Phuong Nguyen1, Diane Kelly1, Amanda Glickman1, Salem Argaw2, Erika Shelton3, David A Peterson4,5, Brian D Berman3. 1. School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 2. School of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. 3. Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. 4. Institute of Neural Computation, University of California San Diego, San Diego, California, USA. 5. Computational Neurobiology Laboratory, Salk Institute of Biological Studies, La Jolla, California, USA.
Abstract
BACKGROUND: The neurophysiological disruptions underlying blepharospasm, a disabling movement disorder characterized by increased blinking and involuntary muscle spasms of the eyelid, remain poorly understood. OBJECTIVE: To investigate the neural substrates underlying reflexive blinking in blepharospasm patients compared to healthy controls using simultaneous functional MRI and surface electromyography. METHODS: Fifteen blepharospasm patients and 15 healthy controls were recruited. Randomly timed air puffs to the left eye were used to induce reflexive eye blinks during two 8-minute functional MRI scans. Continuous surface electromyography and video recordings were used to monitor blink responses. Imaging data were analyzed using an event-related design. RESULTS: Fourteen blepharospasm patients (10 female; 61.6 ± 8.0 years) and 15 controls (11 female; 60.9 ± 5.5 years) were included in the final analysis. Reflexive eye blinks in controls were associated with activation of the right hippocampus and in patients with activation of the left caudate nucleus. Reflexive blinks in blepharospasm patients showed increased activation in the right postcentral gyrus and precuneus, left precentral gyrus, and left occipital cortex compared to controls. Dystonia severity negatively correlated with activity in the left occipital cortex, and disease duration negatively correlated with reflexive-blink activity in the cerebellum. CONCLUSIONS: Reflexive blinking in blepharospasm is associated with increased activation in the caudate nucleus and sensorimotor cortices, suggesting a loss of inhibition within the sensorimotor corticobasal ganglia network. The association between decreasing neural response during reflexive blinking in the cerebellum with disease duration suggests an adaptive role.
BACKGROUND: The neurophysiological disruptions underlying blepharospasm, a disabling movement disorder characterized by increased blinking and involuntary muscle spasms of the eyelid, remain poorly understood. OBJECTIVE: To investigate the neural substrates underlying reflexive blinking in blepharospasmpatients compared to healthy controls using simultaneous functional MRI and surface electromyography. METHODS: Fifteen blepharospasmpatients and 15 healthy controls were recruited. Randomly timed air puffs to the left eye were used to induce reflexive eye blinks during two 8-minute functional MRI scans. Continuous surface electromyography and video recordings were used to monitor blink responses. Imaging data were analyzed using an event-related design. RESULTS: Fourteen blepharospasmpatients (10 female; 61.6 ± 8.0 years) and 15 controls (11 female; 60.9 ± 5.5 years) were included in the final analysis. Reflexive eye blinks in controls were associated with activation of the right hippocampus and in patients with activation of the left caudate nucleus. Reflexive blinks in blepharospasmpatients showed increased activation in the right postcentral gyrus and precuneus, left precentral gyrus, and left occipital cortex compared to controls. Dystonia severity negatively correlated with activity in the left occipital cortex, and disease duration negatively correlated with reflexive-blink activity in the cerebellum. CONCLUSIONS: Reflexive blinking in blepharospasm is associated with increased activation in the caudate nucleus and sensorimotor cortices, suggesting a loss of inhibition within the sensorimotor corticobasal ganglia network. The association between decreasing neural response during reflexive blinking in the cerebellum with disease duration suggests an adaptive role.