Norman B. Schmidt’s research while affiliated with Florida State University and other places

Despite various interventions for anxiety disorders, effects can take months and many individuals do not respond. Activity in the anterior cingulate cortex is a consistent predictor of treatment outcomes, and can be measured by medial frontal theta (MFT) event-related potentials. This study used task-based electroencephalography and MFT to predict anxiety sensitivity treatment response at mid-treatment, 1-week post-treatment, and 6 months post-treatment. Results indicated that lower medial to lateral prefrontal theta phase synchrony was associated with greater symptom improvement.

Development of neurophysiological treatment targets has been an important way to validate and advance treatment implementations. Anxiety Sensitivity (AS), described as a fear of fear, is one of the most well-researched transdiagnostic risk factors for psychopathology and has been demonstrated to be associated with a number of different INT symptoms and disorders, making it an ideal intervention target for treatment of anxiety and mood pathology. Currently, there exists a gap in terms of understanding underlying neural mechanisms of AS and treatment-related change in AS. The current study sought to examine the impact of 2 brief computerized interventions on AS in order to assess the P300 and late positive potential (LPP) event-related potential (ERP) components as an index of both baseline and treatment change in the transdiagnostic anxiety sensitivity construct. Participants received one of the following, with a 1-month follow-up: an anxiety reduction intervention of cognitive anxiety sensitivity treatment (CAST) alone, a mood intervention of cognitive bias modification interpretation (CBM-I), a combined CAST and CBM-I intervention, or a repeated contact control group. Baseline AS was significantly related to baseline P3/LPP, such that higher P3/LPP amplitude (heightened emotional reactivity) is associated with higher AS at intake. Further, treatment-related reductions in AS were associated with higher baseline reactivity: greater AS reductions at month one were associated with higher P3/LPP activity. Heightened emotional response was predictive of better treatment outcomes. Analyses also showed evidence for different mechanisms associated with CAST and CBM-I groups. Specifically, the CAST group evidenced predictions of treatment outcome in parietal areas, where the CBM-I group evidenced predictions in frontal areas. The Combined group evidenced both frontal and parietal activations, consistent with combining the effects from the CAST and CBM-I groups. These findings suggest that the P3/LPP is an index of cognitive-affective processes underlying AS at baseline and has predictive ability in assessing AS treatment outcome in that our observed treatment types engage different neural mechanisms.

Background Suicidal ideation (SI) and suicidal behavior (SB) may have different etiological pathways, particularly related to feedback processing. Identifying ERP components related to these suicide states may help researchers localize and understand these differences. Objective. Our primary purpose was to utilize time-frequency decomposition techniques to assess neurophysiological correlates of SI and SB during positive and negative feedback processing. Methods 271 subjects (55.7% female; mean age=35.75, SD=16.07; 30.6% veterans) completed a questionnaire battery and a multi-task protocol, including a gambling feedback task (Gehring & Willoughby, 2002), while electroencephalography (EEG) was collected using a 96-channel EEG system. Exploratory factor analysis (EFA) was conducted across 20 self-report suicide items selected to index SI and SB from several suicide-relevant questionnaires. EFA results produced 2 factors, corresponding to SI and SB. Time-frequency principal component analyses produced measures across all frequency bands (i.e., delta-FN/P3, delta-SW, theta-FN, alpha, beta-1, beta-2, and gamma). Results Excepting alpha amplitude, all measured frequencies were related to SB, and not SI (across loss and gain, with some loss-gain differences). Alpha, uniquely, showed a relationship to SI and not to SB (across loss and gain, no loss-gain differences). Robust regressions confirmed that the delta, theta, and high-frequency (HF; beta-1, beta-2, and gamma as combined HF loss, gain, and loss-gain difference factors) measures were each independently related to SB. Discussion Broadly, the results indicate that individuals with SB showed heightened neurophysiological response across multiple ERP components (except alpha) to gambling feedback, with significantly greater increases to loss stimuli relative to gain stimuli. General Scientific Summary This study, using time-frequency EEG/ERP measures from a gambling feedback task, supports the theoretical framework that suicidal behavior and suicidal ideation can be indexed separately. Generally, stronger reactivity to all feedback (i.e., loss and gain feedback during a gambling task) is seen in those with suicidal behavior and not in those with suicidal ideation, but with a small separate effect related to suicidal ideation.

Background: Anomalies in default mode network (DMN) activity and alpha (8-12 Hz) oscillations have been independently observed in posttraumatic stress disorder (PTSD). Recent spatiotemporal analyses suggest that alpha oscillations support DMN functioning via inter-regional synchronization and sensory cortical inhibition. Therefore, we examined a unifying pathology of alpha deficits in the visual-cortex-DMN system in PTSD. Methods: Patients with PTSD (N = 25) and two control groups - patients with Generalized Anxiety Disorder (N = 24) and healthy controls (N = 20) - underwent a standard eyes-open resting state (S-RS) and a modified resting state (M-RS) of passively viewing salient images (known to deactivate the DMN). High-density electroencephalogram (hdEEG) were recorded, from which intracortical alpha activity (power and connectivity/Granger causality) was extracted using the exact low-resolution electromagnetic tomography (eLORETA). Results: Patients with PTSD (vs. controls) demonstrated attenuated alpha power in the visual cortex and key hubs of the DMN (posterior cingulate cortex/PCC and medial prefrontal cortex/mPFC) at both states, the severity of which further correlated with hypervigilance symptoms. With increased visual input (at M-RS vs. S-RS), patients with PTSD further demonstrated reduced alpha-frequency directed connectivity within the DMN (PCC to mPFC) and, importantly, from the visual cortex (VC) to both DMN hubs (VC to PCC and VC to mPFC), linking alpha deficits in the two systems. Conclusions: These interrelated alpha deficits align with DMN hypoactivity/hypoconnectivity, sensory disinhibition, and hypervigilance in PTSD, representing a unifying neural underpinning of these anomalies. The identification of visual-cortex-DMN alpha dysrhythmia in PTSD further presents a novel therapeutic target, promoting network-based intervention of neural oscillations.

Intrusive re-experiencing of traumatic events is a hallmark symptom of posttraumatic stress disorder (PTSD). In contrast to abstract, verbal intrusions in other affective disorders, intrusive re-experiencing in PTSD is characterized by vivid sensory details as “flashbacks”. While prevailing PTSD models largely focus on dysregulated emotional processes, we hypothesize that deficient sensory inhibition in PTSD could drive overactivation of sensory representations of trauma memories, precipitating sensory-rich intrusions of trauma. In 86 combat veterans, we examined resting-state alpha (8-12 Hz) oscillatory activity (in both power and posterior→frontal connectivity), given its key role in sensory cortical inhibition, in association with intrusive re-experiencing symptoms. A subset ( N = 35) of veterans further participated in an odor task (including both combat and non-combat odors) to assess olfactory trauma memory and emotional response. We observed a strong association between intrusive re-experiencing symptoms and attenuated resting-state posterior→frontal alpha connectivity, which were both correlated with olfactory trauma memory (but not emotional response). Importantly, olfactory trauma memory was further identified as a full mediator of the relationship between alpha connectivity and intrusive re-experiencing in these veterans, suggesting that deficits in intrinsic sensory inhibition can contribute to intrusive re-experiencing of trauma via heightened trauma memory. Therefore, by permitting unfiltered sensory cues to enter information processing and spontaneously activating sensory representations of trauma, impaired sensory inhibition can constitute a sensory mechanism of intrusive re-experiencing in PTSD. HIGHLIGHTS Alpha oscillations (indexing sensory inhibition) measured in 86 combat veterans Re-experiencing symptom severity was associated with attenuated alpha connectivity Trauma memory for, not emotional response to, odors mediated this relationship Trauma memories may arise via disinhibited activation of sensory representations Sensory systems may be novel target for intrusive re-experiencing symptom treatment

Background Research has explored the influence of trauma type on emotion dysregulation and the role of emotion dysregulation in posttraumatic stress disorder (PTSD). However, it remains unclear whether trauma types differentially impact emotion dysregulation, and whether this in turn contributes to elevated PTSD. The current study tested whether trauma type is related to PTSD symptoms via emotion dysregulation. Methods Trauma-exposed community members (n = 209) completed a semi-structured clinical interview and self-reported on emotion regulation, trauma exposure, PTSD symptoms, and negative affect. Results Interpersonal trauma, sexual assault in particular, is associated with greater emotion dysregulation. Furthermore, emotion dysregulation mediates the effects of trauma type on PTSD symptoms for sexual assault but not other trauma types, and effects remained significant after covarying for negative affectivity. More recent and chronic trauma was not associated with greater emotion dysregulation. Conclusions This study underscores the importance of emotion dysregulation in PTSD development and maintenance. Findings may be used for the development of interventions targeting emotion regulation as a malleable risk factor for PTSD, especially for sexual assault victims.

Distress tolerance (DT), defined as the perceived and/or actual behavioral capacity to tolerate negative emotional states, is considered an important risk factor for various externalizing and internalizing disorders. Despite the importance of DT in the development and maintenance of psychopathology, few reliable and valid indicators of DT have been developed. One potentially useful way to assess DT is through interpretation bias (IB) paradigms. The current study sought to examine the convergent validity, reliability, and clinical utility of a DT-focused IB paradigm by directly measuring an individual's interpretations of distressing information. Participants completed a DT-IB task and self-report questionnaires. Results found an association between DTS self-report and an exaggerated DT-IB. Reliability analyses found the word pairings in our DT-IB task to display good internal consistency. In addition, an exaggerated DT-IB was associated with diagnostic status after covarying for negative affect and self-report DTS and DT-IB was associated with increased levels of negative affect above and beyond self-report DTS. This study is the first to identify specific interpretation biases for distress-related information. Given the transdiagnostic nature of DT and the efficacy and accessibility associated with CBM-I protocols for related constructs, the present findings add considerably to a growing body of literature.

The feedback negativity (FN) event-related potential (ERP) is widely studied during gambling feedback tasks. However, research on FN and anxiety is minimal and the findings are mixed. To clarify these discrepancies, the current study (N = 238) used time-frequency analysis to disentangle overlapping contributions of delta (0-3 Hz) and theta (3-7 Hz) to feedback processing in a clinically anxious sample, with severity assessed through general worry and physiological arousal scales. Greater general worry showed enhanced delta- and theta-FN broadly across both gain and loss conditions, with theta-FN stronger for losses. Regressions indicated delta-FN maintained unique effects, accounted for theta, and explained the blunted time domain FN for general worry. Increased delta was also associated with physiological arousal, but the effects were accounted for by general worry. Broadly, anxiety-related alterations in feedback processing can be explained by an overall heightened sensitivity to feedback as represented by enhanced delta-FN in relation to the general worry facet of anxiety.

Despite the high levels of comorbidity between post-traumatic stress disorder (PTSD) and sleep disturbance, little research has examined the predictors of insomnia and nightmares in this population. The current study tested both PTSD-specific (i.e. PTSD symptoms, comorbid anxiety and depression, nightmares and fear of sleep) and insomnia-specific (i.e. dysfunctional beliefs about sleep, insomnia-related safety behaviours and daily stressors) predictors of sleep quality, efficiency and nightmares in a sample of 30 individuals with PTSD. Participants participated in ecological momentary assessment to determine how daily changes in PTSD- and insomnia-related factors lead to changes in sleep. Multi-level modelling analyses indicated that, after accounting for baseline PTSD symptom severity, PTSD-specific factors were associated with insomnia symptoms, but insomnia-specific factors were not. Only daytime PTSD symptoms and fear of sleep predicted nightmares. Both sleep- and PTSD-related factors play a role in maintaining insomnia among those with PTSD, while nightmares seem to be linked more closely with only PTSD-related factors.

Post-traumatic stress disorder is characterized by exaggerated threat response, and theoretical accounts to date have focused on impaired threat processing and dysregulated prefrontal-cortex-amygdala circuitry. Nevertheless, evidence is accruing for broad, threat-neutral sensory hyperactivity in post-traumatic stress disorder. As low-level, sensory processing impacts higher-order operations, such sensory anomalies can contribute to widespread dysfunctions, presenting an additional aetiological mechanism for post-traumatic stress disorder. To elucidate a sensory pathology of post-traumatic stress disorder, we examined intrinsic visual cortical activity (based on posterior alpha oscillations) and bottom-up sensory-driven causal connectivity (Granger causality in the alpha band) during a resting state (eyes open) and a passive, serial picture viewing state. Compared to patients with generalized anxiety disorder (n = 24) and healthy control subjects (n = 20), patients with post-traumatic stress disorder (n = 25) demonstrated intrinsic sensory hyperactivity (suppressed posterior alpha power, source-localized to the visual cortex-cuneus and precuneus) and bottom-up inhibition deficits (reduced posterior→frontal Granger causality). As sensory input increased from resting to passive picture viewing, patients with post-traumatic stress disorder failed to demonstrate alpha adaptation, highlighting a rigid, set mode of sensory hyperactivity. Interestingly, patients with post-traumatic stress disorder also showed heightened frontal processing (augmented frontal gamma power, source-localized to the superior frontal gyrus and dorsal cingulate cortex), accompanied by attenuated top-down inhibition (reduced frontal→posterior causality). Importantly, not only did suppressed alpha power and bottom-up causality correlate with heightened frontal gamma power, they also correlated with increased severity of sensory and executive dysfunctions (i.e. hypervigilance and impulse control deficits, respectively). Therefore, sensory aberrations help construct a vicious cycle in post-traumatic stress disorder that is in action even at rest, implicating dysregulated triangular sensory-prefrontal-cortex-amygdala circuitry: intrinsic sensory hyperactivity and disinhibition give rise to frontal overload and disrupt executive control, fuelling and perpetuating post-traumatic stress disorder symptoms. Absent in generalized anxiety disorder, these aberrations highlight a unique sensory pathology of post-traumatic stress disorder (ruling out effects merely reflecting anxious hyperarousal), motivating new interventions targeting sensory processing and the sensory brain in these patients.