Stuart R. Steinhauer

Can’t shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals

BACKGROUND Previous research suggests that depressed individuals engage in prolonged elaborative processing of emotional information. A computational neural network model of emotional information processing suggests this process involves sustained amygdala activity in response to processing negative features of information. This study examined whether brain activity in response to emotional stimuli was sustained in depressed individuals, even following subsequent distracting stimuli. METHODS Seven depressed and 10 never-depressed individuals were studied using event-related functional magnetic resonance imaging during alternating 15-sec emotional processing (valence identification) and non-emotional processing (Sternberg memory) trials. Amygdala regions were traced on high-resolution structural scans and co-registered to the functional data. The time course of activity in these areas during emotional and non-emotional processing trials was examined. RESULTS During emotional processing trials, never-depressed individuals displayed amygdalar responses to all stimuli, which decayed within 10 sec. In contrast, depressed individuals displayed sustained amygdala responses to negative words that lasted throughout the following non-emotional processing trials (25 sec later). The difference in sustained amygdala activity to negative and positive words was moderately related to self-reported rumination. CONCLUSIONS Results suggest that depression is associated with sustained activity in brain areas responsible for coding emotional features.

Increased Amygdala and Decreased Dorsolateral Prefrontal BOLD Responses in Unipolar Depression: Related and Independent Features

BACKGROUND Major depressive disorder is characterized by increased and sustained emotional reactivity, which has been linked to sustained amygdala activity. It is also characterized by disruptions in executive control, linked to abnormal dorsolateral prefrontal cortex (DLPFC) function. These mechanisms have been hypothesized to interact in depression. This study explored relationships between amygdala and DLPFC activity during emotional and cognitive information processing in unipolar depression. METHOD Twenty-seven unmedicated patients with DSM-IV unipolar major depressive disorder and 25 never-depressed healthy control subjects completed tasks requiring executive control (digit sorting) and emotional information processing (personal relevance rating of words) during event-related functional magnetic resonance imaging (fMRI) assessment. RESULTS Relative to control subjects, depressed subjects displayed sustained amygdala reactivity on the emotional tasks and decreased DLPFC activity on the digit-sorting task. Decreased relationships between the time-series of amygdala and DLPFC activity were observed within tasks in depression, but different depressed individuals showed each type of bias. CONCLUSIONS Depression is associated with increased limbic activity in response to emotional information processing and decreased DLPFC activity in response to cognitive tasks though these may reflect separate mechanisms. Depressed individuals also display decreased relationships between amygdala and DLPFC activity, potentially signifying decreased functional relationships among these structures.

Use of concurrent pupil dilation assessment to inform interpretation and analysis of fMRI data

Potential contributions of concurrently acquired pupil dilation data to functional magnetic resonance imaging (fMRI) experiments were examined. Sixteen healthy participants completed a working memory task (digit sorting) during measurement of pupil dilation outside the fMRI environment and during concurrent 3T fMRI assessment. Pupil dilation increased parametrically with task difficulty inside and outside the scanner, on a similar time course, suggesting that task demand was similar in both environments. The time course of pupil dilation during digit sorting was similar to the time course of the fMRI signal in the middle frontal gyrus, suggesting that middle-frontal gyrus activity indexed the engagement working memory processes. Incorporating individual differences in pupil dilation improved the sensitivity and specificity of general linear modeling analyses of activity in the middle frontal gyrus, above and beyond standard analytic techniques. Results suggest concurrent pupil dilation during fMRI assessment can help to (1) specify whether task demand is the same inside and outside the fMRI environment, (2) resolve the extent to which fMRI signals reflect different aspects of event-related designs, and (3) explain variation in fMRI data due to individual differences in information processing.

Blink before and after you think: Blinks occur prior to and following cognitive load indexed by pupillary responses

Pupil dilation and blinks provide complementary, mutually exclusive indices of information processing. Though each index is associated with cognitive load, the occurrence of a blink precludes the measurement of pupil diameter. These indices have generally been assessed in independent literatures. We examine the extent to which these measures are related on two cognitive tasks using a novel method that quantifies the proportion of trials on which blinks occur at each sample acquired during the trial. This measure allows cross-correlation of continuous pupil-dilation and blink waveforms. Results indicate that blinks occur during early sensory processing and following sustained information processing. Pupil dilation better reflects sustained information processing. Together these indices provide a rich picture of the time course of information processing, from early reactivity through sustained cognition, and after stimulus-related cognition ends.

The metamorphosis of schizophrenia: from chronicity to vulnerability

On the evidence of long-term follow-up studies of cohorts of patients in Europe the outcome of schizophrenia appears to be changing from chronicity to an episodic course with a more favourable outlook. While the reasons for this change are unclear it is suggested that schizophrenia is characterized essentially by a state of vulnerability to the disorder. This vulnerability may or may not give rise to an episode of illness, depending on the incidence of triggering life event stressors and on the moderating influences of social networks, ecological factors, and premorbid personality. The traditional view of schizophrenia as an essentially chronic condition reflects not so much the natural history of the disorder as iatrogenic influences, lack of satisfactory extra-mural care, the accumulation of a relatively small proportion of truly chronic illnesses and the failure to recognize the termination of an episode of illness in patients with poor premorbid personalities. Evidence for the episodic nature of schizophrenia is presented.

Do the Seconds Turn Into Hours? Relationships between Sustained Pupil Dilation in Response to Emotional Information and Self-Reported Rumination

This study examined relationships between self-reported rumination and sustained pupil dilation, an index of cognitive and emotional processing, in response to emotional information in depressed and never-depressed individuals. Pupil dilation was measured during tasks that required alternating emotional and nonemotional processing. Depressed individuals displayed more sustained pupil dilation in response to stimuli on emotional processing tasks than nondepressed individuals. Such sustained pupil dilation among depressed individuals was particularly apparent in response to negative and personally relevant emotional information. Multiple self-report measures of rumination were moderately correlated with sustained pupil dilation to negative personally relevant information. Results are consistent with the idea that sustained emotional processing of briefly presented stimuli may be associated with the propensity for depressive rumination.

Developmental delay in P300 production in children at high risk for developing alcohol-related disorders.

BACKGROUND Reduction of P300 amplitude in children and adolescents at high risk for developing alcoholism has frequently been reported. It has been hypothesized that this reduction represents a developmental delay in reaching age-appropriate levels in P300 amplitude. Using latent growth analysis of longitudinal data obtained at yearly intervals, this study seeks to define normal growth, and determine if the pattern seen in high-risk children differs from that obtained in normal low-risk controls. METHODS A total of 156 children from either high or low-risk families have been assessed multiple times (two-thirds more than 4 times) using both a clinical assessment (K-SADS) and ERP evaluation performed on the same day. A total of 635 separate assessments were available for modeling. RESULTS Quadratic growth curves revealed a slower rate of change in P300 amplitude in high-risk than low-risk males. High-risk girls showed reduced visual P300 amplitude only when the presence of a K-SADS diagnosis was considered. No differences were seen for P300 latency. CONCLUSIONS This study confirms the hypothesis that when reduction of P300 amplitude is seen in males at high risk for developing alcoholism, it is due to a developmental delay.

Genetic association between reduced P300 amplitude and the DRD2 dopamine receptor A1 allele in children at high risk for alcoholism

BACKGROUND There is evidence that both reduction in P300 amplitude and the presence of the A1 allele are risk markers for alcoholism. We hypothesized that demonstration of a relationship between the marker and the trait in young children who had not begun to drink regularly would provide evidence for dopaminergic mediation of the reduction in P300 often seen among high-risk children. A previous association between the A1 and the P300 amplitude in screened controls supports the hypothesis that this association occurs in the general population. METHODS Children were assessed using both visual and auditory paradigms to elicit event-related potentials (ERPs). The P300 component of the ERP was investigated with respect to the genetic variation of the Taq1A D2 receptor in these children. RESULTS Genetic association between a marker locus (Taq1 A RFLP near the D2 receptor locus) and the amplitude of P300 was found to be present in 58 high-risk children and their relatives (a total of 100 high-risk individuals). CONCLUSIONS A higher proportion of children from alcoholic families may exhibit lower P300 because more of these children carry the A1 allele than is seen in the normal population.

Event-related potentials in alcoholics and their first-degree relatives

Preliminary results are presented for auditory ERPs recorded from members of alcoholic families during performance of a counting task and a choice reaction task. Alcoholic families included three adult male siblings (alcoholic proband, a second affected sib, and an unaffected sib) and parents. Control families included two adult male sibs and parents. In all experimental conditions, the N100 component was decreased in amplitude for all sibs (affected and unaffected) of the alcoholic families. The latency of the P300 component was increased for both affected and unaffected sibs compared to controls in the counting task, indicating a familial difference irrespective of drinking status. In the choice reaction task, longer P300 latencies were observed among the probands and their affected sibs as compared to their unaffected sibs, suggesting that in this more demanding task, increased latency was associated with a significant drinking history. ERP findings for children of the alcoholic probands are also discussed. The effects of differences in task complexity, drinking variables, and criteria for family selection are considered.

Reduced electrodermal activity in psychopathy-prone adolescents

This study tests the hypothesis that psychopathy-prone adolescents show reduced anticipatory skin conductance responding. Electrodermal activity was recorded while participants anticipated and responded to a 105 dB signaled or unsignaled white-noise burst. Using an extreme groups design, the authors used Child Psychopathy Scale (D. R. Lynam, 1997) scores from a community sample of 335 male adolescents (age 16) to form control (n = 65) and psychopathy-prone (n = 65) groups. Significantly more psychopathy-prone participants were nonresponders in the signaled anticipatory (p = .014), signaled responsivity (p = .037), and unsignaled responsivity (p = .003) conditions compared with controls. Anticipatory hyporesponsivity of psychopathy-prone adolescents similar to the electrodermal hyporesponsivity found in psychopathic adults suggests that this autonomic impairment is present by adolescence and may predispose individuals to adult psychopathy.