Basal ganglia and cerebellar circuits have distinct roles in blepharospasm

IntroductionTo identify areas of brain activity associated with involuntary muscle contractions in patients with blepharospasm using functional MRI.Methods15 patients with blepharospasm underwent 8-min resting state scans with spontaneous orbicularis oculi muscle contractions simultaneously recorded using MRI-compatible surface electromyography. Spasm severity and spasm onset/offset were modeled using the amplitude of the electromyography signal (EMG-Amp) and its first temporal derivative (EMG-Onset), respectively, and included in a multiple regression functional MRI analysis using SPM12. Primary outcome was within-group blood-oxygen-level dependent activations that co-varied with EMG-Amp and EMG-Onset following correction for multiple comparisons for an overall cluster corrected p < 0.05. Secondary analyses included testing for correlations between imaging findings and symptom severity, as measured by clinical dystonia rating scales, using an uncorrected voxel-level threshold of p < 0.001.ResultsImaging data from one subject were excluded due to excessive movement. EMG-Amp co-activated within the left sensorimotor cortex and cerebellum, as well as right lingual gyrus and superior temporal gyrus. EMG-Onset co-activated within the left posterior putamen/pallidum and a frontal eye field region in the left superior frontal gyrus. Symptom severity and EMG-Amp significantly co-varied in a small cluster within the left cerebellum.ConclusionOur preliminary findings here suggest that cerebello-cortical circuits in blepharospasm could drive the intensity of eyelid spasms while basal ganglia circuits are associated with the triggering of spasms. This supports the network model for dystonia and identifies specific areas of involvement consistent with known brain regions responsible for control of movement.     

Restoration of functional network state towards more physiological condition as the correlate of clinical effects of pallidal deep brain stimulation in dystonia

BackgroundDeep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms.ObjectivesThe aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome.MethodsThis open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity).ResultsCompared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls.ConclusionsAll in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.     

Variation of circadian activity rhythm according to body mass index in children

Background/objectivesThis study aimed to examine the variations of circadian activity rhythm of children according to objective body mass index (BMI) values, using a novel statistical framework (ie, Functional Linear Modeling, FLM), separately for school- and weekend days.MethodsA total of 107 participants (60 females; mean age: 10.25 ± 0.48 years) wore an actigraph for seven days during a regular school-week. While valid actigraphic data during school days were available for each of these children, this number decreased to 53 (31 females; mean age: 10.28 ± 0.51 years) during weekend days.ResultsExamining the school days, significantly higher motor activity in participants with higher BMI was observed from around 4:00 a.m. to 6:00 a.m., with a peak about 5:00 a.m. On the contrary, applying the FLM to the weekend days actigraphic data, no significantly different variation of circadian activity rhythm was observed, according to BMI.ConclusionsIn this specific sample of children, during school days, higher BMI is associated with higher activity level in a specific time window in the second half of nocturnal sleep. The lack of significant findings during weekend days could be explained because of higher variability of get-up time and/or the reduced sample size. Future longitudinal studies could explore if the higher motor activity in that specific time window qualifies as a predictive marker of the development of overweight and obesity. If so, early preventive strategies directed towards those at higher risk could be effectively implemented.     

Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia

Subanesthetic administration of ketamine is a pharmacological model to elicit positive and negative symptoms of psychosis in healthy volunteers. We used resting‐state pharmacological functional MRI (rsPhfMRI) to identify cerebral networks affected by ketamine and compared them to the functional connectivity (FC) in schizophrenia. Ketamine can produce sedation and we contrasted its effects with the effects of the anxiolytic drug midazolam. Thirty healthy male volunteers (age = 19–37 years) underwent a randomized, three‐way, cross‐over study consisting of three imaging sessions, with 48 hr between sessions. A session consisted of a control period followed by infusion of placebo or ketamine or midazolam. The ENIGMA rsfMRI pipeline was used to derive two long‐distance (seed‐based and dual‐regression) and one local (regional homogeneity, ReHo) FC measures. Ketamine induced significant reductions in the connectivity of the salience network (Cohen's d: 1.13 ± 0.28, p = 4.0 × 10^?3), auditory network (d: 0.67 ± 0.26, p = .04) and default mode network (DMN, d: 0.63 ± 0.26, p = .05). Midazolam significantly reduced connectivity in the DMN (d: 0.77 ± 0.27, p = .03). The effect sizes for ketamine for resting networks showed a positive correlation (r = .59, p = .07) with the effect sizes for schizophrenia‐related deficits derived from ENIGMA's study of 261 patients and 327 controls. Effect sizes for midazolam were not correlated with the schizophrenia pattern (r = ?.17, p = .65). The subtraction of ketamine and midazolam patterns showed a significant positive correlation with the pattern of schizophrenia deficits (r = .68, p = .03). RsPhfMRI reliably detected the shared and divergent pharmacological actions of ketamine and midazolam on cerebral networks. The pattern of disconnectivity produced by ketamine was positively correlated with the pattern of connectivity deficits observed in schizophrenia, suggesting a brain functional basis for previously poorly understood effects of the drug.     

Hubs disruption in mesial temporal lobe epilepsy. A resting‐state fMRI study on a language‐and‐memory network

Mesial temporal lobe epilepsy (mTLE) affects the brain networks at several levels and patients suffering from mTLE experience cognitive impairment for language and memory. Considering the importance of language and memory reorganization in this condition, the present study explores changes of the embedded language‐and‐memory network (LMN) in terms of functional connectivity (FC) at rest, as measured with functional MRI. We also evaluate the cognitive efficiency of the reorganization, that is, whether or not the reorganizations support or allow the maintenance of optimal cognitive functioning despite the seizure‐related damage. Data from 37 patients presenting unifocal mTLE were analyzed and compared to 48 healthy volunteers in terms of LMN‐FC using two methods: pairwise correlations (region of interest [ROI]‐to‐ROI) and graph theory. The cognitive efficiency of the LMN‐FC reorganization was measured using correlations between FC parameters and language and memory scores. Our findings revealed a large perturbation of the LMN hubs in patients. We observed a hyperconnectivity of limbic areas near the dysfunctional hippocampus and mainly a hypoconnectivity for several cortical regions remote from the dysfunctional hippocampus. The loss of FC was more important in left mTLE (L‐mTLE) than in right (R‐mTLE) patients. The LMN‐FC reorganization may not be always compensatory and not always useful for patients as it may be associated with lower cognitive performance. We discuss the different connectivity patterns obtained and conclude that interpretation of FC changes in relation to neuropsychological scores is important to determine cognitive efficiency, suggesting the concept of “connectome” would gain to be associated with a “cognitome” concept.