A 21-year-old male, an undergraduate student from rural south India, presented to our emergency with suicidal thoughts. History revealed three years of academic decline, pathological slowness in routine activities (e.g., bathing, eating, dressing up, and using the toilet), repetitive 'just-right' behaviors (e.g., wiping his mouth after eating, clearing his throat, pulling down his shirt, mixing his food in the plate and walking back and forth until 'feeling satisfied'). As a result, he spent up to three hours completing a meal or his toilet routines. Before presentation to us, he had received trials with two separate courses of electroconvulsive therapy (ECT) - six bitemporal ECTs at first, followed by nine bifrontal) spaced about two months apart. ECT was prescribed because of a further deterioration in his condition over the prior 18-months, with reduced oral intake, weight loss, grossly diminished speech output, and passing urine in bed (as he would remain in bed secondary to his obsessive ambitendency, as disclosed later). His oral intake and speech output improved with both ECT treatments, only to gradually worsen over the next few weeks. Given the potential catatonic phenomena (withdrawn behaviour and mutism) in the background of ongoing academic decline, slowness and stereotypies, he was also treated with oral olanzapine 20mg for eight weeks and risperidone 6mg for six weeks with minimal change in his slowness and repetitive behaviors. He did not receive any antidepressant medications. Psychotherapy was also not considered given the limited feasibility due to the severe withdrawal and near mutism. We could not elicit any contributory clinical history of prodromal or mood symptoms from adolescence when we evaluated his past psychiatric and medical history. Two months after the last ECT treatment, he presented to our emergency services with suicidal thoughts. He was admitted, and mental status examination revealed aggressive (urges to harm himself by jumping in front of a moving vehicle or touching electric outlets) and sexual obsessions with mental compulsions and passing urine in bed (as he could not go to the toilet in time due to obsessive ambitendency). The Yale-Brown Obsessive-Compulsive Scale (YBOCS) severity score was 29 . He had good insight into obsessions, but not the 'just right' repetitive behaviors; it was, therefore, challenging to engage him in psychotherapy. We treated him with escitalopram 40mg and brief psychoeducation before being discharged. After three months, his obsessions had resolved, but pathological slowness, 'just right' phenomena, and passing urine in bed had worsened (YBOCS score 31). 
We then obtained a plain and contrast brain MRI, to rule out an organic aetiology given the atypical nature of symptoms (apparent urinary incontinence) and the poor treatment response. The MRI revealed a wedge-shaped lesion in the right posterior cerebellum, suggestive of a chronic infarct in the posterior inferior cerebellar artery territory ( Figure-1A). MR-angiogram revealed no focal narrowing of intracranial and extracranial vessels. Electroencephalography, cerebrospinal fluid analysis, autoimmune and vasculitis investigations were unremarkable. Echocardiogram was normal and the sickling test for sickle cell anemia was also negative. We specifically inquired about history of loss of consciousness, seizures or motor incoordination, but these were absent. His neurological examination with a detailed focus on cerebellar signs was unremarkable. The International Cooperative Ataxia Rating Scale (ICARS) score was zero. The Cerebellar Cognitive Affective Syndrome (CCAS) scale revealed >3 failed tests - in domains of attention, category switching, response inhibition, verbal fluency, and visuospatial drawing, suggestive of definite CCAS .
Owing to inadequate treatment response and the possibility of OCD secondary to the cerebellar lesion, we discussed with the patient about MRI-informed repetitive transcranial magnetic stimulation (rTMS) and obtained his consent. The presence of a lesion involving a node (cerebellum) within the cerebello-thalamo-cortical circuit - a key pathway for error monitoring  and inhibitory control  - cognitive processes typically impacted in OCD prompted us to utilize a personalized-medicine approach to treatment. We acquired a resting-state functional-MRI echoplanar sequence (8m 20s; 250-volumes) in duplicate - before, and one-month after rTMS treatment on a 3-Tesla scanner (Skyra, Siemens), using a 20-channel coil with the following parameters: TR/TE/FA= 2000ms/30ms/78; voxel=3mm isotropic; FOV=192*192.
Image processing was performed using the FMRIB Software Library (FSL version-5.0.10) . Figure 1 describes how we obtained a seed-to-voxel connectivity map to identify the best connectivity of the cerebellar lesion-seed with voxels in the pre-supplementary motor area (pre-SMA; MNI x=3; y=13; z=58) - a commonly used site for neuromodulation in OCD . This area demonstrates connections with the non-motor (ventral dentate nucleus) parts of the posterolateral cerebellum  and contributes to error processing and inhibitory control along with the cerebellum . 
We augmented escitalopram with rTMS, administered as intermittent theta-burst stimulation (iTBS) to the pre-SMA coordinates ( Figure-1D). Six-hundred pulses were delivered as triplet bursts at theta frequency and 90% of the resting motor threshold (50 Hz; 2s on; 8s off) using a MagPro X100 (MagVenture, Farum, Denmark) device under MR-guided neuronavigation using the BrainSight stereotaxic system (Rogue Research, Montreal, Canada) with a figure-of-eight (MagVenture MCF-B-70) coil held with the handle in line with the sagittal plane, pointing toward the occiput to stimulate the pre-SMA site. We hypothesized that iTBS  to the pre-SMA could adaptively engage the cerebellum lesion, with which it shares neuronal oscillation frequencies, and hence improve the disabling symptoms. He received 27 iTBS sessions, once daily over the next month. Following ten sessions, he began to show a reduction in his repetitive behaviors, and by the 15 th session, he acknowledged that his behaviors were irrational. The YBOCS severity score had reduced to 24 (~22.5% improvement), which remained the same, even at the end of 27 sessions of iTBS treatment. There was no change in the CCAS and ICARS scores. The clinical benefits remained unchanged until three months of follow-up. Subsequently, we observed a gradual reversal to pre-TMS symptom severity. Maintenance TMS was suggested but was not feasible due to logistic reasons and therefore he was initiated on oral fluoxetine that was gradually increased to 80mg/day, with which we observed minimal change in symptoms over the next four months.
The pre- and post-rTMS scans  were parcellated into 48-cortical, 15-subcortical, and 28-cerebellar regions as per the Harvard-Oxford  and the Cerebellum MNI-FLIRT atlases . Average BOLD-signal time-series from each of these nodes, obtained after processing within FSL version-5.0.10, were then concatenated to obtain a Pearson's correlation matrix between 91 nodes, separately for the pre- and post-TMS studies.
We analyzed the two 91 x 91 matrices using the Rank-two ellipse (R2E) seriation technique for node clustering  ( Figure 2). This technique reorders the nodes by moving the ones with a higher correlation closer to the diagonal. Thus, blocks along the diagonal of the matrix visualization show possible functional coactivating clusters.
We observed (a) extended connectivity of the cerebellar network after iTBS treatment as evidenced through its diminished modularity - the larger cerebellar cluster/block had an increased overlap with both anterior and posterior brain networks as observed along the diagonal in ( Figure 2B), and (b) formation of better-defined sub-clusters within the larger cerebellar cluster indicating improved within-network modularity of distinct functional cerebellar networks [e.g., vestibular (lobules IX and X) and cognitive-limbic (crus I/II and vermis)].