Intrinsic brain networks and their role in neurodegenerative disease

Abstract

The talk will cover two recent exciting discoveries in neuroscience: (1) the imaging of intrinsic brain networks (2) evidence that neurodegenerative processes target these networks, which may act as conduits for the transneuronal spread of disease-causing misfolded proteins. Human functional brain imaging has shown that the brain is organized in large-scale networks. These have been identified mainly from resting state functional MRI (rsfMRI) and diffusion tractography (DTI), but also using structural covariance MRI data, MEG, PET and EEG. Intrinsic brain networks consist of usually spatially distinct brain regions that are heavily interconnected and tend to show correlated activity (as measured by fMRI); they are very reproducibly detected, underpin specific brain functions, and allow for efficient parallel and fault-tolerant processing. More recently, the use of graph theory for the analysis of MRI data has yielded specific insights into the organization of these networks. Graph theory is the mathematical framework for analyzing graphs, defined by a set of nodes and edges. Several interesting properties of graphs can be computed to yield insights into the normal organization of the brain, and into mechanisms of neurodegeneration.

Second, recent evidence suggests that some neurodegenerative diseases like Alzheimer’s and Parkinson’s Disease, may involve prion-like spreading of misfolded proteins via neuronal projections. These proteins (tau, beta-amyloid, alpha-synuclein) are thought to cause further protein misfolding, and disease propagation via intrinsic brain networks.

We will review brain imaging evidence supporting this network spread hypothesis.

Biography

I received a B.Eng and M.Eng in Electrical Engineering from McGill University. I then completed my MD at University of Toronto, followed by a residency in neurology at Cornell University Medical Center and at McGill University. I trained in movement disorders and functional brain imaging at the Hammersmith Hospital and National Hospital for Neurology and Neurosurgery, Queen Square, London. I returned to the Montreal Neurological Institute in 1997 where my lab works on various aspects of functional brain imaging with a particular interest in Parkinson’s disease, addiction and appetite control. I am Professor in the departments of Neurology and Neurosurgery and Psychology at McGill.

Broadly speaking my research aims to understand the function of brain regions innervated by dopamine. These interconnected brain areas play a key role in reward, learning, motivation, and decision-making. This research has applications to Parkinson’s Disease, schizophrenia, drug addiction and obesity, and to gaining an understanding of normal brain function. Almost all of my work uses functional brain imaging methods in human subjects. I have also made contributions to basic imaging methodology, most notably in developing a PET technique that allows the measurement of dopamine release in vivo in the human brain.

I use fMRI to model addiction and obesity as a disorder of choice. I have used neuroeconomics approaches to the study of drug craving and hunger, based on the analogy between incentive salience and “economic value”.