Alpha transcranial alternating current stimulation reduces depressive symptoms in people with schizophrenia and auditory hallucinations: a double-blind, randomized pilot clinical trial.

People with schizophrenia exhibit reduced alpha oscillations and frontotemporal coordination of brain activity. Alpha oscillations are associated with top-down inhibition. Reduced alpha oscillations may fail to censor spurious endogenous activity, leading to auditory hallucinations. Transcranial alternating current stimulation (tACS) at the alpha frequency was shown to enhance alpha oscillations in people with schizophrenia and may thus be a network-based treatment for auditory hallucinations. We conducted a double-blind, randomized, placebo-controlled pilot clinical trial to examine the efficacy of 10-Hz tACS in treating auditory hallucinations in people with schizophrenia. 10-Hz tACS was administered in phase at the dorsolateral prefrontal cortex and the temporoparietal junction with a return current at Cz. Patients were randomized to receive tACS or sham for five consecutive days during the treatment week (40 min/day), followed by a maintenance period, during which participants received weekly tACS (40 min/visit) or sham. tACS treatment reduced general psychopathology (p < 0.05, Cohen's d = -0.690), especially depression (p < 0.005, Cohen's d = -0.806), but not auditory hallucinations. tACS treatment increased alpha power in the target region (p < 0.05), increased the frequency of peak global functional connectivity towards 10 Hz (p < 0.05), and reduced left-right frontal functional connectivity (p < 0.005). Importantly, changes in brain functional connectivity significantly correlated with symptom improvement (p < 0.05). Daily 10 Hz-tACS increased alpha power and altered alpha-band functional connectivity. Successful target engagement reduced depression and other general psychopathology symptoms, but not auditory hallucinations. Considering existing research of 10Hz tACS as a treatment for major depressive disorder, our study demonstrates its transdiagnostic potential for treating depression.

An auditory processing abnormality specific to liability for schizophrenia.

Abnormal brain activity during the processing of simple sounds is evident in individuals with increased genetic liability for schizophrenia; however, the diagnostic specificity of these abnormalities has yet to be fully examined. Because recent evidence suggests that schizophrenia and bipolar disorder may share aspects of genetic etiology the present study was conducted to determine whether individuals with heightened genetic liability for each disorder manifested distinct neural abnormalities during auditory processing. Utilizing a dichotic listening paradigm, we assessed target tone discrimination and electrophysiological responses in schizophrenia patients, first-degree biological relatives of schizophrenia patients, bipolar disorder patients, first-degree biological relatives of bipolar patients and nonpsychiatric control participants. Schizophrenia patients and relatives of schizophrenia patients demonstrated reductions in an early neural response (i.e. N1) suggestive of deficient sensory registration of auditory stimuli. Bipolar patients and relatives of bipolar patients demonstrated no such abnormality. Both schizophrenia and bipolar patients failed to significantly augment N1 amplitude with attention. Schizophrenia patients also failed to show sensitivity of longer-latency neural processes (N2) to stimulus frequency suggesting a disorder specific deficit in stimulus classification. Only schizophrenia patients exhibited reduced target tone discrimination accuracy. Reduced N1 responses reflective of early auditory processing abnormalities are suggestive of a marker of genetic liability for schizophrenia and may serve as an endophenotype for the disorder.