Neuroscience
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Epidemiological data show that males are more often and/or more severely affected by symptoms of prefrontal cortical dysfunction in schizophrenia, Parkinson's disease and other disorders in which dopamine circuits associated with the prefrontal cortex are dysregulated. This review focuses on research showing that these dopamine circuits are powerfully regulated by androgens. It begins with a brief overview of the sex differences that distinguish prefrontal function in health and prefrontal dysfunction or decline in aging and/or neuropsychiatric disease. ⋯ Candidate mechanisms by which androgens dynamically control mesoprefrontal dopamine systems and impact prefrontal states of hypo- and hyper-dopaminergia in aging and disease are then considered. This is followed by discussion of a working model that identifies a key locus for androgen modulation of mesoprefrontal dopamine systems as residing within the prefrontal cortex itself. The last sections of this review critically consider the ways in which the organization and regulation of mesoprefrontal dopamine circuits differ in the adult male and female brain, and highlights gaps where more research is needed.
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Identified 40 years ago, the metabotropic glutamate (mGlu) receptors play key roles in modulating many synapses in the brain, and are still considered as important drug targets to treat various brain diseases. Eight genes encoding mGlu subunits have been identified. They code for complex receptors composed of a large extracellular domain where glutamate binds, connected to a G protein activating membrane domain. ⋯ The present review summarizes the approaches used to study their activation process and their pharmacological properties and to demonstrate their existence in vivo. We will highlight how the existence of mGlu heterodimers revolutionizes the mGlu receptor field, opening new possibilities for therapeutic intervention for brain diseases. As illustrated by the number of possible mGlu heterodimers, this study will highlight the need for further research to fully understand their role in physiological and pathological conditions, and to develop more specific therapeutic tools.
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Randomized Controlled Trial
Virtual Reality Action Observation and Motor Imagery to Enhance Neuroplastic Capacity in the Human Motor Cortex: A Pilot Double-blind, Randomized Cross-over Trial.
Neuroplasticity is important for learning, development and recovery from injury. Therapies that can upregulate neuroplasticity are therefore of interest across a range of fields. We developed a novel virtual reality action observation and motor imagery (VR-AOMI) intervention and evaluated whether it could enhance the efficacy of mechanisms of neuroplasticity in the human motor cortex of healthy adults. ⋯ Specifically, participants that did not exhibit the expected increase in MEP amplitude following iTBS in the control condition appear to have greater excitability following iTBS in the VR-AOMI condition (r = -0.72, p < 0.001). Engaging in VR-AOMI might enhance capacity for neuroplasticity in some people who typically do not respond to iTBS. VR-AOMI may prime the brain for enhanced neuroplasticity in this sub-group.
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Accurate movements of the upper limb require the integration of various forms of sensory feedback (e.g., visual and postural information). The influence of these different sensory modalities on reaching movements has been largely studied by assessing endpoint errors after selectively perturbing sensory estimates of hand location. These studies have demonstrated that both vision and proprioception make key contributions in determining the reach endpoint. ⋯ We trained subjects using a velocity-dependent force-field to probe the extent arm posture-dependent influences persisted after exposure to a motion-state dependent perturbation. Changes in the temporal force profiles due to variations in arm posture were not reduced by adaptation to novel movement dynamics, but persisted throughout learning. These results suggest that vision and posture differentially influence the internal estimation of limb state throughout movement and play distinct roles in forming the response to external perturbations during movement.
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Postoperative stroke is a challenging and potentially devastating complication after elective carotid endarterectomy (CEA). We previously demonstrated that transmembrane protein 166 (TMEM166) levels were directly related to neuronal damage after cerebral ischemia-reperfusion injury in rats. In this subsequent clinical study, we aimed to evaluate the prognostic value of TMEM166 in patients suffering from post-CEA strokes. ⋯ Furthermore, circulating TMEM166 concentrations were statistically higher in post-CEA stroke patients than in patients allocated to the control group. Mean plasma concentrations of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also elevated in patients with postoperative strokes. Therefore, based on these findings, we hypothesize that elevated TMEM166 levels, accompanied by a strong inflammatory response, serve as a useful biomarker for risk assessment of postoperative stroke following CEA.