Ipsilesional anodal tDCS enhances the functional benefits of rehabilitation in patients after stroke.

Anodal transcranial direct current stimulation (tDCS) can boost the effects of motor training and facilitate plasticity in the healthy human brain. Motor rehabilitation depends on learning and plasticity, and motor learning can occur after stroke. We tested whether brain stimulation using anodal tDCS added to motor training could improve rehabilitation outcomes in patients after stroke. We performed a randomized, controlled trial in 24 patients at least 6 months after a first unilateral stroke not directly involving the primary motor cortex. Patients received either anodal tDCS (n= 11) or sham treatment (n= 13) paired with daily motor training for 9 days. We observed improvements that persisted for at least 3 months post-intervention after anodal tDCS compared to sham treatment on the Action Research Arm Test (ARAT) and Wolf Motor Function Test (WMFT) but not on the Upper Extremity Fugl-Meyer (UEFM) score. Functional magnetic resonance imaging (MRI) showed increased activity during movement of the affected hand in the ipsilesional motor and premotor cortex in the anodal tDCS group compared to the sham treatment group. Structural MRI revealed intervention-related increases in gray matter volume in cortical areas, including ipsilesional motor and premotor cortex after anodal tDCS but not sham treatment. The addition of ipsilesional anodal tDCS to a 9-day motor training program improved long-term clinical outcomes relative to sham treatment in patients after stroke.

The Homeostatic Interaction Between Anodal Transcranial Direct Current Stimulation and Motor Learning in Humans is Related to GABAA Activity.

BACKGROUND: The relative timing of plasticity-induction protocols is known to be crucial. For example, anodal transcranial direct current stimulation (tDCS), which increases cortical excitability and typically enhances plasticity, can impair performance if it is applied before a motor learning task. Such timing-dependent effects have been ascribed to homeostatic plasticity, but the specific synaptic site of this interaction remains unknown. OBJECTIVE: We wished to investigate the synaptic substrate, and in particular the role of inhibitory signaling, underpinning the behavioral effects of anodal tDCS in homeostatic interactions between anodal tDCS and motor learning. METHODS: We used transcranial magnetic stimulation (TMS) to investigate cortical excitability and inhibitory signaling following tDCS and motor learning. Each subject participated in four experimental sessions and data were analyzed using repeated measures ANOVAs and post-hoc t-tests as appropriate. RESULTS: As predicted, we found that anodal tDCS prior to the motor task decreased learning rates. This worsening of learning after tDCS was accompanied by a correlated increase in GABAA activity, as measured by TMS-assessed short interval intra-cortical inhibition (SICI). CONCLUSION: This provides the first direct demonstration in humans that inhibitory synapses are the likely site for the interaction between anodal tDCS and motor learning, and further, that homeostatic plasticity at GABAA synapses has behavioral relevance in humans.

Sequential bilateral lesser trochanter avulsion fractures in an adolescent patient.

We report the rare case of a 15-year-old boy who sustained sequential bilateral lesser trochanter avulsion fractures over a 6-month period while playing football. No malignancy or associated metabolic bone disease was found. He subsequently made a full recovery with non-operative treatment.

Neuropsychological sequelae following pediatric stroke: a nonlinear model of age at lesion effects.

AIM: The distribution and quality of brain recovery following pediatric arterial ischemic stroke remains controversial. The literature suggests that age at stroke may be an important modulator of neuropsychological outcome, with reports inferring either greater vulnerability or plasticity in the nascent brain. Our aim was to investigate neuropsychological outcomes following pediatric stroke in a clinical sample with reference to age at lesion, lesion laterality, elapsed time from stroke to assessment, and persistent neurological sequelae. METHODS: Using comprehensive neuropsychological assessment batteries, we investigated retrospectively a large (n = 44) and evenly distributed group of children who had ischemic stroke during "infancy" (1 month to 1 year), "early childhood" (1 to 6 years), and "late childhood" (6 to 16 years). RESULTS: Children who suffered a stroke performed significantly worse on a range of neuropsychological measures when compared to a normative sample. However, children who suffered a stroke between 1 and 6 years old demonstrated better preserved neuropsychological profiles than either the earlier (before age 1) or later (after age 6) age groups. In addition, those children suffering a left hemisphere lesion performed more poorly on a range of neuropsychological measures than did children with right hemisphere lesions. INTERPRETATION: Age at stroke is an important determinant of recovery following insult and may modulate neuropsychological and cognitive outcome.

Cortical activation changes underlying stimulation-induced behavioural gains in chronic stroke.

Transcranial direct current stimulation, a form of non-invasive brain stimulation, is showing increasing promise as an adjunct therapy in rehabilitation following stroke. However, although significant behavioural improvements have been reported in proof-of-principle studies, the underlying mechanisms are poorly understood. The rationale for transcranial direct current stimulation as therapy for stroke is that therapeutic stimulation paradigms increase activity in ipsilesional motor cortical areas, but this has not previously been directly tested for conventional electrode placements. This study was performed to test directly whether increases in ipsilesional cortical activation with transcranial direct current stimulation are associated with behavioural improvements in chronic stroke patients. Patients at least 6 months post-first stroke participated in a behavioural experiment (n = 13) or a functional magnetic resonance imaging experiment (n = 11), each investigating the effects of three stimulation conditions in separate sessions: anodal stimulation to the ipsilesional hemisphere; cathodal stimulation to the contralesional hemisphere; and sham stimulation. Anodal (facilitatory) stimulation to the ipsilesional hemisphere led to significant improvements (5-10%) in response times with the affected hand in both experiments. This improvement was associated with an increase in movement-related cortical activity in the stimulated primary motor cortex and functionally interconnected regions. Cathodal (inhibitory) stimulation to the contralesional hemisphere led to a functional improvement only when compared with sham stimulation. We show for the first time that the significant behavioural improvements produced by anodal stimulation to the ipsilesional hemisphere are associated with a functionally relevant increase in activity within the ipsilesional primary motor cortex in patients with a wide range of disabilities following stroke.