The fine line between 'brave' and 'reckless': amygdala reactivity and regulation predict recognition of risk.

BACKGROUND: High sensation-seekers (HSS) pursue novelty even at the cost of self-harm. When challenged, HSS are less anxious, show blunted physiological (cortisol, startle) and neurobiological (prefrontal-limbic) responses, and devalue aversive outcomes. Here, we investigate how these features interact under conditions of physical danger, in distinguishing between adaptive and maladaptive approaches to risk. METHODS: We recruited a cohort of individuals who voluntarily sought out recreational exposure to physical risk, and obtained serial cortisol values over two time-locked days. On the 'baseline' day, we scanned subjects' brains with functional and structural MRI; on the 'skydiving day,' subjects completed a first-time tandem skydive. During neuroimaging, subjects viewed cues that predicted aversive noise; neural data were analyzed for prefrontal-limbic reactivity (activation) and regulation (non-linear complexity), as well as cortical thickness. To probe threat perception, subjects identified aggression for ambiguous faces morphed between neutral and angry poles. RESULTS: Individuals with prefrontal-limbic meso-circuits with less balanced regulation between excitatory and inhibitory components showed both diminished cortisol/anxiety responses to their skydives, as well as less accurate perceptual recognition of threat. This impaired control was localized to the inferior frontal gyrus, with associated cortical thinning. Structural equation modeling suggests that sensation-seeking is primarily mediated via threat-perception, which itself is primarily mediated via neural reactivity and regulation. CONCLUSIONS: Our results refine the sensation-seeking construct to provide important distinctions (brain-based, but with endocrine and cognitive consequences) between the brave, who feel fear but nonetheless overcome it, and the reckless, who fail to recognize danger. This distinction has important real-world implications, as those who fail to recognize risk are less likely to mitigate it.

A disposition to reappraise decreases anterior insula reactivity during anxious anticipation.

Across individuals there is variability in one's inherent tendency to reappraise emotional events in everyday life, which may be related to how worried one becomes in the presence of an anticipated aversive event. The extent to which this natural tendency to reappraise has neurobiological correlates during anxious anticipation is unknown. Neuroimaging research indicates that responses in the anterior insula precede anticipated aversive events and appear to represent one's affective feeling state of anxious anticipation. Successful cognitive reappraisal should weaken this anticipatory insula response. Here, functional magnetic resonance images were acquired while participants completed an anticipation task. We found increased anterior insula activation during aversive anticipation and a negative association between anxious anticipatory right anterior insula reactivity and dispositional reappraisal. Thus, even without the instruction to reappraise, individuals high in dispositional reappraisal tended to have a reduced anticipatory insula response to aversive stimuli, thereby down-regulating a neural substrate for aversive anticipation.

Higher body fat percentage is associated with increased cortisol reactivity and impaired cognitive resilience in response to acute emotional stress.

OBJECTIVE: Cortisol is elevated in individuals with both increased emotional stress and higher percentages of body fat. Cortisol is also known to affect cognitive performance, particularly spatial processing and working memory. We hypothesized that increased body fat might therefore be associated with decreased performance on a spatial processing task, in response to an acute real-world stressor. DESIGN: We tested two separate samples of participants undergoing their first (tandem) skydive. In the first sample (N=78), participants were tested for salivary cortisol and state anxiety (Spielberger State Anxiety Scale) during the plane's 15-min ascent to altitude in immediate anticipation of the jump. In a second sample (N=20), participants were tested for salivary cortisol, as well as cardiac variables (heart rate, autonomic regulation through heart rate variability) and performance on a cognitive task of spatial processing, selective attention and working memory. RESULTS: In response to the skydive, individuals with greater body fat percentages showed significantly increased reactivity for both cortisol (on both samples) and cognition, including decreased accuracy of our task of spatial processing, selective attention and working memory. These cognitive effects were restricted to the stress response and were not found under baseline conditions. There were no body fat interactions with cardiac changes in response to the stressor, suggesting that the cognitive effects were specifically hormone mediated rather than secondary to general activation of the autonomic nervous system. CONCLUSIONS: Our results indicate that, under real-world stress, increased body fat may be associated with endocrine stress vulnerability, with consequences for deleterious cognitive performance.

A systems approach to prefrontal-limbic dysregulation in schizophrenia.

INTRODUCTION: Using a prefrontal-limbic dysregulation model for schizophrenia, we tested whether a dynamic control systems approach in conjunction with neuroimaging might increase detection sensitivity in characterizing the illness. Our analyses were modeled upon diagnostic tests for other dysregulatory diseases, such as diabetes, in which trajectories for the excitatory and inhibitory components of the negative feedback loops that reestablish homeostasis are measured after system perturbation. We hypothesized that these components would show distinct coupling dynamics within the patient population, as compared to healthy controls, and that these coupling dynamics could be quantified statistically using cross-correlations between excitatory and inhibitory time series using fMRI. METHODS: As our perturbation, we activated neural regions associated with the emotional arousal response, using affect-valent facial stimuli presented to 11 schizophrenic patients (all under psychotropic medication) and 65 healthy controls (including 11 individuals age- and sex-matched to the patients) during fMRI scanning. We first performed a random-effects analysis of the fMRI data to identify activated regions. Those regions were then analyzed for group differences, using both standard analyses with respect to the time series peaks, as well as a dynamic analysis that looked at cross-correlations between excitatory and inhibitory time series and group differences over the entire time series. RESULTS: Patients and controls showed significant differences in signal dynamics between excitatory and inhibitory components of the negative feedback loop that controls emotional arousal, specifically between the right amygdala and Brodmann area 9 (BA9), when viewing angry facial expressions (p = 0.002). Further analyses were performed with respect to activation amplitudes for these areas in response to angry faces, both over the entire time series as well as for each time point along the time series. While the amygdala responses were not significantly different between groups, patients showed significantly lower BA9 activation during the beginning of the response (0.000

Nonlinear complexity and spectral analyses of heart rate variability in medicated and unmedicated patients with schizophrenia.

OBJECTIVE: Heart rate variability (HRV) reflects functioning of the autonomic nervous system and possibly also regulation by the neural limbic system, abnormalities of which have both figured prominently in various etiological models of schizophrenia, particularly those that address patients' vulnerability to stress in connection to psychosis onset and exacerbation. This study provides data on cardiac functioning in a sample of schizophrenia patients that were either medication free or on atypical antipsychotics, as well as cardiac data on matched healthy controls. We included a medication-free group to investigate whether abnormalities in HRV previously reported in the literature and associated with atypical antipsychotics were solely the effect of medications or whether they might be a feature of the illness (or psychosis) itself. METHOD: We collected 24-hour ECGs on 19 patients and 24 controls. Of the patients, 9 were medication free and 10 were on atypical antipsychotics. All subject groups were matched for age and gender. Patient groups showed equivalent symptom severity and type, as well as duration of illness. We analyzed the data using nonlinear complexity (symbolic dynamic) HRV analyses as well as standard and relative spectral analyses. RESULTS: For the medication-free patients as compared to the healthy controls, our data show decreased R-R intervals during sleep, and abnormal suppression of all frequency ranges, but particularly the low frequency range, which persisted even after adjusting the spectral data for the mean R-R interval. This effect was exacerbated for patients on atypical antipsychotics. Likewise, nonlinear complexity analysis showed significantly impaired HRV for medication-free patients that was exacerbated in the patients on atypical antipsychotics. CONCLUSIONS: Altogether, the data suggest a pattern of significantly decreased cardiac vagal function of patients with schizophrenia as compared to healthy controls, apart from and beyond any differences due to medication side effects. The data additionally confirm earlier reports of a deleterious effect of atypical antipsychotics on HRV, which may exacerbate an underlying vulnerability in patients. These results support previous evidence that autonomic abnormalities may be a core feature of the illness (or psychosis), and that an even more conservative approach to cardiac risk in schizophrenia than previously thought may therefore be clinically appropriate.

Logical processing, affect, and delusional thought in schizophrenia.

Deficits of logical reasoning have long been considered a hallmark of schizophrenia and delusional disorders. We provide a more precise characterization of "logic" and, by extension, of "deficits in logical reasoning." A model is offered to categorize different forms of logical deficits. This model acknowledges not only problems with making inferences, which is how logic deficits are usually conceived, but also problems in the acquisition and evaluation of premises (i.e., filtering of "input"). Early (1940-1969) and modern (1970-present) literature on logical reasoning and schizophrenia is evaluated within the context of the presented model. We argue that, despite a substantial history of interest in the topic, research to date has been inconclusive on the fundamental question of whether patients with delusional ideation show abnormalities in logical reasoning. This may be due to heterogeneous definitions of "logic," variability in the composition of patient samples, and floor effects among the healthy controls. In spite of these difficulties, the available evidence suggests that deficits in logical reasoning are more likely to occur due to faulty assessment of premises than to a defect in the structure of inferences. Such deficits seem to be provoked (in healthy individuals) or exacerbated (in patients with schizophrenia) by emotional content. The hypothesis is offered that delusional ideation is primarily affect-driven, and that a mechanism present in healthy individuals when they are emotionally challenged may be inappropriately activated in patients who are delusional.