The role of corticospinal tract damage in chronic motor recovery and neurorehabilitation: a pilot study

Background. With diffusion-tensor imaging (DTi) it is possible to estimate the structural characteristics of fiber bundles in vivo. This study used DTi to infer damage to the corticospinal tract (CST) and relates this parameter to (a) the level of residual motor ability at least 1 year poststroke and (b) the outcome of intensive motor rehabilitation with constraint-induced movement therapy (CIMT). Objective. To explore the role of CST damage in recovery and CIMT efficacy. Methods. Ten patients with low-functioning hemiparesis were scanned and tested at baseline, before and after CIMT. Lesion overlap with the CST was indexed as reduced anisotropy compared with a CST variability map derived from 26 controls. Residual motor ability was measured through the Wolf Motor Function Test (WMFT) and the Motor Activity Log (MAL) acquired at baseline. CIMT benefit was assessed through the pre—post treatment comparison of WMFT and MAL performance. Results. Lesion overlap with the CST correlated with residual motor ability at baseline, with greater deficits observed in patients with more extended CST damage. Infarct volume showed no systematic association with residual motor ability. CIMT led to significant improvements in motor function but outcome was not associated with the extent of CST damage or infarct volume. Conclusion. The study gives in vivo support for the proposition that structural CST damage, not infarct volume, is a major predictor for residual functional ability in the chronic state. The results provide initial evidence for positive effects of CIMT in patients with varying, including more severe, CST damage.

Modulation of neuroinflammation by dietary flavonoids

There is increasing evidence to suggest neuroinflammatory processes contribute to the cascade of events that lead to the progressive neuronal damage observed in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. The molecular mechanisms underlying such neurodegenerative processes are rather complex and involve modulation of the mitogen-activated protein kinase (MAPK) and NF-κB pathways leading to the generation of nitric oxide (NO). Such a small molecule may diffuse to the neighbouring neurons and trigger neuronal death through the inhibition of mitochondrial respiration and increases in the reactive oxygen and nitrogen species. Recently, attention has focused on the neuroprotective effects of flavonoids which have been effective in protecting against both age-related cognitive and motor decline in vivo. Although, the precise mechanisms by which flavonoids may exert their neuroprotective effects remain unclear, accumulating evidence suggest that they may exert their neuroprotective effects through the modulation of the MAP Kinase and PI3 Kinase signaling pathways. The aim of the present chapter is to highlight the potential neuroprotective role of dietary flavonoids in terms of their ability to modulate neuroinflammation in the central nervous system. We will provide an outline of the role glial cells play in neuroinflammation and describe the involvement of inflammatory mediators, produced by glia, in the cascade of events leading to neuronal degeneration. We will then present the evidence that flavonoids may modulate neuroinflammation by inhibiting the production of these inflammatory agents and summarise their potential mechanisms of action.

Oxygen/Glucose deprivation induces a reduction in synaptic AMPA receptors on hippocampal CA3 neurons mediated by mGluR1 and adenosine A3 receptors

Hippocampal CA1 pyramidal neurons are highly sensitive to ischemic damage, whereas neighboring CA3 pyramidal neurons are less susceptible. It is proposed that switching of AMPA receptor (AMPAR) subunits on CA1 neurons during an in vitro model of ischemia, oxygen/glucose deprivation (OGD), leads to an enhanced permeability of AMPARs to Ca2+, resulting in delayed cell death. However, it is unclear whether the same mechanisms exist in CA3 neurons and whether this underlies the differential sensitivity to ischemia. Here, we investigated the consequences of OGD for AMPAR function in CA3 neurons using electrophysiological recordings in rat hippocampal slices. Following a 15 min OGD protocol, a substantial depression of AMPAR-mediated synaptic transmission was observed at CA3 associational/commissural and mossy fiber synapses but not CA1 Schaffer collateral synapses. The depression of synaptic transmission following OGD was prevented by metabotropic glutamate receptor 1 (mGluR1) or A3 receptor antagonists, indicating a role for both glutamate and adenosine release. Inhibition of PLC, PKC, or chelation of intracellular Ca2+ also prevented the depression of synaptic transmission. Inclusion of peptides to interrupt the interaction between GluA2 and PICK1 or dynamin and amphiphysin prevented the depression of transmission, suggesting a dynamin and PICK1-dependent internalization of AMPARs after OGD. We also show that a reduction in surface and total AMPAR protein levels after OGD was prevented by mGluR1 or A3 receptor antagonists, indicating that AMPARs are degraded following internalization. Thus, we describe a novel mechanism for the removal of AMPARs in CA3 pyramidal neurons following OGD that has the potential to reduce excitotoxicity and promote neuroprotection

Assessment of motor symptoms and functional impact in prodromal and early Huntington disease.

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess functional impact of motor manifestations in prHD and early HD individuals.

An item response analysis of the motor and behavioral subscales of the unified Huntington's disease rating scale in huntington disease gene expansion carriers

Although the Unified Huntington's Disease Rating Scale (UHDRS) is widely used in the assessment of Huntington disease (HD), the ability of individual items to discriminate individual differences in motor or behavioral manifestations has not been extensively studied in HD gene expansion carriers without a motor-defined clinical diagnosis (ie, prodromal-HD or prHD). To elucidate the relationship between scores on individual motor and behavioral UHDRS items and total score for each subscale, a nonparametric item response analysis was performed on retrospective data from 2 multicenter longitudinal studies. Motor and behavioral assessments were supplied for 737 prHD individuals with data from 2114 visits (PREDICT-HD) and 686 HD individuals with data from 1482 visits (REGISTRY). Option characteristic curves were generated for UHDRS subscale items in relation to their subscale score. In prHD, overall severity of motor signs was low, and participants had scores of 2 or above on very few items. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a lesser extent, saccade velocity, dysarthria, tongue protrusion, pronation/supination, Luria, bradykinesia, choreas, gait, and balance on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. In prHD, depressed mood, anxiety, and irritable behavior demonstrated good discriminative properties. In HD, depressed mood demonstrated a good relationship with the overall behavioral score. These data suggest that at least some UHDRS items appear to have utility across a broad range of severity, although many items demonstrate problematic features.

Reduced cortico-motor facilitation in a normal sample with high traits of autism

Recent research in social neuroscience proposes a link between mirror neuron system (MNS) and social cognition. The MNS has been proposed to be the neural mechanism underlying action recognition and intention understanding and more broadly social cognition. Pre-motor MNS has been suggested to modulate the motor cortex during action observation. This modulation results in an enhanced cortico-motor excitability reflected in increased motor evoked potentials (MEPs) at the muscle of interest during action observation. Anomalous MNS activity has been reported in the autistic population whose social skills are notably impaired. It is still an open question whether traits of autism in the normal population are linked to the MNS functioning. We measured TMS-induced MEPs in normal individuals with high and low traits of autism as measured by the autistic quotient (AQ), while observing videos of hand or mouth actions, static images of a hand or mouth or a blank screen. No differences were observed between the two while they observed a blank screen. However participants with low traits of autism showed significantly greater MEP amplitudes during observation of hand/mouth actions relative to static hand/mouth stimuli. In contrast, participants with high traits of autism did not show such a MEP amplitude difference between observation of actions and static stimuli. These results are discussed with reference to MNS functioning.

Intake fraction of nonreactive motor vehicle exhaust in HongKong

The intake fraction (iF) of nonreactive constituents of exhaust from mobile vehicles in the urban area of HongKong is investigated using available monitoring data for carbon monoxide (CO) as a tracer of opportunity. Correcting for regional transport of carbon monoxide into HongKong, the annual-average iF for nonreactive motor vehicle emissions within the city is estimated to be around 270 per million. This estimated iF is much higher than values previously reported for vehicle emissions in US urban areas, Helsinki and Beijing, and somewhat lower than those reported for a densely populated street canyon in downtown Manhattan, New York City, or for emissions into indoor environments. The reported differences in intakefractions in various cities mainly result from the differences in local population densities. Our analysis highlights the importance of accounting for the influence of upwind transport of pollutants when using ambient data to estimate iF for an urban area. For vehicleexhaust in HongKong, it is found that the in/near vehicle microenvironment contributes similarly to the indoor home environment when accounting for the overall iF for children and adults. Keywords Intakefraction; Vehicle emission; Regional pollutant transport; Carbon monoxide; Exposure

Neural activation and functional connectivity during motor imagery of bimanual everyday actions

Bimanual actions impose intermanual coordination demands not present during unimanual actions. We investigated the functional neuroanatomical correlates of these coordination demands in motor imagery (MI) of everyday actions using functional magnetic resonance imaging (fMRI). For this, 17 participants imagined unimanual actions with the left and right hand as well as bimanual actions while undergoing fMRI. A univariate fMRI analysis showed no reliable cortical activations specific to bimanual MI, indicating that intermanual coordination demands in MI are not associated with increased neural processing. A functional connectivity analysis based on psychophysiological interactions (PPI), however, revealed marked increases in connectivity between parietal and premotor areas within and between hemispheres. We conclude that in MI of everyday actions intermanual coordination demands are primarily met by changes in connectivity between areas and only moderately, if at all, by changes in the amount of neural activity. These results are the first characterization of the neuroanatomical correlates of bimanual coordination demands in MI. Our findings support the assumed equivalence of overt and imagined actions and highlight the differences between uni- and bimanual actions. The findings extent our understanding of the motor system and may aid the development of clinical neurorehabilitation approaches based on mental practice.