Jason Lerch, PhD
Neurosciences & Mental Health
University of Toronto
Department of Medical Biophysics
Mouse Imaging Centre
Phone: 416-813-7654 x 309558
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Alternate Phone: 416-813-7654 x 309536
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Dr. Lerch completed his PhD in the department of Neurology and Neurosurgery at McGill University, where he focused on the study of cortical thickness from human MR images, and followed that with a post-doctoral fellowship at MICe at The Hospital for Sick Children (SickKids). He joined SickKids as a scientist in 2008 and is working both with the Mouse Imaging Centre (MICe) as well as the human imaging group.
- Brain plasticity: how the shape of the brain changes in response to learning
- Neurodevelopmental disorders: from genes to systems to behaviour to treatment
- Understanding what factors influence neuroanatomy
- Developing novel methods for analyzing structural MR images
- Studying human neurological/neuropsychiatric diseases
- The use of imaging to investigate mouse models of disease
Dr. Lerch's work focuses on understanding how the brain alters its shape in health and disease, with a particular focus on neurodevelopmental disorders as well as brain plasticity. To understand these alterations in the brain he has worked on extending and improving image processing and statistical methods for mapping changes in the brain using MR imaging. This has included studies in both humans and mice and focused on image registration approaches as well as the use of deformable models for mapping cortical thickness and surface area. He is also involved in multiple studies that have applied these methods to both childhood and adult studies using both cross-sectional as well as longitudinal designs.
MRI of learning and memory
Research using human imaging, including the famous study of the hippocampus of London Taxi drivers, has indicated that experience and expertise is reflected on local structures of the brain. In order to understand these effects better Dr. Lerch and his team have trained mice on three versions of the Morris water maze and found that they can grow differing regions of the brain depending on the training paradigm used. The initial experiment used ex vivo MRI; the team is now (a) investigating the molecular bases of this type of brain plasticity by using different genetic mouse models; (b) using histology to understand the cellular causes of these volume changes; and (c) using in vivo MRI in order to be able to follow individual mice to map the timecourse of the various stages of learning.
The effect of specialized training on the human brain
There is increasing evidence that subtle variations in our brains reflect past experience. A particularly potent modifier of brain shape appears to be learning a specialized skill, such as a musical instrument, ballet, etc. This part of Dr. Lerch's research program will attempt to delineate precisely how such learning changes our brains, and relate these findings back to work in the mouse in order to ascertain more precise cellular and genetic contributions.
Autism and related neurodevelopmental disorders
Autism and related neurodevelopmental disorders present a complex puzzle: they are highly heritable, yet no single gene accounts for more than 1-2% of cases. Heterogeneity pervades everything, as the core symptoms of social communication difficulties and repetitive behaviours are supplemented by IQs that range from clear intellectual disability to above average, with some patients presenting with seizures, some with language difficulties, etc.
To understand the biology behind autism - and to ask how many autisms are there - Dr. Lerch and his team set out to run a high throughput screen by using MRI to image as many mouse models as they could. With over 70 mouse models (and over 2000 individual mice) they find that heterogeneity is also the order of the day, yet a few brain areas are more consistently affected than others. Moreover, it appears as if three clusters of mouse models share common neuroanatomical substrates. Dr. Lerch is now using this information to, in conjunction with human phase II clinical trials, understand whether we can help predict treatment response.
Methods of analyzing neuroanatomy
The research projects outlined above depend on precise automated measurements of brain shape from MRI. Dr. Lerch and his team use a combination of image registration techniques, tissue classification and deformable models to obtain these measurements. Ongoing research will thus also focus on improving these methods as well as understanding precisely what they can and cannot tell us.
- Canadian Institutes of Health Research (CIHR)
- Alzheimer’s Association
- National Institutes of Health (NIH)
- Ontario Brain Institute (OBI)
- Brain Canada
- Simon’s Foundation (SFARI)
Click here for a full list of publications.
Ellegood J, Anagnostou E, Babineau BA, Crawley JN, Lin L, Genestine M, DiCicco-Bloom E, Lai JK, Foster JA, Peñagarikano O, Geschwind DH, Pacey LK, Hampson DR, Laliberté CL, Mills AA, Tam E, Osborne LR, Kouser M, Espinosa-Becarra F, Xuan Z, Powell CM, Raznahan A, Robins DM, Nakai N, Nakatani J, Takumi T, van Eede MC, Kerr TM, Muller C, Blakely RD, Veenstra-VanderWeele JM, Henkelman RM, Lerch JP. Clustering Autism–using neuroanatomical differences in 26 mouse models related to Autism to gain insight into the heterogeneity of the disorder. Molecular Psychiatry, 2015 20(1):118-125. DOI 10.1038/mp.2014.98 PMID 25199916
Chakravarty MM*, Hamani C*, Martinez-Canabal A, Ellegood J, Laliberte C, Nobrega NJ, Sankar T, Lozano AM, Frankland PW, Lerch JP. Deep brain stimulation of the ventromedial prefrontal cortex causes reorganization of neuronal processes and vasculature in the mouse brain. Neuroimage, 2015 125:422-427. DOI 10.1016/j.neuroimage.2015.10.049 PMID 26525655 *Equal contribution .
Scholz J, Allemang-Grand R, Dazai J, Lerch JP. Environmental enrichment is associated with rapid volumetric brain changes in adult mice. NeuroImage, 2015 109:190-198. DOI 10.1016/j.neuroimage.2015.01.027 PMID 25595504
Raznahan A, Lue Y, Probst F, Greenstein D, Giedd J, Wang C, Lerch JP*, Swerdloff R*. Triangulating the sexually dimorphic brain through high-resolution neuroimaging of murine sex chromosome aneuploidies. Brain Structure and Function, 2015 220(6): 3581-3593. DOI 10.1007/s00429-014-0875-9 PMID 25146308
Friedel M, van Eede MC, Pipitone J, Chakravarty MM, Lerch JP. Pydpiper: a flexible toolkit for constructing novel registration pipelines. Frontiers in Neuroinformatics, 2014 8:67. DOI 10.3389/fninf.2014.00067 PMID 25126069
Steadman PE, Ellegood J, Szulc KU, Turnbull DH, Joyner AL, Henkelman RM, Lerch JP. Genetic effects on cerebellar structure across mouse models of autism using magnetic resonance imaging atlas. Autism Research, 2014 7(1):124-137. DOI 10.1002/aur.1344. PMID 24151012
Raznahan A, Probst F, Palmert MR, Giedd JN, Lerch JP. High resolution whole brain imaging of anatomical variation in XO, XX, and XY mice. NeuroImage, 2013 83:962-968. DOI 10.1016/j.neuroimage.2013.07.052. PMID 23891883
van Eede MC, Scholz J, Chakravarty MM, Henkelman RM, Lerch JP. Mapping registration sensitivity in MR mouse brain images. NeuroImage, 2013 82C:226-236. DOI 10.1016/j.neuroimage.2013.06.004 PMID 23756204
Szulc KU, Lerch JP, Nieman BJ, Bartelle BB, Friedel M, Suero-Abreu GA, Waterson C, Joyner AL, Turnbull DH. 4D MEMRI atlas of neonatal mouse brain development. NeuroImage, 2015 188:49-62. DOI 10.1016/j.neuroimage.2015.05.029 PMID 26037053
Lerch JP, Yiu AP, Martinez-Canabal A, Pekar T, Bohbot VD, Frankland PW, Henkelman RM, Josselyn SA, Sled JG. Maze training in mice induces MRI detectable brain shape changes specific to the type of learning. NeuroImage, 2011 54(3):2086-2095. DOI 10.1016/j.neuroimage.2010.09.086 PMID 20932918