Laboratory of Cognitive Neurobiology

Lab Directors: Douglas Rosene, Ph.D; Mark Moss, Ph.D.; Tara Moore, Ph.D.; Ron Killiany, Ph.D; Farvad Mortazavi, Ph.D.

Overview

MMR Lab

The Laboratory of Cognitive Neurobiology focuses its research efforts on the neurobiological bases of learning and memory in non-human primates. We have particular interest in the structural, physiological, and neurotransmitter correlates of cognitive decline in aging and age-related disease (e.g. hypertension and stroke), the separate and interactive roles of the prefrontal cortices and hippocampal complex in executive function and declarative memory, and the structural and functional changes in the brain as a consequence of prenatal malnutrition. Collaborative studies are conducted on the role of melatonin in sleep and circadian rhythms in the aged monkey; on studies of the brain in human subjects with MCI and Alzheimer’s disease using structural and related MRI techniques; and on the integrity of the blood-brain barrier in aging, hypertension, and substance abuse.

Our research is supported by several NIH grants, including a Program Project on the Neural Bases of Cognition in Aging, a MERIT award grant on Hypertension and Middle Age, and an RO1 on the interaction between prefrontal cortex and the hippocampal formation.

Our laboratory is housed on the seventh floor of the Center for Biomedical Research and consists of four faculty (Mark Moss, Douglas Rosene, Ron Killiany and Tara Moore), three research fellows, and eight graduate students. We have an active laboratory that covers a wide-range of research techniques ranging from in situ hybridization, receptor autoradiography, immunocytochemistry, structural and functional MRI, and automated primate behavioral testing.

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MRI scans showing a coronal view through the brain of young vs. aged human and monkey

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Binding patterns for alpha-1 receptors in the pre-frontal cortex of a young and aged rhesus monkey

 

Methodology

Automated Computer Based Cognitive Testing

We have a suite of four testing chambers in which monkeys are behaviorally assessed on a wide range of cognitive tasks that parallel those used in humans.

Magnetic Resonance Imaging

Our studies utilize a variety of MRI techniques, including structural MRI, functional MRI, and MR spectroscopy. A 3.0T Philips dedicated research magnet is housed in the Evans Biomedical Center, connected directly to our research building.

Immunocytochemistry

We use antibodies directed at particular constituents to label neurons and glia to visualize specific cells in the neuropil. We use this technique to label inflammatory markers, neurotransmitter-related compounds, metabolic markers, etc.

In Situ hybridization

This technique is used to allow the demonstration of specific nucleic acid sequences in their cellular environment in the brain.

Neurophysiology

We routinely use this technique to measure conduction velocity and other parameters of neuronal conduction across or within the cerebral hemisphere to supplement our study of the neurobiological basis of altered cognitive function in the primate.

Reversible lesions

We are working with new techniques such as cortical cooling and Transmagnetic Cranial Stimulation (TMS) to induce temporary dysfunction of a specific cortical region. This allows one to “turn on ” or “turn off ” a particular region of the brain to assess its role in a given function or neuronal circuit.

People

Mark Moss
Dr. Moss’ particular interests focus on (1) the interaction of the prefrontal cortices with the medial temporal lobe limbic system in subserving executive function, rule learning and declarative memory in young adult monkeys; (2) the separate and combined effects of age and hypertension on cognition and blood-brain barrier and white matter integrity in a non-human primate model of hypertensive cerebrovascular disease and (3) parallel studies in normal aged humans and patients with MCI and Alzheimer’s disease.

Douglas Rosene
Dr. Rosene’s particular interests focus on (1) the effect of age on brain integrity, including white matter, neurotransmitter systems and neural transmission in a primate model of normal human aging (2) the interaction of the prefrontal cortices with the medial temporal lobe limbic system 3) the effect of prenatal malnutrition on brain integrity in a rodent model and 4) modeling methods to characterize age-related changes in microcolumns in the cerebral cortex.

Ron Killiany
Ron Killiany has a primary interest in various applications of MRI in animal models and humans alike. He works closely with investigators at Brigham and Womens Hospital and Massachusetts General Hospital to develop and implement imaging sequences to measure selective brain regions as antemortem markers of Alzhimer’s Disease

Tara Moore
Tara Moore has an interest in the neurobiology of the non-human primate prefrontal cortex. She has developed unique behavioral tasks to assess executive function in the monkey and has used a multidisciplinary approach to assess the neurobiological bases of prefrontal cortical dysfunction in aging, hypertension, and cocaine abuse.

Farzad Mortazavi
Dr. Mortazavi’s primary interests are  the effects of normal aging on structure and function of the brain.  Of particular interest: microcolumns, white matter pathways.  He is particularly interested in  3D reconstructions of white-matter pathways and cortical columns using Confocal Microscopy, 2-photon Microscopy and statistical physics for analysis of these types of big data.

Recent Publications:

Long-term Visual and Refractive Outcomes After LASIK for High Myopia and Astigmatism From -8.00 to -14.25 D. Reinstein DZ, Carp GI, Archer TJ, Lewis TA, Gobbe M, Moore J, Moore T. J Refract Surg. 2016 May 1;32(5):290-7. doi: 10.3928/1081597X-20160310-01. PMID: 27163613

Mortazavi F, Wang X, Rosene DL, Rockland KS, (2016) White Matter Neurons in Young Adult and Aged Rhesus Monkey Frontiers in Neuroanatomy  In Press, February 2016.

Pham TA, Hua N, Phinikaridou A, Killiany R, Hamilton J. Early in vivo discrimination of vulnerable atherosclerotic plaques that disrupt: A serial MRI study. 2016 Jan;244:101-7. doi: 10.1016/j.atherosclerosis.2015.11.013. Epub 2015 Nov 14. PMID: 26606442

McKenna F, Koo BB, Killiany R; Alzheimer’s Disease Neuroimaging Initiative. Comparison of ApoE-related brain connectivity differences in early MCI and normal aging populations: an fMRI study.  Brain Imaging Behav. 2015 Sep 26. [Epub ahead of print]  PMID:  26409470

Ngwenya LB, Heyworth NC, Shwe Y, Moore TL, and Rosene DL (2015) Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey.  Frontiers Systems Neuroscience July 2015.  http://dx.doi.org/10.3389/fnsys.2015.00102

For more publications, please see Dr, Rosene, Dr. Moss,  Dr. Moore,  Dr Killiany,  or Dr Mortazavi’s faculty page.