{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T02:31:57Z","timestamp":1792549917104,"version":"4.5.0"},"reference-count":30,"publisher":"Royal College of Psychiatrists","issue":"1","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"unspecified","delay-in-days":290,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur. Psychiatr."],"published-print":{"date-parts":[[2024]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:sec id=\"S0924933824017693_sec1\">\n\t    <jats:title>Background<\/jats:title>\n\t    <jats:p>This study investigates the effects of accelerated high-frequency repetitive transcranial magnetic stimulation (aHF-rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC), on locus coeruleus (LC) functional connectivity in the treatment of refractory medication-resistant major depression (MRD).<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924933824017693_sec2\" sec-type=\"methods\">\n\t    <jats:title>Methods<\/jats:title>\n\t    <jats:p>We studied 12 antidepressant-free refractory MRD patients, focusing on how aHF-rTMS affects the LC, a central component of the brain\u2019s noradrenergic system and key to mood regulation and stress response.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924933824017693_sec3\" sec-type=\"results\">\n\t    <jats:title>Results<\/jats:title>\n\t    <jats:p>A stronger decrease in LC functional connectivity following aHF-rTMS treatment resulted in better clinical improvement. We observed such LC functional connectivity decreases with several brain regions, including the superior frontal gyrus, precentral gyrus, middle occipital gyrus, and cerebellum. Moreover, our exploratory analyses hint at a possible role for E-field modeling in forecasting clinical outcomes. Additional analyses suggest potential genetic and dopaminergic factors influencing changes in LC functional connectivity in relation to clinical response.<\/jats:p>\n\t  <\/jats:sec>\n\t  <jats:sec id=\"S0924933824017693_sec4\" sec-type=\"conclusions\">\n\t    <jats:title>Conclusions<\/jats:title>\n\t    <jats:p>The findings of this study underscore the pivotal role of the LC in orchestrating higher cognitive functions through its extensive connections with the prefrontal cortices, facilitating decision-making, influencing attention, and addressing depressive rumination. Additionally, the observed enhancement in LC-(posterior) cerebellar connectivity not only highlights the cerebellum\u2019s role in moderating clinical outcomes through noradrenergic system modulation but also suggests its potential as a predictive marker for aHF-rTMS efficacy. These results reveal new insights into the neural mechanisms of refractory depression and suggest therapeutic targets for enhancing noradrenergic activity, thereby addressing both cognitive and psychomotor symptoms associated with the disorder.<\/jats:p>\n\t  <\/jats:sec>","DOI":"10.1192\/j.eurpsy.2024.1769","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T09:48:03Z","timestamp":1729158483000},"source":"Crossref","is-referenced-by-count":8,"title":["Exploring potential working mechanisms of accelerated HF-rTMS in refractory major depression with a focus on locus coeruleus 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