Discover the research areas of the Shaikh Lab in the Department of Neurology at Case Western Reserve University School of Medicine.
Perception and Action in Parkinson's Disease
The brain learns from prior perceptual experiences and implements them to improve future action. Action-perception coupling is impaired in people with Parkinson’s disease (PD), failing them in routine tasks. Our studies examined such coupling in three domains: spatial, visual, and eye movement control. Spatial navigation experiments using a motion simulation platform and immersive virtual reality discovered an abnormal perception in PD. Using DBS bioelectric field models and neuroimaging, we found the brain areas and ways to modulate them to improve spatial perception to mitigate falls.
These results formed foundations for the highly innovative and impactful application of brain neuromodulation, such as DBS, to prevent falls and broken bones in older adults. Visual perception requires optimized interaction between the top-down, higher-level cognitive influence of prior experiences and the bottom-up encoding of real-time reflexive visual input. The powerful top-down signal can cause visual hallucinations; we found that PD patients have strong visual priors. We discovered ways to modulate visual priors with DBS.
Stimulation of cortico-subthalamic projections restored the critical impact of bottom-up visual encoding. These pioneering experiments provided a basis for using focused neuromodulation with DBS to treat visual hallucinations. This finding has broad application for treating hallucinations in several neuropsychiatric conditions prevalent in veterans. Binocular control and misalignment of the eyes. Our studies explained the mechanistic underpinning of abnormal binocular control, leading to reading difficulty and double vision in about one-third of PD patients. We further discovered areas of the subthalamic region that can be modulated with DBS to treat eye misalignment. The results provided novel foundations for DBS to treat visuospatial and visuomotor dysfunction in several neurodegenerative conditions.
Six degrees of freedom motion simulator used in our lab to precisely measure various brain functions including perception of one's own motion and vestibular ocular reflex. Sinem was a post doctoral fellow in the lab then and Dr. Shaikh both working on an experimental set up. Current experiments are integrating perceived motion simulation with immersive virtual reality to understand physiological and psychophysics of visual spatial navigation.
Customized Remote Rehab (Adaptive Bike)
We integrate artificial intelligence, wearable sensing, and adaptive control systems modeling to design and validate a novel rehab technique, an adaptive bike. The adaptive bike adjusts the resistance of the pedals according to a behavioral output from the user. In this case, patients are equipped with wearable inertial moment units and are instructed to pedal an adaptive stationary bike. The wearables report patient-specific motor outputs, which are further utilized in clinical measures, and the pre-processed outputs are used as a controller for the adaptive bike. The adaptive bike's pedal resistance changes as the patient’s wearable outputs change. The corresponding methodology eliminates the need for in-person visitation for expert rehab. The ultimate goal of this project is to generate clinical tools that allow remote delivery of precision care, utilizing an in-home and easy-to-use infrastructure.
Sinem was a post doctoral fellow in the lab then and Dr. Shaikh both working on an experimental set up. Current experiments are integrating perceived motion simulation with immersive virtual reality to understand physiological and psychophysics of visual spatial navigation.
Translational Neurology of Eye Movement Disorders
Our lab is one of the few worldwide to study the neuro-ophthalmology of eye movements utilizing computational and engineering approaches. We have practiced a multidisciplinary approach—experimental examination of the eye movement disorder, simulating the phenomenology with conductance-based neuromimetic computational models of brain circuits, and simulation of novel therapeutic effects, and then applying the theoretical concept to design the optimal therapeutic candidate for the treatment of disabling disorder as opsoclonus, oculopalatal tremor, or nystagmus. This approach has discovered the rationale for using various drugs such as beta-blockers, primidone, and benzodiazepine to treat opsoclonus, quinine for oculopalatal tremor, and levetiracetam for acquired pendular nystagmus.
In this images we are utilizing high-frequency deep brain stimulation (DBS). In 2016, Shaikh teamed with Cameron McIntyre, PhD, a fellow investigator and associate director of industry relations at the FES Center. Shaikh’s experience as a vestibular and eye movement scientist, combined with McIntyre’s expertise in DBS provided “the perfect model” to study gait impairments in participants with Parkinson’s disease.
Integrative Network Theory in Dystonia
The third most common movement disorder causing abnormal twisting and turning of the body, dystonia, is traditionally considered a basal ganglia disorder, while contemporary theories emphasize the cerebellum’s role. Our multidisciplinary approach using motion capture techniques with wearable sensors, machine learning, single-unit electrophysiology, and local field potentials suggested that dystonia is due to abnormal brain network function converting a movement velocity signal to a stabilizing position for balance and coordination.
Our studies emphasized the significance of multi-level feedback from the cerebellum, basal ganglia, and proprioception in dystonia. This innovative framework, radically different from traditional beliefs, provided an integrative model for reconciling many conflicting views. The results have profound implications for interpreting basic and clinical studies and identifying other therapeutic targets, raising new prospects for non-invasive and surgical interventions for treating dystonia, which is common and severely disabling in veterans and non-veterans.
In sum, we strive to use a novel and strategic translational approach, using the latest computational and neural engineering techniques to analyze and treat often devastating diseases and the effects of trauma that destroy brain function.
Six degrees of freedom motion simulator used in our lab to precisely measure various brain functions including perception of one's own motion and vestibular ocular reflex. Sinem was a post doctoral fellow in the lab then and Dr. Shaikh both working on an experimental set up. Current experiments are integrating perceived motion simulation with immersive virtual reality to understand physiological and psychophysics of visual spatial navigation.