Vladimir Miskovic

Shyness and timidity in young adults who were born at extremely low birth weight.

OBJECTIVE. Recent studies have noted personality differences among adult survivors of very preterm birth, including higher neuroticism and cautiousness and lower extraversion. We attempted to replicate and extend these recent studies by examining personality characteristics across multiple components of personality that traditionally define personality structure in a birth cohort of young adults born at extremely low birth weight (501–1000 g), the smallest and most at-risk infants. PARTICIPANTS AND METHODS. We assessed 71 (76% of the original birth cohort) extremely low birth weight and 83 (74% of the original cohort) term normal birth weight young adults by using well-validated personality measures, indexing 4 traditional components of personality: temperament (Cheek and Buss shyness and sociability and Eysenck neuroticism and extraversion), motivation (Carver and White behavioral inhibition and behavioral activation), cognitive and affective (Coopersmith self-esteem and University of California, Los Angeles, loneliness), and socialization (Eysenck psychoticism and lie). All of the participants were right-handed and free of neurosensory and psychiatric impairments. RESULTS. Extremely low birth weight adults reported significantly higher shyness, behavioral inhibition, and socialization (a measure of prosocial behavior defined by risk aversion and adherence to societal mores) and lower sociability and emotional well-being than their normal birth weight counterparts, replicating and extending the findings of previous studies. CONCLUSIONS. Young adults who were born at extremely low birth weight and without major impairments are more cautious, shy, and risk aversive and less extraverted than their normal birth weight counterparts, possibly placing them at risk for future psychiatric and emotional problems.

Social fearfulness in the human brain

Social fearfulness is expressed on a continuum of severity from moderate distress to incapacitating fear. The present article focuses on the brain states associated with this broad dimension of social anxiety in humans. In total, 70 published studies are summarized documenting the neural correlates of social anxiety during states of rest, threat-related cognitive-affective activation, and acute symptom provocation. Neural exaggeration in limbic (amygdala) and paralimbic (insula) regions appears to be associated with functional outcomes involving increased attention for and processing of social threat. Evidence is also reviewed showing that social anxiety is characterized by atypical functional connectivity in certain brain networks. Despite a higher prevalence of social anxiety disorder among females, males have been overrepresented in the published clinical studies (constituting approximately 56% of the total participants). We evaluate the prospects of nonhuman animal models of social anxiety and discuss several promising directions for future research. The review highlights the need to adopt an integrative, network-based approach to the study of the neural substrates underlying social anxiety.

Psychopathology in young adults born at extremely low birth weight.

BACKGROUND Little is known about the long-term mental health of extremely low birth weight (ELBW) (<1000 g) survivors. We test whether young adults aged 22 to 26 years born at ELBW differ from normal birth weight (NBW) controls in self-reported levels of psychopathology. METHOD Participants included 142 ELBW survivors (86% response) born between 1977 and 1982 to residents of central-west Ontario, Canada and 133 NBW control subjects (92% response). The Young Adult Self-Report measure was used to create five DSM-IV oriented scales aggregated to form internalizing (depressive problems, anxiety problems, avoidant personality problems) and externalizing (attention deficit-hyperactivity disorder problems and antisocial personality problems) scales. RESULTS After adjusting for family background characteristics, mean scores for ELBW survivors were 3.02 [95% confidence interval (CI) 0.78-5.26] points higher for internalizing problems and no different, i.e. 0.00 (95% CI -1.17 to 1.17), for externalizing problems. There was a sex × group statistical interaction such that being male muted the risk for externalizing problems among those born at ELBW: -2.11 (95% CI -4.21 to -0.01). Stratifying ELBW adults as born small for gestational age (SGA) versus appropriate weight for gestational age (AGA) revealed a significant gradient of risk for levels of internalizing problems that was largest for SGA, i.e. 4.75 (95% CI 1.24-8.26), and next largest for AGA, 2.49 (95% CI 0.11-4.87), compared with NBW controls. CONCLUSIONS Depression, anxiety and avoidant personality problems (internalizing problems) are elevated in young adulthood among ELBW survivors. This effect is relatively small overall but noticeably larger among ELBW survivors born SGA.

Frontal EEG asymmetry and symptom response to cognitive behavioral therapy in patients with social anxiety disorder

Although previous studies have shown that socially anxious individuals exhibit greater relative right frontal electroencephalogram (EEG) activity at rest, no studies have investigated whether improvements in symptoms as a result of treatment are associated with concomitant changes in resting brain activity. Regional EEG activity was measured at rest in 23 patients with social anxiety disorder (SAD) before and after cognitive behavioral therapy (CBT). Results indicated that patients shifted significantly from greater relative right to greater relative left resting frontal brain activity from pre- to posttreatment. Greater left frontal EEG activity at pretreatment predicted greater reduction in social anxiety from pre- to posttreatment and lower posttreatment social anxiety after accounting for pretreatment symptoms. These relations were specific to the frontal alpha EEG asymmetry metric. These preliminary findings suggest that resting frontal EEG asymmetry may be a predictor of symptom change and endstate functioning in SAD patients who undergo efficacious psychological treatment.

Acquired fears reflected in cortical sensory processing: A review of electrophysiological studies of human classical conditioning

The capacity to associate neutral stimuli with affective value is an important survival strategy that can be accomplished by cell assemblies obeying Hebbian learning principles. In the neuroscience laboratory, classical fear conditioning has been extensively used as a model to study learning-related changes in neural structure and function. Here, we review the effects of classical fear conditioning on electromagnetic brain activity in humans, focusing on how sensory systems adapt to changing fear-related contingencies. By considering spatiotemporal patterns of mass neuronal activity, we illustrate a range of cortical changes related to a retuning of neuronal sensitivity to amplify signals consistent with fear-associated stimuli at the cost of other sensory information. Putative mechanisms that may underlie fear-associated plasticity at the level of the sensory cortices are briefly considered, and several avenues for future work are outlined.

Cross-regional cortical synchronization during affective image viewing.

Affective perception has been suggested to involve the coordinated activation of widely distributed cortical networks, including those involved in sensory storage/analysis and higher-order structures, such as the prefrontal cortex that regulate these processes. We measured regional electroencephalogram (EEG) activity while young adult participants viewed images varying in arousal and valence (pleasant, neutral, and unpleasant). Viewing highly arousing images led to a significant enhancement of EEG coherence between prefrontal and posterior electrodes in both cerebral hemispheres. Long distance interhemispheric coherence also increased during affective image viewing, but only among females. Increases in coherent brain electrical activity were specific to oscillations in the beta (14 to 30Hz) bandwidth, while right hemispheric networks oscillating in the theta (4 to 7Hz) range tended to de-synchronize during viewing of affective images. Although directionality could not be inferred, analyses of lead-lag relations showed the prefrontal electrodes leading the posterior clusters, consistent with top-down modulation. Our results suggest large-scale synchronization of cortical cells during affective viewing and emphasize the role of beta oscillations in mediating such binding.

Stability of resting frontal electroencephalogram (EEG) asymmetry and cardiac vagal tone in adolescent females exposed to child maltreatment

The experience of child maltreatment is a known risk factor for the development of psychopathology. Structural and functional modifications of neural systems implicated in stress and emotion regulation may provide one mechanism linking early adversity with later outcome. The authors examined two well-documented biological markers of stress vulnerability [resting frontal electroencephalogram (EEG) asymmetry and cardiac vagal tone] in a group of adolescent females exposed to child maltreatment (n = 38; M age = 14.47) and their age-matched non-maltreated (n = 25; M age = 14.00) peers. Maltreated females exhibited greater relative right frontal EEG activity and lower cardiac vagal tone than controls over a 6-month period. In addition, frontal EEG asymmetry and cardiac vagal tone remained stable in the maltreated group across the 6 months, suggesting that the neurobiological correlates of maltreatment may not simply reflect dynamic, short-term changes but more long lasting alterations. The present findings appear to be the first to demonstrate stability of two biologically based stress-vulnerability measures in a maltreated population. Findings are discussed in terms of plasticity within the neural circuits of emotion regulation during the early childhood period and alternative causal models of developmental psychopathology.

Changes in EEG Cross-Frequency Coupling During Cognitive Behavioral Therapy for Social Anxiety Disorder

Coupling between EEG delta and beta oscillations is enhanced among anxious and healthy individuals during anticipatory anxiety. EEG coupling patterns associated with psychotherapy have not yet been quantified in socially anxious individuals. In this study, we used a double baseline, repeated measures design, in which 25 adults with a principal diagnosis of social anxiety disorder completed 12 weekly sessions of standardized group cognitive behavioral therapy and four EEG assessments: two at pretreatment, one at midtreatment, and one at posttreatment. Treatment was associated with reductions in symptom severity across multiple measures and informants, as well as reductions in delta-beta coupling at rest and during speech anticipation. Moreover, the clinical group exhibited greater coupling at pretreatment than did post hoc control participants with low social anxiety. The EEG cross-frequency profiles in the clinical group normalized by the posttreatment assessment. These findings provide evidence of concomitant improvement in neural and behavioral functioning among socially anxious adults undergoing psychotherapy.

Frontal Electroencephalogram Asymmetry, Salivary Cortisol, and Internalizing Behavior Problems in Young Adults Who Were Born at Extremely Low Birth Weight

The authors examined internalizing behavior problems at middle childhood, adolescence, and young adulthood and brain-based measures of stress vulnerability in 154 right-handed, nonimpaired young adults (M age = 23 years): 71 (30 males, 41 females) born at extremely low birth weight (ELBW; < 1,000 g) and 83 (35 males, 48 females) controls born at normal birth weight (NBW). Internalizing behavior problems increased from adolescence to young adulthood among ELBW individuals. ELBW adults exhibited greater relative right frontal electroencephalogram activity at rest and more concurrent internalizing behavior problems than NBW controls. Being born at ELBW may have subtle influences on brain-behavior relations even in survivors without major impairments and evidence of these influences may not emerge until young adulthood.

Adolescent females exposed to child maltreatment exhibit atypical EEG coherence and psychiatric impairment: Linking early adversity, the brain, and psychopathology

Although the relation between child maltreatment and psychiatric impairment is well documented and preliminary evidence has linked child maltreatment with aberrant cortical connectivity of the left hemisphere, no investigations have attempted to examine these relations in the same study. Here, we examined the links among early adversity, brain connectivity, and functional outcomes. We collected resting regional EEG intra- and interhemispheric alpha-band (7.5-12.5 Hz) coherence and measures of general psychiatric impairment from a cohort of 38 adolescent females exposed to child maltreatment (M age = 14.47) and 24 adolescent females not exposed to child maltreatment (M age = 14.00). Maltreated youths exhibited more left hemisphere EEG coherence than the control youths, suggesting a suboptimal organization of cortical networks. Maltreated participants also showed reduced frontal (anterior) interhemispheric coherence. These differences in brain circuitry remained statistically significant even after controlling for group differences in pubertal status and socioeconomic status. Measures of functional brain connectivity were associated with several subtypes of abuse and neglect. It was important that atypical left hemisphere EEG coherence mediated the effects of child maltreatment on levels of psychiatric impairment. The findings are discussed in the context of models linking early adversity to brain function and psychopathology.