Jeffrey M. Spielberg

The time course of activity in dorsolateral prefrontal cortex and anterior cingulate cortex during top-down attentional control

A network of brain regions has been implicated in top-down attentional control, including left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC). The present experiment evaluated predictions of the cascade-of-control model (Banich, 2009), which predicts that during attentionally-demanding tasks, LDLPFC imposes a top-down attentional set which precedes late-stage selection performed by dACC. Furthermore, the cascade-of-control model argues that dACC must increase its activity to compensate when top-down control by LDLPFC is poor. The present study tested these hypotheses using fMRI and dense-array ERP data collected from the same 80 participants in separate sessions. fMRI results guided ERP source modeling to characterize the time course of activity in LDLPFC and dACC. As predicted, dACC activity subsequent to LDLPFC activity distinguished congruent and incongruent conditions on the Stroop task. Furthermore, when LDLPFC activity was low, the level of dACC activity was related to performance outcome. These results demonstrate that dACC responds to attentional demand in a flexible manner that is dependent on the level of LDLPFC activity earlier in a trial. Overall, results were consistent with the temporal course of regional brain function proposed by the cascade-of-control model.

Trait approach and avoidance motivation: Lateralized neural activity associated with executive function

Motivation and executive function are both necessary for the completion of goal-directed behavior. Research investigating the manner in which these processes interact is beginning to emerge and has implicated middle frontal gyrus (MFG) as a site of interaction for relevant neural mechanisms. However, this research has focused on state motivation, and it has not examined functional lateralization. The present study examined the impact of trait levels of approach and avoidance motivation on neural processes associated with executive function. Functional magnetic resonance imaging was conducted while participants performed a color-word Stroop task. Analyses identified brain regions in which trait approach and avoidance motivation (measured by questionnaires) moderated activation associated with executive control. Approach was hypothesized to be associated with left-lateralized MFG activation, whereas avoidance was hypothesized to be associated with right-lateralized MFG activation. Results supported both hypotheses. Present findings implicate areas of middle frontal gyrus in top-down control to guide behavior in accordance with motivational goals.

Co-occurring anxiety influences patterns of brain activity in depression

Brain activation associated with anhedonic depression and co-occurring anxious arousal and anxious apprehension was measured by fMRI during performance of an emotion word Stroop task. Consistent with EEG findings, depression was associated with rightward frontal lateralization in the dorsolateral prefrontal cortex (DLPFC), but only when anxious arousal was elevated and anxious apprehension was low. Activity in the right inferior frontal gyrus (IFG) was also reduced for depression under the same conditions. In contrast, depression was associated with more activity in the anterior cingulate cortex (dorsal ACC and rostral ACC) and the bilateral amygdala. Results imply that depression, particularly when accompanied by anxious arousal, may result in a failure to implement top-down processing by appropriate brain regions (left DLPFC, right IFG) due to increased activation in regions associated with responding to emotionally salient information (right DLPFC, amygdala).

The role of testosterone and estradiol in brain volume changes across adolescence: a longitudinal structural MRI study.

It has been postulated that pubertal hormones may drive some neuroanatomical changes during adolescence, and may do so differently in girls and boys. Here, we use growth curve modeling to directly assess how sex hormones [testosterone (T) and estradiol (E2)] relate to changes in subcortical brain volumes utilizing a longitudinal design. 126 adolescents (63 girls), ages 10 to 14, were imaged and restudied ∼2 years later. We show, for the first time, that best‐fit growth models are distinctly different when using hormones as compared to a physical proxy of pubertal maturation (Tanner Stage) or age, to predict brain development. Like Tanner Stage, T and E2 predicted white matter and right amygdala growth across adolescence in both sexes, independent of age. Tanner Stage also explained decreases in both gray matter and caudate volumes, whereas E2 explained only gray matter decreases and T explained only caudate volume decreases. No pubertal measures were related to hippocampus development. Although specificity was seen, sex hormones had strikingly similar relationships with white matter, gray matter, right amygdala, and bilateral caudate volumes, with larger changes in brain volume seen at early pubertal maturation (as indexed by lower hormone levels), followed by less robust, or even reversals in growth, by late puberty. These novel longitudinal findings on the relationship between hormones and brain volume change represent crucial first steps toward understanding which aspects of puberty influence neurodevelopment. Hum Brain Mapp 35:5633–5645, 2014.

Issues in localization of brain function: The case of lateralized frontal cortex in cognition, emotion, and psychopathology.

The appeal of simple, sweeping portraits of large-scale brain mechanisms relevant to psychological phenomena competes with a rich, complex research base. As a prominent example, two views of frontal brain organization have emphasized dichotomous lateralization as a function of either emotional valence (positive/negative) or approach/avoidance motivation. Compelling findings support each. The literature has struggled to choose between them for three decades, without success. Both views are proving untenable as comprehensive models. Evidence of other frontal lateralizations, involving distinctions among dimensions of depression and anxiety, make a dichotomous view even more problematic. Recent evidence indicates that positive valence and approach motivation are associated with different areas in the left-hemisphere. Findings that appear contradictory at the level of frontal lobes as the units of analysis can be accommodated because hemodynamic and electromagnetic neuroimaging studies suggest considerable functional differentiation, in specialization and activation, of subregions of frontal cortex, including their connectivity to each other and to other regions. Such findings contribute to a more nuanced understanding of functional localization that accommodates aspects of multiple theoretical perspectives.

Exciting fear in adolescence: does pubertal development alter threat processing?

Highlights • Both risk-taking and threat-reactivity increase in adolescence.• We propose a model of adolescent affective development to help reconcile this paradox.• We posit that puberty may be related to a greater capacity to experience fears as thrills.• Testosterone predicts more threat-activation longitudinally in both amygdala and NAc.• Interactive effects of amygdala and NAc predict sensation seeking and anxiety.

A Longitudinal Study: Changes in Cortical Thickness and Surface Area during Pubertal Maturation

Sex hormones have been shown to contribute to the organization and function of the brain during puberty and adolescence. Moreover, it has been suggested that distinct hormone changes in girls versus boys may contribute to the emergence of sex differences in internalizing and externalizing behavior during adolescence. In the current longitudinal study, the influence of within-subject changes in puberty (physical and hormonal) on cortical thickness and surface area was examined across a 2-year span, while controlling for age. Greater increases in Tanner Stage predicted less superior frontal thinning and decreases in precuneus surface area in both sexes. Significant Tanner Stage and sex interactions were also seen, with less right superior temporal thinning in girls but not boys, as well as greater decreases in the right bank of the superior temporal sulcus surface area in boys compared to girls. In addition, within-subject changes in testosterone over the 2-year follow-up period were found to relate to decreases in middle superior frontal surface area in boys, but increases in surface area in girls. Lastly, larger increases in estradiol in girls predicted greater middle temporal lobe thinning. These results show that within-subject physical and hormonal markers of puberty relate to region and sex-specific changes in cortical development across adolescence.

Brain Network Disturbance Related to Posttraumatic Stress and Traumatic Brain Injury in Veterans

BACKGROUND Understanding the neural causes and consequences of posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) is a high research priority, given the high rates of associated disability and suicide. Despite remarkable progress in elucidating the brain mechanisms of PTSD and mTBI, a comprehensive understanding of these conditions at the level of brain networks has yet to be achieved. The present study sought to identify functional brain networks and topological properties (measures of network organization and function) related to current PTSD severity and mTBI. METHODS Graph theoretic tools were used to analyze resting-state functional magnetic resonance imaging data from 208 veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn, all of whom had experienced a traumatic event qualifying for PTSD criterion A. Analyses identified brain networks and topological network properties linked to current PTSD symptom severity, mTBI, and the interaction between PTSD and mTBI. RESULTS Two brain networks were identified in which weaker connectivity was linked to higher PTSD re-experiencing symptoms, one of which was present only in veterans with comorbid mTBI. Re-experiencing was also linked to worse functional segregation (necessary for specialized processing) and diminished influence of key regions on the network, including the hippocampus. CONCLUSIONS Findings of this study demonstrate that PTSD re-experiencing symptoms are linked to weakened connectivity in a network involved in providing contextual information. A similar relationship was found in a separate network typically engaged in the gating of working memory, but only in veterans with mTBI.

Pubertal testosterone influences threat-related amygdala–orbitofrontal cortex coupling

Growing evidence indicates that normative pubertal maturation is associated with increased threat reactivity, and this developmental shift has been implicated in the increased rates of adolescent affective disorders. However, the neural mechanisms involved in this pubertal increase in threat reactivity remain unknown. Research in adults indicates that testosterone transiently decreases amygdala-orbitofrontal cortex (OFC) coupling. Consequently, we hypothesized that increased pubertal testosterone disrupts amygdala-OFC coupling, which may contribute to developmental increases in threat reactivity in some adolescents. Hypotheses were tested in a longitudinal study by examining the impact of testosterone on functional connectivity. Findings were consistent with hypotheses and advance our understanding of normative pubertal changes in neural systems instantiating affect/motivation. Finally, potential novel insights into the neurodevelopmental pathways that may contribute to adolescent vulnerability to behavioral and emotional problems are discussed.

Depression and Anxious Apprehension Distinguish Frontocingulate Cortical Activity during Top-Down Attentional Control

A network consisting of left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC) has been implicated in top-down attentional control. Few studies have systematically investigated how this network is altered in psychopathology, despite evidence that depression and anxiety are associated with attentional control impairments. Functional MRI and dense-array event-related brain potential (ERP) data were collected in separate sessions from 100 participants during a color-word Stroop task. Functional MRI results guided ERP source modeling to characterize the time course of activity in LDLPFC (300-440 ms) and dACC (520-680 ms). At low levels of depression, LDLPFC activity was indirectly related to Stroop interference and only via dACC activity. In contrast, at high levels of depression, dACC did not play an intervening role, and increased LDLPFC activity was directly related to decreased Stroop interference. Specific to high levels of anxious apprehension, higher dACC activity was related to more Stroop interference. Results indicate that depression and anxious apprehension modulate temporally and functionally distinct aspects of the frontocingulate network involved in top-down attention control.