Adolf Pfefferbaum

Objective
Substantial brain development occurs during adolescence providing the foundation for functional advancement from stimulus-bound “bottom-up” to more mature executive-driven “top-down” processing strategies. The objective was to assess development of EEG markers of these strategies and their role in both preparatory attention (contingent negative variation, CNV) and response monitoring (Error Related Negativity, ERN, and Correct Related Negativity, CRN).
Methods
CNV, ERN and CRN were assessed in 38 adolescents (18 girls), age 11–18 years, using a variation of a letter discrimination task.
Results
Accuracy increased with age and developmental stage. Younger adolescents used a posterior attention network involved in inhibiting irrelevant information. Activity in this juvenile network, as indexed by a posteriorly-biased CNV and CRN decreased with age and advancing pubertal development. Although enhanced frontal CNV, known to be predictive of accuracy in adults, was not detected even in the older adolescents, top-down medial frontal response monitoring processes (ERN) showed evidence of development within the age-range studied.
Conclusions
The data revealed a dissociation of developmental progress, marked by relatively delayed onset of frontal preparatory attention relative to error monitoring.
Significance
This dissociation may render adolescents vulnerable to excessive risk-taking and disinhibited behavior imposed by asynchronous development of component cognitive control processes.

Personal attitude toward ambiguity contributes to individual differences in decision making in uncertain situations. Operationally, these attitudes reflect the various coping strategies elected to overcome the limited information. A key brain region involved in cognitive control for performance adjustments is the dorsal anterior cingulate cortex (dACC). To test how dACC functional network connectivity would be modulated by uncertainty and differ between individuals, 24 healthy participants underwent functional MRI in 3 sequential runs: 1 resting-state and 2 decision-making task runs. Individuals with lower nonplanning impulsiveness made greater use of a Pass option and avoided uncertain ambiguous situations. Seed-based functional connectivity analysis during the task runs revealed that stronger activation synchrony between the left dACC and the right anterior insula correlated with greater use of a Pass response option. During the resting-state, stronger resting-state functional connectivity between the left dACC and the ventral striatum predicted the adoption of Pass as a behavioral strategy and correlated with stronger task-activated synchrony between the dACC and the right anterior insula. Our findings indicate that that the synchrony between the dACC and insula-striatal circuitry was greater in individuals with low compared with high nonplanning impulsiveness and contributed to adopting Pass as a useful behavioral strategy.

Neuroimaging has consistently documented reductions in the brain tissue of alcoholics. Inability to control comorbidity, environmental insult, and nutritional deficiency, however, confound the ability to assess whether ethanol itself is neurotoxic. Here we report monkey oral ethanol self-administration combined with MR imaging to characterize brain changes over 15 months in 18 well-nourished rhesus macaques. Significant brain volume shrinkage occurred in the cerebral cortices of monkeys drinking [greater than or equal to] 3 g/kg ethanol/day (12 alcoholic drinks) at 6 months, and this persisted throughout the period of continuous access to ethanol. Correlation analyses revealed a cerebral cortical volumetric loss of ~0.11% of the intracranial vault for each daily drink (0.25 g/kg), and selective vulnerability of cortical and non-cortical brain regions. These results demonstrate for the first time a direct relation between oral ethanol intake and measures of decreased brain gray matter volume in vivo in primates. Notably, greater volume shrinkage occurred in monkeys with younger drinking onset that ultimately became heavier drinkers than monkeys with older drinking onset. The pattern of volumetric changes observed in nonhuman primates following 15 months of drinking suggests that cerebral cortical gray matter changes are the first macroscopic manifestation of chronic ethanol exposure in the brain.

SRI Authors: Adolf Pfefferbaum, Jaehyeon Park

SRI Authors: Adolf Pfefferbaum

We present a novel approach – DTI-based fiber tract-driven topographical mapping (FTTM) – to map and measure the influence of age on the integrity of interhemispheric fibers and challenge their selective functions with measures of interhemispheric integration of lateralized information. This approach enabled identification of spatially specific topographical maps of scalar diffusion measures and their relation to measures of visuomotor performance. Relative to younger adults, older adults showed lower fiber integrity indices in anterior than posterior callosal fibers. FTTM analysis identified a dissociation in the microstructural-function associates between age groups: in younger adults, genu fiber integrity correlated with interhemispheric transfer time, whereas in older adults, body fiber integrity was correlated with interhemispheric transfer time with topographical specificity along left-lateralized callosal fiber trajectories. Neural co-activation from redundant targets was evidenced by fMRI-derived bilateral extrastriate cortex activation in both groups, and a group difference emerged for a pontine activation cluster that was differently modulated by response hand in older than younger adults. Bilateral processing advantages in older but not younger adults further correlated with fiber integrity in transverse pontine fibers that branch into the right cerebellar cortex, thereby supporting a role for the pons in interhemispheric facilitation. In conclusion, in the face of compromised anterior callosal fibers, older adults appear to use alternative pathways to accomplish visuomotor interhemispheric information transfer and integration for lateralized processing. This shift from youthful associations may indicate recruitment of compensatory mechanisms involving medial corpus callosum fibers and subcortical pathways.