Emily Stern

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.

Detection of Thirty-Second Cognitive Activations in Single Subjects with Positron Emission Tomography: A New Low-Dose H215O Regional Cerebral Blood Flow Three-Dimensional Imaging Technique

Positron emission tomography regional CBF (rCBF) studies of cognitive processes have traditionally required 30–60 mCi of H215O per scan and intersubject averaging to achieve statistical significance. However, intersubject anatomical, functional, and disease variability can make such an approach problematic. A new method that produces significant results in single subjects is presented. It is based upon high-sensitivity three-dimensional imaging and a “slow” bolus administration of >15 mCi of H215O per scan. The method is validated in four normal volunteers using control and auditory-language activation tasks with four scans per condition and statistical parametric mapping analysis. It is demonstrated that the rCBF distribution associated with the cognitive state is detected during the arrival of radiotracer in the brain. This occurs over 30 s and constitutes a critical temporal window during which stimulation should be performed. A 90-s acquisition time is found to produce results of greater significance than a 60-s acquisition time. The implications of the results and the functional neuroanatomical findings are discussed. This method is suitable for the study of individual functional neuroanatomy in many neuropsychological, pharmacologic, and symptom states in normal subjects and in patients with psychiatric and neurologic disorders.

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.

Top-Down Reorganization of Activity in the Visual Pathway after Learning a Shape Identification Task

Learning in shape identification led to global changes in activation across the entire visual pathway, as revealed with whole-brain fMRI. Following extensive training in a shape identification task, brain activity associated with trained shapes relative to the untrained shapes showed: (1) an increased level of activity in retinotopic cortex (RC), (2) a decrease in activation of the lateral occipital cortex (LO), and (3) a decrease in the dorsal attentional network. In addition, RC activations became more correlated (and LO activation, less correlated) with performance. When comparing target-present and target-absent trials within the trained condition, we observed a similar decrease in the dorsal attentional network but not in the visual cortices. These findings indicate a large-scale reorganization of activity in the visual pathway as a result of learning, with the RC becoming more involved (and the LO, less involved) and that these changes are triggered in a top-down manner depending on the perceptual task performed.

SPECT [I-123]iomazenil measurement of the benzodiazepine receptor in panic disorder

BACKGROUND Alterations in benzodiazepine receptor function have long been hypothesized to play a role in anxiety. Animal models of anxiety involving exposure to chronic stress have shown a specific decrease in benzodiazepine receptor binding in frontal cortex and hippocampus. The purpose of this study was to examine benzodiazepine receptor binding patients with panic disorder and comparison subjects. METHODS A quantitative measure related to benzodiazepine receptor binding (Distribution Volume (DV)) was obtained with single photon emission computed tomography (SPECT) imaging of [123I]iomazenil and measurement of radioligand concentration in plasma in patients with panic disorder and healthy controls. DV image data were analyzed using statistical parametric mapping (spm96). RESULTS A decrease in measures of benzodiazepine receptor binding (DV) was found in left hippocampus and precuneus in panic disorder patients relative to controls. Panic disorder patients who had a panic attack compared to patients who did not have a panic attack at the time of the scan had a decrease in benzodiazepine receptor binding in prefrontal cortex. CONCLUSIONS Findings of a decrease in left hippocampal and precuneus benzodiazepine receptor binding may be related to alterations in benzodiazepine receptor binding, or other factors including changes in GABAergic transmission or possible endogenous benzodiazepine compounds. Benzodiazepine receptor function in prefrontal cortex appears to be involved in changes in state-related panic anxiety.

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.

Hippocampal structural changes across the menstrual cycle

Magnetic resonance imaging (MRI) in association with Jacobian‐modulated voxel‐based morphometry (VBM) was used to test for regional variation in gray matter over the menstrual cycle. T1‐weighted anatomical images were acquired using a spoiled gradient recalled acquisition sequence in 21 women. Each subject was scanned twice: once during the postmenstrual late‐follicular phase (Days 10–12 after onset of menses), and once during the premenstrual late‐luteal phase (1–5 days before the onset of menses). Gray matter was relatively increased in the right anterior hippocampus and relatively decreased in the right dorsal basal ganglia (globus pallidus/putamen) in the postmenstrual phase. Verbal declarative memory was increased in the postmenstrual vs. premenstrual phase. This first report of human brain structural plasticity associated with the endogenous menstrual cycle extends well‐established animal findings of hormone‐mediated hippocampal plasticity to humans, and has implications for understanding alterations in cognition and behavior across the menstrual cycle.

Transit time, trailing time, and cerebral blood flow during brain activation : Measurement using multislice, pulsed spin-labeling perfusion imaging

Transit time and trailing time in pulsed spin‐labeling perfusion imaging are likely to be modulated by local blood flow changes, such as those accompanying brain activation. The majority of transit/trailing time is due to the passage of the tagged blood bolus through the arteriole/capillary regions, because of lower blood flow velocity in these regions. Changes of transit/trailing time during activation could affect the quantification of CBF in functional neuroimaging studies, and are therefore important to characterize. In this work, the measurement of transit and trailing times and CBF during sensorimotor activation using multislice perfusion imaging with pulsed arterial spin‐labeling is described. While CBF elevated dramatically (∼︁80.7%) during the sensorimotor activation, sizable reductions of transit time (∼︁0.11 sec) and trailing time (∼︁0.26 sec) were observed. Transit and trailing times were dependent on the distances from the leading and trailing edges of the tagged blood bolus to the location of the imaging slices. The effects of transit/trailing time changes on CBF quantification during brain activation were analyzed by simulation studies. Significant errors can be caused in the estimation of CBF if such changes of transit/trailing time are not taken into account. Magn Reson Med 44:680–685, 2000.

An approach to the psychobiology of personality disorders

Human variability in temperament allows a unique natural experiment where reactivity, self-regulation, and experience combine in complex ways to produce an individual personality. Personality disorders may result from changes in the way past memories filter new information in situations of emotional involvement with others. According to this view, disorders are specific to their initiating circumstances rather than a general difficulty that might extend to classes of information processing remote from triggers for the disorder. A different view suggests a more general deficit in attentional control mechanisms that might extend to a wide range of situations far from those related to the core abnormality. This paper outlines methods for examining these views and presents data from the study of borderline personality disorder, arguing in favor of high negative emotionality being combined with a deficit in an executive attentional control network. Because this attentional network has already been well described in terms of anatomy, the cognitive operations involved, development, chemical modulators, and effects of lesions and candidate genes, these findings may have implications for understanding the disorder and its treatment. We consider these implications in terms of a general approach to the study of personality development and its disorders.

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.