Advance-CTR

Saud Alhusaini, MD, PhD

Assistant Professor of Neurology, The Warren Alpert Medical School of Brown University
Research Profile

Awards

Advance RI-CTR Pilot Projects Program (Cycle 9)

"The Association Between Essential Tremor Cerebellar Subclinical Phenotypes and Genetic Risk factors"

Essential tremor (ET) has long been considered a heritable condition. Indeed, first-degree relatives of ET cases are 5–10 times more likely to develop ET than are members of the general population. Despite the strong evidence of heritability, the genetic causes of ET remain largely unclear. A recent large genetic study identified five genetic variants associated with increased risk for ET. Understanding how these genetic risk variants increase the risk for ET is paramount. Specifically, studying the relationship between these ET genetic risk variants and subclinical features, such as brain structural and functional changes, can inform us about ET's underlying biological and molecular mechanisms and lead us to better ET diagnosis and future treatment targets. 

In this project, Dr. Alhusaini aims to examine the relationship between ET genetic risk factors and brain changes within the cerebellum, a key brain region believed to be affected in ET cases. He will examine cerebellar electrophysiological and neuroimaging changes to determine if they are linked to the recently identified ET genetic risk variants. To perform this study, 60 individuals with ET and 40 matched healthy controls will be recruited. All participants will undergo comprehensive assessments and investigations, including: 

  • A complete clinical evaluation and neurological examination.
  • Genetic testing to test for ET-specific genetic risk variants. 
  • Surface electroencephalogram (EEG) recordings to study the cerebellar electrophysiological changes (i.e., brain waves) associated with tremor.
  • MRI brain to examine cerebellar structural and functional changes

Data analyses will be conducted in two stages: 

  1. The first stage will focus on identifying the cerebellar changes associated with ET. For this step, the EEG and MRI brain-related cerebellar findings between individuals with ET and the healthy controls will be compared. 
  2. The second stage of the study will focus on analyzing the genetic data and examining the relationship between the known ET genetic risk variants and the EEG and MRI brain-related cerebellar findings.

The results of this work will advance understanding of the underlying mechanism of essential tremor (ET) by determining the relationship between ET genetic risk variants and cerebellar changes. Such findings will help reveal new biological pathways that can be future targets for developing better treatment options and disease-modifying therapies.

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