Parkinson’s disease (PD) is usually viewed in terms of motor dysfunction, which results from degeneration of the motor structures of the nigrostriatal network such as substantia nigra, dorsal striatum, and motor cortex, accumulation and aggregation of the protein alpha-synuclein(αSyn) into fibrils, and nigrostriatal network dysfunction.
PD patients also struggle, however, with a host of cognitive and affective symptoms thought to result in part from alpha-synuclein (αSyn)-associated degeneration of structures within the mesocorticolimbic and basal forebrain networks, which includes the ventral tegmental area (VTA), ventral striatum, nucleus basalis, and prefrontal cortex (PFC).
Non-motor symptoms of PD, including cognitive impairments, impulsivity, apathy, and anxiety, are viewed by patients as more detrimental to their quality of life than motor symptoms. Unlike motor symptoms, however, for which there are a variety of treatments, there are few effective therapies for non-motor symptoms of PD.
The seeming diversity of pathogenic mechanisms in PD obscures a common risk factor: age. Mean age of onset in idiopathic PD (which comprises 85% of cases) is 56, and even ‘early onset’ PD is defined as younger than 50.
Despite the role of age as a primary risk factor, interactions between age and αSyn pathology remain largely unstudied, with research in models of αSyn pathology primarily conducted in young adult animals.
Oscillatory patterns in the gamma range (30 – 80 Hz) are important for cognitive tasks including attention and memory, and impaired gamma activity is associated with cognitive impairments in patients with Alzheimer’s disease (AD) and PD as well as normal ageing. Moreover, non-invasive, gamma-band neuromodulation improves cognition and delays progression of neuropathology in mouse models of AD through poorly understood neuroimmune-mediated mechanisms.
The Burns Lab explores the relationship between ageing, electrophysiologic and neuroimmune processes, and neurodegenerative disease. We use advanced immunohistochemical techniques, high resolution light sheet imaging and MRI imaging, and complex behavioral assessments with the long-term goal of determining the neural and behavioral mechanisms underlying cognitive and affective symptoms of synucleinopathies such as Parkinson’s disease dementia, Dementia with Lewy Body, and Multiple System Atrophy, and developing therapeutic strategies that address these symptoms to improve patients’ quality of life.