Topographical working memory in children and adolescents with motor disabilities

Aim: The aim of the present study was to investigate topographical working memory in individuals with motor disabilities. Methods: Topographical working memory was investigated using the Walking Corsi Test in 89 participants with motor disability, mean age 11.5 years, of which 40 with cerebral palsy, 31 with spina bifida, and 18 with orthopaedic or peripheral symptoms. The participants were grouped according to everyday mobility, i.e. walking outdoors, walking indoors, and using wheelchair. A control group constituted 120 typically developing participants, mean age 9.9 years. Results: Individuals with spina bifida, orthopaedic or peripheral symptoms as well as typically developing participants performed significantly larger walking spans than the cerebral palsy group. With respect to mobility, those walking outdoors had significantly larger span than those walking indoors and those using wheelchair for mobility. Conclusions: Participants with outdoor walking in the community, apart from type of motor disability, seem to have improved topographic memory compared to individuals who don’t walk outside and individuals who are mobile through wheelchair. The results highlight the question of development of spatial cognition to enhance participation in social environments. Future research should focus on prematurity in the cerebral palsy group, and on hydrocephalus in the spina bifida group

Contraversive neglect? A modulation of visuospatial neglect in association with contraversive pushing

Objective: Contraversive pushing (CP) is a neurologic disorder characterized by a lateral postural imbalance. Pusher patients actively push toward their contralesional side due to a misperception of the body's orientation in relation to gravity. Although not every patient with CP suffers from spatial neglect (SN), both phenomena are highly correlated in right-hemispheric patients. The present study investigates whether peripersonal visuospatial functioning differs in neglect patients with versus without CP (NP+ vs. NP+ patients). Method: Eighteen right-hemispheric stroke patients with SN were included, of which 17 in a double-blind case-control study and 1 single case with posterior pushing to supplement the discourse. A computer-based visuospatial navigation task, in which lateralized deviation can freely emerge, was used to quantify visuospatial behavior. In addition, visuospatial orienting was monitored using line bisection. Results: Significant intergroup differences were found. The NP+ patients demonstrated a smaller ipsilesional navigational deviation and more cross-over (contralesional instead of ipsilesional deviation) in long line bisection. As such, they demonstrated a contraversive (contralesionally directed) shift in comparison with the NP+ patients. Conclusions: These findings highlight the similarity between 2 systems of space representation. They are consistent with a coherence between the neural processing system that mainly provides for postural control, and the one responsible for nonpredominantly postural, visuospatial behavior

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by which vascular injury exacerbates the cognitive impact of comorbid AD pathology and cerebrovascular pathology. To study the relationship between age, pathogenic amyloid precursor protein (APP), white matter inflammation, cerebrovascular disease, and executive dysfunction, the transgenic rat model of AD (TgAPP21) was evaluated for astrocytosis, microgliosis and cognitive impairment. The TgAPP21 rat was found to demonstrate spontaneously increased white matter microglia activation, impaired reversal learning, and a regressive impairment of behavioural flexibility, a key subdomain of executive function. The TgAPP21 rat also developed a precocious increase in white matter microglia activation. However, this was not matched by a continued increase in behavioural inflexibility, suggesting a dynamic and age-dependent relationship between white matter inflammation and behavioural flexibility. Hypertension induced by chronic angiotensin-II infusion impaired both wildtype (Wt) and TgAPP21 rats’ working memory and behavioural flexibility. However, while Wt rats demonstrated a linear increase in white matter astrocytosis in response to blood pressure elevation, normotensive TgAPP21 rats already had an increased baseline level of white matter astrocytosis and further increase in response to hypertension was not observed. TgAPP21 rats also demonstrated a greater vulnerability to cerebrovascular disease, as focal striatal ischemic injury resulted in reduced set shifting efficiency. Thus, the TgAPP21 rat is an important model for studying the complex relationship between age, pathogenic APP, and cerebrovascular disease and their impact on executive dysfunction. These findings support the emerging significance of white matter inflammation and executive dysfunction in the pathophysiology of ageing, AD, and VCI

Integrative Genomics Implicates Disruption Of Prenatal Neurogenesis In Congenital Hydrocephalus

Congenital Hydrocephalus (CH) affects 1/1000 live births and costs the US healthcare system over $2 billion annually. Mainstay therapies, hinging on surgical cerebrospinal fluid diversion, exhibit high failure rates and substantial morbidity. Limited understanding of pathogenesis warrants identification of crucial genetic drivers underlying CH and their impact on brain development. This pioneering study integrates gene discovery from the largest whole-exome sequenced CH cohort with transcriptional networks (modules) and cell-type markers from the latest transcriptomic atlases of the mid-gestational human brain to uncover the genomic and molecular architecture of CH. Exome analysis of 381 radiographically-confirmed, neurosurgically-treated sporadic CH probands (including 232 case-parent trios) identified genes with rare de novo or transmitted mutations conferring disease risk. Transcriptome analyses identified mid-gestational brain modules and cell-types enriched for cohort-determined CH risk genes, known genes previously implicated in isolated and syndromic forms of CH, and risk genes of Autism Spectrum Disorder (ASD) and Developmental Disorder (DD). Genetic drivers of CH converge in a neurodevelopmental network and in early neurogenic cell-types, implicating genetic disruption of early brain development as a primary patho-mechanism for a significant subset of CH patients. Genetic and transcriptional overlap with ASD and DD may explain persistence of these conditions in CH patients despite surgical intervention, while greater potency of CH-enriched neural precursors may account for increased frequency of structural brain abnormalities in CH than in ASD or DD alone

Behavior is movement only but how to interpret it? Problems and pitfalls in translational neuroscience-a 40-year experience

Translational research in behavioral neuroscience seeks causes and remedies for human mental health problems in animals, following leads imposed by clinical research in psychiatry. This endeavor faces several problems because scientists must read and interpret animal movements to represent human perceptions, mood, and memory processes. Yet, it is still not known how mammalian brains bundle all these processes into a highly compressed motor output in the brain stem and spinal cord, but without that knowledge, translational research remains aimless. Based on some four decades of experience in the field, the article identifies sources of interpretation problems and illustrates typical translational pitfalls. (1) The sensory world of mice is different. Smell, hearing, and tactile whisker sensations dominate in rodents, while visual input is comparatively small. In humans, the relations are reversed. (2) Mouse and human brains are equated inappropriately: the association cortex makes up a large portion of the human neocortex, while it is relatively small in rodents. The predominant associative cortex in rodents is the hippocampus itself, orchestrating chiefly inputs from secondary sensorimotor areas and generating species-typical motor patterns that are not easily reconciled with putative human hippocampal functions. (3) Translational interpretation of studies of memory or emotionality often neglects the ecology of mice, an extremely small species surviving by freezing or flight reactions that do not need much cognitive processing. (4) Further misinterpretations arise from confounding neuronal properties with system properties, and from rigid mechanistic thinking unaware that many experimentally induced changes in the brain do partially reflect unpredictable compensatory plasticity. (5) Based on observing hippocampal lesion effects in mice indoors and outdoors, the article offers a simplistic general model of hippocampal functions in relation to hypothalamic input and output, placing hypothalamus and the supraspinal motor system at the top of a cerebral hierarchy. (6) Many translational problems could be avoided by inclusion of simple species-typical behaviors as end-points comparable to human cognitive or executive processing, and to rely more on artificial intelligence for recognizing patterns not classifiable by traditional psychological concepts

Selective Lesion of Cholinergic Neurons of the Septal-Hippocampal Tract: Memory and Learning

It is hypothesized that the loss of cholinergic function in the medial septum (MS), observed early in many forms of dementia, contributes to memory losses characterized in these diseases. The studies of this dissertation examined whether the selective loss of cholinergic neurons in the MS impairs acquisition of a delayed matching-to-position (DMP) spatial memory task. The results suggest a significant contribution of MS cholinergic neurons in acquisition of the DMP task. Specifically, 192 IgG-saporin SAP lesioned rats acquired the task at a slower rate and required more days to reach criterion. The results also suggest that male rats typically adopt a consistent turning strategy early in the training process, which is independent of extra-maze cues. For animals to reach criterion, an alternative learning strategy was adopted; one dependent on extra-maze cues. Cholinergic lesion of the MS resulted in a greater reliance on a consistent turning strategy, which accounted for the slower rate of acquisition of the DMP task. Steroid sulfatase inhibitors increase whole brain DHEAS levels, enhance ACh release in the hippocampus, and enhance memory. The present study also investigated the cognitive effects of sulfatase inhibition in SAP lesioned animals. Steroid sulfatase inhibition further impaired acquisition of the DMP task in SAP lesioned rats while having no effect on cholinergically intact animals. Since DHEAS displayed memory enhancing properties in rodents, we also investigated the effects of DHEAS administration on MS SAP lesioned animals. DHEAS treatment had no significant effect on the acquisition of the DMP task in the SAP treated or control animals. The final study of this dissertation examined the effect of arousal on DMP performance in SAP lesion of the medial septum. Arousal, induced by the IP injection of saline, decreased the number of days SAP lesioned rats needed to reach criterion and also improved the rate of acquisition. The results suggest that a mild aversive stimulus can attenuate cognitive deficits caused by MS cholinergic lesions