Altered Central Multisensory Processing in Post-concussion Vestibular Dysfunction

Project Summary/Abstract
Patients with persistent post-concussion vestibular dysfunction (PCVD) demonstrate visual motion sensitivity
characterized by visual and motion stimuli inducing vestibular symptoms. We hypothesize that patients may
acutely benefit from altered weighting of multisensory, particularly visual, input into vestibular processing
networks to compensate for central or peripheral vestibular impairment, although this may persist and become
maladaptive, leading to persistent vestibular symptoms. However, the changes in multisensory processing that
underlie PCVD are largely theoretical and represent a significant knowledge gap in our understanding.
In a recent pilot study, we found selective increased activation in the primary vestibular cortex and vestibular
multisensory processing regions in patients with subacute PCVD during a novel task-based fMRI visual-
vestibular paradigm as well as altered resting-state fMRI connectivity between visual and vestibular processing
centers, which correlates with symptom severity. Our central hypothesis is that persistent PCVD is due to altered
multisensory vestibular processing, with increased activation/connectivity of visual and oculomotor inputs into
the vestibular network.
Prior efforts to classify concussion based upon clinical symptoms have been limited as pre-existing
symptoms may mimic post-concussion symptoms. We hypothesize that defining endophenotypes for PCVD
patients using a combination of clinical and neuroimaging metrics will better subdivide this population and will
correlate with response to vestibular rehabilitation therapy (VRT).
To assess these hypotheses, we propose the following three Specific Aims: (1) define regional brain
activation that distinguishes PCVD patients from concussion recovered and control groups using a novel visual-
vestibular task-based fMRI paradigm and correlations with subjective and objective vestibular testing; (2) identify
alterations in functional networks and dynamic states in the PCVD group compared to recovered and control
groups at rest and correlations with subjective and objective vestibular testing; and (3) stratify PCVD subjects
into endophenotypes using clinical and neuroimaging metrics and determine the predictive power of these
endophenotypes to predict VRT response. We propose a longitudinal study with three groups: (1) subacute
PCVD patients, (2) patients with prior symptomatic concussion but who have since recovered, and (3) healthy
controls. All subjects will undergo comprehensive vestibular testing and brain MRI. PCVD subjects will repeat
clinical testing after completion of VRT. We expect to confirm and expand our preliminary data findings as well
as develop endophenotypes that will be predictive model of VRT response. The proposed study will fill in current
gaps in knowledge, drive the development of novel therapies, identify neuroimaging/clinical patterns that predict
therapy response, and lead to the development of tailored, patient-centric therapy programs.

Grant Number: 5R01NS119683-04
NIH Institute/Center: NIH
Principal Investigator: Jason Allen