{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:22:08Z","timestamp":1768566128750,"version":"3.49.0"},"posted":{"date-parts":[[2023,4,3]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":52,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>Transcranial electrical stimulation (tES) may improve psychosis symptoms, but few investigations have targeted brain regions causally linked to psychosis symptoms. We implemented a novel montage targeting the extrastriate visual cortex (eVC) previously identified by lesion network mapping in the manifestation of visual hallucinations.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To determine if lesion network guided HD-tES to the eVC is safe and efficacious in reducing symptoms related to psychosis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Design, Setting, and Participants<\/jats:title>\n                  <jats:p>Single-center, nonrandomized, single-blind trial using a crossover design conducted in two 4-week phases beginning November 2020, and ending January 2022. Participants were adults 18-55 years of age with a diagnosis of schizophrenia, schizoaffective or psychotic bipolar disorder as confirmed by the Structured Clinical Interview for DSM-V, without an antipsychotic medication change for at least 4 weeks. A total of 8 participants consented and 6 participants enrolled. Significance threshold set to &lt;0.1 due to small sample size.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Interventions<\/jats:title>\n                  <jats:p>6 Participants first received HD-tDCS (direct current), followed by 4 weeks of wash out, then 4 received 2Hz HD-tACS (alternating current). Participants received 5 consecutive days of daily (2 \u00d7 20min) stimulation applied bilaterally to the eVC.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Main Outcomes and Measures<\/jats:title>\n                  <jats:p>Primary outcomes included the Positive and Negative Syndrome Scale (PANSS) total, positive, negative, and general scores, biological motion task, and Event Related Potential (ERP) measures obtained from a steady state visual evoked potential (SSVEP) task across each 4-week phase. Secondary outcomes included the Montgomery-Asperg Depression Rating Scale (MADRS), Global Assessment of Functioning (GAF), velocity discrimination task, visual working memory task, and emotional ERP across each 4-week phase.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    HD-tDCS improved general psychopathology in the short-term (d=0.47; p\n                    <jats:sub>fdr<\/jats:sub>\n                    =0.03), with long-term improvements in general psychopathology (d=0.62; p\n                    <jats:sub>fdr<\/jats:sub>\n                    =0.05) and GAF (d=-0.56; p\n                    <jats:sub>fdr<\/jats:sub>\n                    =0.04) with HD-tACS. HD-tDCS reduced SSVEP P1 (d=0.25; p\n                    <jats:sub>fdr<\/jats:sub>\n                    =0.005), which correlated with general psychopathology (\u03b2=0.274, t=3.59, p=0.04). No significant differences in safety or tolerability measures were identified.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions and Relevance<\/jats:title>\n                  <jats:p>Lesion network guided HD-tES to the eVC is a safe, efficacious, and promising approach for reducing general psychopathology via changes in neuroplasticity. These results highlight the need for larger clinical trials implementing novel targeting methodologies for the treatments of psychosis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Trial Registration<\/jats:title>\n                  <jats:p>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                    Identifier:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04870710\">NCT04870710<\/jats:ext-link>\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key Points<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Question<\/jats:title>\n                    <jats:p>Is lesion network guided neurostimulation an efficacious, safe, and targeted approach for treating psychosis?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>In this single-center, nonrandomized, crossover, single-blind trial of 6 outpatients with psychosis, improvement in general psychopathology was seen in the short-term with HD-tDCS (high-definition transcranial direct current stimulation) and long-term with HD-tACS (alternating current) targeting the extrastriate visual cortex (eVC). HD-tDCS reduced early visual evoked responses which linked to general psychopathology improvements. Overall, both stimulations were well tolerated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Meaning<\/jats:title>\n                    <jats:p>Study findings suggest that lesion network guided HD-tES to the eVC is a safe, efficacious, and promising approach for reducing general psychopathology via neuroplastic changes.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.1101\/2023.03.31.23287980","type":"posted-content","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T11:45:18Z","timestamp":1680522318000},"source":"Crossref","is-referenced-by-count":2,"title":["Efficacy and Tolerability of Lesion Network Guided Transcranial Electrical Stimulation in Outpatients with Psychosis Spectrum Illness: A Nonrandomized Controlled 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