Patients with bipolar illness have a wide range of clinical responses to medicinal treatment. Greater knowledge of the underlying neuronal circuitry involved in bipolar treatment response subtypes should help researchers better understand treatment resistance and find a surgical target for deep brain stimulation (DBS) specific to the condition. Even though there has been a lot of imaging research done on the disease, there aren’t many comparative imaging evaluations of treatment responsiveness. There are no DBS targets established specifically for bipolar disorder patients. As a result, authors compared healthy controls to those who are responsive to treatment (RSP) and those who are resistant to treatment (REF) in terms of cingulum bundle axonal connection about corticostriatal-thalamocortical (CSTC) loops involved in bipolar illness (HCs). Twenty-five bipolar disorder patients (13 RSP and 12 REF) were scanned with diffusion sequences for probabilistic diffusion-weighted tractography analysis. MRTrix was used for image processing and tractography. For 10 anterior cingulum bundle subregions, region of interest (ROI) masks were manually developed, incorporating surgical targets previously assessed to treat bipolar illness (cingulotomy and subgenual cingulate DBS targets). FreeSurfer was used to build cortical and subcortical ROIs of brain areas considered to be related to bipolar disorder and described in animal tract-tracing models. Each group was compared in axonal projections from the cingulum bundle subregion ROIs to cortical/subcortical ROIs.

Cingulum bundles and CSTC loops showed significant changes across groups. The RSP group exhibited more connections between the rostral cingulum bundle and the medial orbitofrontal cortex, part of the limbic CSTC loop. In contrast, the REF group had more connections between the rostral cingulum bundle and the thalamus. In addition, both RSP and REF subjects had lower dorsal cingulum bundle dorsal connectivity (dorsal anterior/posterior cingulate, dorsomedial/lateral frontal cortex) and higher ventral cingulum bundle dorsal connectivity (subgenual cingulate, frontal pole, lateral orbitofrontal cortex) involving limbic and associative CSTC loops compared to HCs. The findings show that bipolar treatment responsiveness is linked to significant changes in cingulum bundle connectivity compared to CSTC loops, leading to identifying a surgical target for bipolar disorder therapy by DBS in the future.