Parcel-guided rTMS for depression

Abstract

Transcranial magnetic stimulation (TMS) is an approved intervention for treatment-resistant depression (TRD), but current targeting approaches are only partially successful. Our objectives were (1) to examine the feasibility of MRIguided TMS in the clinical setting using a recently published surface-based, multimodal parcellation in patients with TRD who failed standard TMS (sdTMS); (2) to examine the neurobiological mechanisms and clinical outcomes underlying MRI-guided TMS compared to that of sdTMS. We used parcel-guided TMS (pgTMS) to target the left dorsolateral prefrontal cortex parcel 46. Resting-state functional connectivity (rsfc) was assessed between parcel 46 and predefined nodes within the default mode and visual networks, following both pgTMS and sdTMS. All patients (n = 10) who had previously failed sdTMS responded to pgTMS. Alterations in rsfc between frontal, default mode, and visual networks differed significantly over time between groups. Improvements in symptoms correlated with alterations in rsfc within each treatment group. The outcome of our study supports the feasibility of pgTMS within the clinical setting. Future prospective, double-blind studies of pgTMS vs. sdTMS appear warranted.

Proof of concept study to develop a novel connectivity-based electric-field modelling approach for individualized targeting of transcranial magnetic stimulation treatment

“…Consistent with previous work implicating the junction of BA9 and BA46 as a potentially optimal site of stimulation for depression symptoms, we show with both MADRS and HAMD scores that are model predicts the largest symptom reduction at this location (47). Our model adds to the work suggesting that targeting rsFC networks can inform TMS targeting (40), and are consistent with the findings that individualized rsFC maps may be most informative (39).…”

“…Importantly, active rTMS to the l dlPFC has been shown to reduce anticorrelation between the dlPFC and sgACC (53, 58, 59), and prospective targeting based on individualized dlPFC – sgACC connectivity leads to a greater reduction in symptoms compared to traditional targeting (53, 54). In addition, there is some research to suggest that individualized targeting of BA46 through a parcel guided approach can improve treatment response in patients who have previously failed standard TMS targeted at the dlPFC using the 5-cm rule (28). Based on this work, it could be argued that the current state-of-the-art for individualized TMS targeting for depression is to target sites in the left dlPFC with maximal connectivity with the subgenual cingulate cortex.…”

“…In the current work, we apply this modeling approach to two targets, a positive control left dlPFC and a negative control motor cortex (M1), based on targeting guidelines from the literature (See Supplemental Tables 1 and 2). We use bootstrapping to estimate the reliability of the targets identified using this approach at the single-subject level, and permutation testing to determine whether this approach makes group-level predictions that are consistent with the literature (28–30).…”

Deficits in Pre-attentive Processing of Spatial Location and Negative Symptoms in Subjects at Clinical High Risk for Schizophrenia

“…Deficits in MMN generation in Sz are associated with impaired activation of superior temporal auditory cortex as reflected in both ERP source localization ( 8 , 9 ) and fMRI ( 10 , 11 ) studies, as well as reduced activation of subcortical regions such as inferior colliculus and thalamus ( 12 ). During MMN paradigms, activation is also observed within prefrontal cortex and a salience network that includes insula and anterior cingulate cortex ( 9 , 11 , 13 ). By contrast, MMN is associated with de-activation of visual and dorsal attention systems ( 11 ).…”

Network Diffusion Embedding Reveals Transdiagnostic Subnetwork Disruption and Potential Treatment Targets in Internalizing Psychopathologies

“…Although rTMS is generally effective, MDD remission following treatment is 30-40% (George et al, 2013), indicating a need for developing better therapeutic paradigms, such as personalized treatment protocols. In line with these goals, a study that used MRI guidance to enhance targeting of specific regions of the dlPFC, all rTMS-resistant MDD PTs responded to this new approach (Moreno-Ortega et al, 2020). Another study used fMRI guidance to individually targeted cortical emotion regulation systems to improve rTMS efficacy (Luber et al, 2017).…”