Faculty Profile

Michael A. Christie, PhD


Instructor in Psychiatry, Harvard Medical School
Research Scientist, Department of Psychiatry, VA Boston Healthcare System

See publications


Society Memberships

Sleep Research Society
Society for Neuroscience
International Behavioral Neurosciences Society

Research Unit(s)

Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System

Research Interests

Dr. Christie is currently an instructor in the laboratories of Drs. McCarley and Strecker at Harvard Medical School and the Brockton VA Medical Center (part of the Boston VA Healthcare System). The McCarley/Strecker laboratory is primarily involved in the examination of systems controlling sleep and wake states, by means of electrophysiological, neuropharmacological, anatomical, and behavioral investigation. To date Dr. Christie has taken responsibility for rejuvenating the ‘behavioral core’ of the laboratory. To this end he elected to focus on a small number of tasks and get them up-and-running, rather than continue to expend resources on a variety of different tasks, some with questionable usefulness. Having established a number of core tasks Dr. Christie has recently developed an animal-analogue of a human test of sustained attention (the psychomotor vigilance task) commonly used in sleep research. As the behavioral core is now capable of answering empirical questions about the effect of sleep disruption on cognition, and the ability of various compounds to ameliorate or induce these effects, Dr. Christie has recently begun a series of experiments aimed at furthering our understanding of the neurobiology of sleep, and how sleep loss/disruption acts in the brain to produce deficits of attention and memory.

Dr. Christie received his doctoral degree under the supervision of Dr. John Dalrymple-Alford in the Department of Psychology at the University of Canterbury, Christchurch, New Zealand. In the first part of his doctoral dissertation, a qualitative review of the literature concerning the human serial reaction time (SRT; a test of implicit/non-declarative memory) concluded that damage to extrapyramidal brain systems disrupts SRT performance whereas limbic system neuropathology (LSN) leaves performance intact. However, a meta-analysis of the human SRT literature unexpectedly revealed that neuropathological patients with explicit memory disorders (i.e. limbic system deficits) are impaired on the SRT task, although less severely than patients with extrapyramidal damage. To address the theoretical and conceptual issues raised by these discoveries, a number of experiments were performed. A novel rat-SRT task was designed that used intra-cranial self-stimulation to promote prolonged, rapid and continuous responding. Intact rats that experienced a switch from a repeating to a random sequence under these conditions demonstrated a clear interference effect (reaction time slowing), the primary measure of SRT performance. A radio-frequency lesion study using these optimal conditions showed that small caudate-nucleus lesions impaired, whereas small hippocampal lesions facilitated, rat-SRT performance. Hence, this second SRT task was proven to be a valid animal-analogue of the human SRT task, as rats performed it in a manner similar to that shown by humans and relied on the same neural substrate to perform the task as humans. In addition, this second task resolved the discrepancy identified by the meta-analysis of the human SRT literature by demonstrating that LSN dysfunction does not impair SRT performance. This suggests that the LSN deficit identified by the meta-analysis was a function of non-specific (i.e. non-LSN) forms of brain damage common to many neurodegenerative and neuropathological conditions.

Dr. Christie completed his first postdoctoral fellowship under the mentorship of Dr. Steven Hersch at Massachusetts General Hospital. Dr. Hersch’s main theme is the development of compounds for the treatment of Huntington’s Disease. Dr. Christie completed numerous dose-response studies examining the ability of various compounds (inc. CoQ-10, cysteamine, C2-8, and phenylbutyrate) to ameliorate, or halt entirely, the aggressive phenotype of (R6/2) mice transgenic for the Huntington’s gene, or the somewhat less aggressive CAG-140 partial knock-in phenotype. Dr. Christie developed, adapted and used a number of tests of cognitive function with the transgenic mice, including: open field activity, novel object recognition, serial reaction time testing (a test of non-declarative memory), 5-choice serial reaction time (a test of divided attention), and pre-pulse inhibition (a test of sensorimotor-gating, a very simple cognitive function). During this fellowship Dr. Christie also developed a mouse-model of his rat-serial reaction time task (SRT), and was able to adapt the rat-SRT protocol he developed during his Ph.D. research for use with mice. While adapting tests from rats to mice is never straightforward the additional complication of the mice being transgenic (and thus both short lived and severely debilitated towards the end of their lifespan) made the attempt especially difficult, and it’s success especially rewarding.

Besides his research activities, Dr. Christie has participated in the laboratory’s undergraduate internship program, where he acts as a mentor, assisting students from local universities to gain experience in laboratory research. He provides a welcome environment, fostering students’ interests in psychology, neuroscience and basic sleep research.  

Mentor(s)


Teaching

PC 343 Research in Biopsychology, Stonehill College

Honors and Awards
Hereditary Disease Foundation Post Doctoral Research Fellowship (2003-2005)

Harvard Medical School Fellowship in Sleep, Circadian and Respiratory Neurobiology (2005-2006)

Selected Publications

Consedine NS, Christie MA, Neugut AI. Physician, affective, and cognitive variables differentially predict 'initiation' versus 'maintenance' PSA screening  profiles in diverse groups of men.
Br J Health Psychol. 2009 May;14(Pt 2):303-22. Epub 2008 Sep 20. [PMID: 18808732]

Christie MA, McKenna JT, Connolly NP, McCarley RW, Strecker RE. 24 hours of sleep deprivation in the rat increases sleepiness and decreases vigilance: introduction of the rat-psychomotor vigilance task.
J Sleep Res. 2008 Dec;17(4):376-84. Epub 2008 Oct 6. Erratum in: J Sleep Res. 2009 Mar;18(1):143. [PMID: 19021853]

McKenna JT, Cordeira JW, Christie MA, Tartar JL, McCoy JG, Lee E, McCarley RW, Strecker RE. Assessing sleepiness in the rat: a multiple sleep latencies test compared to polysomnographic measures of sleepiness.
J Sleep Res. 2008 Dec;17(4):365-75. Epub 2008 Sep 13. [PMID: 18823428]

Christie MA, Bolortuya Y, Chen LC, McKenna JT, McCarley RW, Strecker RE. Microdialysis elevation of adenosine in the basal forebrain produces vigilance impairments in the rat psychomotor vigilance task.
Sleep. 2008 Oct 1;31(10):1393-8. [PMID: 18853936]

Christie MA, Hersch SM. Demonstration of nondeclarative sequence learning in mice: development of an animal analog of the human serial reaction time task.
Learn Mem. 2004 Nov-Dec;11(6):720-3. Epub 2004 Nov 10. [PMID: 15537741]

Christie MA, Dalrymple-Alford JC. A new rat model of the human serial reaction time task: contrasting effects of caudate and hippocampal lesions.
J Neurosci. 2004 Feb 4;24(5):1034-9. [PMID: 14762121]

Mitchell AS, Dalrymple-Alford JC, Christie MA. Spatial working memory and the brainstem cholinergic innervation to the anterior thalamus.
J Neurosci. 2002 Mar 1;22(5):1922-8. [PMID: 11880522]

Christie MA, Dalrymple-Alford JC. Behavioural consequences of frontal cortex grafts and enriched environments after sensorimotor cortex lesions.
J Neural Transplant Plast. 1995;5(4):199-210. [PMID: 7578436]

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