Normalization of aberrant pretherapeutic dynamic functional connectivity of extrastriate visual system in patients who underwent thalamotomy with stereotactic radiosurgery for essential tremor: a resting-state functional MRI study

Abstract

OBJECTIVE The tremor circuitry has commonly been hypothesized to be driven by one or multiple pacemakers within the cerebello-thalamo-cortical pathway, including the cerebellum, contralateral motor thalamus, and primary motor cortex. However, previous studies, using multiple methodologies, have advocated that tremor could be influenced by changes within the right extrastriate cortex, at both the structural and functional level. The purpose of this work was to evaluate the role of the extrastriate cortex in tremor generation and further arrest after left unilateral stereotactic radiosurgery thalamotomy (SRS-T). METHODS The authors considered 12 healthy controls (HCs, group 1); 15 patients with essential tremor (ET, right-sided, drug-resistant; group 2) before left unilateral SRS-T; and the same 15 patients (group 3) 1 year after the intervention, to account for delayed effects. Blood oxygenation level–dependent functional MRI during resting state was used to characterize the dynamic interactions of the right extrastriate cortex, comparing HC subjects against patients with ET before and 1 year after SRS-T. In particular, the authors applied coactivation pattern analysis to extract recurring whole-brain spatial patterns of brain activity over time. RESULTS The authors found 3 different sets of coactivating regions within the right extrastriate cortex in HCs and patients with pretherapeutic ET, reminiscent of the “cerebello-visuo-motor,” “thalamo-visuo-motor” (including the targeted thalamus), and “basal ganglia and extrastriate” networks. The occurrence of the first pattern was decreased in pretherapeutic ET compared to HCs, whereas the other two patterns showed increased occurrences. This suggests a misbalance between the more prominent cerebellar circuitry and the thalamo-visuo-motor and basal ganglia networks. Multiple regression analysis showed that pretherapeutic standard tremor scores negatively correlated with the increased occurrence of the thalamo-visuo-motor network, suggesting a compensatory pathophysiological trait. Clinical improvement after SRS-T was related to changes in occurrences of the basal ganglia and extrastriate cortex circuitry, which returned to HC values after the intervention, suggesting that the dynamics of the extrastriate cortex had a role in tremor generation and further arrest after the intervention. CONCLUSIONS The data in this study point to a broader implication of the visual system in tremor generation, and not only through visual feedback, given its connections to the dorsal visual stream pathway and the cerebello-thalamo-cortical circuitry, with which its dynamic balance seems to be a crucial feature for reduced tremor. Furthermore, SRS-T seems to bring abnormal pretherapeutic connectivity of the extrastriate cortex to levels comparable to those of HC subjects.

Resting State Functional Connectivity Signatures of MRgFUS Vim Thalamotomy in Parkinson's Disease: A Preliminary Study

“…In line with Xiong et al (42) we observed the involvement of the second-order, functionally highly-specialized, visual area in the pathogenesis of tremor in PD. Also, such contribution was already evidenced in ET (37,40,41,89). Our finding of a reduced interaction between specific subareas of the occipital lobe and the cerebellar hemisphere supports the evidence that the remote influence between structurally segregated regions with distinct functional profiles may exist even in the absence of direct anatomical projections, through indirect polysynaptic pathways of connection (41,90).…”

“…Also, such contribution was already evidenced in ET ( 37 , 40 , 41 , 89 ). Our finding of a reduced interaction between specific subareas of the occipital lobe and the cerebellar hemisphere supports the evidence that the remote influence between structurally segregated regions with distinct functional profiles may exist even in the absence of direct anatomical projections, through indirect polysynaptic pathways of connection ( 41 , 90 ). Although the precise function of the OFusG has not been fully revealed yet, it has been implicated in high-level visual processing, such as categorical recognition of visual stimuli ( 91 , 92 ), and in those processes characterized by high recurrence of perceptual ambiguity ( 93 ).…”

“…To the best of our knowledge, there are only a few studies describing functional correlates of Vim ablation, and the potential mechanisms of connectivity reorganization over time after lesional procedures on Vim (mainly based on stereotactic radiosurgical thalamotomy) are yet to be recognized. To date, the literature on PD only includes at most 10 patients (34)(35)(36)(37)(38)(39)(40)(41)(42).…”

TbCAPs: A toolbox for co-activation pattern analysis

“…In several works, counts or occurrences (that is, how many times a given CAP is expressed) were used as metrics of interest [20,21,22]. We verified that our suggested metrics also include the information rendered by the counts: as seen in Figure 1B, the average correlation across CAPs between counts and in-degree, out-degree or resilience exceeded 0.8 (respectively ρ = 0.83 ± 0.11, ρ = 0.85 ± 0.08 and ρ = 0.81 ± 0.07).…”

“…Since then, co-activation pattern analysis has started to gain momentum as a potent tool to reveal functional brain dynamics subtleties: analyses taking the posterior cingulate cortex (PCC) as a seed revealed alterations of spatial intensity level and occurrence in specific CAPs [19,20], while in adolescent depression, [21] showed that the time spent in a specific frontoinsular-default network CAP positively correlated with symptoms severity. CAP analysis also enabled to track the renormalisation of CAP occurrences in patients with essential tremor following surgical intervention [22].…”