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

Abstract

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.

Figure 1

Outline for experimental design for each stimulation session. (A) Experiment 1: Behavioural study. White blocks represent response time task, grey blocks represent grip force task. VAS = visual analogue scale; to assess fatigue, pain, discomfort and attention. (B) Experiment 2: Functional MRI study. White blocks represent simple response time task, grey blocks choice response time task and black blocks are rest periods. tDCS = transcranial direct current stimulation.

Figure 2

Behavioural effects of tDCS. (A) Experiment 1. Anodal stimulation to the ipsilesional M1 led to a significant decrease in response times. No significant difference was seen with cathodal stimulation. (B) Experiment 2. Anodal tDCS led to a significant shortening of response times. No change in response times was seen in response to cathodal tDCS. Columns represent mean ± SE. Significant differences (P < 0.05) between conditions (asterisk) and within session (section symbol) are highlighted.

Figure 3

(A) Areas of increased motor-related activation in response to the simple response time task after anodal stimulation compared with sham [i.e. for the contrast (anodal post–anodal pre)–(sham post–sham pre)]. The column graph (top right) shows the mean change in activity within these suprathreshold regions and demonstrates a significant increase in activity within these areas after anodal stimulation and no change after sham stimulation. (B) Areas of increased motor-related activity in response to the simple response time task after cathodal stimulation compared with sham. The graph (centre right) demonstrates an increase in activity within these suprathreshold regions in response to cathodal stimulation but not to sham. (C) Areas of increased motor-related activity after anodal tDCS compared with sham (blue), increased motor-related activity after cathodal tDCS compared with sham (yellow) and areas of increased motor-related activity common to both stimulation conditions (green). (D) Areas of significant correlation between change in motor-related activation after anodal stimulation (i.e. the contrast anodal post–anodal pre) and change in response times after anodal stimulation. The plot (bottom right) demonstrates this relationship within in the areas shown. BOLD = blood oxygen level-dependent; PMd = dorsal premotor cortex; RT = response time; SMA = supplementary motor area.