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Biomedical subjects

Scott L Rauch

Publications and source records attributed to Scott L Rauch.

At least 73 records · Page 4Linked to original sources

Amygdala and insular responses to emotionally valenced human faces in small animal specific phobia.

BACKGROUND: Contemporary neurobiological models suggest that the amygdala plays an important role in the pathophysiology of anxiety disorders. However, it is not clear to what extent this concept applies across anxiety disorders. Several studies have examined brain function in specific phobias but did not demonstrate amygdala responses or use specific probes of the amygdala. METHODS: Ten subjects with specific small animal phobia and 10 matched control subjects were studied with functional magnetic resonance imaging. Subjects viewed emotionally expressive and neutral faces, and amygdala blood oxygenation level dependent responses from each group were compared. RESULTS: There was a significant response to the fearful versus neutral faces in the amygdala across both groups but no diagnosis x condition interaction. Post hoc analysis of the whole brain revealed a significantly greater response to the fearful versus neutral faces in the right insular cortex of the specific phobia group than in the control group. CONCLUSIONS: Amygdala hyperresponsivity to emotional faces was not observed in subjects with small animal specific phobia, in contrast to findings in other anxiety disorders (e.g., posttraumatic stress disorder). This suggests a restricted role for the amygdala in specific phobia. The insular hyperresponsivity to fearful versus neutral faces in the subjects with specific phobias warrants further study.

Adult↗

Neurobiology of emotion perception I: The neural basis of normal emotion perception.

There is at present limited understanding of the neurobiological basis of the different processes underlying emotion perception. We have aimed to identify potential neural correlates of three processes suggested by appraisalist theories as important for emotion perception: 1) the identification of the emotional significance of a stimulus; 2) the production of an affective state in response to 1; and 3) the regulation of the affective state. In a critical review, we have examined findings from recent animal, human lesion, and functional neuroimaging studies. Findings from these studies indicate that these processes may be dependent upon the functioning of two neural systems: a ventral system, including the amygdala, insula, ventral striatum, and ventral regions of the anterior cingulate gyrus and prefrontal cortex, predominantly important for processes 1 and 2 and automatic regulation of emotional responses; and a dorsal system, including the hippocampus and dorsal regions of anterior cingulate gyrus and prefrontal cortex, predominantly important for process 3. We suggest that the extent to which a stimulus is identified as emotive and is associated with the production of an affective state may be dependent upon levels of activity within these two neural systems.

Animals↗

Neurobiology of emotion perception II: Implications for major psychiatric disorders.

To date, there has been little investigation of the neurobiological basis of emotion processing abnormalities in psychiatric populations. We have previously discussed two neural systems: 1) a ventral system, including the amygdala, insula, ventral striatum, ventral anterior cingulate gyrus, and prefrontal cortex, for identification of the emotional significance of a stimulus, production of affective states, and automatic regulation of emotional responses; and 2) a dorsal system, including the hippocampus, dorsal anterior cingulate gyrus, and prefrontal cortex, for the effortful regulation of affective states and subsequent behavior. In this critical review, we have examined evidence from studies employing a variety of techniques for distinct patterns of structural and functional abnormalities in these neural systems in schizophrenia, bipolar disorder, and major depressive disorder. In each psychiatric disorder, the pattern of abnormalities may be associated with specific symptoms, including emotional flattening, anhedonia, and persecutory delusions in schizophrenia, prominent mood swings, emotional lability, and distractibility in bipolar disorder during depression and mania, and with depressed mood and anhedonia in major depressive disorder. We suggest that distinct patterns of structural and functional abnormalities in neural systems important for emotion processing are associated with specific symptoms of schizophrenia and bipolar and major depressive disorder.

Brain↗

Inhibited and uninhibited infants "grown up": adult amygdalar response to novelty.

Infants with an inhibited temperament tend to develop into children who avoid people, objects, and situations that are novel or unfamiliar, whereas uninhibited children spontaneously approach novel persons, objects, and situations. Behavioral and physiological features of these two temperamental categories are moderately stable from infancy into early adolescence and have been hypothesized to be due, in part, to variation in amygdalar responses to novelty. We found that adults who had been categorized in the second year of life as inhibited, compared with those previously categorized as uninhibited, showed greater functional MRI signal response within the amygdala to novel versus familiar faces.

Adult↗

Selectively reduced regional cortical volumes in post-traumatic stress disorder.

Different subterritories of anterior cingulate cortex (ACC) and adjacent ventromedial frontal cortex have been shown to serve distinct functions. This scheme has influenced contemporary pathophysiologic models of psychiatric disorders. Prevailing neurocircuitry models of post-traumatic stress disorder (PTSD) implicate dysfunction within pregenual ACC and subcallosal cortex (SC), as well as amygdala and hippocampus. In the current study, cortical parcellation of magnetic resonance imaging data was performed to test for volumetric differences in pregenual ACC and SC, between women with PTSD and trauma-exposed women without PTSD. The PTSD group exhibited selectively decreased pregenual ACC and SC volumes. These results are consistent with contemporary schemes regarding functional and structural dissection of frontal cortex, and suggest specific regional cortical pathology in PTSD.

Cerebral Cortex↗

Differential amygdalar response to novel versus newly familiar neutral faces: a functional MRI probe developed for studying inhibited temperament.

BACKGROUND: As a prelude to future studies of subjects with different temperaments, we sought to develop a probe to measure differential amygdalar responses to novel versus familiar stimuli. Prior neuroimaging studies of the amygdala in humans to date have focused principally on responses to emotional stimuli, primarily aversive, rather than to novelty per se. METHODS: Eight normal subjects aged 22.4 +/- 1.3 years were scanned using functional magnetic resonance imaging (fMRI) during passive viewing of novel and familiar faces. RESULTS: Using this newly developed paradigm, we found greater fMRI blood oxygenation level dependent (BOLD) signal response within the right amygdala to novel versus familiar faces--all with neutral expression. Furthermore, although a new facial identity was always presented in the novel condition, signal in the amygdala declined over time as it did for the familiar condition. CONCLUSIONS: These results suggest that at least one primary function of the amygdala is to detect and process unexpected or unfamiliar events that have potential biological import, of which stimuli symbolic of fear or threat are but one possible example. We propose that this experimental paradigm will be useful for examining brain responses to novelty in different temperamental groups, as well as various psychiatric disorders.

Adult↗

Brain habituation during repeated exposure to fearful and neutral faces: a functional MRI study.

Central nervous system habituation in humans was studied using functional magnetic resonance imaging and repeated presentations of single fearful and neutral faces. Habituation of blood-oxygenation-level-dependent (BOLD) signal during exposure to face stimuli, collapsed over fearful and neutral expressions, was evident in the right amygdala and hippocampus, as well as in the medial/inferior temporal cortex bilaterally. In the hippocampus, significantly greater habituation was evident on the right as compared to the left side, which could reflect the visual nature of the stimuli. There were no time by expression interaction effects in these regions, suggesting similar neural attenuation rates to fearful and neutral face stimuli. These results indicate that brain regions involved in novelty detection and memory processing habituate at similar rates regardless of whether the face in focus displays an aversive emotional expression or not.

Brain↗

A preliminary morphometric magnetic resonance imaging study of regional brain volumes in body dysmorphic disorder.

Morphometric magnetic resonance imaging (MRI) was used to compare regional brain volumes in eight women with body dysmorphic disorder (BDD) and eight healthy comparison subjects. The BDD group exhibited a relative leftward shift in caudate asymmetry and greater total white matter vs. the comparison group. Findings with respect to the caudate nucleus are consistent with both the conceptualization of BDD as an obsessive-compulsive spectrum disorder, and the 'striatal topography model' of obsessive-compulsive disorders.

Brain↗

Impaired hippocampal recruitment during normal modulation of memory performance in schizophrenia.

BACKGROUND: Patients with schizophrenia demonstrate poor verbal memory, ascribed to impaired prefrontal and hippocampal function. Healthy adults can increase recall accuracy following encoding interventions, such as item repetition and the formation of semantic associations. We examined the effects of these interventions on both memory performance and retrieval-related hippocampal activity in healthy adults and patients with schizophrenia. METHODS: Twelve patients with schizophrenia and twelve healthy control subjects participated. During study, subjects counted either the number of meanings or T-junctions in words seen only once or repeated four times. At test, O15-positron emission tomography scans were acquired while subjects completed word-stems with previously studied items. RESULTS: Control subjects recalled more words overall, but both groups demonstrated similar performance benefits following deeper encoding. Both item repetition and the use of a semantic encoding task were associated with memory retrieval-related hippocampal recruitment in control but not schizophrenic participants. Patients with schizophrenia demonstrated greater activation of prefrontal cortical areas during word retrieval. CONCLUSIONS: Despite a lack of hippocampal recruitment, patients with schizophrenia showed intact modulation of memory performance following both encoding interventions. Impaired hippocampal recruitment, in concert with greater prefrontal activation, may reflect a specific deficit in conscious recollection in schizophrenia.

Hippocampus↗

Neurocircuitry of anxiety disorders.

A major focus in the field of anxiety in the past decade, and an area of intense ongoing interest, is the delineation of the basic neurocircuitry underlying normal and pathologic anxiety. Preclinical work defining the basic neurocircuitry responsible for fear responding has fueled neuroimaging investigations attempting to model the neurocircuitry of the anxiety disorders. Herewith, the authors review neuroimaging findings contributing to the development and refinement of neuroanatomic models for post-traumatic stress disorder, panic disorder, and social anxiety disorder.

Amygdala↗

Neuroimaging and neurocircuitry models pertaining to the neurosurgical treatment of psychiatric disorders.

Neurocircuitry models of obsessive-compulsive disorder (OCD) and major depression (MD) are described, focusing on relevant supporting neuroimaging data. Corticostriatothalamocortical circuitry is implicated in OCD. In MD, the relation between "dorsal" and "ventral" cortical compartments is emphasized; the amygdala, hippocampus, and pregenual anterior cingulate are implicated in the pathophysiology of MD and are potential targets for treatment. The neuroanatomy of psychiatric neurosurgical procedures and related neuroimaging findings are reviewed. Finally, anticipated future directions of research in this field are discussed.

Brain↗

Stereotactic cingulotomy.

Cingulotomy can be helpful in certain patients with severe, disabling, and treatment-refractory major affective disorders, OCD, and chronic anxiety states. This form of psychosurgical treatment should only be carried out by an expert multidisciplinary team with experience in these disorders. Cingulotomy should be considered as one part of an entire treatment plan and must be followed by an appropriate psychiatric rehabilitation program. Many patients are greatly improved after cingulotomy, and the complications or side effects are few. Cingulotomy remains an important therapeutic option for disabling psychiatric disease and is probably underutilized.

Major Depressive Disorder↗

Neurosurgery for intractable obsessive-compulsive disorder and depression: critical issues.

Intractable OCD and depression cause tremendous suffering in those affected and in their families. The impaired ability to function of those affected imposes a heavy burden on society as a whole. Existing data suggest that lesion procedures offer benefit to a large proportion (ranging from about 35%-70%) of patients with intractable OCD and depression. The literature also suggests that although serious long-term adverse events have occurred, these are relatively infrequent overall. Methodologic limitations of the earlier reports on any of these procedures were described previously in this article. The major academic centers conducting this work have since been obtaining systematic prospective data using modern assessment tools. Nevertheless, even with improved methodologies, more recent studies confront some remaining issues that have been difficult to overcome fully. First, the number of patients who have received any one procedure has been relatively small, constraining statistical power. This limits the ability of researchers to enhance patient selection based on clinical characteristics. This is important, because patients with intractable OCD and depression referred for neurosurgery have high rates of comorbid Axis I diagnoses, personality disorders, and functional impairments, which may have value in predicting response. Other features, such as age of onset, chronicity, and symptom subtypes, may be likewise useful. Another key factor in response may be postoperative management, which has varied most over time but also across patients enrolled in trials. As noted previously, randomized controlled trials of neurosurgical treatment for intractable psychiatric illness have not been reported, although one has been proposed for gamma knife capsulotomy in intractable OCD [23]. The development of deep brain stimulation has also made sham-controlled studies possible and also allows within-patient designs to be considered. Bearing these problems in mind, the literature does provide important guidance on a number of key points, including approaches to referral, patient selection, and the need for long-term prospective follow-up and postoperative management. Nevertheless, important gaps in knowledge remain in all these areas. Research is expected to narrow these gaps in a number of ways, including patient selection, optimizing the procedures themselves, and understanding the mechanisms of therapeutic action. Neuroimaging studies will play a key role in achieving these aims (see the article by Rauch in this issue). So will cross-species translational research on the anatomy and physiology of the pathways implicated in the pathophysiology and response to treatment in these disorders. Future research in psychiatric neurosurgery must proceed cautiously. A recent editorial statement of the OCD-DBS Collaborative Group [26] recommends a minimum set of standards for any multidisciplinary teams contemplating work in this domain. The rationale for those standards is found throughout this issue and is especially developed in the article by Fins. The need for safe and effective therapeutic options for people suffering with these severe illnesses is just as clear. The experience over the last several decades provides grounds for careful optimism that refined lesion procedures or reversible deep brain stimulation may relieve suffering and improve the lives of people with these devastating disorders.

Brain↗

Novelty responses and differential effects of order in the amygdala, substantia innominata, and inferior temporal cortex.

Recent studies of amygdala function have focused on examining responses to emotionally valenced versus neutral stimuli. However, electrophysiologic and neuroimaging studies also suggest that novel neutral faces activate the amygdala, though few investigations have examined the effects of novelty and its relation to changes in stimulus condition. To further investigate how the human amygdala and related structures react to novel neutral faces and to stimulus condition changes, we evaluated human brain responses to blocks containing multiple novel and single repeated face stimuli, presented in two different orders, using functional magnetic resonance imaging (fMRI). Significantly increased signal was present in the amygdala, substantia innominata (SI), and inferior temporal cortex (ITC) to the contrast of multiple novel versus single faces. However, these regions differed in their responses based on whether a stimulus condition was presented 1st or 2nd, with the amygdala and SI having significantly different response profiles than the ITC. Specifically, greater responses to stimuli presented 2nd (i.e., after a condition change) were found in the amygdala and SI, but not in the ITC. Furthermore, the response difference to the Multiple versus Single contrast was greatest in the amygdala and SI, when single faces were presented 1st, and multiple faces presented 2nd, but this pattern was the reverse in the ITC. We speculate that the signal changes to neutral faces in the amygdala and SI with respect to condition (multiple or single faces) and stimulus order may relate to the involvement of these structures in novelty detection and the orienting response.

Adult↗

Neuroimaging studies of amygdala function in anxiety disorders.

Neuroimaging research has helped to advance neurobiological models of anxiety disorders. The amygdala is known to play an important role in normal fear conditioning and is implicated in the pathophysiology of anxiety disorders. The amygdala may also be a target for the beneficial effects of cognitive-behavioral and medication treatments for anxiety disorders. In the current paper, we review neuroimaging research pertaining to the role of the amygdala in anxiety disorders and their treatment. Moreover, we discuss the development of new neuroimaging paradigms for measuring aspects of amygdala function, as well as the function of related brain regions. We conclude that such tools hold great promise for facilitating progress in relevant basic neuroscience as well as clinical research domains.

Amygdala↗

Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for treatment of major depression.

OBJECT: Neurosurgical procedures are a viable intervention for severe, treatment-refractory major depression, although they have been associated with only modest rates of efficacy. The purpose of this study was to identify possible neuroimaging predictors of treatment response to anterior cingulotomy in patients with major depression. METHODS: Thirteen patients underwent stereotactic anterior cingulotomy for treatment-refractory major depression. Symptom severity was measured using the Beck Depression Inventory (BDI) both before and approximately 12 months after surgery. The authors performed [18F]fluorodeoxyglucose-positron emission tomography (PET) studies in all patients preoperatively. Statistical parametric mapping methods were used to test for loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in BDI scores. The mean (+/- standard deviation) change in the BDI score from the preoperative period (43.7 +/- 7.8) to the postoperative period (30.5 +/- 21.3) was 33.1 +/- 45.4%. Two loci--the left subgenual prefrontal cortex and left thalamus--were identified as sites at which preoperative metabolism was significantly correlated with subsequent improvement in depressive symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at these loci were associated with better postoperative results. CONCLUSIONS: Possible PET scanning predictors of treatment response were identified in patients with major depression who had undergone anterior cingulotomy. Further research will be necessary to determine the reproducibility of this finding. If confirmed, the availability of an index for noninvasively predicting a patient's response to cingulotomy for the treatment of major depression would be of great clinical value.

Adult↗

Neural circuitry of anxiety: evidence from structural and functional neuroimaging studies.

Present understanding of the neural circuitry of anxiety has come from a variety of sources, including animal, clinical, and most recently, neuroimaging studies. Evidence from these sources has converged to form a translational bridge from animal models to human pathophysiology. In particular, the classical fear conditioning paradigm has served as a foundation for this bridge. Proposed models for the neural circuitry of normal anxiety as well as the anxiety disorders are discussed. A brief review of specific findings from neuroimaging studies of posttraumatic stress disorder, specific phobia, social phobia, obsessive-compulsive disorder, and generalized anxiety disorder is also provided.

Anxiety↗