Developmental Coordination Disorder: Disruption of the Cerebello-Cerebral Network evidenced by SPECT

Little is known about the neurobiological substrate of developmental coordination disorder (DCD), a neuro-developmental syndrome with significant, negative impact on the motor, cognitive and affective level throughout lifespan. This paper reports the clinical, neurocognitive and neuroradiological findings of a 19-year-old patient with typical DCD. As demonstrated by mild ataxia and a close semiological correspondence with the recently acknowledged ‘cerebellar cognitive affective syndrome’, clinical and neurocognitive investigations unambiguously indicated functional disruption of the cerebellum. Structural MRI of the brain confirmed cerebellar involvement revealing a slight anterior/superior asymmetry of vermal fissures consistent with rostral vermisdysplasia. Although this abnormality of vermal fissuration is generally considered an incidental neuroradiological finding without any clinical relevance, a potentially subtle impact on the developmental level has never been formally excluded. In addition to a generally decreased perfusion of the cerebellum, a quantified Tc-99m-ECD SPECT disclosed functional suppression of the anatomoclinically suspected supratentorial regions involved in the execution of planned actions, visuo-spatial processing and affective regulation. Based on these findings, it is hypothesised that the cerebellum is crucially implicated in the pathophysiologcial mechanisms of DCD, reflecting disruption of the cerebello-cerebral network involved in the execution of planned actions, visuo-spatial cognition and affective regulation

Development of a psychiatric disorder linked to cerebellar lesions

Cerebellar dysfunction plays a critical role in neurodevelopmental disorders with long-term behavioral and neuropsychiatric symptoms. A 43-year-old woman with a cerebellum arteriovenous malformation and history of behavioral dysregulation since childhood is described. After the rupture of the cerebellar malformation in adulthood, her behavior morphed into specific psychiatric symptoms and cognitive deficits occurred. The neuropsychological assessment evidenced impaired performance in attention, visuospatial, memory, and language domains. Moreover, psychiatric assessment indicated a borderline personality disorder. Brain MRI examination detected macroscopic abnormalities in the cerebellar posterior lobules VI, VIIa (Crus I), and IX, and in the posterior area of the vermis, regions usually involved in cognitive and emotional processing. The described patient suffered from cognitive and behavioral symptoms that are part of the cerebellar cognitive affective syndrome. This case supports the hypothesis of a cerebellar role in personality disorders emphasizing the importance of also examining the cerebellum in the presence of behavioral disturbances in children and adults

The bounds of education in the human brain connectome

Inter-individual heterogeneity is evident in aging; education level is known to contribute for this heterogeneity. Using a cross-sectional study design and network inference applied to resting-state fMRI data, we show that aging was associated with decreased functional connectivity in a large cortical network. On the other hand, education level, as measured by years of formal education, produced an opposite effect on the long-term. These results demonstrate the increased brain efficiency in individuals with higher education level that may mitigate the impact of age on brain functional connectivity.This work was funded by the European Commission (FP7): “SwitchBox” (Contract HEALTH-F2-2010-259772) and co-financed by the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). José M. Soares, Paulo Marques, and Nadine C. Santos are supported by fellowships of the project “SwitchBox”; Ricardo Magalhães is supported by a fellowship from the project FCT ANR/NEU-OSD/0258/2012 funded by FCT/MEC (www.fct.pt) and by ON.2 – ONOVONORTE – North Portugal Regional Operational Programme 2007/2013, of the National Strategic Reference Framework (NSRF) 2007/2013, through FEDER

Quantification of volumetric morphometry and optical property in the cortex of human cerebellum at micrometer resolution

The surface of the human cerebellar cortex is much more tightly folded than the cerebral cortex. Volumetric analysis of cerebellar morphometry in magnetic resonance imaging studies suffers from insufficient resolution, and therefore has had limited impact on disease assessment. Automatic serial polarization-sensitive optical coherence tomography (as-PSOCT) is an emerging technique that offers the advantages of microscopic resolution and volumetric reconstruction of large-scale samples. In this study, we reconstructed multiple cubic centimeters of ex vivo human cerebellum tissue using as-PSOCT. The morphometric and optical properties of the cerebellar cortex across five subjects were quantified. While the molecular and granular layers exhibited similar mean thickness in the five subjects, the thickness varied greatly in the granular layer within subjects. Layer-specific optical property remained homogenous within individual subjects but showed higher cross-subject variability than layer thickness. High-resolution volumetric morphometry and optical property maps of human cerebellar cortex revealed by as-PSOCT have great potential to advance our understanding of cerebellar function and diseases

Effects of attention and perceptual uncertainty on cerebellar activity during visual motion perception

Recent clinical and neuroimaging studies have revealed that the human cerebellum plays a role in visual motion perception, but the nature of its contribution to this function is not understood. Some reports suggest that the cerebellum might facilitate motion perception by aiding attentive tracking of visual objects. Others have identified a particular role for the cerebellum in discriminating motion signals in perceptually uncertain conditions. Here, we used functional magnetic resonance imaging to determine the degree to which cerebellar involvement in visual motion perception can be explained by a role in sustained attentive tracking of moving stimuli in contrast to a role in visual motion discrimination. While holding the visual displays constant, we manipulated attention by having participants attend covertly to a field of random-dot motion or a colored spot at fixation. Perceptual uncertainty was manipulated by varying the percentage of signal dots contained within the random-dot arrays. We found that attention to motion under high perceptual uncertainty was associated with strong activity in left cerebellar lobules VI and VII. By contrast, attending to motion under low perceptual uncertainty did not cause differential activation in the cerebellum. We found no evidence to support the suggestion that the cerebellum is involved in simple attentive tracking of salient moving objects. Instead, our results indicate that specific subregions of the cerebellum are involved in facilitating the detection and discrimination of task-relevant moving objects under conditions of high perceptual uncertainty. We conclude that the cerebellum aids motion perception under conditions of high perceptual demand

Altered Cerebellar-Cerebral Functional Connectivity in Geriatric Depression

Although volumetric and activation changes in the cerebellum have frequently been reported in studies on major depression, its role in the neural mechanism of depression remains unclear. To understand how the cerebellum may relate to affective and cognitive dysfunction in depression, we investigated the resting-state functional connectivity between cerebellar regions and the cerebral cortex in samples of patients with geriatric depression (n = 11) and healthy controls (n = 18). Seed-based connectivity analyses were conducted using seeds from cerebellum regions previously identified as being involved in the executive, default-mode, affective-limbic, and motor networks. The results revealed that, compared with controls, individuals with depression show reduced functional connectivity between several cerebellum seed regions, specifically those in the executive and affective-limbic networks with the ventromedial prefrontal cortex (vmPFC) and increased functional connectivity between the motor-related cerebellum seed regions with the putamen and motor cortex. We further investigated whether the altered functional connectivity in depressed patients was associated with cognitive function and severity of depression. A positive correlation was found between the Crus II–vmPFC connectivity and performance on the Hopkins Verbal Learning Test-Revised delayed memory recall. Additionally, the vermis–posterior cinglate cortex (PCC) connectivity was positively correlated with depression severity. Our results suggest that cerebellum–vmPFC coupling may be related to cognitive function whereas cerebellum–PCC coupling may be related to emotion processing in geriatric depression

Visuomotor adaptive improvement and aftereffects are impaired differentially following cerebellar lesions in SCA and PICA territory

The aim of the present study was to elucidate the contribution of the superior and posterior inferior cerebellum to adaptive improvement and aftereffects in a visuomotor adaptation task. Nine patients with ischemic lesions within the territory of the posterior inferior cerebellar artery (PICA), six patients with ischemic lesions within the territory of the superior cerebellar artery (SCA) and 17 age-matched controls participated. All subjects performed center-out reaching movements under 60° rotation of visual feedback. For the assessment of aftereffects, we tested retention of adaptation and de-adaptation under 0° visual rotation. From this data we also quantified five measures of motor performance. Cerebellar lesion-symptom mapping was performed using magnetic resonance imaging subtraction analysis. Adaptive improvement during 60° rotation was significantly degraded in PICA patients and even more in SCA patients. Subtraction analysis revealed that posterior (Crus I) as well as anterior cerebellar regions (lobule V) showed a common overlap related to deficits in adaptive improvement. However, for aftereffect measures as well as for motor performance variables only SCA patients, but not PICA patients showed significant differences to control subjects. Subtraction analysis showed that affection of lobules V and VI were more common in patients with impaired retention and de-adaptation, respectively. Data shows that areas both within the superior and posterior inferior cerebellum are involved in adaptive improvement. However, only the superior cerebellum including lobules V and VI appears to be important for aftereffects and therefore true adaptive ability

Unusual presentation of basilar artery stroke secondary to patent foramen ovale: a case report

<p>Abstract</p> <p>Introduction</p> <p>We report a case of a patient presenting with neuropsychiatric manifestations secondary to paradoxical embolism</p> <p>Case presentation</p> <p>Unexplained rapid onset of confusion with amnesia and minimal neurological deficits can be a manifestation of various systemic causes of which stroke, either ischemic or hemorrhagic, is one. Thorough and systematic evaluation of these patients can be highly rewarding in terms of optimizing patient outcome. We report the case of a 45-year-old woman whose initial presentation was with acute onset of confusion, memory loss with personality change and headaches. A differential diagnosis of systemic illness and cerebral pathology was entertained. She was empirically treated for neurological infection. Brain imaging revealed bilateral thalamic and cerebellar infarction. Further evaluation with an aim to define the etiology, revealed the diagnosis of Patent Foramen Ovale with paradoxical embolism. The differential diagnosis of unexplained rapid onset of confusion, amnesia with minimal motor neurological deficits and relevant appropriate investigations are discussed in this case report.</p> <p>Conclusion</p> <p>This case highlights the importance of recognising the atypical manifestations of posterior fossa stroke. In young patients presenting with non-focal neuropsychiatric manifestations, paradoxical embolism, secondary to patent foramen ovale is a possible cause.</p

Cerebellar Integrity in the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia Continuum

Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology