Person: Silbersweig, David
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Silbersweig
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David
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Silbersweig, David
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Publication Beyond the amygdala: Linguistic threat modulates peri-sylvian semantic access cortices(Elsevier BV, 2015) Weisholtz, Daniel; Root, James C.; Butler, Tracy; Tüscher, Oliver; Epstein, Jane; Pan, Hong; Protopopescu, Xenia; Goldstein, Martin; Isenberg, Nancy; Brendel, Gary; LeDoux, Joseph; Silbersweig, David; Stern, EmilyIn this study, healthy volunteers were scanned using functional magnetic resonance imaging (fMRI) to investigate the neural systems involved in processing the threatening content conveyed via visually presented “threat words.” The neural responses elicited by these words were compared to those elicited by matched neutral control words. The results demonstrate that linguistic threat, when presented in written form, can selectively engage areas of lateral temporal and inferior frontal cortex, distinct from the core language areas implicated in aphasia. Additionally, linguistic threat modulates neural activity in visceral/emotional systems (amygdala, parahippocampal gyrus and periaqueductal gray), and at earlier stages of the visual-linguistic processing stream involved in visual word form representations (ventral occipitotemporal cortex). We propose a model whereby limbic activation modulates activity at multiple nodes along the visual-linguistic-semantic processing stream, including a perisylvian “semantic access network” involved in decoding word meaning, suggesting a dynamic interplay between feedforward and feedback processes.Publication Altered threat and safety neural processing linked to persecutory delusions in schizophrenia: a two-task fMRI study(Elsevier BV, 2015) Perez, David; Pan, Hong; Weisholtz, Daniel; Root, James C.; Tuescher, Oliver; Fischer, David; Butler, Tracy; Vago, David R.; Isenberg, Nancy; Epstein, Jane; Landa, Yulia; Smith, Thomas; Savitz, Adam J.; Silbersweig, David; Stern, EmilyPersecutory delusions are a clinically important symptom in schizophrenia associated with social avoidance and increased violence. Few studies have investigated the neurobiology of persecutory delusions, which is a prerequisite for developing novel treatments. The aim of this two-paradigm functional magnetic resonance imaging (fMRI) study is to characterize social “real world” and linguistic threat brain activations linked to persecutory delusions in schizophrenia (n=26) using instructed-fear/safety and emotional word paradigms. Instructed-fear/safety activations correlated to persecutory delusion severity demonstrated significant increased lateral orbitofrontal cortex and visual association cortex activations for the instructed-fear vs. safety and instructed-fear vs. baseline contrasts; decreased lateral orbitofrontal cortex and ventral occipital-temporal cortex activations were observed for the instructed-safety stimuli vs. baseline contrast. The salience network also showed divergent fear and safety cued activations correlated to persecutory delusions. Emotional word paradigm analyses showed positive correlations between persecutory delusion severity and left-lateralized linguistic and hippocampal–parahippocampal activations for the threat vs. neutral word contrast. Visual word form area activations correlated positively with persecutory delusions for both threat and neutral word vs. baseline contrasts. This study links persecutory delusions to enhanced neural processing of threatening stimuli and decreased processing of safety cues, and helps elucidate systems-level activations associated with persecutory delusions in schizophrenia.Publication Differential activity of subgenual cingulate and brainstem in panic disorder and PTSD(Elsevier BV, 2011) Tuescher, Oliver; Protopopescu, Xenia; Pan, Hong; Cloitre, Marylene; Butler, Tracy; Goldstein, Martin; Root, James C.; Engelien, Almut; Furman, Daniella; Silverman, Michael; Yang, Yihong; Gorman, Jack; LeDoux, Joseph; Silbersweig, David; Stern, EmilyMost functional neuroimaging studies of panic disorder (PD) have focused on the resting state, and have explored PD in relation to healthy controls rather than in relation to other anxiety disorders. Here, PD patients, Posttraumatic stress disorder (PTSD) patients, and healthy control subjects were studied with functional magnetic resonance imaging utilizing an instructed fear conditioning paradigm incorporating both Threat and Safe conditions. Relative to PTSD and control subjects, PD patients demonstrated significantly less activation to the Threat condition and increased activity to the Safe condition in the subgenual cingulate, ventral striatum and extended amygdala, as well as in midbrain periaquaeductal grey, suggesting abnormal reactivity in this key region for fear expression. PTSD subjects failed to show the temporal pattern of activity decrease found in control subjects.Publication Diurnal cortisol amplitude and fronto-limbic activity in response to stressful stimuli(Elsevier BV, 2009) Cunningham-Bussel, Amy; Root, James C.; Butler, Tracy; Tuescher, Oliver; Pan, Hong; Epstein, Jane; Weisholtz, Daniel; Pavony, Michelle; Silverman, Michael; Goldstein, Martin; Altemus, Margaret; Cloitre, Marylene; LeDoux, Joseph; McEwen, Bruce; Stern, Emily; Silbersweig, DavidThe 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.Publication Top-Down Reorganization of Activity in the Visual Pathway after Learning a Shape Identification Task(Elsevier BV, 2005) Sigman, Mariano; Pan, Hong; Yang, Yihong; Stern, Emily; Silbersweig, David; Gilbert, Charles D.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.Publication Frontolimbic neural circuit changes in emotional processing and inhibitory control associated with clinical improvement following transference-focused psychotherapy in borderline personality disorder(Wiley, 2015) Perez, David L.; Vago, David R.; Pan, Hong; Root, James; Tuescher, Oliver; Fuchs, Benjamin H.; Leung, Lorene; Epstein, Jane; Cain, Nicole M.; Clarkin, John F.; Lenzenweger, Mark F.; Kernberg, Otto F.; Levy, Kenneth N.; Silbersweig, David; Stern, EmilyAim Borderline personality disorder (BPD) is characterized by self-regulation deficits, including impulsivity and affective lability. Transference-Focused Psychotherapy (TFP) is an evidence-based treatment proven to reduce symptoms across multiple cognitive-emotional domains in BPD. This pilot study aims to investigate neural activation associated with, and predictive of, clinical improvement in emotional and behavioral regulation in BPD following TFP. Methods BPD subjects (N=10) were scanned pre- and post-TFP treatment using a within-subjects design. A disorder-specific emotional-linguistic go/no-go fMRI paradigm was used to probe the interaction between negative emotional processing and inhibitory control. Results Analyses demonstrated significant treatment-related effects with relative increased dorsal prefrontal (dorsal anterior cingulate, dorsolateral prefrontal, and frontopolar cortices) activation, and relative decreased ventrolateral prefrontal cortex and hippocampal activation following treatment. Clinical improvement in constraint correlated positively with relative increased left dorsal anterior cingulate cortex activation. Clinical improvement in affective lability correlated positively with left posterior-medial orbitofrontal cortex/ventral striatum activation, and negatively with right amygdala/parahippocampal activation. Post-treatment improvements in constraint were predicted by pre-treatment right dorsal anterior cingulate cortex hypoactivation, and pre-treatment left posterior-medial orbitofrontal cortex/ventral striatum hypoactivation predicted improvements in affective lability. Conclusions These preliminary findings demonstrate potential TFP-associated alterations in frontolimbic circuitry and begin to identify neural mechanisms associated with a psychodynamically-oriented psychotherapy.