Jane Epstein

Increased anterior cingulate and caudate activity in bipolar mania

BACKGROUND Executive control of cognition, emotion, and behavior are disrupted in the manic state of bipolar disorder. Whereas frontal systems are implicated in such dysfunction, the localization of functional brain abnormalities in the manic state is not well understood. METHODS We utilized a high-sensitivity H(2)(15)0 positron emission tomography technique to investigate regions of increased brain activity in mania, compared to euthymia, in bipolar disorder. RESULTS The principal findings were manic state-related increased activity in left dorsal anterior cingulate, and left head of caudate. CONCLUSIONS The findings suggest that the manic state of bipolar disorder may be associated with heightened activity in a frontal cortical-subcortical neural system that includes the anterior cingulate and caudate.

Differential Time Courses and Specificity of Amygdala Activity in Posttraumatic Stress Disorder Subjects and Normal Control Subjects

BACKGROUND Previous neuroimaging studies have demonstrated exaggerated amygdala responses to negative stimuli in posttraumatic stress disorder (PTSD). The time course of this amygdala response is largely unstudied and is relevant to questions of habituation and sensitization in PTSD exposure therapy. METHODS We applied blood oxygen level dependent functional magnetic resonance imaging and statistical parametric mapping to study amygdala responses to trauma-related and nontrauma-related emotional words in sexual/physical abuse PTSD and normal control subjects. We examined the time course of this response by separate analysis of early and late epochs. RESULTS PTSD versus normal control subjects have a relatively increased initial amygdala response to trauma-related negative, but not nontrauma-related negative, versus neutral stimuli. Patients also fail to show the normal patterns of sensitization and habituation to different categories of negative stimuli. These findings correlate with measured PTSD symptom severity. CONCLUSIONS Our results demonstrate differential time courses and specificity of amygdala response to emotional and control stimuli in PTSD and normal control subjects. This has implications for pathophysiologic models of PTSD and treatment response. The results also extend previous neuroimaging studies demonstrating relatively increased amygdala response in PTSD and expand these results to a largely female patient population probed with emotionally valenced words.

Neural substrates of the interaction of emotional stimulus processing and motor inhibitory control: An emotional linguistic go/no-go fMRI study

Neural substrates of behavioral inhibitory control have been probed in a variety of animal model, physiologic, behavioral, and imaging studies, many emphasizing the role of prefrontal circuits. Likewise, the neurocircuitry of emotion has been investigated from a variety of perspectives. Recently, neural mechanisms mediating the interaction of emotion and behavioral regulation have become the focus of intense study. To further define neurocircuitry specifically underlying the interaction between emotional processing and response inhibition, we developed an emotional linguistic go/no-go fMRI paradigm with a factorial block design which joins explicit inhibitory task demand (i.e., go or no-go) with task-unrelated incidental emotional stimulus valence manipulation, to probe the modulation of the former by the latter. In this study of normal subjects focusing on negative emotional processing, we hypothesized activity changes in specific frontal neocortical and limbic regions reflecting modulation of response inhibition by negative stimulus processing. We observed common fronto-limbic activations (including orbitofrontal cortical and amygdalar components) associated with the interaction of emotional stimulus processing and response suppression. Further, we found a distributed cortico-limbic network to be a candidate neural substrate for the interaction of negative valence-specific processing and inhibitory task demand. These findings have implications for elucidating neural mechanisms of emotional modulation of behavioral control, with relevance to a variety of neuropsychiatric disease states marked by behavioral dysregulation within the context of negative emotional processing.

Mesolimbic Activity Associated with Psychosis in Schizophrenia: Symptom-specific PET Studies

ABSTRACT: Hallucinations and paranoid delusions are prominent among the positive symptoms of schizophrenia. Such psychotic symptoms are notable for their aberrant representations of, and relation to, the external world and for the emotional/motivational valence associated with the representations. As mesolimbic structures, including the amygdala and ventral striatum, are thought to play a significant role in imparting emotional valence to external stimuli, we here examine the mesolimbic findings of H215O PET studies designed to probe the functional neuroanatomy of psychosis.

Human fear-related motor neurocircuitry

Using functional magnetic resonance imaging and an experimental paradigm of instructed fear, we observed a striking pattern of decreased activity in primary motor cortex with increased activity in dorsal basal ganglia during anticipation of aversive electrodermal stimulation in 42 healthy participants. We interpret this pattern of activity in motor neurocircuitry in response to cognitively-induced fear in relation to evolutionarily-conserved responses to threat that may be relevant to understanding normal and pathological fear in humans.

Fear-related activity in subgenual anterior cingulate differs between men and women

Functional magnetic resonance imaging in association with an instructed fear/anticipatory anxiety paradigm was used to explore sex differences in the human fear response. During anticipation of mild electrodermal stimulation, women, as compared with men, demonstrated increased activity in the subgenual anterior cingulate cortex and functionally related regions of the insula and brainstem. The subgenual anterior cingulate cortex is a region critical for emotional control implicated in the pathogenesis of psychiatric disease. Present findings suggest a contributory neural substrate for the greater susceptibility of women to anxiety and affective disorders, and emphasize the importance of considering participant sex when designing and interpreting functional neuroimaging studies.

Neural Plasticity After Acquired Brain Injury: Evidence from Functional Neuroimaging

The reorganization of the adult central nervous system after damage is a relatively new area of investigation. Neuroimaging methods, such as functional magnetic resonance imaging, diffusion tensor imaging, and positron emission tomography, have the ability to identify, in vivo, some of the processes involved in these neuroplastic changes and can help with diagnosis, prognosis, and potentially treatment approaches. In this article, traumatic brain injury and stroke are used as examples in which neural plasticity plays an important role in recovery. Basic concepts related to brain remodeling, including spontaneous reorganization and training‐induced recovery, as well as characteristics of reorganization in successful recovery, are reviewed. The microscopic and molecular mechanisms that underlie neural plasticity and neurogenesis are briefly described. Finally, exciting future directions for the evaluation, diagnosis, and treatment of severe brain injury are explored, with an emphasis on how neuroimaging can help to inform these new approaches.

Diurnal cortisol amplitude and fronto-limbic activity in response to stressful stimuli

The development and exacerbation of many psychiatric and neurologic conditions are associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis as measured by aberrant levels of cortisol secretion. Here we report on the relationship between the amplitude of diurnal cortisol secretion, measured across 3 typical days in 18 healthy individuals, and blood oxygen level dependant (BOLD) response in limbic fear/stress circuits, elicited by in-scanner presentation of emotionally negative stimuli, specifically, images of the World Trade Center (WTC) attack. Results indicate that subjects who secrete a greater amplitude of cortisol diurnally demonstrate less brain activation in limbic regions, including the amygdala and hippocampus/parahippocampus, and hypothalamus during exposure to traumatic WTC-related images. Such initial findings can begin to link our understanding, in humans, of the relationship between the diurnal amplitude of a hormone integral to the stress response, and those neuroanatomical regions that are implicated as both modulating and being modulated by that response.

Frontolimbic function and cortisol reactivity in response to emotional stimuli

Frontolimbic structures involved in fear conditioning have also been associated with hypothalamic–pituitary–adrenal (HPA)-axis modulation, including amygdaloid, hippocampal, and ventromedial prefrontal cortex regions. Although HPA-axis function and endocrine changes have been investigated in the context of stress provocation, much research has not been conducted using functional neuroimaging in the study of the HPA axis and frontolimbic function in response to emotional stimuli. Using functional magnetic resonance imaging, the association of blood-oxygen-level dependent signal with salivary cortisol in response to an emotional visual scene paradigm was investigated, with prescan and postscan salivary cortisol analyzed as a covariate of interest during specific conditions. Cortisol reactivity to the paradigm was positively associated with amygdalar and hippocampal activity and negatively associated with ventromedial prefrontal cortex activity in conditions involving emotional imagery.

Impact of neuroleptic medications on continuous performance test measures in schizophrenia

Attentional deficits, as measured by the continuous performance test (CPT), have been reliably detected in schizophrenic patients. Schizophrenic patients show greater impairment on CPT tasks than normal control subjects and subjects with chronic alcoholism or major affective disorder (Nuechterlein and Dawson 1984). The deficits in CPT performance found in remitted (Wohlberg and Kornetsky 1973) and acutely psychotic schizophrenic patients suggest impaired attention may be a core neurocognitive deficit. Impaired CPT performance has also been found in subjects with schizotypal features (Obiols et al 1993) and in children of schizophrenic subjects (Cornblatt and ErlenmeyerKimling 1985), raising the possibility that this deficit may represent a marker of vulnerability to the development of schizophrenia-related disorders. Unfortunately, efforts to delineate the relationship between attentional impairment, as measured by CPT performance, and the pathophysiology, phenomenology, and genetics of schizophrenia have been hampered by a poor understanding of the influence of confounding variables, particularly medication status. Though multiple studies have examined the effects of neuroleptic medication on CPT measures in schizophrenia, results have been contradictory (Medalia et al 1988). Many of these studies used a cross-sectional design and/or failed to examine practice effects. The use of a cross-sectional design for CPT studies with schizophrenic subjects is especially problem-