[Where Does Repetitive Negative Thinking in Depression Originate? From Right Thalamo-Cortical Circuits to...

Repetitive negative thinking (RNT) is a pervasive symptom associated with a poor prognosis in patients with major depressive disorder (MDD). This review examines the thalamo-cortical circuits underlying RNT, distinguishing between trait and state-RNT. Functional magnetic resonance imaging studies have revealed that RNT intensity correlates with hyperconnectivity between the right thalamic nuclei and prefrontal cortex, default mode, and language-related cortical areas. We discuss a novel noninvasive neuromodulation approach using low-intensity focused ultrasound (LIFU). Targeting the anterior limb of the internal capsule (ALIC) successfully reduced thalamo-cortical functional connectivity. Although a single sonication did not acutely improve state-RNT, this modulation was accompanied by acute improvements in positive affect and autonomic nervous system balance. These findings suggest that LIFU is a promising tool for personalized, non-invasive brain circuit probing in MDD and highlight the current limitations for future research.