Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Atrophy of the striatum, a structure deep in the brain important for the control of movement, is the neuropathological hallmark of HD, and is associated with motor symptoms such as chorea and dystonia in the late or ‘manifest’ stage of the disease. However, non-motor symptoms, including cognitive decline and emotional lability, can precede motor symptoms by years and occur before detectable structural brain changes.
This mismatch between cognitive-behavioral symptoms and detectable structural changes in early HD suggests that brain dysfunction in these patients needs to be studied and understood at the functional level, that is, in terms of disordered activity and connectivity within and between implicated brain networks. By applying an independent components analysis to resting state (rs) fMRI data we have discovered widespread changes in the functional connectivity of brain networks in patients with early stage Huntington's disease (HD) who do not yet meet clinical disease criteria or demonstrate detectable brain changes on structural MR imaging. Our results suggest that rs-fMRI has the potential to serve as an imaging biomarker for early HD diagnosis and progression and as a potential tool for assessing treatment efficacy in clinical trials.
Currently, there is no cure for HD or treatment to slow its progression. In recent years, however, behavioral ‘brain-training’ programs have emerged that attempt to treat neuropsychiatric disease by recruiting the brain’s inherent neuroplasticity mechanisms. Our HD project is a collaboration with Dr. Melanie Cheung at the University of Auckland in New Zealand, and Dr. Mike Merzenich of the Brain Plasticity Institute in San Francisco. Dr. Cheung works with families affected by HD among the Māori, the indigenous people of New Zealand. The prevalence of HD among the Māori is ten times the world average making them a unique population in which to study HD.
Working together Drs. Cheung and Merzenich have developed a computer-based HD resilience-training program that targets the striatal and cortical pathways affected early in the Huntington’s disease process. The same early-HD patients in whom we have documented brain network changes are now undergoing this intensive brain-training program. This work will test whether this intervention improves or impedes the progression of HD symptoms. Moreover, by scanning these patients (and a control population) both before and after training we will be able to determine whether this clinical improvement is accompanied by a rebalancing of activity across these networks that we can capture with our functional connectivity measures.