, and impaired monitoring, planning, and cognitive flexibility, which were ataxia independent. Patients with seizures (n = 9) and without seizures (n = 8) did not differ significantly in cognitive performance. There were significant correlations between short-term visuospatial memory impairment and posterior cerebellar lobe cortical thickness (bilateral lobule VI, IX, and right X). Cognitive flexibility deficiencies correlated with cerebral cortical thickness in the left middle frontal, cingulate, opercular, and temporal gyri. Cerebellar cortical thickness in several bilateral regions was correlated with motor impairment. CONCLUSIONS: Patients with spinocerebellar ataxia type 10 show significant memory and executive dysfunction that can be correlated with deterioration in the posterior lobe of the cerebellum and prefrontal, cingulate, and middle temporal cortices. © 2021 International Parkinson and Movement Disorder Society.

Cerebellar Degeneration Signature in Huntington's Disease.

Recent findings suggest a significant effect of the cerebellar circuit deterioration on the clinical manifestation of Huntington's disease, calling for a better understanding of the cerebellar degeneration in this disorder. Recent brain imaging analyses have provided conflicting results regarding the cerebellar changes during the progression of this disease. To help in resolving this controversy, we examined the cerebellar gray matter structural integrity from a cohort of HD patients. Whole brain voxel-based morphometry (VBM) and spatially unbiased atlas template of the human cerebellum (SUIT) analyses were done from T1-weighted brain images. Our results showed a significant cerebellar degeneration without any sign of volume increase. The highest cerebellar degeneration was identified in Crus I right lobule, Crus II bilaterally, and left VIIb, and left VIIIa lobules. The cerebellar degeneration signature, which controls for severity of degeneration, showed a degeneration pattern that included regions I-IV, Crus II, VIIb, VIIIa, VIIIb and X.

Sensory information from a slipping object elicits a rapid and automatic shoulder response.

Humans have the remarkable ability to hold, grasp, and manipulate objects. Previous work has reported rapid and coordinated reactions in hand and shoulder muscles in response to external perturbations to the arm during object manipulation; however, little is known about how somatosensory feedback of an object slipping in the hand influences responses of the arm. We built a handheld device to stimulate the sensation of slipping at all five fingertips. The device was integrated into an exoskeleton robot that supported it against gravity. The setup allowed us to decouple somatosensory stimulation in the fingers from forces applied to the arm, two variables that are highly interdependent in real-world scenarios. Fourteen participants performed three experiments in which we measured their arm feedback responses during slip stimulation. Slip stimulations were applied horizontally in one of two directions, and participants were instructed to either follow the slip direction or move the arm in the opposite direction. Participants showed shoulder muscle responses within ∼67 ms of slip onset when following the direction of slip but significantly slower responses when instructed to move in the opposite direction. Shoulder responses were modulated by the speed but not the distance of the slip. Finally, when slip stimulation was combined with mechanical perturbations to the arm, we found that sensory information from the fingertips significantly modulated the shoulder feedback responses. Overall, the results demonstrate the existence of a rapid feedback system that stabilizes handheld objects.NEW & NOTEWORTHY We tested whether the sensation of an object slipping from the fingers modulates shoulder feedback responses. We found rapid shoulder feedback responses when participants were instructed to follow the slip direction with the arm. Shoulder responses following mechanical joint perturbations were also potentiated when combined with slipping. These results demonstrate the existence of fast and automatic feedback responses in the arm in reaction to sensory input to the fingertips that maintain grip on handheld objects.

A representative template of the neonatal cerebellum.

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.

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

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.

Motor and cognitive impairments in spinocerebellar ataxia type 7 and its correlations with cortical volumes.

Spinocerebellar Ataxia Type 7 (SCA7) is a neurodegenerative disorder caused by cytosine-adenine-guanine (CAG) repeat expansion. It is clinically characterized by ataxia and visual loss. To date, little is known about SCA7 cognitive impairments and its relationship with grey matter volume (GMV) changes. The aim of this study was to explore SCA7 patients' performance in specific components of auditory-verbal neuropsychological tests and to correlate their scores with genetic mutation, severity of ataxia and GMV. We assessed verbal memory and verbal fluency proficiencies in 31 genetically confirmed SCA7 patients, and compared their results with 32 healthy matched volunteers; we also correlated CAG repeats and severity of motor symptoms with performance in the auditory-verbal tests. SCA7 patients exhibited deficiencies in several components of these cognitive tasks, which were independent of motor impairments and showed no relation to CAG repeats. Based on Resonance Images performed in 27 patients we found association between ataxia severity and GMV in "sensoriomotor" cerebellum, as well as correlations of impaired verbal memory and semantic fluency scores with GMV in association cortices, including the right parahippocampal gyrus. To our knowledge, this is the first report of deficits in the organization of semantic information and in the evocation of verbal material, as well as greater susceptibility to proactive interference in SCA7 patients. These findings bring novel information about specific cognitive abilities in SCA7 patients, particularly verbal memory and fluency, and their relation with GMV variations in circumscribed brain regions, including association cortices known to have functional relationships with the cerebellum.

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.

Functional Network Development During the First Year: Relative Sequence and Socioeconomic Correlations.

The first postnatal year is characterized by the most dramatic functional network development of the human lifespan. Yet, the relative sequence of the maturation of different networks and the impact of socioeconomic status (SES) on their development during this critical period remains poorly characterized. Leveraging a large, normally developing infant sample with multiple longitudinal resting-state functional magnetic resonance imaging scans during the first year (N = 65, scanned every 3 months), we aimed to delineate the relative maturation sequence of 9 key brain functional networks and examine their SES correlations. Our results revealed a maturation sequence from primary sensorimotor/auditory to visual to attention/default-mode, and finally to executive control networks. Network-specific critical growth periods were also identified. Finally, marginally significant positive SES-brain correlations were observed at 6 months of age for both the sensorimotor and default-mode networks, indicating interesting SES effects on functional brain maturation. To the best of our knowledge, this is the first study delineating detailed longitudinal growth trajectories of all major functional networks during the first year of life and their SES correlations. Insights from this study not only improve our understanding of early brain development, but may also inform the critical periods for SES expression during infancy.

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

BACKGROUND: 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. METHODS: Fourteen genetically confirmed SCA2 patients and aged-matched healthy controls participated in the study. Voxel-based morphometry and resting-state functional magnetic resonance imaging (fMRI) were done to analyze structural and functional brain changes. Independent component analysis and dual regression were used for intrinsic network comparison. Significant functional connectivity differences were correlated with the behavioral scores. RESULTS: Seed-based analysis found reduced functional connectivity within the cerebellum and between the cerebellum and frontal/parietal cortices. Cerebellar functional connectivity increases were found with parietal, frontal, and temporal areas. Intrinsic network analysis found a functional decrease in the cerebellar network, and increase in the default-mode and fronto-parietal networks. Further analysis showed significant correlations between clinical scores and the abnormal functional connectivity strength. CONCLUSION: Our findings show significant correlations between functional connectivity changes in key areas affected in SCA2 and these patients' motor and neuropsychological impairments, adding an important insight to our understanding of the pathophysiology of SCA2.

Disruption of visual and motor connectivity in spinocerebellar ataxia type 7.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal-dominant neurodegenerative disorder characterized by progressive ataxia and retinal dystrophy. It is caused by a CAG trinucleotide expansion in the ataxin7 gene. Anatomical studies have shown severe cerebellar degeneration and region-specific neocortical atrophy in SCA7 patients. However, the impact of the neurodegeneration on the functional integration of the remaining tissue is still unknown. The aim of this study was to examine functional connectivity abnormalities in areas with significant gray matter atrophy in SCA7 patients and their relationship with number of CAG repeats. Using a combination of voxel-based morphometry and resting-state fMRI, we studied 26 genetically confirmed SCA7 patients and aged-matched healthy controls. In SCA7 patients we found reduced functional interaction between the cerebellum and the middle and superior frontal gyri, disrupted functional connectivity between the visual and motor cortices, and increased functional coordination between atrophied areas of the cerebellum and a range of visual cortical areas compared with healthy controls. The degree of mutation expansion showed a negative effect on both the functional interaction between the right anterior cerebellum and the left superior frontal gyrus and the connectivity between the right anterior cerebellum and left parahippocampal gyrus. We found abnormal functional connectivity patterns, including both hypo- and hyperconnectivity, compared with controls. These abnormal patterns show reasonable association with the severity of gene mutation. Our findings suggest that aberrant changes are prevalent in both motor and visual systems, adding significantly to our understanding of the pathophysiology of SCA7.

Cognitive Decline and White Matter Integrity Degradation in Myotonic Dystrophy Type I.

BACKGROUND AND PURPOSE: Myotonic Dystrophy Type I (DM1) is a neurodegenerative, genetic, and multisystemic disorder with a large variety of symptoms due to a CTG trinucleotide expansion located on Dystrophia Myotonica Protein Kinase (DMPK) gene. Previous reports have shown cognitive deterioration in these patients. Given that white matter (WM) degradation has also been reported in DM1 patients, here we explored if alterations in the cognitive profile of DM1 patients could be related to the deterioration of WM. METHODS: A total of 22 classic DM1 patients with age range (18-56 years) and 22 matched healthy control subjects were neuropsychological evaluated by the Cambridge Neuropsychological Test Automated (CANTAB). Patients were evaluated with the Muscular Impairment Rating Scale (MIRS). We then evaluated the cerebral WM integrity using the Fractional Anisotropy (FA) index obtained from the Diffusion Tensor Imaging (DTI) data acquired with a 3T MR scanner. RESULTS: DM1 patients showed generalized reduction of WM integrity across the brain. Similarly, patients' neuropsychological evaluation showed significant deficits in memory and problem-solving tasks. Correlation analyses showed a significant correlation between FA deterioration at frontal, temporomedial, and parietal lobes and delayed matched to sample deficits. CONCLUSIONS: Our results suggest that despite the pervasive WM integrity loss in DM1 disorder, specific memory impairments can be associated to discreet areas of WM deterioration in these patients.

Bilateral Proximal Forearm Transplantation: Case Report at 7 Years.

BACKGROUND: Although return of function has been reported in patients undergoing proximal forearm transplantations (PFTs), reports of long-term function are limited. In this study, we evaluated the clinical progress and function 7 years postoperatively in a patient who underwent bilateral PFT. CASE PRESENTATION: A 58-year-old man underwent bilateral PFT in May 2012. Transplantation involved all of the flexor and extensor muscles of the forearm. Neurorrhaphies of the median, ulnar, and radial nerves were epineural and 7 cm proximal to the elbow. Immunosuppressive maintenance medications during the first 3 years postoperatively were tacrolimus, mycophenolate, and steroids, and later, tacrolimus, sirolimus, and steroids. Forearm function was evaluated annually using the Disabilities of the Arm, Shoulder, and Hand; Carroll; Hand Transplantation Score System; Short Form-36; and Kapandji scales. We also evaluated his grip and pinch force. RESULTS: Postoperatively, the patient developed hypertriglyceridemia and systemic hypertension. He experienced 6 acute rejections, and none were resistant to steroids. Motor function findings in his right/left hand were: grip strength: 10/13 kg; key pinch: 3/3 kg; Kapandji score: 6/9 of 10; Carroll score: 66/80; Hand Transplantation Score System score: 90/94. His preoperative Disabilities of the Arm, Shoulder, and Hand score was 50 versus 18, postoperatively; his Short Form-36 score was 90. This function improved in relation with the function reported in the second year. CONCLUSIONS: Seven years following PFT, the patient gained limb strength with a functional elbow and wrist, although with diminished digital dexterity and sensation. Based on data presented by other programs and our own experience, PFT is indicated for select patients.

Functional boundaries in the human cerebellum revealed by a multi-domain task battery.

There is compelling evidence that the human cerebellum is engaged in a wide array of motor and cognitive tasks. A fundamental question centers on whether the cerebellum is organized into distinct functional subregions. To address this question, we employed a rich task battery designed to tap into a broad range of cognitive processes. During four functional MRI sessions, participants performed a battery of 26 diverse tasks comprising 47 unique conditions. Using the data from this multi-domain task battery, we derived a comprehensive functional parcellation of the cerebellar cortex and evaluated it by predicting functional boundaries in a novel set of tasks. The new parcellation successfully identified distinct functional subregions, providing significant improvements over existing parcellations derived from task-free data. Lobular boundaries, commonly used to summarize functional data, did not coincide with functional subdivisions. The new parcellation provides a functional atlas to guide future neuroimaging studies.

Neuroanatomical substrates involved in unrelated false facial recognition.

Identifying faces is a process central for social interaction and a relevant factor in eyewitness theory. False recognition is a critical mistake during an eyewitness's identification scenario because it can lead to a wrongful conviction. Previous studies have described neural areas related to false facial recognition using the standard Deese/Roediger-McDermott (DRM) paradigm, triggering related false recognition. Nonetheless, misidentification of faces without trying to elicit false memories (unrelated false recognition) in a police lineup could involve different cognitive processes, and distinct neural areas. To delve into the neural circuitry of unrelated false recognition, we evaluated the memory and response confidence of participants while watching faces photographs in an fMRI task. Functional activations of unrelated false recognition were identified by contrasting the activation on this condition vs. the activations related to recognition (hits) and correct rejections. The results identified the right precentral and cingulate gyri as areas with distinctive activations during false recognition events suggesting a conflict resulting in a dysfunction during memory retrieval. High confidence suggested that about 50% of misidentifications may be related to an unconscious process. These findings add to our understanding of the construction of facial memories and its biological basis, and the fallibility of the eyewitness testimony.

Extensive cerebellar and thalamic degeneration in spinocerebellar ataxia type 10.

INTRODUCTION: Spinocerebellar ataxia type 10 (SCA10) is a hereditary neurodegenerative disorder caused by repeat expansions in the ATXN10 gene. Patients present with cerebellar ataxia frequently accompanied by seizures. Even though loss of cerebellar Purkinje neurons has been described, its brain degeneration pattern is unknown. Our aim was to characterize the gray and white matter degeneration patterns in SCA10 patients and the association with clinical features. METHODS: We enrolled 18 patients with molecular diagnosis of SCA10 and 18 healthy individuals matched for age and sex. All participants underwent brain MRI including high-resolution anatomical and diffusion images. Whole-brain Tract-Based Spatial Statistics (TBSS) and Voxel-Based Morphometry (VBM) were performed to identify white and grey matter degeneration respectively. A second analysis in the cerebellum identified the unbiased pattern of degeneration. Motor impairment was assessed using the SARA Scale. RESULTS: TBSS analysis in the patient group revealed white matter atrophy exclusively in the cerebellum. VBM analysis showed extensive grey matter degeneration in the cerebellum, brainstem, thalamus, and putamen. Significant associations between cerebellar degeneration and SARA scores were found. Additionally, degeneration in thalamic GM and WM in the cerebellar lobule VI were significantly associated with the presence of seizures. CONCLUSION: The results show that besides cerebellum and brainstem, brain degeneration in SCA10 includes predominantly the putamen and thalamus; involvement of the latter is strongly associated with seizures. Analysis of the unbiased degeneration pattern in the cerebellum suggests lobules VIIIb, IX, and X as the primary cerebellar targets of the disease, which expands to the anterior lobe in later stages.