Neural activation and connectivity during cued eye blinks in Chronic Tic Disorders

Abstract

Objective: The pathophysiology of Chronic Tic Disorders (CTDs), including Tourette Syndrome, remains poorly understood. The goal of this study was to compare neural activity and connectivity during a voluntary movement (VM) paradigm that involved cued eye blinks among children with and without CTDs. Using the precise temporal resolution of electroencephalography (EEG), we used the timing and location of cortical source resolved spectral power activation and connectivity to map component processes such as visual attention, cue detection, blink regulation and response monitoring. We hypothesized that neural activation and connectivity during the cued eye blink paradigm would be significantly different in regions typically associated with effortful control of eye blinks, such as frontal, premotor, parietal, and occipital cortices between children with and without CTD.

Method: Participants were 40 children (23 with CTD, 17 age-matched Healthy Control [HC]), between the ages of 8-12 (mean age = 9.5) years old. All participants underwent phenotypic assessment including diagnostic interviews, behavior rating scales and 128-channel EEG recording. Upon presentation of a cue every 3 s, children were instructed to make an exaggerated blink.

Results: Behaviorally, the groups did not differ in blink number, latency, or ERP amplitude. Within source resolved clusters located in left dorsolateral prefrontal cortex, posterior cingulate, and supplemental motor area, children with CTD exhibited higher gamma band spectral power relative to controls. In addition, significant diagnostic group differences in theta, alpha, and beta band power in inferior parietal cortex emerged. Spectral power differences were significantly associated with clinical characteristics such as tic severity and premonitory urge strength. After calculating dipole density for 76 anatomical regions, the CTD and HC groups had 70% overlap of top regions with the highest dipole density, suggesting that similar cortical networks were used across groups to carry out the VM. The CTD group exhibited significant information flow increase and dysregulation relative to the HC group, particularly from occipital to frontal regions.

Conclusion: Children with CTD exhibit abnormally high levels of neural activation and dysregulated connectivity among networks used for regulation and effortful control of voluntary eye blinks.

Keywords: Attention network; EEG; Gamma power; Pediatric; Tourette syndrome.

Fig. 1

Computation of source-level connectivity. This schematic illustrates the anatomical normalization of dipole-represented independent components (ICs) and computation of pairwise dipole density across anatomical regions of interest (ROIs).

Fig. 2

Blink validation analyses indicate no significant group differences in blink number, latency, or ERP amplitude in raw and cleaned EOG data. (a) Histogram of blink latency shows probabilistic distribution of blink occurrence within a trial. Each bin is 100 ms and the sum of all binned values is 1 for each group. There were no significant group differences in blink count or latency. (b) A whole-head topography at the the blink ERP peak (group average = 488 ms) and locations of five frontal EEG electrodes used for analysis. (c) Blink ERP of minimally-processed raw data (see Supplemental Materials S5) show no significant group difference in ERP mean peak-window amplitude (indicated by dark line above the ERP peak). The dotted line (~0 uV) shows the back projected potentials at the same frontal electrodes from the three frontal EOG-IC clusters, which account for 13% of total ICs but 93% of the blink ERP. (d) Magnification (57×) of the cleaned EOG-IC data indicates overlap of the blink ERP for both groups. CTD = Chronic Tic Disorder, HC=Healthy Control, ERP = event related potential, EOG = Electroculography, IC = independent component.

Fig. 3

Group differences in oscillatory activity during cued eye blink initiation and execution. Significant differences in spectral power were apparent in frontal, pre-motor, and parietal regions. Outlined in black are pixels significant at p < .05, corrected. Solid line at latency = 0 is blink cue onset. Dotted line indicates the group mean for blink latency. CTD = Chronic Tic Disorder, HC=Healthy Control, Post Cing = Posterior Cingulate, DLPFC = Dorsolateral prefrontal cortex, SMA = supplemental motor area, Inf = inferior, Hz = hertz, dB = decibel.

Fig. 4

Dipole Density for Tic and Control groups. Pictures on left show Combined dipole density in brain from sagittal, radial and axial views. Percent of dipole density is presented by group and combined. Top regions overlapped by 70%, however the healthy control (HC) group had more frontal regions (60%) and Chronic Tic Disorder (CTD) group had more posterior regions (80%) with the highest dipole density. L = left, R = right, Supp = supplemental, Sup = superior, Ant = anterior.

Fig. 5

Connectivity analysis results. A. The connectivity matrix of 76 × 76 anatomical ROIs. Significant edges are color-coded. B. One frame of the information flow movie at 420 ms after the blink cue onset seen from a sagittal and axial views. The bottom panel shows the envelope of the significant edges between 2 and 13 Hz. C. The four most dominant edges showing group differences (p < .05). CTD patients failed to suppress information flow from occipital to frontal/central and motor to intraparietal/occipital. Solid black line at Latency = 0 is the blink cue onset. Dotted line indicates mean blink latency. RPDC = renormalized partial directed coherence.