Five-day course of paired associative stimulation fails to improve motor function in stroke patients.

BACKGROUND: Non-invasive brain stimulation has been studied as a therapeutic adjunct for upper-limb recovery in patients with stroke. One type of stimulation, paired associative stimulation (PAS), has effects on plasticity in both patients and healthy participants. Lasting several hours, these effects are reversible and topographically specific. OBJECTIVE: The goal was to investigate the presence of a lasting increase in motor cortex plasticity for extensor wrist muscles - extensor carpi radialis (ECR) - and an improvement in upper-limb function after 5 days of daily PAS in patients at the subacute post-stroke stage. METHODS: A total of 24 patients (mean [SD] age 50.1 [12.1] years, weeks since stroke 10.1 [5.3]) were included in a double-blind, placebo-controlled trial and randomly assigned to the PAS or sham group (n=13 and n=11). For the PAS group, patients underwent a 5-day course of electrical peripheral stimulation combined with magnetic cortical stimulation applied to the ECR muscle in a single daily session at 0.1Hz for 30min; patients with sham treatment received minimal cortical stimulation. Both patient groups underwent 2 hr of conventional physiotherapy. Variations in the motor evoked potential (MEP) surface area of the ECR muscle and Fugl-Meyer Assessment-Upper-Limb motor scores were analysed up to day 12. RESULTS: The 2 groups did not differ in electrophysiological or motor parameters. Repeated PAS sessions seemed to affect only patients with low initial cortical excitability. We found considerable variability in PAS effects between patients and across the sessions. CONCLUSION: We failed to induce a lasting effect with PAS in the present study. PAS does not seem to be the main method for post-stroke brain stimulation. Perhaps recruitment of patients could be more selective, possibly targeting those with a wide altered ipsilesional corticomotor pathway.

Anodal tDCS Combined With Radial Nerve Stimulation Promotes Hand Motor Recovery in the Acute Phase After Ischemic Stroke.

BACKGROUND AND OBJECTIVE: The question of the best therapeutic window in which noninvasive brain stimulation (NIBS) could potentiate the plastic changes for motor recovery after a stroke is still unresolved. Most of the previous NIBS studies included patients in the chronic phase of recovery and very few in the subacute or acute phase. We investigated the effect of transcranial direct current stimulation (tDCS) combined with repetitive peripheral nerve stimulation (rPNS) on the time course of motor recovery in the acute phase after a stroke. METHODS: Twenty patients enrolled within the first few days after a stroke were randomized in 2 parallel groups: one receiving 5 consecutive daily sessions of anodal tDCS over the ipsilesional motor cortex in association with rPNS and the other receiving the same rPNS combined with sham tDCS. Motor performance (primary endpoint: Jebsen and Taylor Hand Function Test [JHFT]) and transcranial magnetic stimulation cortical excitability measures were obtained at baseline (D1), at the end of the treatment (D5), and at 2 and 4 weeks' follow-up (D15 and D30). RESULTS: The time course of motor recovery of the 2 groups of patients was different and positively influenced by the intervention (Group × Time interaction P = .01). The amount of improvement on the JHFT was greater at D15 and D30 in the anodal tDCS group than in the sham group. CONCLUSION: These results show that early cortical neuromodulation with anodal tDCS combined with rPNS can promote motor hand recovery and that the benefit is still present 1 month after the stroke.

Impaired visual hand recognition in preoperative patients during brachial plexus anesthesia: importance of peripheral neural input for mental representation of the hand.

BACKGROUND: Perceptual illusions described in healthy subjects undergoing regional anesthesia (RA) are probably related to short-term plastic brain changes. We addressed whether performance on an implicit mental rotation task reflects these RA-induced changes in body schema brain representations. Studying these changes in healthy volunteers may shed light on normal function and the central mechanisms of pain. METHODS: Performance pattern was studied in upper limb-anesthetized subjects on a left/right hand judgment task, which is known to involve motor imagery processes relating to hand posture. Three conditions were used: control (i.e., absence of deafferentation), RA (i.e., deafferentation), and vision (i.e., deafferentated limb exposed to view). To limit potential bias such as order effect, the control state was recorded in a randomized manner. RESULTS: All subjects described perceptual illusions of their anesthetized limb. They were slower and less accurate on the task during RA compared with control. Response patterns were similar in all conditions, suggesting sensitivity of performance to arm/hand biomechanical constraints. Vision was associated with an increase in the proportion of correct responses and a reduction of the response times in hand judgment and was accompanied by disappearance of the lateralization of the underlying mental representations, which was identified during RA. CONCLUSIONS: These results suggest the following: (1) the right/left judgment task involves mental simulation of hand movements, (2) underlying mental representations and their neural substrates are subject to acute alterations after RA, and (3) the proprioceptive deficit induced by RA is influenced by the subject's ability to see the anesthetized limb.

Transition from rest to movement: brain correlates revealed by functional connectivity.

It is suggested that resting state networks reflecting correlated neural regional activities participate significantly in brain functioning. A fundamental issue is to understand how these networks interact and how their activities change during behavioral transitions. Our aim was to understand better with functional MRI connectivity how the brain switched from a "resting" to a movement-related state by exploring the transitory readiness state for an intended movement of the right hand. Our study does not address movement preparation occurring in a time scale of milliseconds before movement which has been widely studied but movement-readiness which can last longer. At rest, in the absence of overt goal-directed behavior, a "default-mode" network, whose main areas are the posterior cingulate cortex and precuneus (PCC/Pcu), shows high activity interpreted as day dreaming, free association, stream of consciousness, and inner rehearsal. We found that, during rest, the "default-mode" network and the sensorimotor network were not functionally correlated. During movement-readiness, the two networks were functionally correlated through an interaction between the PCC/Pcu and the medial superior parietal cortex in the upper precuneus. The complex PCC/Pcu has been shown to be involved in retrieval and/or setting up spatial attributes for motor imagery, and thus, would be a key region in the movement-readiness phase. It might functionally connect to the medial superior parietal cortex to initiate the movement programming through retrieval of suited movement parameters. The anterior cingulum, functionally correlated to the primary sensorimotor cortex during movement-readiness would have a motivational role or could generate predictions about the movement.

Induction of cortical plastic changes in wrist muscles by paired associative stimulation in the recovery phase of stroke patients.

BACKGROUND: Paired associative stimulation (PAS) combining peripheral nerve and transcranial magnetic stimulation (TMS) have been proposed to induce long-term changes in excitability of the cerebral cortex and potentially optimize motor recovery in stroke patients. OBJECTIVE: This pilot study examined whether short-lasting changes in cortical excitability could be induced by a single session of PAS within the first months after stroke. METHODS: Six hemiparetic patients with a subcortical stroke were included. The single session PAS protocol was applied at 1, 5, and 12 months after stroke. During the follow-up, the clinical recovery of wrist function was assessed in parallel to the PAS study by the Fugl-Meyer motor scale and dynamometry of wrist extension. RESULTS: The PAS protocol induced a significant extensor carpi radialis motor evoked potential facilitation (mean +78.5%) on the paretic side 5 months after stroke. The facilitation was still present 12 months after stroke but on average smaller (+30 %). CONCLUSIONS: These electrophysiological findings suggest that patients with subcortical infarcts may respond to PAS in an earlier than later period after stroke. If the clinical efficacy of interventions such as PAS is confirmed, it could be proposed early as add-on therapy to optimize training-induced plasticity processes.

Subthalamic nucleus stimulation reduces abnormal motor cortical overactivity in Parkinson disease.

BACKGROUND: Based on the basal ganglia model, it has been hypothesized that the efficacy of high-frequency stimulation of the subthalamic nucleus (STN) against parkinsonian symptoms relies on the activation of cortical premotor regions. In previous positron emission tomography activation studies, STN high-frequency stimulation was associated with selective activation of midline premotor areas during hand movements but mainly reduced the regional cerebral blood flow in movement-related areas, peculiarly at rest. OBJECTIVE: To investigate with positron emission tomography the role of regional cerebral blood flow reduction in the clinical improvement provided by STN high-frequency stimulation. METHODS: Seven patients with advanced Parkinson disease, who were markedly improved by bilateral STN high-frequency stimulation, underwent positron emission tomography with H2(15)O while the right STN electrode was turned off. The patients were studied at rest and during right-hand movements in 3 electrode conditions: no stimulation, inefficient low-frequency stimulation, and efficient high-frequency stimulation. RESULTS: The main effect of high-frequency stimulation was to reduce regional cerebral blood flow in the left primary sensorimotor cortex, the lateral premotor cortex, the right cerebellum, and the midline premotor areas. The selective activation of the anterior cingulate cortex and the left primary sensorimotor cortex during hand movement under STN high-frequency stimulation was attributed to decreased regional cerebral blood flow at rest, rather than increased activation induced by STN high-frequency stimulation. Akinesia was correlated with the abnormal overactivity in the contralateral primary sensorimotor cortex and the ipsilateral cerebellum. CONCLUSION: High-frequency stimulation of the STN acts through the reduction of abnormal resting overactivity in the motor system, allowing selective cortical activation during movement.