Task-based fNIRS biomarkers of HD-tDCS treatment for negative symptoms in schizophrenia

Negative symptoms of schizophrenia are highly disabling and remain insufficiently responsive to pharmacological treatment. High-definition transcranial direct current stimulation (HD-tDCS) targeting the left dorsolateral prefrontal cortex (DLPFC) may improve these symptoms, but its neurophysiological correlates remain unclear.

This study was a secondary fNIRS analysis of a randomized, double- blind, sham-controlled trial. Sixty clinically stable patients with schizophrenia and predominant negative symptoms received active or sham online HD-tDCS over the left DLPFC while performing a two-back working memory task. Functional near-infrared spectroscopy was used to assess prefrontal activation during the two-back task and verbal fluency task (VFT), as well as resting-state functional connectivity. Graph- theoretical analyses quantified global efficiency (Eg) and local efficiency (Eloc). Negative symptoms were assessed using the PANSS factor score for negative symptoms (FSNS) and the Scale for the Assessment of Negative Symptoms (SANS).

Active HD-tDCS was associated with significantly greater increases in left DLPFC activation during both the two-back task and VFT compared with sham stimulation. Resting-state Eg and Eloc did not differ significantly between groups. Changes in task-evoked fNIRS signals were not significantly correlated with improvements in negative symptoms. However, lower resting-state Eloc was significantly associated with greater negative symptom severity.

Online HD-tDCS enhanced task-evoked left DLPFC activation in schizophrenia, but these changes were not directly related to clinical improvement. Resting-state local efficiency may better reflect the severity of negative symptoms than task-based activation, suggesting a potential role for intrinsic prefrontal network organization in schizophrenia.