Principal Investigator:  Richard J. Maddock, M.D.

The panic response is an "alarm" mechanism which may have adaptive value in the face of threat.  However, in patients with panic disorder, this response repeatedly occurs at inappropriate times.  The regulatory web that governs this neurobiological process appears to be disordered.  Current research in my laboratory attempts to elucidate the nature of this dysfunction using a variety of neuroscience methods, including cognitive, metabolic and pharmacological challenge studies and functional neuroimaging.  The most consistent cognitive finding in panic disorder is that such patients exhibit longer response latencies to emotionally salient words on various cognitive tasks, including color naming and lexical decision tasks.  FMRI studies in our lab have shown that emotionally salient words consistently activate the retrosplenial region of the posterior cingulate gyrus, and the right amygdala in normal subjects.  Differences in the brain response to such stimuli in panic patients may suggest brain regions implicated in the pathogenesis of panic disorder.  Comparative studies in panic disorder patients are undergoing data analysis.  Several lines of evidence suggest that panic patients respond abnormally to metabolic challenges which affect the regulation of pH, including sodium lactate infusions and CO2 inhalation.  In our lab we have shown that panic patients consistently have an exaggerated systemic lactic acid response to alkalosis.  More recently, Dager and colleagues have reported the same abnormality within the brains of panic patients.  Magnetic resonance spectroscopy studies of brain energy metabolism and pH regulation in response to metabolic challenges in panic patients are being planned to test competing models of the mechanism of this metabolic abnormality.

Principal Investigator:  Richard J. Maddock, M.D.

Any comprehensive understanding of the pathogenesis of anxiety disorders must incorporate a biopsychosocial perspective, as elements from each domain can influence the onset, continuation, and recovery from these illnesses.  In addition to neuroscientific studies of anxiety disorders, our lab also conducts cognitive, clinical and treatment research, with a special emphasis on panic disorder and post traumatic stress disorder.  Current projects include studies of the effects of emotional stimuli on memory and attentional processes and hemispheric lateralization, diagnostic and treatment studies of underlying anxiety disorders in chest pain patients, studies of the relationship between parental representations and symptom patterns in anxiety patients, and ongoing clinical trials of new medications for anxiety disorders.

Principal Investigator:   Ruth Salo, Ph.D.
E-mail:  resalo@ucdavis.edu

In the past decade the use of the stimulant methamphetamine has increased in schizophrenia patients as well as the general population. In persons without a psychiatric diagnosis methamphetamine is known to be neurotoxic to dopaminergic rich frontostriatal brain regions, including the anterior cingulate cortex and the prefrontal cortex with accompanying deficits in attention and executive control.   Little is known however about the additive effects of methamphetamine abuse on brain function and cognitive control in schizophrenia patients.  Our research program is examining the effects of methamphetamine abuse on brain function and attention in schizophrenia patients using Functional Magnetic Resonance Imaging [fMRI], magnetic resonance spectroscopy [MRS]  and experimental measures of cognitive control. The use of MRS in conjunction with fMRI will determine whether or not neuronal pathology as measured with MRS is linked to functional brain activation as measured by fMRI during tests of cognitive control. These data will provide insight into the neural substrates underlying attentional control and may contribute to clinical interventions in those schizophrenia patients who abuse stimulants.

Principal Investigator:  Ruth Salo, Ph.D.
E-mail:  resalo@ucdavis.edu

There is increasing evidence that methamphetamine is neurotoxic to dopaminergic frontostriatal brain regions with corresponding deficits in selective attention and cognitive control. Our research program is investigating the relationship between alterations in brain function and attentional control in methamphetamine abusers. We are employing magnetic resonance spectroscopy [MRS] and diffusion tensor imaging [DTI] in conjunction with sensitive computerized measures of attention to examine these links. Our findings thus far indicate a dysregulation of attentional control associated with long-term methamphetamine abuse. Such breakdowns in attentional control may contribute to behaviors associated with maladaptive decision-making often associated with drug-seeking behavior. Careful characterization of cognitive functioning is relevant to the treatment of substance abuse as many treatment programs rely on cognitive behavioral therapy as part of their intervention approach.