Biopsychology
Gerard Bruder, Ph.D., Research
Scientist VI, Acting Chief
W. Crawford Clark, Ph.D., Research Scientist VI
Steven Fairhurst, M.S., Research
Scientist III
Chara Malapani, M.D., Ph.D.,
Research Scientist V
Michael Terman, Ph.D., Research
Scientist VI
James Towey, Ph.D., Research
Scientist IV
Ziad Boulos, Ph.D., Research Scientist V
Jürgen Kayser, Ph.D., Research Scientist IV
Craig E. Tenke, Ph.D., Research Scientist IV
Jiuan Su Terman, Ph.D., Research Scientist IV
We are sad to report that John Gibbon, Chief of the Department of Biopsychology since its inception in 1986, died on January 16, 2001. The Department and the Institute mourn the passing of a brilliant researcher and a wonderful person.
As a successor to the noted Psychophysiology Department, which was directed by the late Dr. Samuel Sutton, the Biopsychology Department at Psychiatric Institute has continued that tradition of distinction. Originally concerned with psychological research in animals and patients, it has more recently developed an increased emphasis on the neurobiological systems underlying psychopathology. Dr. John Gibbon an eminent researcher on cognitive issues in timing behavior, was chief of the Department until his recent death. The Department's Acting Chief now is Dr. Gerard Bruder.
Using behavioral, cognitive, and physiological measures, the Biopsychology department continues its central mission to investigate brain-behavior relationships in terms of underlying neural and psychological mechanisms. The department comprises four research units Psychophysiology, Light Therapy, Temporal Cognition and Pain and one training unit for under-represented minorities, the NIMH-sponsored Career Opportunities in Research.
Drs. Bruder and Towey, who direct the Psychophysiology Unit, investigate neurophysiologic and cognitive functions of psychiatric disorders, in keeping with the tradition of the late Dr. Samuel Sutton. With Drs. Craig Tenke, Jurgen Kayser, and their clinical collaborators in the Depression Evaluation Service, they continue their NIMH-funded study of right-left brain asymmetries in depressive disorders. Using cognitive tests and measures of brain potentials, they have found that abnormalities of regional brain activation in depressive disorder are related to important clinical features, such as diagnostic subtype and responsiveness to treatments for depression. Dr. Bruder reviewed evidence concerning the potential of electrophysiologic and perceptual tests as predictors of therapeutic response to antidepressants. The findings of several studies suggest that depressed patients who respond favorably to an SSRI antidepressant (most notably Prozac) differ from non-responders in both their frontal brain activation and right-left brain asymmetry. Drs. Kayser, Bruder, and Tenke also published a study in which brain potentials of depressed patients and healthy controls were measured to emotional pictures. Depressed patients differ from controls in not showing an increase in a late brain potential (P3) to emotional pictures over the right parietal region of the brain. In collaboration with Drs. Kengen and Pine in the Department of Child Psychiatry, they have also found that depressed adolescents display some of the same abnormalities of right-left brain asymmetries that have been found in depressed adults. In addition, Drs. Bruder, Kayser, Tenke, and Towey continued their NIMH-funded study of brain potentials in schizophrenia, in collaboration with members of the Mental Health Clinical Research Center. The fine temporal resolution of their electrophysiologic measures has enabled them to investigate the time course of neurocognitive deficits in schizophrenia. In a recent publication, they reported finding a marked reduction of negative brain potentials in schizophrenia beginning about 100 milliseconds after the onset of auditory stimuli. Drs. Towey and Bruder also continued their study of brain potential correlates of cognitive function and cortical arousal in obsessive-compulsive disorder (OCD). Since their clinical collaborators in the Anxiety Disorders Clinic have helped develop effective drug and/or behavior therapies to treat OCD, there has been a sharp decline in the number of OCD patients who visit the clinic and volunteer for these ongoing brain wave studies. Currently, they are studying treatment-refractory OCD patients, in collaboration with Dr. Brian Fallon of the Anxiety Disorders Clinic, recording brain potentials before and after two weeks of drug treatment with intravenous clomipramine and/or oral clomipramine using a double-blind, placebo-controlled design.
Click here to visit the Psychophysiology website
Click here to visit the Psychophysiology website
Light Therapy/Clinical Chronobiology
Drs. Michael Terman and Jiuan Su-Terman, who direct the clinical chronobiology program, are continuing an NIMH-supported five-year trial with patients who have seasonal affective disorder (SAD). Three distinct treatments are being compared in separate groups: post-awakening bright light therapy, dawn simulation, and high-intensity negative air ionization (the latter two administered during sleep). The project follows from their recent demonstration that bright light and negative ion therapy were both superior to a placebo treatment, low-intensity ionization (Arch Gen Psychiatry, 1998, 55, 875-882), and their finding that light-induced circadian rhythm phase advances are a specific antidepressant mechanism of action (Arch Gen Psychiatry, 2001, 58, 69-75). A grant supplement is supporting extension of this work to nonseasonal, chronically depressed patients, in a two-center collaboration with Dr. Namni Goel, Wesleyan University (a recent postdoctoral fellow in the group). In related animal laboratory work under a grant from NINDS, the Termans are collaborating with Dr. Ziad Boulos in studies of dusk and dawn twilight effects on the phase and duration of daily activity in hamsters. While the Termans have used circulating melatonin levels as an index of circadian rhythm phase in depressed patients, a new project with Dr. M. Mila Macchi, postdoctoral fellow, is assessing psychiatric measures in Neurological Institute patients who have experienced pineal gland resection with loss of ability to produce the hormone. With collaborators at Yale University and Case Western Reserve University, the Termans have completed a pilot study of bright light therapy for patients with antepartum depression. Regardless of seasonal pattern, major improvement was obtained over 3-5 weeks of daily exposure in the morning. If results are sustained in a pending controlled trial, light therapy might provide a preferable alternative to antidepressant drugs in this vulnerable population. In another new NIH-sponsored project, Drs. Boulos and Macchi are testing the utility of evening light exposure as a jet-lag countermeasure for traveler subjects arriving in New York from Zurich.
The Termans' program has received international scholarly as well as media attention. M. Terman serves as president of the Center for Environmental Therapeutics, a nonprofit research and educational agency.
Temporal Cognition
Drs. John Gibbon and Chara Malapani, who co-directed the Temporal Cognition Unit during 2000, continued to investigate CNS functions underlying the interval time sense in animals and humans. Dr. Gibbon's research, which was mainly basic in character (e.g., behavioral studies using animals) and the new lines of research that Dr. Malapani brought to the Unit (e.g., drug treatment studies using humans and animals) were supported by two RO1 grants from the NIMH. Both lines of research received a renewal award, the first in 1999 and the second one in 2000, for a period of five years. Their most recent animal/behavioral studies of variability in temporal memory were based on a new theoretical thrust developed by Drs. John Gibbon and Randy Gallistel (Rutgers University), as detailed this year in Psychological Review (Gallistel & Gibbon, 2000). This reanalysis of temporal control in conditioning ties mnemonic and dynamic learning effects to basic timing mechanisms known to underlie many nervous system functions. This year also, Dr. Malapani initiated a drug study with animals (pigeons and rats), in collaboration with Drs. Peter Balsam & John Horvitz (Columbia University) that helps clarify the role of dopaminergic systems in animal and human timing (Oyama, et al., 2000). This new direction of the animal research is closely linked with the human research being conducted currently in the Unit. It is aimed at developing and/or using existing animal models of human diseases (i.e., Parkinson's disease, schizophrenia) that are known to involve specific brain areas (the basal ganglia cortical frontal loops) and neuro-chemical systems (central dopaminergic systems). New experiments to test these animal models of human diseases have been designed by our Unit to access distinct psychological processes inherent in temporal cognition, such as storage, retrieval, and decision mechanisms. The human work, ongoing in the Temporal Cognition Unit, focuses on isolating the neural substrates underlying either the storage and/or the retrieval process of temporal memory (Malapani, et al., 2000; Gibbon & Malapani, 2000). Previous research has shown that dopaminergic deregulation in the human striatum associated with Parkinson's disease (PD) distorts temporal memory (Malapani, et al., 1998). More recently, Drs. Gibbon and Malapani designed experiments that in a cross-drug study separated storage from retrieval deficits in patients with damage to the basal ganglia (Malapani, Deweer & Gibbon, 2000; Malapani, et al., 2000). Using deep brain stimulation (DBS) with PD patients, Dr. Malapani also showed that the subthalamic nucleus, in the indirect pathway from striatum to the frontal cortex, is specifically involved in the retrieval process (Malapani, et al., submitted). Interestingly, the different phychophysical profiles of the "retrieval-like" deficit seen in ageing and the retrieval distortion associated with PD led to a new line of experiments exploring the role of distinct kinds of feed-back in correcting those deficits (Rakitin, Gibbon & Malapani, 2000; Rakitin, et al., submitted). This line of research has also led to a new study that looks at the effects of dopaminergic drugs on timing distortions seen with ageing (underway at the Irving Research Center of the Neurological Institute), in collaboration with Dr. Yaakov Stern (Sergievsky Center) and Dr. Brian Rakitin. Dr. Rakitin, who joined the Unit in 1997 as a post-doctoral research fellow and has recently received a K-award from NIH, has been an extremely active and valuable member of our Unit. The research related to his own grant, NIA K01-00991, titled "Control and Consequences of Timing Deficits in Ageing", examines the degree to which the timing abilities in different subject groups are sensitive to interference from non-timing cognitive processes. In short, 2000 was a very productive year for the Temporal Cognition Unit in terms of research reports being written, elegant new experiments being designed, and large amounts of data being collected (e.g., >100 human subjects were tested). Also noteworthy was a new collaboration Dr. Malapani established during 2000 with Dr. Joy Hirsch, the new recruit for functional Magnetic Resonance Imaging (fMRI) research at Columbia University. Dr. Malapani sponsored a talented graduate student of Dr. Hirsch, Daniel Engber, concerning his NSF grant application (submitted 11/2000) to study the subcortical mechanisms of temporal cognition using fMRI. Pilot testing is already underway.
One potential benefit from our Unit's ongoing research should be an improved understanding of the brain mechanisms whereby the time sense indexes the passage of time (its accumulation) and records (i.e., stores/encodes) relevant time intervals in memory. Life flows inexorably forward and our only hold on the past is our memory for events, their times, and the relations between them. The flexibility that nearly all species exhibit in being able to store and retrieve indices of quality when making decisions is fundamental to higher order cognitive skills. Deepening our understanding of the neurobiology of learning and memory for time should provide some salient insights concerning the diagnosis, prognosis, and treatment of psychiatric and neurological human brain diseases.
As the year unfolded, it became increasingly clear that Dr. John Gibbon was no longer able to continue his long, valiant struggle with cancer. His untimely death was a devastating blow that has left a major void. To honor his fond memory and his life's work, Dr. Malapani and the rest of this Unit redoubled their research efforts, including their commitment to making a newly designed Temporal Cognition lab all that John Gibbon wanted it to be.
Pain
Dr. Clark directs the Pain Unit that continues to study the dimensions and clusters underlying pain and related emotional states, as well as memory for pain. In collaboration with John Kuhl, he was recently awarded a five-year grant from the National Institute of Dental and Craniofacial Research. That study evaluates gender, ethnocultural, and menstrual cycle differences in pain sensation and pain report. Special focus is being placed on (1) gender differences in neurosensory sensitivity, (2) differences in psychosocial and personal factors which influence report bias (stoicism or squeamishness), and (3) differences in the meanings associated with words used to describe sensory and emotional experiences (semantics). Using cluster analysis, they recently demonstrated that some descriptors of pain symptoms (e.g., disturbing, distressing, nauseating) are considered descriptors of sensory pain by men, but of emotional pain by women. There are also ethnocultural differences.
Dr. Clark's ongoing research also includes validation and cross-cultural studies of the Multidimensional Affect and Pain Survey (MAPS). In collaboration with Dr. J. Yang, for example, he found that pre-surgery scores on a Chinese translation of the MAPS for expected postoperative pain by oncology patients in Hong Kong predicted both post-surgery morphine consumption and unreinforced button-pressing behavior on a Patient Controlled Analgesia pump. Patients who, according to the MAPS questionnaire, were more anxious before surgery consumed more morphine postoperatively. It was also demonstrated that women required almost half the dose of morphine (in mg/kg of body weight) to titrate to the same level of postoperative pain as did men, strongly suggesting a physiological basis for the difference. Another surprising finding was that intensity scores on a pain rating scale failed to correlate with descriptors of the sensory aspects of pain, such as tearing, pulling, and stabbing, but did correlate with descriptors of the emotional aspects, such as anxious, angry, and annoyed. These results call into serious question whether patient's responses to simple pain rating scales provide a sound basis for the administration of analgesics. The validity of the MAPS continues to be tested in collaborative studies with Dr. M. L. Keohan of the CPMC Oncology Service, and with Dr. G. Carli and colleagues in the Institute of Human Physiology at the University of Siena (using an Italian translation).
With Drs. J.P. Mohr (Neurology), R.N. Wharton (Psychiatry), and S. Bennett Clark (Biopsychology), Dr. Clark continues the study of sensory measures which predict the occurrence of post-stroke pain and its treatment with the antidepressant Zoloft. This study is being supported by the Nathaniel Wharton Foundation for Research and Education in Brain, Body, and Behavior, and by Pfizer.
Dr. Clark continues on the Advisory Board of the Center for Mind/Life Healing, a program of the Columbia University Department of Psychiatry, and on the Board of Directors of the Eastern Pain Association. Dr. Clark is a co-investigator/collaborator on grants with Dr. S. Comer of the Department of Substance Abuse (changes in pain perception during the menstrual cycle), Dr. T. Walsh of the Department of Child Psychiatry (bulimia and pain perception), and at the CPMC Center for Complementary and Alternative Medicine (Dr. F. Kronenberg, Director).
Career Opportunities in Research (COR)
In July 1999, Dr. Towey was awarded
a five-year training grant from NIMH, a Career Opportunities in Research
(COR) training grant to help strengthen research and research training
experiences in scientific disciplines related to mental health at Mercy
College, a four-year undergraduate institution serving mostly female and
minority students. In collaboration with faculty at Psychiatric Institute/Columbia
University serving as Research Mentors (e.g., Drs. J. Gibbon, G. Bruder
, H. Bird, C. Hoven, W. Fifer, M. Myers, M. Fischman, A. Bisaga, F. Kronenberg),
Dr. Towey is working with faculty and staff at Mercy College to implement
a two-year COR Training Program for which five highly talented third-
and fourth-year honor students are selected each year as recipients of
a pre-baccalaureate National Research Service Award (NRSA). In addition
to NRSA stipends, tuition aid, and support services, these COR Trainees
receive one to two years of special course work at Mercy College in conjunction
with research training at Psychiatric Institute. This COR Training program
is designed to improve the student's qualifications to gain entry to and
to complete successfully a graduate program of study leading to Ph.D.
and/or M.D. degrees for research careers in mental health. Besides his/her
own Honors Thesis Project, each COR Trainee also collaborates on a group
research project, for which Dr. Towey was awarded additional pilot funds
from NIH/EARDA, to survey health trends among Mercy College students (e.g.,
tobacco smoking, binge drinking, unsafe sex, anxiety, depression). The
Office of Special Populations at NIMH has strongly encouraged Dr. Towey
to apply for two complimentary training grants. In partnership with senior
faculty at PI, one is designed to help two or more qualified faculty from
Mercy College to carve out a research area in mental health; the other
targets high school students, motivating them to pursue careers in mental
health research. The first grant application is under review (in Council);
the second is being prepared for a June 1 submission.
Dr. John Gibbon
and Dr. Eric Kandel