The Dysfunction of the Cerebellum and Its Cerebellum-Reward-Sensorimotor Loops in Chronic Spontaneous Urticaria

Abstract

Chronic spontaneous urticaria (CSU) is a common itchy skin disease. Despite its prevalence, the neuropathology of CSU is uncertain. In this study, we explored resting state functional connectivity (rs-FC) changes in CSU, as well as how the symptom changes following intervention can modulate rs-FC. Forty patients and 40 healthy controls (HCs) were recruited. Following an intervention, 32 patients participated in a second scan approximately 6 weeks after the first scan. Compared with healthy controls, CSU subjects exhibited higher regional homogeneity (ReHo) values in the cerebellum, which were positively associated with urticaria activity scores over 7 days (UAS7) at baseline. After an intervention accompanied with clinical improvement, we found that ReHo values decreased at the cerebellum and increased at the bilateral primary somatosensory cortex (SI)/primary motor cortex (MI)/supplementary motor area (SMA). Using the cerebellum as a seed, CSU subjects exhibited increased rs-FC with reward regions when compared with HCs and exhibited decreased rs-FC at the right orbitofrontal cortex and right sensorimotor region following the intervention. The improvement rate values were positively associated with reduced rs-FC values in the two regions. Using the cluster of SI/MI/SMA as a seed, CSU patients exhibited decreased rs-FC with the left putamen, caudate, accumbens, and thalamus following the intervention. These results demonstrate the altered cerebellar activity and cerebellum-reward-sensorimotor loops in CSU.

Functional and anatomical brain connectivity in psoriasis patients and healthy controls: a pilot brain imaging study after exposure to mentally induced itch

“…Interestingly, we showed that the cerebellum is widely involved in this network, as previously suggested 43 . An itch–scratch processing loop consisting of the cerebellum, the SI/MI/SMA and the reward system is possible 43 .…”

“…42 Interestingly, we showed that the cerebellum is widely involved in this network, as previously suggested. 43 An itchscratch processing loop consisting of the cerebellum, the SI/MI/ SMA and the reward system is possible. 43 Like in pain, the cerebellum may modulate stimuli through cerebro-cerebellar loops involving the dorsolateral prefrontal cortex 44 and projections from the inferior olive that transmit information to the cerebellum 45 or projections from the peri-aqueductal grey formation (PAG).…”

“…46,47 Hence, the role of cerebellum could be mostly of a sensitive nature. 43,48 Allowing the threshold to be more stringent would lead to the splitting of the previous network into two subnetworks. The first network would mainly include the cingulate cortex, the parahippocampal gyrus, the temporal pole, the left insula, the left lingual gyrus and lobules III and VIII of the cerebellar vermis.…”

“…Like in pain, the cerebellum may modulate stimuli through cerebro‐cerebellar loops involving the dorsolateral prefrontal cortex 44 and projections from the inferior olive that transmit information to the cerebellum 45 or projections from the peri‐aqueductal grey formation (PAG) 46,47 . Hence, the role of cerebellum could be mostly of a sensitive nature 43,48 …”

Is chronic urticaria more than skin deep?

“…The authors concluded that CSU may be associated with disrupted reward, motivation, and motor processing [42 ]. These investigators published a recent original article which demonstrated the altered cerebellar activity and cerebellum‐reward‐sensorimotor loops in CSU; these changes in cerebellar activity were shown to decline with treatment when urticarial activity is decreased [43 ].…”