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Biomedical subjects

S L Rauch

Publications and source records attributed to S L Rauch.

At least 19 recordsLinked to original sources

Anger in healthy men: a PET study using script-driven imagery.

BACKGROUND: An understanding of the neurobiological basis of normal emotional processing is useful in formulating hypotheses regarding the pathophysiology of psychiatric illnesses. METHODS: This study examined the mediating functional neuroanatomy of anger in eight healthy men. Narrative scripts were developed from autobiographical information to induce anger and neutral states. The subjects imagined the content of the narrative scripts to induce anger during positron emission tomography to measure normalized regional cerebral blood flow (rCBF). Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. Statistical parametric maps were constructed to reflect the Anger versus Neutral state contrast. RESULTS: Anger was associated with activation of the left orbitofrontal cortex, right anterior cingulate cortex affective division, and bilateral anterior temporal poles. CONCLUSIONS: These results suggest that the subjective experience of anger is associated with rCBF increases in anterior paralimbic regions of the brain.

Adult

Neural activation during sexual and competitive arousal in healthy men.

To investigate the mediating neuroanatomy of positively valenced arousal, we used script-driven imagery in conjunction with positron emission tomography to measure relative regional cerebral blood flow (rCBF) during sexual and competitive arousal, as well as neutral comparison states. Subjects were eight healthy right-handed men. Psychophysiologic responses and subjective ratings confirmed that the desired state manipulations were achieved. Statistical parametric mapping revealed similar patterns of rCBF changes for both positively valenced arousal conditions: increases were found within anterior cingulate and anterior temporal cortex as well as the ventral globus pallidus; decreases were found within widespread heteromodal association areas. These results complement findings from studies of other normal and pathological emotional states, and provide new insights regarding the neural substrates of pleasurable arousal in healthy men.

Adult

Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop.

BACKGROUND: The anterior cingulate cognitive division (ACcd) plays a central role in attentional processing by: 1) modulating stimulus selection (i.e., focusing attention) and/or 2) mediating response selection. We hypothesized that ACcd dysfunction might therefore contribute to producing core features of attention-deficit/hyperactivity disorder (ADHD), namely inattention and impulsivity. ADHD subjects have indeed shown performance deficits on the Color Stroop, an attentional/cognitive interference task known to recruit the ACcd. Recently, the Counting Stroop, a Stroop-variant specialized for functional magnetic resonance imaging (fMRI), produced ACcd activation in healthy adults. In the present fMRI study, the Counting Stroop was used to examine the functional integrity of the ACcd in ADHD. METHODS: Sixteen unmedicated adults from two groups (8 with ADHD and 8 matched control subjects) performed the Counting Stroop during fMRI. RESULTS: While both groups showed an interference effect, the ADHD group, in contrast to control subjects, failed to activate the ACcd during the Counting Stroop. Direct comparisons showed ACcd activity was significantly higher in the control group. ADHD subjects did activate a frontostriatal-insular network, indicating ACcd hypoactivity was not caused by globally poor neuronal responsiveness. CONCLUSIONS: The data support a hypothesized dysfunction of the ACcd in ADHD.

Adolescent

Organizational strategies mediate nonverbal memory impairment in obsessive-compulsive disorder.

BACKGROUND: Previous neuropsychological studies of obsessive-compulsive disorder (OCD) have indicated impaired executive functioning and nonverbal memory. The extent to which impaired executive functioning impacts nonverbal memory has not been established. The current study investigated the mediating effects of organizational strategies used when copying a figure on subsequent nonverbal memory for that figure. METHODS: We examined neuropsychological performance in 20 unmedicated subjects with OCD and 20 matched normal control subjects. Subjects were administered the Rey-Osterrieth Complex Figure Test (RCFT) and neuropsychological tests assessing various aspects of executive function. RESULTS: OCD subjects differed significantly from healthy control subjects in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in immediate percent recall were significantly mediated by copy organizational strategies. Further exploratory analyses indicated that organizational problems in OCD may be related to difficulties shifting mental and/or spatial set. CONCLUSIONS: Immediate nonverbal memory problems in OCD subjects were mediated by impaired organizational strategies used during the initial copy of the RCFT figure. Thus, the primary deficit was one affecting executive function, which then had a secondary effect on immediate memory. These findings are consistent with current theories proposing frontal-striatal system dysfunction in OCD.

Adult

A method for assessing the accuracy of intersubject registration of the human brain using anatomic landmarks.

Several groups have developed methods for registering an individual's 3D MRI by deforming a standard template. This achievement leads to many possibilities for segmentation and morphology that will impact nuclear medical research in areas such as activation and receptor studies. Accordingly, there is a need for methods that can assess the accuracy of intersubject registration. We have developed a method based on a set of 128 anatomic landmarks per hemisphere, both cortical and subcortical, that allows assessment of both global and local transformation accuracy. We applied our method to compare the accuracy of two standard methods of intersubject registration, AIR 3.0 with fifth-order polynomial warping and the Talairach stereotaxic transformation (Talairach and Tournoux, 1988). SPGR MRI's (256 x 256 x 160) of six normal subjects (age 18-24 years) were derformed to match a standard template volume. To assess registration accuracy the landmarks were located on both the template volume and the transformed volumes by an experienced neuroanatomist. The resulting list of coordinates was analyzed graphically and by ANOVA to compare the accuracy of the two methods and the results of the manual analysis. ANOVA performed over all 128 landmarks showed that the Woods method was more accurate than Talairach (left hemisphere F = 2.8, P < 0.001 and right hemisphere F =2.4, P < 0.006). The Woods method provided a better brain surface transformation than did Talairach (F = 18.0, P < 0.0001), but as expected there was a smaller difference for subcortical structures and both had an accuracy <1 mm for the majority of subcortical landmarks. Overall, both the Woods and Talairach method located about 70% of landmarks with an error of 3 mm or less. More striking differences were noted for landmark accuracy </=1 mm, where the Woods method located about 40% and Talairach about 23%. These results demonstrate that this anatomically based assessment method can help evaluate new methods of intersubject registration and should be a helpful tool in appreciating regional differences in accuracy. Consistent with expectation, we confirmed that the Woods nonlinear registration method was more accurate than Talairach. Landmark-based anatomic analyses of intersubject registration accuracy offer opportunities to explore the relationship among structure, function and architectonic boundaries in the human brain.

Adolescent

Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation.

OBJECTIVE: The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). METHOD: Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. RESULTS: In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus. CONCLUSIONS: The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus.

Adult

Use of factor-analyzed symptom dimensions to predict outcome with serotonin reuptake inhibitors and placebo in the treatment of obsessive-compulsive disorder.

OBJECTIVE: No consistent predictors of outcome have been identified for the pharmaco-therapy of obsessive-compulsive disorder (OCD). Recent factor analytic studies have identified meaningful symptom dimensions that may be related to response to serotonin reuptake inhibitors and other treatments. METHOD: A total of 354 outpatients with primary OCD were administered the Yale-Brown Obsessive Compulsive Scale Symptom Checklist, and its 13 main symptom categories were factor analyzed by using principal components analysis. The identified symptom dimensions were then entered into multiple regression models as outcome predictors of response to serotonin reuptake inhibitors and placebo response in a group of 150 nondepressed subjects who completed six double-blind, placebo-controlled trials with a serotonin reuptake inhibitor (clomipramine, fluvoxamine, fluoxetine, sertraline, and paroxetine). Eighty-four patients received a serotonin reuptake inhibitor and 66, placebo. RESULTS: The principal components analysis identified five factors that explained 65.5% of variance in outcome: symmetry/ordering, hoarding, contamination/cleaning, aggressive/checking, and sexual/religious obsessions. Serotonin reuptake inhibitors were significantly superior to placebo on all outcome measures. Initial severity of OCD was related to greater posttreatment severity of OCD. Higher scores on the hoarding dimension predicted poorer outcome following treatment with serotonin reuptake inhibitors, after control for baseline severity. No predictors of placebo response were identified. Exclusion of clomipramine did not modify the overall results, suggesting a cross-serotonin reuptake inhibitor effect. CONCLUSIONS: The identified symptom dimensions are largely congruent with those identified in earlier reports. Patients with OCD vary in their response to treatment with serotonin reuptake inhibitors. The presence of hoarding obsessions and compulsions is associated with poorer response to serotonin reuptake inhibitors.

Adolescent

The emotional counting Stroop paradigm: a functional magnetic resonance imaging probe of the anterior cingulate affective division.

BACKGROUND: The emotional counting Stroop (ecStroop) functional magnetic resonance imaging (fMRI) activation paradigm was designed to recruit the anterior cingulate affective division (ACad). METHODS: Nine normal, healthy male and female subjects (mean age 24.2 years) reported via button press the number of neutral and negative words that appeared on a screen while reaction time and fMRI data were acquired. RESULTS: We observed a) greater ACad activation for negative versus neutral words during initial presentation blocks; b) lower overall ACad signal intensity during task performance (i.e., both negative and neutral words) compared to the baseline fixation condition; and c) no reaction time increase to negative versus neutral words. CONCLUSIONS: In a companion study of a cognitive version of the counting Stroop (Bush et al 1998), these same 9 subjects a) activated the more dorsal anterior cingulate cognitive division; b) also showed the overall decrease in ACad signal intensity; and c) demonstrated a reliable reaction time effect. Taken together, these data offer a within-group spatial dissociation of AC function based upon information content (i.e., cognitive vs. emotional) and/or presence of behavioral interference. We propose that the ecStroop will be a useful fMRI probe of ACad function in anxiety disorders.

Adult

Differences in cerebral activation during smooth pursuit and saccadic eye movements using positron-emission tomography.

BACKGROUND: Abnormalities of smooth pursuit eye movements occur commonly in schizophrenia, but the pathophysiological significance of these abnormalities is unknown. To address this, the authors conducted a pilot study in which we examined differences in regional cerebral activation using positron-emission tomography (PET) in normal volunteers as they performed two types of eye movements. METHODS: Cerebral activation in 10 normal volunteers was studied using C15O2 PET while subjects tracked a visual target using smooth pursuit and saccadic eye movements. A left-hand movement comparison task provided a physiologic landmark for verification of the location of the frontal eye fields (FEFs). RESULTS: Subjects exhibited FEF activation during both smooth pursuit and saccadic eye movements, which was greater in the latter. During smooth pursuit, subjects also exhibited increased cerebral activation in the left temporal-occipital border and left superior frontal cortex and decreased activation in medial superior parietal and insular regions relative to saccades. Other cortical visual and eye-movement brain regions also demonstrated differences in activation between the two visual tasks. CONCLUSIONS: Significant fEF activation appears to underlie both smooth pursuit and saccadic eye movements but may be more critical in the former. Dysfunction of the frontal lobe, and possibly of other areas in the pursuit pathway such as the temporo-occipital motion area, may contribute to observed eye-movement abnormalities in patients with schizophrenia.

Adolescent

Thalamic deactivation during early implicit sequence learning: a functional MRI study.

Previous research has implicated the striatum in implicit sequence learning. However, imaging findings have been inconsistent with regard to activity within the thalamus during performance of such tasks. Contemporary models of cortico-striato-thalamic circuitry suggest opposing influences on thalamic activity; suppression of thalamic activity is mediated by the indirect pathway and enhancement is mediated by the direct pathway. Using functional magnetic resonance imaging, we studied activity within human thalamus during early and late phases of an implicit sequence learning task known to reliably recruit the striatum. Significant deactivation (decreased signal relative to a baseline condition) was observed within the thalamus during early implicit learning. This finding is consistent with models of cortico-striato-thalamic function and specifically supports a profile of early 'thalamic gating' via the indirect pathway.

Basal Ganglia

Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge.

Functional magnetic resonance imaging (fMRI) of the human brain was used to study whether the amygdala is activated in response to emotional stimuli, even in the absence of explicit knowledge that such stimuli were presented. Pictures of human faces bearing fearful or happy expressions were presented to 10 normal, healthy subjects by using a backward masking procedure that resulted in 8 of 10 subjects reporting that they had not seen these facial expressions. The backward masking procedure consisted of 33 msec presentations of fearful or happy facial expressions, their offset coincident with the onset of 167 msec presentations of neutral facial expressions. Although subjects reported seeing only neutral faces, blood oxygen level-dependent (BOLD) fMRI signal in the amygdala was significantly higher during viewing of masked fearful faces than during the viewing of masked happy faces. This difference was composed of significant signal increases in the amygdala to masked fearful faces as well as significant signal decreases to masked happy faces, consistent with the notion that the level of amygdala activation is affected differentially by the emotional valence of external stimuli. In addition, these facial expressions activated the sublenticular substantia innominata (SI), where signal increases were observed to both fearful and happy faces--suggesting a spatial dissociation of territories that respond to emotional valence versus salience or arousal value. This study, using fMRI in conjunction with masked stimulus presentations, represents an initial step toward determining the role of the amygdala in nonconscious processing.

Adult

Impaired recruitment of the hippocampus during conscious recollection in schizophrenia.

Poor attention and impaired memory are enduring and core features of schizophrenia. These impairments have been attributed either to global cortical dysfunction or to perturbations of specific components associated with the dorsolateral prefrontal cortex (DLPFC), hippocampus and cerebellum. Here, we used positron emission tomography (PET) to dissociate activations in DLPFC and hippocampus during verbal episodic memory retrieval. We found reduced hippocampal activation during conscious recollection of studied words, but robust activation of the DLPFC during the effort to retrieve poorly encoded material in schizophrenic patients. This finding provides the first evidence of hippocampal dysfunction during episodic memory retrieval in schizophrenia.

Adult

Tourette's disorder with and without obsessive-compulsive disorder in adults: are they different?

Clinical research has documented a bidirectional overlap between Tourette's disorder (TD) and obsessive-compulsive disorder (OCD) from familial-genetic, phenomenological, comorbidity, and natural history perspectives. Patients with Tourette's disorder plus obsessive-compulsive disorder (TD + OCD), a putative subtype, share features of both. The purpose of this exploratory study was to evaluate correlates of patients with TD, OCD, and TD + OCD to determine whether TD + OCD is a subtype of TD, OCD, or an additive form of both. Sixty-one subjects with TD, OCD, or TD + OCD were evaluated with the Structured Clinical Interview for DSM-III-R supplemented with additional modules. The three groups differed in the rates of bipolar disorder (p < .04), social phobia (p < .02), body dysmorphic disorder (p < .002), attention deficit hyperactivity disorder (p < .03), and substance use disorders (p < .04). These findings were accounted for by the elevated rates of the disorders in the TD + OCD group compared with the TD and OCD groups. These finding are most consistent with the hypothesis that TD + OCD is a more severe disorder than TD and OCD and may be more etiologically linked to TD than to OCD. These findings highlight the importance of assessment of the full spectrum of psychiatric comorbidity in patients with TD and OCD.

Adult

Robot-aided functional imaging: application to a motor learning study.

The purpose of this study was to examine the neural activity underlying an implicit motor learning task. In particular, our goals were to determine whether initial phases of procedural learning of a motor task involve areas of the brain distinct from those involved in later phases of learning the task, and what changes in neural activity coincide with performance improvement. We describe a novel integration of robotic technology with functional brain imaging and its use in this study of implicit motor learning. A portable robotic device was used to generate forces that disturbed the subjects' arm movements, thereby generating a "virtual mechanical environment" that the subjects learned to manipulate. Positron emission tomography (PET) was used to measure indices of neural activity underlying learning of the motor task. Eight health, right-handed male subjects participated in the study. Results support the hypothesis that different stages of implicit learning (early and late implicit learning) occur in an orderly fashion, and that distinct neural structures may be involved in these different stages. In particular, neuroimaging results indicate that the cortico-striatal loop may play a significant role during early learning, and that the cortico-cerebellar loop may play a significant role during late learning.

Adult

The counting Stroop: an interference task specialized for functional neuroimaging--validation study with functional MRI.

The anterior cingulate cortex has been activated by color Stroop tasks, supporting the hypothesis that it is recruited to mediate response selection or allocate attentional resources when confronted with competing information-processing streams. The current study used the newly developed "Counting Stroop" to identify the mediating neural substrate of cognitive interference. The Counting Stroop, a Stroop variant allowing on-line response time measurements while obviating speech, was created because speaking produces head movements that can exceed those tolerated by functional magnetic resonance imaging (fMRI), preventing the collection of vital performance data. During this task, subjects report by button-press the number of words (1-4) on the screen, regardless of word meaning. Interference trials contain number words that are incongruent with the correct response (e.g., "two" written three times), while neutral trials contain single semantic category common animals (e.g., "bird"). Nine normal right-handed adult volunteers underwent fMRI while performing the Counting Stroop. Group fMRI data revealed significant (P < or = 10(-4) activity in the cognitive division of anterior cingulate cortex when contrasting the interference vs. neutral conditions. On-line performance data showed 1) longer reaction times for interference blocks than for neutral ones, and 2) decreasing reaction times with practice during interference trials (diminished interference effects), indicating that learning occurred. The performance data proved to be a useful guide in analyzing the image data. The relative difference in anterior cingulate activity between the interference and neutral conditions decreased as subjects learned the task. These findings have ramifications for attentional, cognitive interference, learning, and motor control mechanism theories.

Adult

The functional neuroanatomy of anxiety: a study of three disorders using positron emission tomography and symptom provocation.

Previous neuroimaging research has contributed insights regarding the neural substrates of specific psychiatric disorders. The purpose of this study was to determine the shared mediating neuroanatomy of anxiety symptoms across three different anxiety disorders. Data were pooled from 23 right-handed adult outpatients meeting criteria for obsessive-compulsive disorder, simple phobia, or posttraumatic stress disorder. Relative regional cerebral blood flow (rCBF) was measured using positron emission tomography in the context of symptom provocation paradigms. Symptom severity was measured via self-reports. The analysis of pooled imaging data indicated activation in right inferior frontal cortex, right posterior medial orbitofrontal cortex, bilateral insular cortex, bilateral lenticulate nuclei, and bilateral brain stem foci during the symptomatic versus control conditions. A positive correlation was found between rCBF at one brain stem locus and subjective anxiety scores (r = .744, p < .001). These findings suggest that elements of the paralimbic belt together with right inferior frontal cortex and subcortical nuclei mediate symptoms across different anxiety disorders. In addition, activation at one brain stem locus appears to be associated with the subjective severity of anxiety. Further studies are warranted to determine whether these same brain systems mediate normal anxiety states as well.

Adult

Reduced basal ganglia volumes in trichotillomania measured via morphometric magnetic resonance imaging.

A morphometric magnetic resonance imaging (MRI) study compared volumes of brain structures in 10 female subjects with trichotillomania (repetitive hair-pulling) versus 10 normal controls matched for sex, age, handedness, and education. Three-dimensional MRI scans were blindly normalized and segmented using well-characterized semiautomated intensity and differential contour algorithms by signal intensity-frequency histograms. Consistent with one a priori hypothesis, left putamen volume was found to be significantly smaller in trichotillomania subjects as compared with normal matched controls. This is the first report of a structural brain abnormality in trichotillomania. Results are discussed in terms of putative relationships between trichotillomania, Tourette's syndrome, and obsessive-compulsive disorder.

Adult