Laura Hack

Jul 5, 2024 | nature.com | Leonardo Tozzi |Claire Bertrand |Laura Hack |TeChieh Chen |Yosef A. Berlow |Kelvin Lim | +8 more

We previously identified a cognitive biotype of depression characterized by treatment resistance, impaired cognitive control behavioral performance and dysfunction in the cognitive control circuit, comprising the dorsolateral prefrontal cortex (dLPFC) and dorsal anterior cingulate cortex (dACC). Therapeutic transcranial magnetic stimulation (TMS) to the left dLPFC is a promising option for individuals whose depression does not respond to pharmacotherapy. Here, 43 veterans with treatment-resistant depression were assessed before TMS, after early TMS and post-TMS using functional magnetic resonance imaging during a Go–NoGo paradigm, behavioral cognitive control tests and symptom questionnaires. Stratifying veterans at baseline based on task-evoked dLPFC–dACC connectivity, we demonstrate that TMS-related improvement in cognitive control circuit connectivity and behavioral performance is specific to individuals with reduced connectivity at baseline (cognitive biotype +), whereas individuals with intact connectivity at baseline (cognitive biotype −) did not demonstrate significant changes. Our findings show that dLPFC–dACC connectivity during cognitive control is both a promising diagnostic biomarker for a cognitive biotype of depression and a response biomarker for cognitive improvement after TMS applied to the dLPFC. The authors investigate functional connectivity before and after transcranial magnetic stimulation in veterans with treatment-resistant depression stratified by cognitive biotype, demonstrating associated brain connectivity-mediated improvement in cognitive behavioral task performance.

Jun 17, 2024 | nature.com | Leonardo Tozzi |Xue Zhang |Adam R. Pines |Emily Zhai |Sarah Chang |Laura Hack | +11 more

There is an urgent need to derive quantitative measures based on coherent neurobiological dysfunctions or ‘biotypes’ to enable stratification of patients with depression and anxiety. We used task-free and task-evoked data from a standardized functional magnetic resonance imaging protocol conducted across multiple studies in patients with depression and anxiety when treatment free (n = 801) and after randomization to pharmacotherapy or behavioral therapy (n = 250). From these patients, we derived personalized and interpretable scores of brain circuit dysfunction grounded in a theoretical taxonomy. Participants were subdivided into six biotypes defined by distinct profiles of intrinsic task-free functional connectivity within the default mode, salience and frontoparietal attention circuits, and of activation and connectivity within frontal and subcortical regions elicited by emotional and cognitive tasks. The six biotypes showed consistency with our theoretical taxonomy and were distinguished by symptoms, behavioral performance on general and emotional cognitive computerized tests, and response to pharmacotherapy as well as behavioral therapy. Our results provide a new, theory-driven, clinically validated and interpretable quantitative method to parse the biological heterogeneity of depression and anxiety. Thus, they represent a promising approach to advance precision clinical care in psychiatry. Personalized brain circuit measures quantified using a new imaging technology in 801 patients with depression and anxiety identify six biotypes with unique symptoms, behaviors and responses to different types of treatment.