We have developed advanced 3D volumetric Magnetic Resonance Imaging (MRI) methods to analyze in vivo different brain structures such as hippocampus, amygdala, cingulate gyrus, entorhinal cortex, and prefrontal cortex. Recently we described for the first time in vivo quantification of the inner structure of the hippocampus within the entire hippocampal formation and subdivisions using ultrahigh resolution MRI. Application of this unique technique allows us for the first time to study hippocampal neuroplasticity and neurogenesis in-vivo that has been impossible to date. We also developed reliable Diffusion Tensor Imaging (DTI)-tractography protocols to study major limbic and paralimbic white matter connections of the human brain. Furthermore, our group, using DTI tractography, delineated, for the first time, different white matter connections within the frontal lobes; these connections had not been investigated in detail due to their complex organization and therefore relatively difficult delineation.
Aging brainOur second research area is normal and pathological aging. Our group demonstrated a specific anterior-posterior gradient of hippocampal volume loss and relative amygdala preservation associated with normal aging that contrasts with the preferential reduction of anterior hippocampal volumes in Alzheimer’s and Parkinson’s diseases. We conducted the largest study to date to examine hippocampal volume in Parkinson’s disease and only the second to examine the amygdala in vivo in this clinical population. Recently we conducted one of the largest and most detailed studies of age-related changes in brain white matter. We demonstrated that frontal regions are the most sensitive to the aging process (confirming the frontal theory of aging) while temporal and visual cortical areas showed relative preservation with age. Furthermore, more recently we for the first time demonstrated regional age-related changes in the prefrontal white matter tracts of the human brain. Our group was recently awarded a CIHR grant (2011-2016) in order to provide new insights into the relationship between cognitive aging and brain structure that were simply not previously possible when a single brain structure was studied or a single imaging method was used. Combining neuroanatomical and cognitive measures will reveal if and how structural brain changes correspond to age-related decline in cognitive functions.
Major depressionOur third research focus is on brain changes in major depressive disorder (MDD). Previously, our group demonstrated for the first time that hippocampal volume changes in depression are mainly localized to the hippocampal tail and head and that these volume reductions are associated with past childhood abuse. We also found that an increase in amygdala volume in depression was associated with a reduction in anterior cingulate gyrus and ventromedial prefrontal cortical volumes and lower fractional anisotropy of the uncinate fasciculus, the white matter tract that links these regions. In addition to these findings we demonstrated that depressed patients with a history of childhood abuse show lower fractional anisotropy in medial and ventromedial prefrontal white matter and dorsal cingulum, in addition to the uncinate fasciculus. These findings are of particular interest in that chronic deep brain stimulation (DBS), a promising therapy for treatment-resistant MDD, targets ventromedial prefrontal white matter projections. More recently, our pilot high-field MRI study showed for the first time that MDD patients had significant reductions in cornu ammonis and subiculum subfield volumes in vivo and that long-term antidepressant treatment was associated with larger dentate gyrus volumes, consistent with the neurogenic hypothesis of antidepressant action. These results provided the first in vivo evidence that hippocampal subfields are differentially affected in MDD and by antidepressants.
Collaborators: Dr. Esther Fujiwara, Dr. Richard Camicoli, Dr. Roger Dixon, Dr. Nick Coupland, Dr. Peter Silverstone, Dr. Jeremy Caplan, and Dr. Matt Brown