Breaking the Negative Symptom Barrier: A Novel Neuromodulation Strategy Using HD-tDCS Primed iTBS in Schizophrenia

Negative symptoms in schizophrenia are associated with long-term disability and poor functional outcomes. These symptoms remain inadequately addressed by current pharmacological and psychosocial interventions. Neuromodulation strategies, such as combining transcranial magnetic stimulation and transcranial direct current stimulation, are emerging as promising noninvasive options.

This study aimed to assess the efficacy and safety of combining cathodal high-definition transcranial direct current stimulation with intermittent theta burst stimulation for reducing negative symptoms in patients with schizophrenia.

In this randomized, double-blind, sham-controlled trial, 40 inpatients diagnosed with schizophrenia with predominantly negative symptoms were assigned to receive either active or sham priming with high-definition transcranial direct current stimulation followed by intermittent theta burst stimulation. Treatment was delivered twice daily over 2 weeks. Clinical assessments were conducted at baseline, after 2 and 4 weeks, using standard rating scales for symptom severity (PANSS, SANS) and global functioning.

Both active and sham groups showed significant within-group improvement in overall symptom scores over time. The active stimulation group demonstrated significantly greater reductions in total and attention-related negative symptom scores. Improvements were also observed in cognitive and depressive domains. The treatment was well tolerated, with only mild and transient side effects reported.

Priming intermittent theta burst stimulation with high-definition transcranial direct current stimulation appears to be a safe and potentially effective approach for targeting negative symptoms in schizophrenia.