Modulation of brain activity with transcranial direct current stimulation: Targeting regions implicated in impaired illness awareness in schizophrenia

Background: Impaired illness awareness or insight into illness (IIA) is a common feature of schizophrenia that contributes to medication nonadherence and poor clinical outcomes. Neuroimaging studies suggest IIA may arise from interhemispheric imbalance in frontoparietal regions, particularly in the posterior parietal area (PPA) and the dorsolateral prefrontal cortex (dlPFC). In this pilot study, we examined the effects of transcranial direct current stimulation (tDCS) on brain regions implicated in IIA. Methods: Eleven patients with schizophrenia with IIA (≥3 PANSS G12) and 10 healthy controls were included. A crossover design was employed where all participants received single-session bi-frontal, bi-parietal, and sham stimulation in random order. For each condition, we measured (i) blood oxygen level-dependent (BOLD) response to an illness awareness task pre- and post-stimulation, (ii) regional cerebral blood-flow (rCBF) prior to and during stimulation, and (iii) changes in illness awareness. Results: At baseline, patients with schizophrenia showed higher BOLD-response to an illness awareness task in the left-PPA compared to healthy controls. Bi-parietal stimulation reduced the interhemispheric imbalance in the PPA compared to sham stimulation. Relatedly, bi-parietal stimulation increased rCBF beneath the anode (21% increase in the right-PPA), but not beneath the cathode (5.6% increase in the left-PPA). Bi-frontal stimulation did not induce changes in rCBF. We found no changes in illness awareness. Conclusion: Although single-session tDCS did not improve illness awareness, this pilot study provides mechanistic justification for future investigations to determine if multi-session bi-parietal tDCS can induce sustained changes in brain activity in the PPA in association with improved illness awareness.