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 stimu-
lation 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 improve-
ments (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.