Past events

A fundamental problem in brain research is how distributed brain systems work together to give rise to behavior. I seek to advance our understanding of principles underlying the dynamic interaction between multiple neural systems, how the different systems co-operate and/or compete to give rise to goal-directed behavior, and the dynamics of the system when one or more of its components fail. Magnetic resonance imaging (MRI) methods allow us to simultaneously measure the function of multiple brain systems. In humans we can characterize the functional organization and specialization, and compare the system between health and disease. In animal models we can further dissect the circuits underlying these dynamics. In my work I aim to identify functional networks that span multiple cortical and subcortical regions, characterize their responses in the presence and absence of overt behavior, and modulate the observed dynamics. To advance these goals, I am developing new tools that will allow us to study large-scale neural systems across species. In this talk, I will review recent studies that use functional neuroimaging in humans and animal models. I will describe how spontaneous fluctuations of the blood oxygenation level-dependent (BOLD) signal measured with MRI in awake resting humans, reveal functional subdivisions in the medial temporal lobe memory system and parietal and prefrontal cortical components linked to it. I will describe results from non-human primates demonstrating that this functional organization persists across the species, highlighting cortical components that have undergone considerable areal expansion in humans relative to non-human primates, how this method can be used to identify homologue regions, and more generally, what can be learned from a comparative perspective. In the second part of my talk I will describe recent efforts to selectively modulate system dynamics. A lentivirus was used to target excitatory neurons in the rat cortex with light-activated cation channel channelrhodopsin-2. Using photostimulation to activate these neurons we were able to drive the BOLD response locally and in regions anatomically connected to the infected site in a variety of stimulation paradigms. I will discuss implications for understanding the BOLD signal and prospects for this approach in studying the microcircuit as well as large-scale brain dynamics. Finally, I will discuss the challenges and promises of whole-brain imaging in small animals, and how this work can provide avenues to bridge between a basic understanding of human behavior, large-scale neural dynamics, and psychiatric disorders where such dynamics are disrupted.

Diminished levels of docosahexaenoic acid (DHA, 22:6n-3), the major polyunsaturated fatty acid (FA) synthesized from alpha linolenic acid (ALA, 18:3n-3), have been implicated in changes in neurotransmitter production, ion channels disruption and impairments of a variety of cognitive, behavioural and motor functions in the developing and the adult mammal. We studied neuronal migration in the cortex and hippocampus of newborn and postnatal rats after ALA-deficiency, beginning on the 2nd day after conception and continuing for three weeks after birth. A marked decrease in the migration of bromodeoxyuridine(+)/NeuN(+)/Neurofilament(+) and glia fibrilary acidic protein(-) neuronal cells to the dense cortical plate was accompanied by a corresponding abundance of non-migrating cells in several regions such as cortical layers IV-VI, corpus callosum and the sub-ventricular zone of ALA-deficient newborn. Similarly, a delayed migration of cells to CA1 and dentate gyrus areas was noticed while most cells were retained in the subicular area adjacent to the hippocampus. The delay in migration was transient most likely due to a temporary reelin disorganization. In addition to these changes a drastic reduction in tyrosine hydroxylase (TH) and vesicular monoamine transporter-2 (VMAT-2) levels, both of which are prerequisites for appropriate synthesis and transport of DA were noticed by RNA subtractive hybridization and proteomic techniques. Concomitantly, a large increase in DA receptors DAR1 and DAR2 were noticed. The transient impairment induced by ALA deprivation may compromise the organization of neuronal assemblies and result in aberrant neuronal connectivity (lateral connections) to enhance the risk of neurodevelopmental disorders including cerebral palsy.

The cortico-basal ganglia pathway is involved in normal motor control and implicated in multiple movement disorders. We used focal microinjections of the GABA-A antagonist bicuculline to the sensorimotor putamen of behaving primates to induce stereotyped tics similar to those observed in human Tourette syndrome. The tics were accompanied by synchronized phasic changes in the local field potential and single cell activity of neurons throughout the cortico-basal ganglia loop. We also used focal injection of bicuculline to different functional domains of the globus pallidus external segment (GPe) to induce a variety of hyper-behavioral symptoms. These, symptoms varied between dyskinesia, stereotypy and attention deficit depending on injection site within the motor, limbic and associative domains respectively. The injections led to distributed uncorrelated changes in firing pattern throughout the cortico-basal ganglia loop. The neurophysiological findings and their implication on models of information processing in the basal ganglia will be discussed in the lecture.