Cognitive control (CC) involves a top–down mechanism to flexibly respond to complex stimuli and is impaired in schizophrenia.

This study investigated the impact of increasing complexity of CC processing in 140 subjects with psychosis and 39 healthy adults, with assessments of behavioral performance, neural regions of interest and symptom severity.

The lowest level of CC (Stroop task) was impaired in all patients; the intermediate level of CC (Faces task) with explicit emotional information was most impaired in patients with first episode psychosis. Patients showed activation of distinct neural CC and reward networks, but iterative learning based on the higher-order of CC during the trust game, was most impaired in chronic schizophrenia. Subjects with first episode psychosis, and patients with lower symptom load, demonstrate flexibility of the CC network to facilitate learning, which appeared compromised in the more chronic stages of schizophrenia.

These data suggest optimal windows for opportunities to introduce therapeutic interventions to improve CC.

As part of the Research Domain Criteria (RDoC) initiative, the NIMH seeks to improve experimental measures of cognitive and positive valence systems for use in intervention research. However, many RDoC tasks have not been psychometrically evaluated as a battery of measures. Our aim was to examine the factor structure of 7 such tasks chosen for their relevance to schizophrenia and other forms of serious mental illness. These include the n-back, Sternberg, and self-ordered pointing tasks (measures of the RDoC cognitive systems working memory construct); flanker and continuous performance tasks (measures of the RDoC cognitive systems cognitive control construct); and probabilistic learning and effort expenditure for reward tasks (measures of reward learning and reward valuation constructs).

The sample comprised 286 cognitively healthy participants who completed novel versions of all 7 tasks via an online recruitment platform, Prolific, in the summer of 2022. The mean age of participants was 38.6 years (SD = 14.5, range 18-74), 52% identified as female, and stratified recruitment ensured an ethnoracially diverse sample. Excluding time for instructions and practice, each task lasted approximately 6 minutes. Task order was randomized. We estimated optimal scores from each task including signal detection d-prime measures for the n-back, Sternberg, and continuous performance task, mean accuracy for the flanker task, win-stay to win-shift ratio for the probabilistic learning task, and trials completed for the effort expenditure for reward task. We used parallel analysis and a scree plot to determine the number of latent factors measured by the 7 task scores. Exploratory factor analysis with oblimin (oblique) rotation was used to examine the factor loading matrix.

The scree plot and parallel analyses of the 7 task scores suggested three primary factors. The flanker and continuous performance task both strongly loaded onto the first factor, suggesting that these measures are strong indicators of cognitive control. The n-back, Sternberg, and self-ordered pointing tasks strongly loaded onto the second factor, suggesting that these measures are strong indicators of working memory. The probabilistic learning task solely loaded onto the third factor, suggesting that it is an independent indicator of reinforcement learning. Finally, the effort expenditure for reward task modestly loaded onto the second but not the first and third factors, suggesting that effort is most strongly related to working memory.

Our aim was to examine the factor structure of 7 RDoC tasks. Results support the RDoC suggestion of independent cognitive control, working memory, and reinforcement learning. However, effort is a factorially complex construct that is not uniquely or even most strongly related to positive valance. Thus, there is reason to believe that the use of at least 6 of these tasks are appropriate measures of constructs such as working memory, reinforcement learning and cognitive control.

Cognitive deficits in first-episode psychosis (FEP) are well documented, particularly aspects of cognitive control, which is one of the primary hypothesized functions of the frontoparietal network (FPN). The clinical features of psychotic disorders are known to differ between men and women, but little work has systematically studied neurobiological differences between the sexes, particularly in FEP. The current study aimed to examine sexual dimorphisms in structural integrity of the frontoparietal network (FPN) and its role in cognitive control in FEP.

A total of 111 FEP patients (68 male, 43 female) and 55 healthy control participants (35 male, 20 female) from the Human Connectome Project for Early Psychosis underwent T1-weighted magnetic resonance imaging and neuropsychological testing were included in the study. Regions of interest (ROIs) included: left and right superior frontal gyrus, left and right middle frontal gyrus, left inferior frontal gyrus, left and right inferior parietal gyrus, right caudate and left thalamus. Using high-dimensional brain mapping procedures, surface shape of the caudate and thalamus was characterized using Large Deformation Diffeomorphic Metric Mapping, and cortical thickness of frontal and parietal regions was estimated using the FreeSurfer toolkit. Cognitive control was assessed using the Fluid Cognition Composite score from the NIH Toolbox Cognition Battery. Multivariate ANOVA models tested group differences, separated by sex, in cortical thickness ROIs, in addition to a whole-brain vertex-wise analysis. Vertex-wise statistical surface t-maps evaluated differences in subcortical surface shape, and Pearson correlations tested relationships between brain regions and Fluid Cognition performance.

Results of deep brain region comparisons between schizophrenia males (SCZM) and schizophrenia females (SCZF) groups revealed significant outward deformation at the tail of the right caudate and significant inward deformation along the dorsal aspects of the right caudate. Additionally, significant inward deformation in multiple nuclei of the left thalamus were revealed. Significant negative relationships between Fluid Cognition and the left superior/middle frontal gyrus (r = -0.24, p = 0.05) in the male FEP group were observed. Additionally, significant positive relationships between Fluid Cognition and left inferior frontal gyrus (r = 0.35, p = 0.02) and left inferior parietal gyrus (r = 0.35, p = 0.02) in the female FEP group were found.

Overall, findings revealed significant brain differences of the FPN in deep-brain structures only, including abnormal caudal and thalamic shape, in male FEP compared to female FEP, providing evidence of the importance to examine sex differences in deep-brain regions at the first episode. Differential brain relationships with cognitive control also highlight sex-specific presentations that may aid in clinical management and further characterization of the illness in early stages.

Pain is a mechanism for attention disruption due, in part, to a shared reliance on the prefrontal cortex (PFC). Amongst older adults, the experience of pain is both prevalent and functionally impactful. Dual-task walking (DTW) paradigms are a useful means of assessing the impact of pain on attentional control and known to be sensitive to changes in the cortical hemodynamic response within the PFC. To date, however, few studies have utilized such paradigms to examine the impact of self-reported pain on attentional control via assessment of cognitive, gait and neuroimaging outcomes. Examining these associations would facilitate a better understanding of the ways in which pain may negatively impact neural efficiency, thereby increasing risk of adverse functional outcomes, in healthy aging.

Study participants (N= 408; mean age = 76 ± 6.5ys; % female =55.4) were grouped into pain (n= 266) and no pain (n= 142) groups based upon their responses on the MOS-PSS and MOS-PES. These questionnaires were also used to assess self-reported levels of pain severity and interference amongst individuals with reported pain. Functional near-infrared spectroscopy was used to measure intraindividual variability (IIV) of the cortical hemodynamic response within the PFC during a DTW paradigm which consisted of Single-Task-Walk (STW), Cognitive Interference (Alpha), and Dual-Task-Walk (DTW) conditions. Participants walked along an electronic walkway and quantitative gait data were extracted in order to assess IIV in stride length during STW and DTW conditions. The rate of correct letter generation was used as a measure of cognitive accuracy during Alpha and DTW conditions. Linear mixed effects models (LMEMs) were used to examine the effects of perceived pain on neural and behavioral responses as well as on the change in these outcomes form single- to dual-task conditions. Stratified LMEMs were used to examine whether these associations differed by gender.

LMEMs revealed that perceived pain presence was associated with reduced IIV in PFC oxygenation (estimate = -0.032, p = 0.037) and reduced IIV in stride length in the DTW condition (estimate = -1.180, p = 0.006). High pain severity was associated with a greater increase in stride length IIV from STW to DTW (estimate = -1.301, p = 0.039). Stratified LMEMs revealed that the association between pain and neural IIV was significant in only males (estimate = -0.049, p = 0.037), while the association between pain and gait IIV was significant in only females (estimate = -1.712, p = .008).

Study results suggest that self-reported pain over one month is associated with differential patterns of neural and behavioral responding amongst healthy, community-dwelling older adults. Furthermore, it appears that males are more susceptible to the neural effects of pain, while females are more susceptible to the behavioral effects under attention-demanding conditions. In this population, these patterns may reflect a tendency towards inefficient neural and behavioral modifications in response to perceived pain. These findings highlight the need for clinical use of routine pain assessments and, when appropriate, the implementation of timely and effective pain treatments in aging.

Because cognitive resources are limited, models of cognitive control predict that additional control is engaged only if it improves task performance. Increased response caution, which occurs when individuals increase the threshold of information needed before making a decision, is one example of cognitive control adaptation. While previous studies have measured increased response caution via increased reaction time, the diffusion model can be used to derive a boundary separation parameter that directly indexes response caution and eliminates capturing alternative influences on reaction time. This study aims to determine if school-aged children, either with or without ADHD, show adaptive changes in response caution during a set-shifting task. These groups have demonstrated mixed results when analyzing reaction time, so this study utilizes diffusion modeling to measure response caution more directly. The set-shifting task presents switches in a random order such that they cannot be predicted; therefore, increasing response caution is only adaptive following errors, called post-error slowing (PES), but not following switch trials. It is predicted that children will show increased response caution only when adaptive. If child with ADHD adapt their response caution fundamentally differently, then there will be individual differences in change in boundary separation.

Children ages 8-12 with (n=193) and without (n=70) ADHD completed the Navon set-shifting task. Participants saw one of four global shapes made up of local shapes and were asked to identify one or the other based upon the background color. Of the 144 trials, 70 presented a switch between global and local. Trials were presented in the same randomized order for all participants, self-paced, and followed by feedback on correctness. The diffusion model parameters boundary separation (a), drift rate (v), and nondecision time (Ter) were estimated by condition, including a) post-error versus after correct and b) post-switch versus post-same. For PES analyses, only participants with a sufficient number of errors for modeling were included (ADHD n=113, control n=19).

Participants were slower on trials immediately following errors (F(1, 130)=119.76, p<.001, n2=.48) and switches (F(1, 261)=154.93, p<.001, n2=.37). In PES, slowing was attributable to increased boundary separation, F(1, 130)=16.11, p<.001, n2=.11, as well as slower drift rate and longer nondecision time (both p<.01, n2 >.05). However, as predicted, post-switch slowing was only attributable slower drift rate and longer nondecision time (both p<.001, n2 >.10), not increased boundary separation, F(1, 261)=0.77, p=.38, n2<.01. Overall, children with ADHD had slower drift rates (F(1, 261)=4.63, p<.001, n2=.10) and narrower boundary separation (F(1, 261)=10.56, p=.001, n2=.04). However, there were no ADHD x trial-type interactions for PES or post-switch (both p>.33, n2<.01).

School-aged children demonstrated increased response caution following errors, but not following switches. This demonstrates an adaptive use of cognitive control. The diffusion model was crucial in determining this, as reaction time slowed following switches for reasons unrelated to cognitive control. Additionally, although children with ADHD demonstrated slower drift rates and narrower boundary separation overall, they showed no differences when adapting response caution.

Cognitive fatigue (CF) is a common, yet poorly understood symptom in neurological disorders (e.g., multiple sclerosis, Parkinson’s disease, stroke). Studies show that reward plays a central role in CF. For instance, introducing or increasing reward often improves task performance. It is less clear, however, how reward affects subjective (self-reported) CF (SCF). This study examined the effect of reward type (monetary or performance feedback) and frequency (infrequent or frequent) on SF.

In an online between-subjects study, 400 participants completed a computerized cognitive switching task and were randomly grouped into one of the five possible groups based on reward condition: [1] infrequent monetary reward, [2] frequent monetary reward, [3] infrequent performancefeedback reward, [4] frequent performance feedback reward, and [5] a no-reward group. SCF was assessed using the Visual Analog Scale of Fatigue (VAS-F) during the task. Mixed effects models were used to estimate the influence of reward type and frequency on task performance and SCF.

We found that the monetary groups were significantly faster (p<.001) compared to the feedback and no-reward groups, and that the frequent group was faster (p=.05) compared to the infrequent group. Reward type and frequency did not have a significant effect on VAS-F scores. However, when we looked at each reward group, we found that the monetary-infrequent reward group was associated with a decrease in VAS-F scores on average compared to the no-reward group (p=.04).

The type and frequency of reward influence aspects of task performance (response time but not accuracy). Findings suggest that money had a greater effect on response time and may decrease SCF in cognitively healthy individuals when provided infrequently. Future studies should examine how these findings translate to clinical populations. Continued work is needed to understand how and which specific behavioral reward manipulations reduce fatigue, which could eventually lead to improved assessment and our ability to target fatigue across clinical populations.

Blast-related traumatic brain injury (bTBI) is one of the most common injuries among Veterans who have served in recent wars in Iraq and Afghanistan. Despite representing a distinct mechanism of injury, long-term clinical and functional outcomes of bTBI are generally comparable with non-blast-related traumatic brain injury (TBI). However, controversy remains over whether bTBI etiology differentially impacts emotional regulation and neurocognition - particularly with respect to post-traumatic stress disorder (PTSD) and verbal and visual memory. Through diffusion tensor imaging (DTI), the present study investigates the microstructural pathophysiology of bTBI, compared to non-blast TBI, in neural pathways involved in emotional regulation and cognitive control.

Participants included 36 Veterans (25% female; age M = 36.33, SD = 10.11; years of education M = 15.67, SD = 2.34). Axial diffusivity (AD) in networks of emotional and cognitive control was acquired using magnetic resonance imaging (MRI) with a DTI protocol. Analyses of variance (ANOVA) were used to compare Veterans with self-reported bTBI (n = 23) to those with non-blast-related TBI (n = 13).

In the left hemisphere, Veterans with bTBI exhibited significantly smaller AD in axonal projections from the caudate nucleus (CN) to the orbitofrontal cortex (OFC), as well as in projections from the putamen to the OFC (p < 0.05). In the right hemisphere, Veterans with bTBI also exhibited significantly smaller AD in networks connecting the hippocampus to the amygdala (p < 0.05).

Compared to Veterans with non-blast-related TBI, Veterans with bTBI exhibited decreased AD in neural pathways from the CN to the OFC, the putamen to the OFC, and the hippocampus to the amygdala - indicative of increased axonal injury in these areas. Our results suggest that, on a microstructural level, emotional and cognitive networks are susceptible to longitudinal blast-related white matter damage. This is consistent with the literature in post-concussion syndrome (PCS) and provides a potential mechanism underlying results previously reported from this sample, describing subjective cognitive complaints in the absence of objective clinical deficits. As such, therapies that target networks of emotional and cognitive control may be particularly beneficial for Veterans with bTBI.