Neural model of dopaminergic control of arm movements in Parkinson’s disease bradykinesia

Patients suffering from Parkinson’s disease display a number of symptoms such a resting tremor, bradykinesia, etc. Bradykinesia is the hallmark and most disabling symptom of Parkinson’s disease (PD). Herein, a basal ganglia-cortico-spinal circuit for the control of voluntary arm movements in PD bradykinesia is extended by incorporating DAergic innervation of cells in the cortical and spinal components of the circuit. The resultant model simulates successfully several of the main reported effects of DA depletion on neuronal, electromyographic and movement parameters of PD bradykinesia

Limitations of the isolated GP-STN network

An in vitro mouse slice preparation from control and MPTP-treated mice in which functional reciprocal GP-STN connectivity is maintained, does not produce oscillatory bursting or synchronous activity neuronal activity. Pharmacological interventions that produce bursting activity do so without concomitant neuronal synchrony, or a requirement for glutamate or GABA transmission. Pre-treatment with MPTP did not alter this behaviour. Thus, we have no evidence that the functionally connected, but isolated, GP — STN network can act as a pacemaker for synchronous correlated activity in the basal ganglia and must conclude that other inputs such as those from cortex and/or striatum are required

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Socially valid outcomes of intervention for people with mental retardation and challenging behaviour : a preliminary descrptive analysis of the views of different stakeholders.

Potentially salient outcomes of intervention for challenging behavior shown by people with mental retardation (MR) were identified by focus groups and through a literature review. Items generated by this process were subsequently rated by 150 respondents from seven stakeholder groups: 28 people with MR, 9 parents of people with MR, 22 clinical psychologists, 7 psychiatrists, 31 nurses, 33 managers, and 20 direct support workers. Results indicated that reduction in the severity of challenging behavior was considered the most important outcome of intervention for a child/young adult living with his or her family by four of the seven stakeholder groups; reduction in the severity of challenging behavior was considered the most important outcome of intervention for an adult living in a community-based group home by three of the seven stakeholder groups; alternative outcomes considered to be the most important by stakeholder groups included increased friendships and relationships, changes in the perceptions of individuals by others, learning of alternative ways of getting needs met, increased control, and empowerment; there were moderate levels of agreement on the relative importance of outcomes between individual members of stakeholder groups who did not have MR; there were high levels of agreement on the relative importance of outcomes between stakeholder groups of people who did not have MR; and levels of agreement on the relative importance of outcomes between people with MR and members of all other stakeholder groups did not reach the level of statistical significance