Faculty Bibliography

BACKGROUND: In the conditioned fear paradigm, repeated pairing of an aversive unconditioned stimulus (US) (e.g. electric shock) with a neutral conditioned stimulus (CS) (e.g. bright light) results in a conditioned fear response to the light alone. Animal studies have shown that the amygdala plays a critical role in acquisition of conditioned fear responses, while the medial prefrontal cortex (including anterior cingulate), through inhibition of amygdala responsiveness, has been hypothesized to play a role in extinction of fear responses. No studies have examined neural correlates of fear conditioning and extinction in patients with post-traumatic stress disorder (PTSD). METHOD: Women with early childhood sexual-abuse-related PTSD (n = 8) and women without abuse or PTSD (n = 11) underwent measurement of psychophysiological (skin conductance) responding as well as positron emission tomographic (PET) measurement of cerebral blood flow during habituation, acquisition and extinction conditions. During habituation subjects were repeatedly exposed to a blue square on a screen. During acquisition, exposure to the blue square (CS) was paired with an electric shock to the forearm (US). With extinction, subjects were again exposed to the blue squares without shock. On a different day subjects went through the same procedure with electric shocks administered randomly in the absence of the blue square. RESULTS: Skin conductance responding to the CS was consistent with the development of conditioned responses with this paradigm. PTSD patients had increased left amygdala activation with fear acquisition, and decreased anterior cingulate function during extinction, relative to controls. CONCLUSIONS: These findings implicate amygdala and anterior cingulate in the acquisition and extinction of fear responses, respectively, in PTSD.

Magnetic resonance imaging (MRI) has opened a new window to the brain. Measuring hippocampal volume with MRI has provided important information about several neuropsychiatric disorders. We reviewed the literature and selected all English-language, human subject, data-driven papers on hippocampal volumetry, yielding a database of 423 records. Smaller hippocampal volumes have been reported in epilepsy, Alzheimer's disease, dementia, mild cognitive impairment, the aged, traumatic brain injury, cardiac arrest, Parkinson's disease, Huntington's disease, Cushing's disease, herpes simplex encephalitis, Turner's syndrome, Down's syndrome, survivors of low birth weight, schizophrenia, major depression, posttraumatic stress disorder, chronic alcoholism, borderline personality disorder, obsessive-compulsive disorder, and antisocial personality disorder. Significantly larger hippocampal volumes have been correlated with autism and children with fragile X syndrome. Preservation of hippocampal volume has been reported in congenital hyperplasia, children with fetal alcohol syndrome, anorexia nervosa, attention-deficit and hyperactivity disorder, bipolar disorder, and panic disorder. Possible mechanisms of hippocampal volume loss in neuropsychiatric disorders are discussed.

The advance of neuroimaging techniques has resulted in a burgeoning of studies reporting abnormalities in brain structure and function in a number of neuropsychiatric disorders. Measurement of hippocampal volume has developed as a useful tool in the study of neuropsychiatric disorders. We reviewed the literature and selected all English-language, human subject, data-driven papers on hippocampal volumetry, yielding a database of 423 records. From this database, the methodology of all original manual tracing protocols were studied. These protocols differed in a number of important factors for accurate hippocampal volume determination including magnetic field strength, the number of slices assessed and the thickness of slices, hippocampal orientation correction, volumetric correction, software used, inter-rater reliability, and anatomical boundaries of the hippocampus. The findings are discussed in relation to optimizing determination of hippocampal volume.

Brain imaging studies have mapped out the neural circuitry of posttraumatic stress disorder (PTSD), implicating brain areas sensitive to stress such as the hippocampus. Animal studies show that antidepressants promote hippocampal neurogenesis and block the effects of stress on the hippocampus. We found that treatment of PTSD patients for a year with the serotonin reuptake inhibitor (SSRI) paroxetine resulted in a 5% increase in hippocampal volume and a 35% improvement in verbal declarative memory function. Patients subjectively reported an improvement in cognition and work performance. These studies are consistent with the idea that antidepressants have a beneficial effect on hippocampal function in PTSD patients.