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.

Excitability modulation of the motor system induced by transcranial direct current stimulation: A multimodal approach

“…After the anodal stimulation, we observed an increase in the cortical response not only over the stimulated cortex (Stagg et al, 2009a;Stagg et al, 2011) but also over the contralateral homotopic areas. This result is consistent with a recent study (Zheng et al, 2011) that reports a positive correlation between the stimulated motor cortex and the contralateral one, supporting a possible coupling of neuroactivity between motor regions (although in our study, the stimulated hemisphere was more strongly activated than the contralateral region).…”

The impact of transcranial direct current stimulation (tDCS) combined with modified constraint-induced movement therapy (mCIMT) on upper limb function in chronic stroke: a double-blind randomized controlled trial

“…Thereby, the priming activation by tDCS could have optimized the plastic effects induced by the intensive training of the paretic upper limb and lead to more remarkable clinical gains. Previous findings have demonstrated that the degree of behavioural improvement immediately following tDCS was correlated with the stimulation-induced changes in the affected hemisphere activity [42]. However, it is probable that the magnitude of the affected hemisphere activation is dependent on whether neural circuits are directly or indirectly activated.…”

The Physiological Basis of Brain Stimulation

“…Whether or not tDCS is able to interact at a synaptic level with endogenous plasticity-induction protocols is not only an interesting academic question but also has important implications for the use of tDCS as an adjunctive therapy in recovery of function after brain injury, such as a stroke. A single session of anodal tDCS applied to the motor cortex within the ipsilesional hemisphere has been demonstrated to improve function in the chronic stages of stroke recovery for short periods of time (Hummel et al, 2005(Hummel et al, , 2006Stagg et al, 2012). Additionally, daily applications of tDCS with the anode placed over the M1 in the ipsilesional hemisphere and the cathode placed over M1 in the contralesional hemisphere appear to induce longer-lasting behavioral improvements (Lindenberg, Renga, Zhu, Nair, & Schlaug, 2010).…”