This meta-analytic connectivity modeling (MACM) study explores the functional connectivity of the cerebellum with the cerebrum in social cognitive processes. In a recent meta-analysis, Van Overwalle, Baetens, Mariën, and Vandekerckhove (2014) documented that the cerebellum is implicated in social processes of "body" reading (mirroring; e.g., understanding other persons' intentions from observing their movements) and "mind" reading (mentalizing, e.g., inferring other persons' beliefs, intentions or personality traits, reconstructing persons' past, future, or hypothetical events). In a recent functional connectivity study, Buckner et al. (2011) offered a novel parcellation of cerebellar topography that substantially overlaps with the cerebellar meta-analytic findings of Van Overwalle et al. (2014). This overlap suggests that the involvement of the cerebellum in social reasoning depends on its functional connectivity with the cerebrum. To test this hypothesis, we explored the meta-analytic co-activations as indices of functional connectivity between the cerebellum and the cerebrum during social cognition. The MACM results confirm substantial and distinct connectivity with respect to the functions of (a) action understanding ("body" reading) and (b) mentalizing ("mind" reading). The consistent and strong connectivity findings of this analysis suggest that cerebellar activity during social judgments reflects distinct mirroring and mentalizing functionality, and that these cerebellar functions are connected with corresponding functional networks in the cerebrum.
Although insights in cerebellar neurocognition and affect are continuously growing, little is known about the role of the brainstem in cognitive and behavioural processing. In this paper, it is hypothesized that the brainstem is an inherent functional part of the cerebellocerebral network subserving cognition and affect, and that isolated brainstem damage may cause a constellation of symptoms closely resembling the cerebellar cognitive affective syndrome (CCAS) following cerebellar pathology. In order to investigate these premises, the available literature on cognitive and affective disturbances following brainstem lesions was critically reviewed starting from the pioneer descriptions in the 1950s till June 2012. Three personal cases were added to a study group of 75 cases with isolated vascular brainstem damage. In a cohort of 30 patients that allowed construction of anatomoclinical correlations in a reliable way, a range of cognitive and behavioural symptoms, typically associated with impairment of cortical or limbic areas, were identified. Executive dysfunction, attentional deficits and a decline in general intellectual capacity represent the most common cognitive findings, but memory, visuospatial skills, language and praxis may be impaired as well. Almost half of the cases presented with behavioural or affective changes. Analysis of SPECT findings indicates that functional suppression of frontal, parietal and to a lesser extent also the temporal areas are common phenomena after isolated brainstem stroke. As reflected by diaschisis affecting the cerebellocerebral network, a loss of excitatory input from the brainstem to the cerebellum and cerebrum may induce disruption of several cortical regions as well as emotional control centres resulting in and a constellation of symptoms closely resembling the CCAS. The pathophysiological mechanism underlying brainstem-induced cognitive and affective disturbances is discussed.
Objective:To investigate the molecular basis of a Belgian family with autosomal recessive adult-onset neuronal ceroid lipofuscinosis (ANCL or Kufs disease [KD]) with pronounced frontal lobe involvement and to expand the findings to a cohort of unrelated Belgian patients with frontotemporal dementia (FTD).Methods:Genetic screening in the ANCL family and FTD cohort (n = 461) was performed using exome sequencing and targeted massive parallel resequencing.Results:We identified a homozygous mutation (p.Ile404Thr) in the Cathepsin F (CTSF) gene cosegregating in the ANCL family. No other mutations were found that could explain the disease in this family. All 4 affected sibs developed motor symptoms and early-onset dementia with prominent frontal features. Two of them evolved to akinetic mutism. Disease presentation showed marked phenotypic variation with the onset ranging from 26 to 50 years. Myoclonic epilepsy in one of the sibs was suggestive for KD type A, while epilepsy was not present in the other sibs who presented with clinical features of KD type B. In a Belgian cohort of unrelated patients with FTD, the same heterozygous p.Arg245His mutation was identified in 2 patients who shared a common haplotype.Conclusions:A homozygous CTSF mutation was identified in a recessive ANCL pedigree. In contrast to the previous associations of CTSF with KD type B, our findings suggest that CTSF genetic testing should also be considered in patients with KD type A as well as in early-onset dementia with prominent frontal lobe and motor symptoms.
Previous research has shown that cyclin-dependent kinases (Cdks) that play physiological roles in cell cycle regulation become activated in post-mitotic neurons after ischemic stroke, resulting in apoptotic neuronal death. In this article, we report our results using the widely used oxygen–glucose deprivation (OGD) in vitro model of ischemic stroke on primary mouse cortical neurons to investigate whether Cdk7, as part of the Cdk-activating kinase (CAK) complex that activates cell cycle Cdks, might be a regulator of ischemic neuronal death and may potentially constitute a therapeutic target for neuroprotection. We found no evidence of neuroprotection with either pharmacological or genetic invalidation of Cdk7. Despite the well-established idea that apoptosis contributes to cell death in the ischemic penumbra, we also found no evidence of apoptosis in the OGD model. This could explain the absence of neuroprotection following Cdk7 invalidation in this model. Neurons exposed to OGD seem predisposed to die in an NMDA receptor-dependent manner that could not be prevented further downstream. Given the direct exposure of neurons to anoxia or severe hypoxia, it is questionable how relevant OGD is for modeling the ischemic penumbra. Due to remaining uncertainties about cell death after OGD, caution is warranted when using this in vitro model to identify new stroke therapies.
Background and objectives: We provide a case analysis for a 28-year-old, native Dutch-speaking lady who developed Foreign Accent Syndrome (FAS), a few weeks after falling down the staircase. In addition to FAS, which gave the impression she spoke with a German accent, German(-like) words and structures occurred. Speech symptoms were aggravated by increased stress, fatigue or emotional pressure, and this triggered jargon speech. It was hypothesized her FAS and jargon developed on a functional basis. Methods: In-depth analyses of the patient's medical background, neuropsychological and neurolinguistic tests and psychodiagnostic exams were done. The patient participated in an fMRI experiment. In a syllable repetition paradigm, motor speech activations were compared to those of healthy individuals, to see whether they were altered, which would be expected in case of a neurological etiology.
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