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Principal Investigator: Kathryn Amy Cross
Organization: UNIVERSITY OF CALIFORNIA LOS ANGELES
Fiscal Year: 2024
Award: $242,055
Funding agency: National Institute of Neurological Disorders and Stroke
PROJECT SUMMARY
A promising strategy to improve neuromodulation therapies (e.g. deep brain stimulation) in Parkinson’s
Disease (PD) is to develop stimulation paradigms that target specific neural signals. Most previous work has
aimed to identify and reduce pathologic signals. An unexplored alternative approach is to identify and enhance
neural signals that promote movement. Several scenarios known to improve movement in PD patients are the
presence of visual movement targets, rhythmic auditory stimuli, and motivational incentives. The goal of this
proposal is to capitalize on these scenarios to identify biomarkers of movement facilitation that may serve as
targets for future neuromodulation therapies. This approach has potential to provide novel therapies for
symptoms refractory to current treatments, such as freezing of gait. Previous work examining neural
mechanisms of movement facilitation in PD have yielded inconsistent results. This may be due to a failure to
account for well-known heterogeneity in behavioral benefits across PD patients and the assumption that
different cueing phenomena exert motor benefits through a single neural mechanism. The studies proposed
here test the overarching hypothesis that 3 different types of cues (visual targets, rhythmic auditory stimuli and
reward incentives) facilitate movement through distinct neuroanatomic circuits and electrophysiological
mechanisms, by leveraging known variability in behavioral cueing benefits across patients. Aim 1 is to
demonstrate behavioral dissociations between the 3 forms of movement facilitation within patients and relate
variability in cueing benefits to integrity of dissociable neuroanatomic circuits as measured by resting state and
diffusion tensor magnetic resonance imaging (MRI). Aim 2 is to characterize the electrophysiological correlates
of behavioral benefits for the different cue types using electroencephalography (EEG) and intraoperative
electrophysiological recordings obtained during implantation of deep brain stimulator in the globus pallidus
internus. This work will augment my prior skills in task fMRI, transcranial magnetic stimulation (TMS) and
electrophysiology by extending training in multiple modalities (high density EEG, resting state fMRI, DTI); build
my analytic skills in advanced multivariate statistics; and advance my expertise in PD motor physiology. My
mentorship team comprises experts in PD neurophysiology and neuromodulation therapies, and non-invasive
studies of inter-individual differences in motor neurophysiology. Coursework in multivariate statistics and
seminars in advanced EEG and neuroimaging applications will further my development. The environment at
UCLA has a rich interdisciplinary neuroimaging community, state-of-the-art image acquisition facilities including
Ahmanson-Lovelace Brian Mapping Center and Staglin Center for Cognitive Neuroscience and a renowned
clinical Movement Disorders Division. The career development plan forges a path to become an independent
physician-scientist, using multiple modalities to characterize neurophysiologic biomarkers of heterogeneous
disease features in Parkinson’s disease to improve therapy development and delivery.
Terms: <Affect><Age><Auditory><Basal Ganglia><Basal Nuclei><Behavioral><Biological Markers><Brain><Brain Nervous System><Cell Communication and Signaling><Cell Signaling><Communities><Complication><Cues><Cyclicity><Data><Deep Brain Stimulation><Development><Development Plans><Diffusion><Disabling><Disease><Disorder><Dissociation><Dorsal><EEG><Electrocorticogram><Electroencephalogram><Electroencephalography><Electrophysiology><Electrophysiology (science)><Encephalon><Environment><Failure><Freezing><Functional MRI><Functional Magnetic Resonance Imaging><Future><Gait><Globus Pallidus><Goals><Heterogeneity><Image><Incentives><Independent Living><Individual Differences><Injury><Intracellular Communication and Signaling><Kinesis><MR Imaging><MR Tomography><MRI><MRIs><Magnetic Resonance Imaging><Maps><Measures><Mediating><Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance><Mentorship><Methods><Modality><Motivation><Motor><Motor output><Movement><NMR Imaging><NMR Tomography><Nerve Impulse Transmission><Nerve Transmission><Neuranatomies><Neuranatomy><Neuroanatomies><Neuroanatomy><Neuronal Transmission><Neurophysiology / Electrophysiology><Nuclear Magnetic Resonance Imaging><Operative Procedures><Operative Surgical Procedures><Paralysis Agitans><Parietal><Parkinson><Parkinson Disease><Participant><Pathologic><Patients><Periodicity><Physicians><Physiology><Primary Parkinsonism><QOL><Quality of life><Refractory><Research><Rest><Rewards><Rhythmicity><STN stimulation><Scientist><Sensory><Severity of illness><Signal Transduction><Signal Transduction Systems><Signaling><Stimulus><Surgical><Surgical Interventions><Surgical Procedure><Symptoms><System><Techniques><Testing><Training><Transcranial magnetic stimulation><Ventral Striatum><Visual><Work><Zeugmatography><ages><auditory stimulus><axon signaling><axon-glial signaling><axonal signaling><behavior measurement><behavior prediction><behavioral measure><behavioral measurement><behavioral prediction><bio-markers><biologic marker><biological signal transduction><biomarker><biomarker identification><body movement><career development><clinical movement disorder><cognitive neuroscience><deep brain stimulator><density><develop therapy><developmental><diffused><diffuses><diffusing><diffusions><disease severity><electrocorticography><electrophysiological><fMRI><falls><forging><glia signaling><glial signaling><identification of biomarkers><identification of new biomarkers><imaging><implantation><improve symptom><improved><injuries><insight><intervention development><kinematic model><kinematics><marker identification><motor deficit><motor disease><motor disorder><motor dysfunction><motor symptom><nerve signaling><neural control><neural imaging><neural mechanism><neural network><neural regulation><neural signaling><neuro-imaging><neuroimaging><neurological imaging><neuromechanism><neuromodulation><neuromodulatory><neuronal signaling><neurophysiological><neurophysiology><neuroregulation><neurotransmission><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel therapeutics><novel therapy><pallidum><rehab strategy><rehabilitation strategy><response><skills><statistics><subthalamic nucleus stimulation><surgery><symptom improvement><symptomatic improvement><therapy development><time interval><tractography><treatment development><visual motor><visuomotor>