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Raised in the rural community of Glenevis, Alberta, Vanderwolf went on to earn a BSc from the University of Alberta and completed graduate work with Donald Hebb at McGill University, completing his PhD in 1962.. Following completion of his PhD, Case spent a year at the California Institute of Technology with Roger Sperry (1962–1963) and another year with Konrad Akert, the Founder of the Brain Research Institute of the University of Zurich (1963–1964).
Vanderwolf spent over 30 years at the University of Western Ontario in London, Ontario, during which time he published over 140 papers on the relation of hippocampal, neocortical, and pyriform cortical activity to behavior and the dependence of many of these brain-behavior relations on the activity of central neurons that release the transmitter substances acetylcholine and serotonin.. As early as 1964, he was among the first investigators to carefully study the correlation between observable motor activity and brain waves. Recording from the thalamus and hippocampus of the behaving rat, he found a reliable relationship between ‘voluntary movement’ and rhythmic (theta) EEG activity. This early paper (Vanderwolf and Heron, 1964) was followed up by a detailed account of a variety of motor behaviors and hippocampal theta oscillation (Vanderwolf, 1969). He showed that in the waking rat, hippocampal EEG is dominated by thetaoscillations (6 to 10 Hz; for this he coined a new term, rhythmic slow activity or RSA) during locomotion, rearing, exploratory head turning, and sniffing. In contrast, in other observable behaviors such as eating, drinking, grooming, and immobility, theta is replaced by ‘large amplitude irregular activity’ (LIA).His work also includes research on the brain mechanisms involved in olfaction. Vanderwolf's work is relevant to the problems of consciousness, memory, motor control and such human disorders as Alzheimer's disease and depression.
He has published two books, An Odyssey Through the Brain, Behavior and Mind and The Evolving Brain: The Mind and the Neural Control of Behavior that provide an overview of his academic career and research findings. In 2000, he was awarded an honorary degree from the University of Lethbridge.
He died on June 16,2015 in London,Ontario.