Auditory Control Enhancement (ACE) in Schizophrenia

Auditory hallucinations associated with schizophrenia (Sz) are pervasive, debilitating, and disturbing. Unfortunately, they are also difficult to treat - auditory hallucinations persist in about 25% of cases despite pharmacotherapy and treatment of cognitive symptoms (the symptoms most strongly related to global functioning) is modest at best. We propose a novel, inexpensive, and noninvasive intervention to address treatment-refractory symptoms, a critical need in Sz. Auditory hallucinations and impaired cognition in schizophrenia are not independent. Both are associated with system-level dysfunction of the fronto-temporal auditory control network, comprising auditory/verbal perceptual areas in temporoparietal junction (TPJ) and cognitive/behavioral control systems in ventrolateral prefrontal cortex (VLPFC). VLPFC traditionally inhibits and reattributes perceptual misrepresentations in most people. For those with schizophrenia, impairment of auditory cognitive control makes this impossible. Data from our lab suggest that auditory control network dysfunction may be central to the early etiology of the disorder. Auditory control enhancement (ACE) is designed to improve auditory control network function, thereby increasing inhibition of spurious auditory system activity in temporoparietal cortex and reducing auditory hallucinations. ACE combines a time-tested psychotherapeutic behavioral training program with targeted non-invasive brain stimulation using transcranial Direct Current Stimulation (tDCS). To further develop ACE for efficacy trials, we plan to investigate neural markers of target engagement in two sham-controlled experiments. Aim 1 will determine whether tDCS of right vlPFC (anode) and left TPJ (cathode) during MRI alters electric field measures and blood oxygenation level dependent (BOLD) response during stimulation to demonstrate that markers of tDCS current flow and BOLD fluctuate with induced current, and these fluctuations align spatially with computer models. Aim 2 will examine feasibility of subject retention and blinding for ACE. Aim 3 will examine the degree to which ACE modifies behavioral, neurophysiological, and hemodynamic markers of target engagement using neural oscillatory and cerebral blood flow (CBF) measures. ACE represents a novel, transformative intervention with long-lasting effects that has the potential to change the treatment of schizophrenia and vastly improve the outcome for afflicted individuals.