Age-Related Declines in Occipital GABA are Associated with Reduced Fluid Processing Ability.

RATIONALE AND OBJECTIVES: Healthy aging is associated with pervasive declines in cognitive, motor, and sensory functioning. There are, however, substantial individual differences in behavioral performance among older adults. Several lines of animal research link age-related reductions of gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter, to age-related cognitive, motor, and sensory decline. Our study used proton magnetic resonance spectroscopy (MRS) at 3T to explore whether occipital GABA declines with age in humans and whether individual differences in occipital GABA are linked to individual differences in fluid processing ability. MATERIALS AND METHODS: We used a MEGA-PRESS sequence that combines frequency spectral editing with a point-resolved spectroscopy sequence to quantify GABA. Spectra were obtained from a 30 × 30 × 25 mm voxel placed in the occipital cortex of 20 young adults (mean age 20.7 years) and 18 older adults (mean age 76.5 years). Participants also performed 11 fluid processing tasks outside the scanner, the results of which were z-scored and averaged to calculate a summary measure of fluid processing ability. Regression analysis was employed to determine the relationship between GABA concentrations in the occipital cortex and a summary measure of fluid processing ability. RESULTS: Occipital GABA was significantly lower in older participants compared to the younger participants. We also observed a significant positive relationship between occipital GABA and fluid processing ability. In fact, higher GABA was associated with better task performance in 10 of the 11 tasks. CONCLUSION: These findings suggest that GABA levels decline with age in humans and are associated with declines in fluid processing ability.

Buffering social influence: neural correlates of response inhibition predict driving safety in the presence of a peer.

Adolescence is a period characterized by increased sensitivity to social cues, as well as increased risk-taking in the presence of peers. For example, automobile crashes are the leading cause of death for adolescents, and driving with peers increases the risk of a fatal crash. Growing evidence points to an interaction between neural systems implicated in cognitive control and social and emotional context in predicting adolescent risk. We tested such a relationship in recently licensed teen drivers. Participants completed an fMRI session in which neural activity was measured during a response inhibition task, followed by a separate driving simulator session 1 week later. Participants drove alone and with a peer who was randomly assigned to express risk-promoting or risk-averse social norms. The experimentally manipulated social context during the simulated drive moderated the relationship between individual differences in neural activity in the hypothesized cognitive control network (right inferior frontal gyrus, BG) and risk-taking in the driving context a week later. Increased activity in the response inhibition network was not associated with risk-taking in the presence of a risky peer but was significantly predictive of safer driving in the presence of a cautious peer, above and beyond self-reported susceptibility to peer pressure. Individual differences in recruitment of the response inhibition network may allow those with stronger inhibitory control to override risky tendencies when in the presence of cautious peers. This relationship between social context and individual differences in brain function expands our understanding of neural systems involved in top-down cognitive control during adolescent development.

Neural responses to exclusion predict susceptibility to social influence.

PURPOSE: Social influence is prominent across the lifespan, but sensitivity to influence is especially high during adolescence and is often associated with increased risk taking. Such risk taking can have dire consequences. For example, in American adolescents, traffic-related crashes are leading causes of nonfatal injury and death. Neural measures may be especially useful in understanding the basic mechanisms of adolescents' vulnerability to peer influence. METHODS: We examined neural responses to social exclusion as potential predictors of risk taking in the presence of peers in recently licensed adolescent drivers. Risk taking was assessed in a driving simulator session occurring approximately 1 week after the neuroimaging session. RESULTS: Increased activity in neural systems associated with the distress of social exclusion and mentalizing during an exclusion episode predicted increased risk taking in the presence of a peer (controlling for solo risk behavior) during a driving simulator session outside the neuroimaging laboratory 1 week later. These neural measures predicted risky driving behavior above and beyond self-reports of susceptibility to peer pressure and distress during exclusion. CONCLUSIONS: These results address the neural bases of social influence and risk taking; contribute to our understanding of social and emotional function in the adolescent brain; and link neural activity in specific, hypothesized, regions to risk-relevant outcomes beyond the neuroimaging laboratory. Results of this investigation are discussed in terms of the mechanisms underlying risk taking in adolescents and the public health implications for adolescent driving.

Role of visual integration in gaze perception and emotional intelligence in schizophrenia.

BACKGROUND: Individuals with schizophrenia demonstrate a wide range of social cognitive deficits that significantly compromise functioning. Early visual processing is frequently disrupted in schizophrenia, and growing evidence suggests a role of perceptual dysfunctions in socioemotional functioning in the disorder. This study examined visual integration (the ability to effectively integrate individual, local visual features into a holistic representation), a target construct of basic perception identified by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative, and its relationship with eye- contact perception and emotional intelligence in schizophrenia. METHODS: Twenty-nine participants with schizophrenia (SCZ) and 23 healthy controls (HC) completed tasks measuring visual integration (Coherent Motion Task, Contour Integration Task), an eye-contact perception task, and a measure of emotional intelligence. RESULTS: SCZ participants showed compromised visual integration as suggested by poorer performance on the Contour Integration Task relative to HC. Visual integration was a significant predictor of eye-contact perception and emotional intelligence among SCZ. The amounts of variances in these 2 social cognitive areas accounted for by visual integration were comparable to and overlapped with those accounted for by the diagnosis of schizophrenia. CONCLUSIONS: Individuals with schizophrenia showed compromised visual integration, and this may play a significant role in the observed deficits in higher level processing of social information in the disorder.

Congruency sequence effects are driven by previous-trial congruency, not previous-trial response conflict.

Congruency effects in distracter interference tasks are often smaller after incongruent trials than after congruent trials. However, the sources of such congruency sequence effects (CSEs) are controversial. The conflict monitoring model of cognitive control links CSEs to the detection and resolution of response conflict. In contrast, competing theories attribute CSEs to attentional or affective processes that vary with previous-trial congruency (incongruent vs. congruent). The present study sought to distinguish between conflict monitoring and congruency-based accounts of CSEs. To this end, we determined whether CSEs are driven by previous-trial reaction time (RT)-a putative measure of response conflict-or by previous-trial congruency. In two experiments using a face-word Stroop task (n = 49), we found that current-trial congruency effects did not vary with previous-trial RT independent of previous-trial congruency. In contrast, current-trial congruency effects were influenced by previous-trial congruency independent of previous-trial RT. These findings appear more consistent with theories that attribute CSEs to non-conflict processes whose recruitment varies with previous-trial congruency than with theories that link CSEs to previous-trial response conflict.

Better living through transparency: improving the reproducibility of fMRI results through comprehensive methods reporting.

Recent studies suggest that a greater proportion of published scientific findings than expected cannot be replicated. The field of functional neuroimaging research is no exception to this trend, with estimates of false positive results ranging from 10 % to 40 %. While false positive results in neuroimaging studies stem from a variety of causes, incomplete methodological reporting is perhaps the most obvious: Most published reports of neuroimaging studies provide ambiguous or incomplete descriptions of their methods and results. If neuroimaging researchers do not report methods and results in adequate detail, independent scientists can neither check their work for errors nor accurately replicate their efforts. Thus, I argue that comprehensive methods reporting is essential for reproducible research. I recommend three strategies for improving transparency and reproducibility in neuroimaging research: improving natural language descriptions of research protocols; sharing source code for data collection and analysis; and sharing formal, machine-readable representations of methods and results. Last, I discuss the technological and cultural barriers to implementing these recommendations and suggest steps toward overcoming those barriers.

The congruency effect in the posterior medial frontal cortex is more consistent with time on task than with response conflict.

The posterior medial frontal cortex (pMFC) is thought to play a pivotal role in enabling the control of attention during periods of distraction. In line with this view, pMFC activity is ubiquitously greater in incongruent trials of response-interference (e.g., Stroop) tasks than in congruent trials. Nonetheless, the process underlying this congruency effect remains highly controversial. We therefore sought to distinguish between two competing accounts of the congruency effect. The conflict monitoring account posits the effect indexes a process that detects conflict between competing response alternatives, which is indexed by trial-specific reaction time (RT). The time on task account posits the effect indexes a process whose recruitment increases with time on task independent of response conflict (e.g., sustained attention, arousal, effort, etc.). To distinguish between these accounts, we used functional MRI to record brain activity in twenty-four healthy adults while they performed two tasks: a response-interference task and a simple RT task with only one possible response. We reasoned that demands on a process that detects response conflict should increase with RT in the response-interference task but not in the simple RT task. In contrast, demands on a process whose recruitment increases with time on task independent of response conflict should increase with RT in both tasks. Trial-by-trial analyses revealed that pMFC activity increased with RT in both tasks. Moreover, pMFC activity increased with RT in the simple RT task enough to fully account for the congruency effect in the response-interference task. These findings appear more consistent with the time on task account of the congruency effect than with the conflict monitoring account.

Prefrontal cholinergic mechanisms instigating shifts from monitoring for cues to cue-guided performance: converging electrochemical and fMRI evidence from rats and humans.

We previously reported involvement of right prefrontal cholinergic activity in veridical signal detection. Here, we first recorded real-time acetylcholine release in prefrontal cortex (PFC) during specific trial sequences in rats performing a task requiring signal detection as well as rejection of nonsignal events. Cholinergic release events recorded with subsecond resolution ("transients") were observed only during signal-hit trials, not during signal-miss trials or nonsignal events. Moreover, cholinergic transients were not observed for consecutive hits; instead they were limited to signal-hit trials that were preceded by factual or perceived nonsignal events ("incongruent hits"). This finding suggests that these transients mediate shifts from a state of perceptual attention, or monitoring for cues, to cue-evoked activation of response rules and the generation of a cue-directed response. Next, to determine the translational significance of the cognitive operations supporting incongruent hits we used a version of the task previously validated for use in research in humans and blood oxygenation level-dependent (BOLD)-functional magnetic resonance imaging. Incongruent hits activated a region in the right rostral PFC (Brodmann area 10). Furthermore, greater prefrontal activation was correlated with faster response times for incongruent hits. Finally, we measured tissue oxygen in rats, as a proxy for BOLD, and found prefrontal increases in oxygen levels solely during incongruent hits. These cross-species studies link a cholinergic response to a prefrontal BOLD activation and indicate that these interrelated mechanisms mediate the integration of external cues with internal representations to initiate and guide behavior.

Neural congruency effects in the multi-source interference task vanish in healthy youth after controlling for conditional differences in mean RT.

According to the conflict monitoring model of cognitive control, reaction time (RT) in distracter interference tasks (e.g., the Stroop task) is a more precise index of response conflict than stimulus congruency (incongruent vs. congruent). The model therefore predicts that RT should be a reliable predictor of activity in regions of the posterior medial frontal cortex (pMFC) that are posited to detect response conflict. In particular, pMFC activity should be (a) greater in slow-RT than in fast-RT trials within a given task condition (e.g., congruent) and (b) equivalent in RT-matched trials from different conditions (i.e., congruent and incongruent trials). Both of these effects have been observed in functional magnetic resonance imaging (MRI) studies of adults. However, neither effect was observed in a recent study of healthy youth, suggesting that (a) the model does not accurately describe the relationship between RT and pMFC activity in this population or (b) the recent study was characterized by high variability due to a relatively small sample size. To distinguish between these possibilities, we asked a relatively large group of healthy youth (n = 28) to perform a distracter interference task - the multi-source interference task (MSIT) - while we recorded their brain activity with functional MRI. In this relatively large sample, both of the model's predictions were confirmed. We conclude that the model accurately describes the relationship between pMFC activity and RT in healthy youth, but that additional research is needed to determine whether processes unrelated to response conflict contribute to this relationship.

Optimizing the order of operations for movement scrubbing: Comment on Power et al.

A recent study by Power and colleagues shows that BOLD artifacts induced by head movement can substantially alter patterns of resting-state functional connectivity and proposes a novel procedure for reducing these artifacts by deleting (or "scrubbing") movement-contaminated volumes. The authors acknowledge that this work is descriptive and not prescriptive, and note that future studies may refine the proposed scrubbing method. Nevertheless, it is worth pointing out that this method can be improved substantially by a single transposition in the order of operations. Temporal filtering is known to introduce ringing artifacts that emanate from sharp transitions in signal intensity. The method proposed in the target article applies temporal filtering before deleting contaminated volumes-in effect, spreading movement-related artifacts backwards and forwards in time, but deleting only the originally contaminated data. Using simulated data, we show that deleting and replacing contaminated volumes before temporal filtering removes a greater proportion of artifactual signal while retaining a greater proportion of the original data.

On the plurality of (methodological) worlds: estimating the analytic flexibility of FMRI experiments.

How likely are published findings in the functional neuroimaging literature to be false? According to a recent mathematical model, the potential for false positives increases with the flexibility of analysis methods. Functional MRI (fMRI) experiments can be analyzed using a large number of commonly used tools, with little consensus on how, when, or whether to apply each one. This situation may lead to substantial variability in analysis outcomes. Thus, the present study sought to estimate the flexibility of neuroimaging analysis by submitting a single event-related fMRI experiment to a large number of unique analysis procedures. Ten analysis steps for which multiple strategies appear in the literature were identified, and two to four strategies were enumerated for each step. Considering all possible combinations of these strategies yielded 6,912 unique analysis pipelines. Activation maps from each pipeline were corrected for multiple comparisons using five thresholding approaches, yielding 34,560 significance maps. While some outcomes were relatively consistent across pipelines, others showed substantial methods-related variability in activation strength, location, and extent. Some analysis decisions contributed to this variability more than others, and different decisions were associated with distinct patterns of variability across the brain. Qualitative outcomes also varied with analysis parameters: many contrasts yielded significant activation under some pipelines but not others. Altogether, these results reveal considerable flexibility in the analysis of fMRI experiments. This observation, when combined with mathematical simulations linking analytic flexibility with elevated false positive rates, suggests that false positive results may be more prevalent than expected in the literature. This risk of inflated false positive rates may be mitigated by constraining the flexibility of analytic choices or by abstaining from selective analysis reporting.

Neural responses to infants linked with behavioral interactions and testosterone in fathers.

Few fMRI studies have investigated the brain-behavioral basis of parenting in human fathers. Ten fathers were videotaped and gave salivary testosterone samples while interacting with their 2-4 months old infants, and viewed video clips of their own infant and an unfamiliar age-, ethnicity- and sex-matched other infant during an fMRI protocol. Infant stimuli activated a network of prefrontal and subcortical brain regions. Furthermore, a subset of these regions activated significantly more to own (OWN) than other (OTHER) infants. Finally, neural responses to OWN versus OTHER were linked with paternal sensitivity, paternal reciprocity, and testosterone. In sum, our results provide a novel perspective on the links between brain, behavior, and hormones in fathers.

The secret lives of experiments: methods reporting in the fMRI literature.

Replication of research findings is critical to the progress of scientific understanding. Accordingly, most scientific journals require authors to report experimental procedures in sufficient detail for independent researchers to replicate their work. To what extent do research reports in the functional neuroimaging literature live up to this standard? The present study evaluated methods reporting and methodological choices across 241 recent fMRI articles. Many studies did not report critical methodological details with regard to experimental design, data acquisition, and analysis. Further, many studies were underpowered to detect any but the largest statistical effects. Finally, data collection and analysis methods were highly flexible across studies, with nearly as many unique analysis pipelines as there were studies in the sample. Because the rate of false positive results is thought to increase with the flexibility of experimental designs, the field of functional neuroimaging may be particularly vulnerable to false positives. In sum, the present study documented significant gaps in methods reporting among fMRI studies. Improved methodological descriptions in research reports would yield significant benefits for the field.

Neural broadening or neural attenuation? Investigating age-related dedifferentiation in the face network in a large lifespan sample.

Previous studies have found that cortical responses to different stimuli become less distinctive as people get older. This age-related dedifferentiation may reflect the broadening of the tuning curves of category-selective neurons (broadening hypothesis) or it may be due to decreased activation of category-selective neurons (attenuation hypothesis). In this study, we evaluated these hypotheses in the context of the face-selective neural network. Over 300 participants, ranging in age from 20 to 89 years, viewed images of faces, houses, and control stimuli in a functional magnetic resonance imaging session. Regions within the core face network and extended face network were identified in individual subjects. Activation in many of these regions became significantly less face-selective with age, confirming previous reports of age-related dedifferentiation. Consistent with the broadening hypothesis, this dedifferentiation in the fusiform face area (FFA) was driven by increased activation to houses. In contrast, dedifferentiation in the extended face network was driven by decreased activation to faces, consistent with the attenuation hypothesis. These results suggest that age-related dedifferentiation reflects distinct processes in different brain areas. More specifically, dedifferentiation in FFA activity may be due to broadening of the tuning curves for face-selective neurons, while dedifferentiation in the extended face network reflects reduced face- or emotion-selective activity.

Removing the effect of response time on brain activity reveals developmental differences in conflict processing in the posterior medial prefrontal cortex.

In functional magnetic resonance imaging (fMRI) studies, researchers often attempt to ensure that group differences in brain activity are not confounded with group differences in mean reaction time (RT). However, even when groups are matched for performance, they may differ in terms of the RT-BOLD relationship: the degree to which brain activity varies with RT on a trial-by-trial basis. Group activation differences might therefore be influenced by group differences in the relationship between brain activity and time on task. Here, we investigated whether correcting for this potential confound alters group differences in brain activity. Specifically, we reanalyzed data from a functional MRI study of response conflict in children and adults, in which conventional analyses indicated that conflict-related activity did not differ between groups. We found that the RT-BOLD relationship was weaker in children than in adults. Consequently, after removing the effect of RT on brain activity, children exhibited greater conflict-related activity than adults in both the posterior medial prefrontal cortex and the right dorsolateral prefrontal cortex. These results identify the RT-BOLD relationship as an important potential confound in fMRI studies of group differences. They also suggest that the magnitude of the RT-BOLD relationship may be a useful biomarker of brain maturity.

The influence of response conflict on voluntary task switching: a novel test of the conflict monitoring model.

The conflict monitoring model of cognitive control posits that response conflict triggers a top-down enhancement of a task's representation in working memory. In the present study, we conducted a novel test of the conflict monitoring model using a voluntary task switching paradigm. We predicted that a task's representation would be enhanced following events associated with high response conflict (i.e., incongruent trials and incorrect responses), leading participants to voluntarily choose to repeat that task more often after these events than after events associated with low response conflict (i.e., congruent trials and correct responses). In two experiments, performance following incongruent trials was consistent with the conflict monitoring model. However, performance following incorrect trials did not fit with the model's predictions. These findings provide novel support for the conflict monitoring model while revealing new effects of incorrect trials that the model cannot explain.

Age differences in neural distinctiveness revealed by multi-voxel pattern analysis.

Current theories of cognitive aging argue that neural representations become less distinctive in old age, a phenomenon known as dedifferentiation. The present study used multi-voxel pattern analysis (MVPA) to measure age differences in the distinctiveness of distributed patterns of neural activation evoked by different categories of visual images. We found that neural activation patterns within the ventral visual cortex were less distinctive among older adults. Further, we report that age differences in neural distinctiveness extend beyond the ventral visual cortex: older adults also showed decreased distinctiveness in early visual cortex, inferior parietal cortex, and medial and lateral prefrontal cortex. Neural distinctiveness scores in early and late visual areas were highly correlated, suggesting shared mechanisms of age-related decline. Finally, we investigated whether older adults can compensate for altered processing in visual cortex by encoding stimulus information across larger numbers of voxels within the visual cortex or in regions outside visual cortex. We found no evidence that older adults can increase the distinctiveness of distributed activation patterns, either within or beyond the visual cortex. Our results have important implications for theories of cognitive aging and highlight the value of MVPA to the study of neural coding in the aging brain.

Variations of response time in a selective attention task are linked to variations of functional connectivity in the attentional network.

Although variations of response time (RT) within a particular experimental condition are typically ignored, they may sometimes reflect meaningful changes in the efficiency of cognitive and neural processes. In the present study, we investigated whether trial-by-trial variations of response time (RT) in a cross-modal selective attention task were associated with variations of functional connectivity between brain regions that are thought to underlie attention. Sixteen healthy young adults performed an audiovisual selective attention task, which involved attending to a relevant visual letter while ignoring an irrelevant auditory letter, as we recorded their brain activity using functional magnetic resonance imaging (fMRI). In line with predictions, variations of RT were associated with variations of functional connectivity between the anterior cingulate cortex and various other brain regions that are posited to underlie attentional control, such as the right dorsolateral prefrontal cortex and bilateral regions of the posterior parietal cortex. They were also linked to variations of functional connectivity between anatomically early and anatomically late regions of the relevant-modality visual cortex whose communication is thought to be modulated by attentional control processes. By revealing that variations of RT in a selective attention task are linked to variations of functional connectivity in the attentional network, the present findings suggest that variations of attention may contribute to trial-by-trial fluctuations of behavioral performance.

Age-related neural dedifferentiation in the motor system.

Recent neuroimaging studies using multi-voxel pattern analysis (MVPA) show that distributed patterns of brain activation elicited by different visual stimuli are less distinctive in older adults than in young adults. However, less is known about the effects of aging on the neural representation of movement. The present study used MVPA to compare the distinctiveness of motor representations in young and older adults. We also investigated the contributions of brain structure to age differences in the distinctiveness of motor representations. We found that neural distinctiveness was reduced in older adults throughout the motor control network. Although aging was also associated with decreased gray matter volume in these regions, age differences in motor distinctiveness remained significant after controlling for gray matter volume. Our results suggest that age-related neural dedifferentiation is not restricted to sensory perception and is instead a more general feature of the aging brain.