This study aimed to evaluate a novel rTMS protocol for treatment-resistant depression (TRD), using an EEG 10–20 system guided dual-target accelerated approach of right lateral orbitofrontal cortex (lOFC) inhibition followed by left dorsolateral prefrontal cortex (dlPFC) excitation, along with comparing 20 Hz dlPFC accelerated TMS v. sham.

Seventy five patients participated in this trial consisting of 20 sessions over 5 consecutive days comparing dual-site (cTBS of right lOFC followed sequentially by 20 Hz rTMS of left dlPFC), active control (sham right lOFC followed by 20 Hz rTMS of left dlPFC) and sham control (sham for both targets). Resting-state fMRI was acquired prior to and following treatment.

Hamilton Rating Scale for Depression (HRSD-24) scores were similarly significantly improved at 4 weeks in both the Dual and Single group relative to Sham. Planned comparisons immediately after treatment highlighted greater HRSD-24 clinical responders (Dual: 47.8% v. Single:18.2% v. Sham:4.3%, χ2 = 13.0, p = 0.002) and in PHQ-9 scores by day 5 in the Dual relative to Sham group. We further showed that accelerated 20 Hz stimulation targeting the left dlPFC (active control) is significantly better than sham at 4 weeks. Dual stimulation decreased lOFC-subcallosal cingulate functional connectivity. Greater baseline lOFC-thalamic connectivity predicted better therapeutic response, while decreased lOFC-thalamic connectivity correlated with better response.

Our novel accelerated dual TMS protocol shows rapid clinically relevant antidepressant efficacy which may be related to state-modulation. This study has implications for community-based accessible TMS without neuronavigation and rapid onset targeting suicidal ideation and accelerated discharge from hospital.

The prediction of alcohol consumption in youths and particularly biomarkers of resilience, is critical for early intervention to reduce the risk of subsequent harmful alcohol use.

At baseline, the longitudinal relaxation rate (R1), indexing grey matter myelination (i.e. myeloarchitecture), was assessed in 86 adolescents/young adults (mean age = 21.76, range: 15.75–26.67 years). The Alcohol Use Disorder Identification Test (AUDIT) was assessed at baseline, 1- and 2-year follow-ups (12- and 24-months post-baseline). We used a whole brain data-driven approach controlled for age, gender, impulsivity and other substance and behavioural addiction measures, such as problematic cannabis use, drug use-related problems, internet gaming, pornography use, binge eating, and levels of externalization, to predict the change in AUDIT scores from R1.

Greater baseline bilateral anterior insular and subcallosal cingulate R1 (cluster-corrected family-wise error p < 0.05) predict a lower risk for harmful alcohol use (measured as a reduction in AUDIT scores) at 2-year follow-up. Control analyses show that other grey matter measures (local volume or fractional anisotropy) did not reveal such an association. An atlas-based machine learning approach further confirms the findings.

The insula is critically involved in predictive coding of autonomic function relevant to subjective alcohol cue/craving states and risky decision-making processes. The subcallosal cingulate is an essential node underlying emotion regulation and involved in negative emotionality addiction theories. Our findings highlight insular and cingulate myeloarchitecture as a potential protective biomarker that predicts resilience to alcohol misuse in youths, providing novel identifiers for early intervention.