Local neuroanatomical and tract-based proxies of optimal subcallosal cingulate deep brain stimulation.

BACKGROUND: Deep brain stimulation of the subcallosal cingulate area (SCC-DBS) is a promising neuromodulatory therapy for treatment-resistant depression (TRD). Biomarkers of optimal target engagement are needed to guide surgical targeting and stimulation parameter selection and to reduce variance in clinical outcome. OBJECTIVE/HYPOTHESIS: We aimed to characterize the relationship between stimulation location, white matter tract engagement, and clinical outcome in a large (n = 60) TRD cohort treated with SCC-DBS. A smaller cohort (n = 22) of SCC-DBS patients with differing primary indications (bipolar disorder/anorexia nervosa) was utilized as an out-of-sample validation cohort. METHODS: Volumes of tissue activated (VTAs) were constructed in standard space using high-resolution structural MRI and individual stimulation parameters. VTA-based probabilistic stimulation maps (PSMs) were generated to elucidate voxelwise spatial patterns of efficacious stimulation. A whole-brain tractogram derived from Human Connectome Project diffusion-weighted MRI data was seeded with VTA pairs, and white matter streamlines whose overlap with VTAs related to outcome ('discriminative' streamlines; Puncorrected < 0.05) were identified using t-tests. Linear modelling was used to interrogate the potential clinical relevance of VTA overlap with specific structures. RESULTS: PSMs varied by hemisphere: high-value left-sided voxels were located more anterosuperiorly and squarely in the lateral white matter, while the equivalent right-sided voxels fell more posteroinferiorly and involved a greater proportion of grey matter. Positive discriminative streamlines localized to the bilateral (but primarily left) cingulum bundle, forceps minor/rostrum of corpus callosum, and bilateral uncinate fasciculus. Conversely, negative discriminative streamlines mostly belonged to the right cingulum bundle and bilateral uncinate fasciculus. The best performing linear model, which utilized information about VTA volume overlap with each of the positive discriminative streamline bundles as well as the negative discriminative elements of the right cingulum bundle, explained significant variance in clinical improvement in the primary TRD cohort (R = 0.46, P < 0.001) and survived repeated 10-fold cross-validation (R = 0.50, P = 0.040). This model was also able to predict outcome in the out-of-sample validation cohort (R = 0.43, P = 0.047). CONCLUSION(S): These findings reinforce prior indications of the importance of white matter engagement to SCC-DBS treatment success while providing new insights that could inform surgical targeting and stimulation parameter selection decisions.

Electrophysiological Responses to Rapidly-Presented Affective Stimuli Predict Individual Differences in Subsequent Attention.

We are constantly surrounded by a dynamically changing perceptual landscape that can influence our behavior even without our full conscious awareness. Emotional processing can have effects on subsequent attention, but there are mixed findings on whether it induces attentional enhancement or interference. The present study used a new multimodal approach to explain and predict such attentional effects based on individual differences in response to emotional stimuli. We briefly presented affective pictures (neutral, positive, erotic, mutilation, and horror categories) for 80 ms, immediately followed by a cued flanker task that was unrelated to the pictures. Event-related potentials (ERPs), skin conductance response (SCR), and reaction time (RT) were measured for each participant. We found that, in general, affective pictures induced higher electrophysiological responses compared with neutral pictures [P300 and late positive potential (LPP) in the erotic condition; P300, LPP, and SCR in the horror condition]. In particular, individuals who showed a strong ERP response to the pictures were impeded in the erotic condition (only P300) and facilitated in the horror condition (both P300 and LPP). Those who did not show a significant ERP or SCR response to the pictures were facilitated in the erotic condition and impeded in the horror condition. Furthermore, it was possible to classify the direction of the attentional effect from the participants' P300, LPP, and SCR responses. These results demonstrate that underlying individual differences in emotional processing must be considered in understanding and predicting the effects of emotions on attention and cognition.