Department of Psychiatry Faculty

Ralph Hoffman, MD Professor of Psychiatry Yale-New Haven Psychiatric Hospital LV 108 Tel: 203-688-9734 Fax: 203-785-9709 Email: ralph.hoffman@yale.edu

Education

1971, Sc.B., Mathematics, Brown University
1976, M.D., Albert Einstein College of Medicine

Research Interest

Research efforts have been primarily directed to advancing our understanding of schizophrenia and to develop better treatments.

One set of studies focuses on the pathophysiology and treatment of auditory hallucinations. These studies rely on fMRI data, which have permitted maps of the time course of activation preceding onset of hallucinations and are also used to map abnormal functional connectivity. Dr. Hoffman's research group is also collecting high resolution structural MRI data to identify brain areas with grey matter loss that are specific to schizophrenic patients with auditory hallucinations. These functional and structural MRI data are also used to position "suppressive, 1-Hz rTMS for a clinical trial. A long-term objective of these studies is to develop potent somatic interventions for refractory psychotic disorders that combine rTMS, medication and psychosocial treatments.

A second set of studies utilizes computer simulations of complex neural networks capable of complex language comprehension and production of story-based narratives. These simulations, which are being developed via a collaboration with Professor Risto Miikkulainen (Department of Computer Science, University of Texas, Austin) are subjected to lesions and neuromodulatory disturbances within and between modules. The overall objective is to determine which disturbances cause these neural systems to most clearly reproduce language disturbances characteristic of persons with schizophrenia, i.e., positive thought disorder, negative thought disorder, and fixed delusions. The latter are simulated as the narrative production of locked-in, repetitively reproduced untrue emotion-charged stories. Simulation studies are conducted in parallel with a human subject study involving narrative memory and reproduction that compares patients with schizophrenia and normal controls. Types of memory distortion exhibited by actual patients will be used to set parameters for the computer simulations to enhance their fidelity in reproducing actual psychopathology.

Dr. Hoffman's third research focus has been to characterize complex interactions of neurocognitive and psychosocial factors that predict induction of schizophrenia. This work in part is based on a data collected from a randomized clinical trial of persons with prodromal symptoms of schizophrenia comparing olanzapine and placebo. In parallel with this study, Dr. Hoffman is undertaking computer simulations designed to estimate the complexity of gene-gene and gene-environment interactions that produce schizophrenia.

Areas of expertise:
Auditory hallucinations
Schizophrenia
Transcranial magnetic stimulation
Neurolinguistics and computational linguistics
Computer simulations of neural networks
Functional magnetic resonance imaging

Recent Publications

Hoffman, R.E., Gueorguieva, R., Hawkins, K.A., Varanko, M., Boutros, N.N., Wu, Y.-T., Carroll, K., Krystal, J.H.. Temporoparietal transcranial magnetic stimulation for auditory hallucinations: safety, efficacy and predictors in a fifty patient sample. Biological Psychiatry 2005; 58:97-104.

Hoffman, R.E., McGlashan, T.M. NMDA receptor hypofunction versus excessive synaptic elimination as models of schizophrenia (commentary). Behavioral and Brain Science 2003;26:92.

Hoffman, R.E., Hawkins, K.A., Gueorguieva, R. Boutros, N.N., Rachid, F., Carroll, K., Krystal, J.H. transcranial magnetic stimulation of left temporoparietal cortex and medication-resistant auditory hallucinations. Archives of General Psychiatry 2003;60:49-56

Siekmeier P.J., Hoffman, R.E. Enhanced semantic priming in schizophrenia: a computer model based on excessive pruning of local connections in association cortex. British Journal of Psychiatry 2002; 180:345-350.

Hoffman, R.E., Cavus, I. Slow transcranial magnetic stimulation, long-term depotentiation, and brain hyperexcitability disorders. American Journal of Psychiatry 2002;159:1093-1102.

Hoffman, R.E., Shi, W.-X., Bunney, B.S. Anatomic basis of sequence-dependent predictability exhibited by nigral dopamine firing patterns. Synapse 39:133-138, 2001.

Hoffman, R.E., Quinlan, D.M., Mazure, C.M., McGlashan, T.M. Cortical instability and the mechanism of mania: A neural network simulation and perceptual test. Biological Psychiatry 49: 500-509, 2001

Hoffman, R.E., Boutros, N.N., Hu, S., Berman, R,M., Krystal, J.H., Charney, D.S. Transcranial magnetic stimulation and auditory hallucinations in schizophrenia. Lancet 355: 1073-5, 2000

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