Brain Patterns May Predict Psychiatric Problems in Adulthood

Batya Swift Yasgur, MA, LSW

July 31, 2017

After age 30 years, underdevelopment of the brain network that controls inhibition is tied to self-reported psychological problems, including depression and anxiety, new research shows.

Investigators at the University of Toronto, Canada, found that among younger individuals, a neural signature of superior inhibition emerged in both static and dynamic connectivity analyses.

However, in individuals older than 30 years, superior inhibition was more apparent in static connectivity patterns linked to increased reward or cognitive profile. In that group, those who did not show a strong later adulthood pattern of specialized brain mechanisms for dealing with novel social challenges were more likely to report anxiety, depression, and difficulties with attention and aggression.

"We wanted to identify neural markers as well as age windows when one can actually detect subtle signs of impairment that may predict subsequent psychopathology," Dr Petrican told Medscape Medical News.

"Our finding that may have clinical relevance is dealing with so-called late-inhibition profile, a delayed development of more specialized brain mechanisms for dealing with complex social and cognitive situations, and to look for brain change as well as associated cognitive problems that may be shared across psychopathologies, such as depression and anxiety," she said.

The study was published online July 17 in the Journal of Neuroscience.

Fine Tuning the Brain

"The brain's functional architecture changes across different contexts and life stages," the authors write. An increasing body of research points to the importance of the brain's intrinsic functional architecture for "optimal adaptation across the lifespan."

The brain's functional architecture evolves and changes longitudinally as a "reflection of development and accumulated behavioral changes," as well as cross-sectionally as "a function of the various demands faced by an individual."

Characterizing these changes is valuable in advancing understanding of the "distinct mechanisms through which a specific predisposition impacts behavior in distinct circumstances and life changes," the authors note.

"We were interested both in how cognition can regulate emotional reaction and how they can work symbiotically," Dr Petrican said.

"There has been a great deal of work on why it is important to control emotions — specifically, negative emotions, but even positive emotions — and oftentimes, people who are good at controlling emotions also do well on tasks that tap cognitive/executive control," she added.

A core feature of this strength is the "ability to attend to relevant information in the present moment and tune out irrelevant information." But "high cognitive control" used for memory tasks may not be the same as that used when "controlling emotions in social situations," she explained.

Cognitive control "moderately correlates with fluid IQ, which helps people respond to novel situations and does not necessarily draw on previous knowledge," she said.

"We wanted to see what brain mechanisms enable people with high cognitive control to respond to mental challenges — memory — vs responding to stimuli that evoke a sense of reward. Do individuals high on control recruit different mechanisms on tasks such as memory, vs emotionally relevant information?"

A second component of the research was to observe whether cognitive control underwent changes over time. The researchers chose to study individuals who were in their twenties and to mid thirties because prior evidence suggests that neural substrates of neural control continue to develop during this period.

"Although most existing investigations assume that the functional neural architecture is stable across time, there is accumulating evidence that the brain demonstrates significant temporal fluctuations, not only in activity but also in connectivity patterns," the authors write.

"It is a matter of fine-tuning," Dr Petrican said. "These brain mechanisms start to respond in a more differentiated, specialized, refined manner at that age."

Predicting Poorer Function

To investigate these situational effects on the neural architecture of inhibition, the researchers engaged the study participants in two tasks that involve inhibition but are nevertheless "likely to illuminate distinguishable mechanisms."

The first was a cognitive task involving a working memory assignment that required continual updating of information, a context demanding inhibitory control.

The second utilized social and financial rewards derived from a theory-of-mind and a decision-making task. In total, the researchers measured working memory, social cognition, and incentive processing.

Participants (n = 359) were drawn from the Human Connectome Project (HCP) and had already completed behavioral and fMRI assessment. Of the sample, 174 were men and 185 were women. The majority (n = 301) were right-handed. Participants with a mental health disorder and structural abnormalities, as revealed by MRI structural scans, were excluded.

To evaluate inhibitory control, the National Institutes of Health Flanker Inhibitory Control and Attention test, completed on day 2 of the participants' HCP schedule, measured the ability of the participants to focus on a given target stimulus while inhibiting attention to stimuli flanking it.

To measure psychological functioning, participants completed the Achenbach Adult Self-Report (ASR) for persons aged 18 to 59 uears on the day of their session 1 fMRI appointment. The ASR consists of several subscales designed to elicit reactions of participants to a problem: the Anxious/Depressed, the Withdrawn, the Somatic Complaints, the Thought Problem, the Attention, the Aggressive Behavior, the Rule Breaking, and the Intrusive Behavior Problem Subscales.

Functional MRI tests focused on working memory and social cognition (theory of mind). Participants also completed an incentive processing test, in which they were required to guess the number on a mystery card in order to win or lose money.

The researchers found that superior inhibitory control on the flanker task predicted faster responses on both high- and low-reward value trials (Spearman's rhos of 0.20 and 0.16 respectively; P < .005 for both) and in both working memory conditions (Spearman's rhos of 0.19 and 0.24; P < .001 for both).

"The whole-brain connectivity measures documented similarities and differences in the dynamic and stable neural architecture of inhibition across two task contexts, varying in cognitive load and reward value," the authors write.

From a dynamic point of view, "a context-free signature emerged as stronger segregation of internal cognition (DMN, or default mode) and environmentally driven control (salience [SAL], cingulo-opercular [CON]) systems," they report.

Across both contexts, younger individuals who had superior inhibition demonstrated greater temporal cohesion in the DMN, the CON, and the SAL. As a function of increasing inhibitory control over time, the nodes within each of these three networks were increasingly more likely to interact with one another rather than with nodes from other networks.

When the researchers conducted stable connectivity analyses, they found context-free (greater DMN segregation) signatures of inhibition. They also found context-specific signatures of inhibition (greater frontoparietal [FPC] segregation for higher cognitive load; greater attentional and environmentally driven control system segregation for greater reward value).

Superior inhibition in more mature adulthood "was typified by reduced segregation in the DMN, with increasing reward value and increased ventral attention." However, there was reduced CON and subcortical system segregation with increasing cognitive load.

The researchers utilized a two-level hierarchical linear model in which standardized scores on the eight ASR subscales were nested within individuals. Several other variables, such as handedness and years of education, were included in the analysis. However, the "robust standard error results" revealed a significant two-way interaction only between age and scores on the late inhibition connectivity profile.

On further statistical analysis, they found that the association between scores on the late inhibition profile and psychological problems started becoming significant (P < .05) for individuals older than 30 years of age. (Those participants were >0.4232 standard deviations older than the average age of the sample.) At that region-of-significance boundary, the association between scores on the late inhibition profile and psychological problems was negative (b = -0.0657, SD = 0.0334, t = -1.972).

The effect of this interaction "can be interpreted as evidence that expression of the late inhibition-linked neural profile after the age of 30 shields against psychological problems (ie, adults over 30 who express this profile more strongly show fewer psychological problems than those over 30 who show a weaker expression of this profile)," the authors write.

Failure to evidence this neural profile after the age of 30 "predicted poorer life functioning."

Boosting Cognitive Control

"Our results suggest that distinguishable neural mechanisms underlie individual differences in cognitive control during different young adult stages and across tasks, thereby underscoring the importance of better understanding the interplay among dispositional, developmental and contextual factors in shaping adaptive versus maladaptive patterns of thought and behavior," the authors conclude.

Dr Petrican notes that she does not know of any studies that suggest ways of enhancing the brain mechanisms associated with superior cognitive control. "It is an open question, so I cannot offer recommendations, I can only speculate."

She suggested, "perhaps exposure to a more diverse range of social situations may help with developing more specialized neural mechanisms for dealing more efficiently with those circumstances."

Additionally, "exposure to mental challenges and more years of education can also provide benefit in increasing cognitive control by leading to more specialized brain mechanisms for dealing with cognitive challenges."

This work was supported by the Canadian Institutes of Health Research and the Canada Research Chairs program. The authors have disclosed no relevant financial relationships.

J Neurosci. Published online July 17, 2017. Abstract

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