Corticomotor Plasticity Predicts Clinical Efficacy of Combined Neuromodulation and Cognitive Training in Alzheimer’s Disease

Objective: To investigate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training for treatment of cognitive symptoms in patients with Alzheimer’s disease (AD). A secondary objective was to analyze associations between brain plasticity and cognitive effects of treatment. Methods: In this randomized, sham-controlled, multicenter clinical trial, 34 patients with AD were assigned to three experimental groups receiving 30 daily sessions of combinatory intervention. Participants in the real/real group (n = 16) received 10 Hz repetitive transcranial magnetic stimulation (rTMS) delivered separately to each of six cortical regions, interleaved with computerized cognitive training. Participants in the sham rTMS group (n = 18) received sham rTMS combined with either real (sham/real group, n = 10) or sham (sham/sham group, n = 8) cognitive training. Effects of treatment on neuropsychological (primary outcome) and neurophysiological function were compared between the 3 treatment groups. These, as well as imaging measures of brain atrophy, were compared at baseline to 14 healthy controls (HC). Results: At baseline, patients with AD had worse cognition, cerebral atrophy, and TMS measures of cortico-motor reactivity, excitability, and plasticity than HC. The real/real group showed significant cognitive improvement compared to the sham/sham, but not the real/sham group. TMS-induced plasticity at baseline was predictive of post-intervention changes in cognition, and was modified across treatment, in association with changes of cognition. Interpretation: Combined rTMS and cognitive training may improve the cognitive status of AD patients, with TMS-induced cortical plasticity at baseline serving as predictor of therapeutic outcome for this intervention, and potential mechanism of action. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01504958.publishersversionpublishe

Transcranial direct current stimulation: animal models and epidural recordings

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Transcranial direct current stimulation effects on the excitability of corticospinal axons of the human cerebral cortex

Background: Transcranial direct current stimulation (tDCS) of the human cerebral cortex modulates cortical excitability non-invasively in a polarity-specific manner: anodal tDCS leads to lasting facilitation of motor cortex excitability. Objective: To further elucidate the underlying physiological mechanisms of tDCS. Methods: We recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation of the primary motor cortex before and after a 20 min period of anodal tDCS in a conscious patient who had electrode implanted in the cervical epidural space for the control of pain. We performed magnetic stimulation of the motor cortex using a direction of the induced current in the brain capable of activating both corticospinal axons, evoking D-wave activity, and cortico-cortical axons projecting upon corticospinal cells, evoking I-wave activity. Results: Anodal tDCS increased the excitability of cortical circuits generating both D and I-wave activity, with a more prolonged effect on D-wave activity. The changes in motor evoked potential recorded from hand muscles produced by tDCS were in agreement with the effects produced on intracortical circuitry. Conclusions: Epidural recordings of corticospinal activity in our patient indicate that anodal tDCS develops its facilitatory effects by an increase in the excitability of corticospinal axons and by an increase of activity in cortico-cortical projections onto pyramidal tract neurones, modulating motor cortex excitability with both synaptic (I waves) and non-synaptic (D waves) mechanisms

Aortic dissection in the thrombolysis era: Rare but potentially fatal cause of stroke

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Prognostic Value of EEG Microstates in Acute Stroke

Given the importance of neuronal plasticity in recovery from a stroke and the huge variability of recovery abilities in patients, we investigated neuronal activity in the acute phase to enhance information about the prognosis of recovery in the stabilized phase. We investigated the microstates in 47 patients who suffered a first-ever mono-lesional ischemic stroke in the middle cerebral artery territory and in 20 healthy control volunteers. Electroencephalographic (EEG) activity at rest with eyes closed was acquired between 2 and 10\uc2\ua0days (T0) after ischemic attack. Objective criteria allowed for the selection of an optimal number of microstates. Clinical condition was quantified by the National Institute of Health Stroke Scale (NIHSS) both in acute (T0) and stabilized (T1, 5.4 \uc2\ub1 1.7 months) phases and Effective Recovery (ER) was calculated as (NIHSS(T1)-NIHSS(T0))/NIHSS(T0). The microstates A, B, C and D emerged as the most stable. In patients with a left lesion inducing a language impairment, microstate C topography differed from controls. Microstate D topography was different in patients with a right lesion inducing neglect symptoms. In patients, the C vs D microstate duration differed after both a left and a right lesion with respect to controls (C lower than D in left and D lower than C in right lesion). A preserved microstate B in acute phase correlated with a better effective recovery. A regression model indicated that the microstate B duration explained the 11% of ER variance. This first ever study of EEG microstates in acute stroke opens an interesting path to identify neuronal impairments with prognostic relevance, to develop enriched compensatory treatments to drive a better individual recovery

Use of transcranial magnetic stimulation of the brain in stroke rehabilitation

Preliminary studies suggest that stimulation of the motor cortex enhances motor recovery after stroke. Most of these studies employed transcranial magnetic stimulation of the brain and two different approaches have been evaluated. The first approach is based on the use of protocols of stimulation that increase cortical excitability, targeting the hemisphere in which the stroke occurred in order to enhance the output of the motor cortex and the response to physiotherapy. The second approach is based on the use of protocols of stimulation that suppress cortical excitability, targeting the intact hemisphere in order to counteract the imbalance due to the increased interhemispheric inhibition onto the lesioned cortex, and reducing the potential negative interference of the intact hemisphere with the function of the affected one. Cumulatively, preliminary studies suggest that transcranial magnetic stimulation might be a suitable method to combine with physiotherapy and improve recovery of useful limb function in stroke patients. However, further studies are needed to determine the best stimulation parameters and how to select patients who are likely to respond to this treatment

Benedictine hand of 'central' origin

No abstrac

Gluten-related Recurrent Peripheral Facial Palsy

Abstract not availabl

Motor cortex stimulation for ALS: open label extension study of a previous small trial

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