Neurostimulation for Stroke Rehabilitation.

Neurological injuries such as strokes can lead to important loss in motor function. Thanks to neuronal plasticity, some of the lost functionality may be recovered over time. However, the recovery process is often slow and incomplete, despite the most effective conventional rehabilitation therapies. As we improve our understanding of the rules governing activity-dependent plasticity, neuromodulation interventions are being developed to harness neural plasticity to achieve faster and more complete recovery. Here, we review the principles underlying stimulation-driven plasticity as well as the most commonly used stimulation techniques and approaches. We argue that increased spatiotemporal precision is an important factor to improve the efficacy of neurostimulation and drive a more useful neuronal reorganization. Consequently, closed-loop systems and optogenetic stimulation hold theoretical promise as interventions to promote brain repair after stroke.

Paired Associative Stimulation Fails to Induce Plasticity in Freely Behaving Intact Rats.

Paired associative stimulation (PAS) has been explored in humans as a noninvasive tool to drive plasticity and promote recovery after neurologic insult. A more thorough understanding of PAS-induced plasticity is needed to fully harness it as a clinical tool. Here, we tested the efficacy of PAS with multiple interstimulus intervals in an awake rat model to study the principles of associative plasticity. Using chronically implanted electrodes in motor cortex and forelimb, we explored PAS parameters to effectively drive plasticity. We assessed changes in corticomotor excitability using a closed-loop, EMG-controlled cortical stimulation paradigm. We tested 11 PAS intervals, chosen to force the coincidence of neuronal activity in the motor cortex and spinal cord of rats with timings relevant to the principles of Hebbian spike timing-dependent plasticity. However, despite a relatively large number of stimulus pairings (300), none of the tested intervals reliably changed corticospinal excitability relative to control conditions. Our results question PAS effectiveness under these conditions.

Impaired Motor Learning Following a Pain Episode in Intact Rats.

Motor learning and pain are important factors influencing rehabilitation. Despite being mostly studied independently from each other, important interactions exist between them in the context of spinal cord injury, whether to the spinal cord or the body. Ongoing or recent past episodes of nociceptive activity can prevent motor learning in spinalized rats. In intact animals, it has been proposed that supraspinal activity could counter the repressive effect of nociception on motor system plasticity, but this has not yet been verified in behavioral conditions. The aim of this study was to test whether a recent episode of nociception affects subsequent motor learning in intact animals. We trained rodents to walk on a custom-made horizontal ladder. After initial training, the rats underwent a week-long rest, during which they were randomly assigned to a control group, or one out of two pain conditions. Nociceptive stimuli of different durations were induced through capsaicin or Complete Freund's Adjuvant injections and timed so that the mechanical hypersensitivity had entirely subsided by the end of the resting period. Training then resumed on a modified version of the horizontal ladder. We evaluated the animals' ability to adapt to the modified task by measuring their transit time and paw misplacements over 4 days. Our results show that prior pain episodes do affect motor learning in neurologically intact rats. Motor learning deficits also seem to be influenced by the duration of the pain episode. Rats receiving a subcutaneous injection of capsaicin displayed immediate signs of mechanical hypersensitivity, which subsided rapidly. Nonetheless, they still showed learning deficits 24 h after injection. Rats who received a Complete Freund's Adjuvant injection displayed mechanical hypersensitivity for up to 7 days during the resting period. When trained on the modified ladder task upon returning to normal sensitivity levels, these rats exhibited more prolonged motor learning deficits, extending over 3 days. Our results suggest that prior pain episodes can negatively influence motor learning, and that the duration of the impairment relates to the duration of the pain episode. Our results highlight the importance of addressing pain together with motor training after injury.

Characteristics of the King-Devick test in the assessment of concussed patients in the subacute and later stages after injury.

Although the King-Devick (K-D) test has been used frequently in assessing sports related concussion early after injury, its characteristics over time after injury and in patients with prolonged persistent symptoms are unknown. The purpose of this paper was to: evaluate the ability of the K-D Test to distinguish patients seen early after concussion from those with symptoms persisting more than 3 months compared to controls, assess changes in the K-D test times over time after concussion, and determine the relationship of K-D times to the Stroop Color and Word Test scores. We performed cross-sectional comparisons of patients with recent concussive brain injury (acute group) and those with symptoms persisting more than 3 months to healthy controls on the K-D test, the Sports Concussion Assessment Tool 3 (SCAT3), and the Stroop Color and Word Test. Longitudinal comparisons of the acute group over time within the first month after injury were also made. Post-concussive syndrome (PCS) patients had significantly higher K-D times compared to controls (p = 0.01), while the acute group did not differ from controls(p = 0.33). K-D times at the second visit for the acute group were similar to those of controls (54.7 vs. 49.6, p = 0.31). While SCAT3 scores improved over time in the acute group, the K-D scores did not change between the first and second visit (55.2 vs. 54.7, p = 0.94). K-D scores correlated significantly with the Stroop scores for all three participant groups. The K-D test is likely useful very early after concussion in conjunction with baseline scores, and while scores in PCS patients remain elevated, they can be confounded by factors such as pre-morbid depression and medication use. High correlations with Stroop scores also suggest that performance on the K-D test can by proxy provide additional insight about cognitive function and predict performance on more cognitively demanding tasks.

Gray matter atrophy in patients with mild cognitive impairment/Alzheimer's disease over the course of developing delusions.

OBJECTIVE: We conducted a neuroimaging analysis to understand the neuroanatomical correlates of gray matter loss in a group of mild cognitive impairment and early Alzheimer's disease patients who developed delusions. METHODS: With data collected as part of the Alzheimer's Disease Neuroimaging Initiative, we conducted voxel-based morphometry to determine areas of gray matter change in the same Alzheimer's Disease Neuroimaging Initiative participants, before and after they developed delusions. RESULTS: We identified 14 voxel clusters with significant gray matter decrease in patient scans post-delusional onset, correcting for multiple comparisons (false discovery rate, p < 0.05). Major areas of difference included the right and left insulae, left precuneus, the right and left cerebellar culmen, the left superior temporal gyrus, the right posterior cingulate, the right thalamus, and the left parahippocampal gyrus. CONCLUSIONS: Although contrary to our initial predictions of enhanced right frontal atrophy, our preliminary work identifies several neuroanatomical areas, including the cerebellum and left posterior hemisphere, which may be involved in delusional development in these patients.

Grey matter atrophy in mild cognitive impairment / early Alzheimer disease associated with delusions: a voxel-based morphometry study.

OBJECTIVES: Grey matter atrophy in the right hemisphere has been shown to be more severe in dementia patients with delusions, suggesting a neuroanatomical localization that may be pertinent to impending neurodegeneration. Delusional symptoms may arise when atrophy in these areas reduces the regulatory functions of the right hemisphere, in tandem with asymmetric neuropathology in the left hemisphere. We hypothesized that delusional patients with either amnestic mild cognitive impairment (MCI) or early Alzheimer Disease (AD) would experience more pronounced grey matter atrophy in the right frontal lobe compared with matched patients without delusions. METHODS: We used neuroimaging and clinical data obtained from the Alzheimer's Disease Neuroimaging Initiative. A comparison group of twenty-nine nondelusional MCI/early AD participants were compared with twenty-nine delusional participants using voxel-based morphometry, matched at baseline by age, sex, education, and Mini-Mental State Exam score. All included participants were diagnosed with amnestic MCI at study baseline. RESULTS: Fifteen voxel clusters of decreased grey matter in participants with delusions were detected. Prominent grey matter decrease was observed in the right precentral gyrus, right inferior frontal gyrus, right insula, and left middle occipital gyrus, areas that may be involved in control of thought and emotions. CONCLUSION: Greater right fronto-temporal grey matter atrophy was observed in MCI or early AD participants with delusions compared to matched patients without delusions. Consistent with our predictions, asymmetric grey matter atrophy in the right hemisphere may contribute to development of delusions through loss of executive inhibition.

Antisaccadic Eye Movements Are Correlated with Corpus Callosum White Matter Mean Diffusivity, Stroop Performance, and Symptom Burden in Mild Traumatic Brain Injury and Concussion.

Antisaccades are thought to involve higher level inputs from neural centers involved in rapid eye movement inhibition and control. Previous work has demonstrated that performance on the antisaccade task can help in the assessment of injury in acute and/or chronic mild traumatic brain injury (mTBI). In this exploratory study, we performed cross-sectional and longitudinal comparisons of rapid eye movement, followed by correlations of antisaccade performance with assessments of symptom burden, diffusion tensor imaging, and a neuropsychological test of response inhibition. Significant deficits in antisaccade median latency, F(2, 31) = 3.65, p = 0.04 and prosaccade error mean duration, F(2, 31) = 3.63, p = 0.04 were found between patient groups and controls: the former was correlated with loss of white matter integrity in the splenium of the corpus callosum in acute mTBI, rho = 0.90, p = 0.0005. Furthermore, increased antisaccade median latency was also correlated with poor performance on an executive functioning task, r (2) = 0.439, p = 0.03, and greater symptom burden, r (2) = 0.480, p = 0.02 in the acute mTBI patients. Our preliminary research suggests that the antisaccade task could be useful as a neurological marker for mTBI and concussion, but more work is required.

Eye movement measurement in diagnostic assessment of disorders of consciousness.

We review the literature to appraise the evidence supporting or disputing the use of eye movement measurement in disorders of consciousness (DOC) with low levels of arousal or awareness, such as minimally conscious state (MCS), vegetative state (VS), and coma for diagnostic and prognostic purposes. We will focus on the effectiveness of each technique in the diagnostic classification of these patients and the gradual trend in research from manual to computerized tracking methods. New tools have become available at clinicians' disposal to assess eye movements with high spatial and temporal fidelity. The close relationship between eye movement generation and organic dysfunction in the brain allows these tools to be applied to the assessment of severe DOC as a unique supplementary toolset. We posit that eye tracking can improve clinical diagnostic precision for DOC, a key component of assessment that often dictates the course of clinical care in DOC patients. We see the emergence of long-term eye-tracking studies with seamless integration of technology in the future to improve the performance of clinical assessment in DOC.