Bypassing Striatal Learning Mechanisms Using Delayed Feedback to Circumvent Learning Deficits in Traumatic Brain Injury.

OBJECTIVE: Feedback facilitates learning by guiding and modifying behaviors through an action-outcome contingency. As the majority of existing studies have focused on the immediate presentation of feedback, the impact of delayed feedback on learning is understudied. Prior work demonstrated that learning from immediate and delayed feedback employed distinct brain regions in healthy individuals, and compared to healthy individuals, individuals with traumatic brain injury (TBI) are impaired in learning from immediate feedback. The goal of the current investigation was to assess the effects of delayed vs immediate feedback on learning in individuals with TBI and examine brain networks associated with delayed and immediate feedback processing. SETTING: Nonprofit research organization. PARTICIPANTS: Twenty-eight individuals with moderate-to-severe TBI. DESIGN: Participants completed a paired-associate word learning task while undergoing magnetic resonance imaging. During the task, feedback was presented either immediately, after a delay, or not at all (control condition). MAIN MEASURES: Learning performance accuracy, confidence ratings, post-task questionnaire, and blood oxygen level-dependent signal. RESULTS: Behavioral data showed that delayed feedback resulted in better learning performance than immediate feedback and no feedback. In addition, participants reported higher confidence in their performance during delayed feedback trials. During delayed vs immediate feedback processing, greater activation was observed in the superior parietal and angular gyrus. Activation in these areas has been previously associated with successful retrieval and greater memory confidence. CONCLUSION: The observed results might be explained by delayed feedback processing circumventing the striatal dopaminergic regions responsible for learning from immediate feedback that are impaired in TBI. In addition, delayed feedback evokes less of an affective reaction than immediate feedback, which likely benefited memory performance. Indeed, compared to delayed feedback, positive or negative immediate feedback was more likely to be rated as rewarding or punishing, respectively. The findings have significant implications for TBI rehabilitation and suggest that delaying feedback during rehabilitation might recruit brain regions that lead to better functional outcomes.

Secondary task engagement drives the McCabe effect in long-term memory.

Processing that occurs while information is held in working memory is critical in long-term retention of that information. One counterintuitive finding is that the concurrent processing required during complex span tasks typically impairs immediate memory, while also leading to improved delayed memory. One proposed mechanism for this effect is retrieval practice that occurs each time memory items are displaced to allow for concurrent processing during complex span tasks. Other research has instead suggested that increased free time during complex span procedures underlies this effect. In the present study, we presented participants with memory items in simple, complex, and slow span tasks and compared their performance on immediate and delayed memory tests. We found that how much a participant engaged with the secondary task of the complex span task corresponded with how strongly they exhibited a complex span boost on delayed memory performance. We also probed what participants were thinking about during the task, and found that participants' focus varied depending both on task type and secondary task engagement. The results support repeated retrieval as a key mechanism in the relationship between working memory processing and long-term retention. Further, the present study highlights the importance of variation in individual cognitive processing in predicting long-term outcomes even when objective conditions remain unchanged.

General Mathematical Ability Predicts PASAT Performance in MS Patients: Implications for Clinical Interpretation and Cognitive Reserve.

OBJECTIVES: The Paced Auditory Serial Addition Test (PASAT) is used to assess cognitive status in multiple sclerosis (MS). Although the mathematical demands of the PASAT seem minor (single-digit arithmetic), cognitive psychology research links greater mathematical ability (e.g., algebra, calculus) to more rapid retrieval of single-digit math facts (e.g., 5+6=11). The present study evaluated the hypotheses that (a) mathematical ability is related to PASAT performance and (b) both the relationship between intelligence and PASAT performance as well as the relationship between education and PASAT performance are both mediated by mathematical ability. METHODS: Forty-five MS patients were assessed using the Wechsler Test of Adult Reading, PASAT and Calculation Subtest of the Woodcock-Johnson-III. Regression based path analysis and bootstrapping were used to compute 95% confidence intervals and test for mediation. RESULTS: Mathematical ability (a) was related to PASAT (ß=.61; p<.001) and (b) fully mediated the relationship between Intelligence and PASAT (ß=.76; 95% confidence interval (CI95)=.28, 1.45; direct effect of Intelligence, ß=.42; CI95=-.39, 1.23) as well as the relationship between Education and PASAT (ß=2.43, CI95=.81, 5.16, direct effect of Education, ß=.83, CI95=-1.95, 3.61). DISCUSSION: Mathematical ability represents a source of error in the clinical interpretation of cognitive decline using the PASAT. Domain-specific cognitive reserve is discussed.

Individual Differences in Working Memory Capacity Predicts Responsiveness to Memory Rehabilitation After Traumatic Brain Injury.

OBJECTIVE: To explore how individual differences affect rehabilitation outcomes by specifically investigating whether working memory capacity (WMC) can be used as a cognitive marker to identify who will and will not improve from memory rehabilitation. DESIGN: Post hoc analysis of a randomized controlled clinical trial designed to treat learning and memory impairment after traumatic brain injury (TBI): 2 × 2 between-subjects quasiexperimental design (2 [group: treatment vs control] × 2 [WMC: high vs low]). SETTING: Nonprofit medical rehabilitation research center. PARTICIPANTS: Participants (N=65) with moderate to severe TBI with pre- and posttreatment data. INTERVENTIONS: The treatment group completed 10 cognitive rehabilitation sessions in which subjects were taught a memory strategy focusing on learning to use context and imagery to remember information. The placebo control group engaged in active therapy sessions that did not involve learning the memory strategy. MAIN OUTCOME MEASURE: Long-term memory percent retention change scores for an unorganized list of words from the California Verbal Learning Test-II. RESULTS: Group and WMC interacted (P=.008, ηp(2)=.12). High WMC participants showed a benefit from treatment compared with low WMC participants. Individual differences in WMC accounted for 45% of the variance in whether participants with TBI in the treatment group benefited from applying the compensatory treatment strategy to learn unorganized information. CONCLUSIONS: Individuals with higher WMC showed a significantly greater rehabilitation benefit when applying the compensatory strategy to learn unorganized information. WMC is a useful cognitive marker for identifying participants with TBI who respond to memory rehabilitation with the modified Story Memory Technique.

Working memory mediates the relationship between intellectual enrichment and long-term memory in multiple sclerosis: an exploratory analysis of cognitive reserve.

Some individuals with multiple sclerosis (MS) show decrements in long-term memory (LTM) while other individuals do not. The theory of cognitive reserve suggests that individuals with greater pre-morbid intellectual enrichment are protected from disease-related cognitive decline. How intellectual enrichment affords this benefit remains poorly understood. The present study tested an exploratory meditational hypothesis whereby working memory (WM) capacity may mediate the relationship between intellectual enrichment and verbal LTM decline in MS. Intellectual enrichment, verbal LTM, and WM capacity were estimated with the Wechsler Test of Adult Reading and Peabody Picture Vocabulary Test, delayed recall of the Hopkins Verbal Learning Test-Revised and Logical Memory of the Wechsler Memory Scale, and Digit Span Total, respectively. Intellectual enrichment predicted LTM (B=.54; p=.003) and predicted WM capacity (B=.91; p<.001). WM capacity predicted LTM, (B=.44; p<.001) and fully mediated the relationship between intellectual enrichment (B=.24; p=.27) and LTM (B=.33, p=.03), Sobel test, Z=3.31, p<.001. These findings implicate WM capacity as an underlying mechanism of cognitive reserve and are an initial first step in understanding the relationship between intellectual enrichment, WM, and LTM in MS.

Flexibility within working memory and the focus of attention for sequential verbal information does not depend on active maintenance.

The focus of attention seems to be a static element within working memory when verbal information is serially presented, unless additional time is available for processing or active maintenance. Experiment 1 manipulated the reward associated with early and medial list positions in a probe recognition paradigm and found evidence that these nonterminal list positions could be retrieved faster and more accurately if participants were appropriately motivated-without additional time for processing or active maintenance. Experiment 2 used articulatory suppression and demonstrated that the underlying maintenance mechanism cannot be attributed to rehearsal, leaving attentional refreshing as the more likely mechanism. These findings suggest that the focus of attention within working memory can flexibly maintain nonterminal early and medial list representations at the expense of other list representations even when there is not additional time for processing or active maintenance. Maintenance seems to be accomplished through an attentional refreshing mechanism.

The Effects of Mind-Wandering, Cognitive Load, and Task Engagement on Working Memory Performance in Remote Online Experiments.

Recent changes in environments from in-person to remote present several issues for work, education, and research, particularly related to cognitive performance. Increased distraction in remote environments may lead to increases in mind-wandering and disengagement with tasks at hand, whether virtual meetings, online lectures, or psychological experiments. The present study investigated mind-wandering and multitasking effects during working memory tasks in remote and in-person environments. In two experiments, participants completed a working memory task with varied cognitive load during a secondary task. After each working memory trial, participants reported their mind-wandering during that trial. Some participants completed the procedures in-person, while others completed the procedures remotely. Overall, remote participants reported significantly more mind-wandering and poorer secondary task performance than in-person participants, but this pattern was not reflected in working memory accuracy. Both groups exhibited similar multitasking effects on performance. Additional analyses found that for remote participants, task engagement better predicted working memory performance than either cognitive load or mind-wandering rates but did not indicate a tradeoff in resources between tasks. Together, these results demonstrate the importance of considering multiple metrics when assessing performance and illustrate that making assumptions about the equivalence of remote and in-person work is a risky proposition.

Using potential performance theory to analyze systematic and random factors in enumeration tasks.

Prior research has shown that as the number of items being enumerated increases, performance decreases, especially when the amount of time is limited. Researchers studying nonverbal enumeration have found that random noise increases as a function of the number of items presented. Over a series of 2 experiments, the authors used potential performance theory to expand these findings and discover precisely how much random noise actually influences observed performance and what performance might look like in the absence of random factors. Participants briefly viewed a visual stimulus comprising a set of 4 to 9 dots presented horizontally (Experiment 1) or randomly (Experiment 2) on a computer monitor. Findings from both experiments indicate that the decrease in performance for larger set sizes resulted almost entirely from a reduction in consistency (or an increase in random noise), whereas potential performance remained fairly constant until the maximum set size.

ALFF response interaction with learning during feedback in individuals with multiple sclerosis.

Amplitude of low-frequency fluctuations (ALFF) is defined as changes of BOLD signal during resting state (RS) brain activity. Previous studies identified differences in RS activation between healthy and multiple sclerosis (MS) participants. However, no research has investigated the relationship between ALFF and learning in MS. We thus examine this here. Twenty-five MS and nineteen healthy participants performed a paired-associate word learning task where participants were presented with extrinsic or intrinsic performance feedback. Compared to healthy participants, MS participants showed higher local brain activation in the right thalamus. We also observed a positive correlation in the MS group between ALFF and extrinsic feedback within the left inferior frontal gyrus, and within the left superior temporal gyrus in association with intrinsic feedback. Healthy participants showed a positive correlation in the right fusiform gyrus between ALFF and extrinsic feedback. Findings suggest that while MS participants do not show a feedback learning impairment compared to the healthy participants, ALFF differences might suggest a general maladaptive pattern of task unrelated thalamic activation and adaptive activation in frontal and temporal regions. Results indicate that ALFF can be successfully used at capturing pathophysiological changes in local brain activation in MS in association with learning through feedback.

Altered functional connectivity during performance feedback processing in multiple sclerosis.

Effective learning from performance feedback is vital for adaptive behavior regulation necessary for successful cognitive performance. Yet, how this learning operates in clinical groups that experience cognitive dysfunction is not well understood. Multiple sclerosis (MS) is an autoimmune, degenerative disease of the central nervous system characterized by physical and cognitive dysfunction. A highly prevalent impairment in MS is cognitive fatigue (CF). CF is associated with altered functioning within cortico-striatal regions that also facilitate feedback-based learning in neurotypical (NT) individuals. Despite this cortico-striatal overlap, research about feedback-based learning in MS, its associated neural underpinnings, and its sensitivity to CF, are all lacking. The present study investigated feedback-based learning ability in MS, as well as associated cortico-striatal function and connectivity. MS and NT participants completed a functional magnetic resonance imaging (fMRI) paired-word association task during which they received trial-by-trial monetary, non-monetary, and uninformative performance feedback. Despite reporting greater CF throughout the task, MS participants displayed comparable task performance to NTs, suggesting preserved feedback-based learning ability in the MS group. Both groups recruited the ventral striatum (VS), caudate nucleus, and ventromedial prefrontal cortex in response to the receipt of performance feedback, suggesting that people with MS also recruit cortico-striatal regions during feedback-based learning. However, compared to NT participants, MS participants also displayed stronger functional connectivity between the VS and task-relevant regions, including the left angular gyrus and right superior temporal gyrus, in response to feedback receipt. Results indicate that CF may not interfere with feedback-based learning in MS. Nonetheless, people with MS may recruit alternative connections with the striatum to assist with this form of learning. These findings have implications for cognitive rehabilitation treatments that incorporate performance feedback to remediate cognitive dysfunction in clinical populations.

Intentional inferences are not more likely than unintentional ones: some evidence against the intentionality bias hypothesis.

We conducted a study to test the hypothesis that inferences about intentionality are biased toward an intentional interpretation. Contrary to previous research, participants were no more likely to judge ambiguous actions as intentional in a speeded compared to an unspeeded condition. Further, participants were faster to respond and more consistent in responding to unintentional rather than intentional actions.

Motor speed does not impact the drift rate: a computational HDDM approach to differentiate cognitive and motor speed.

The drift diffusion model (DDM) is a widely applied computational model of decision making that allows differentiation between latent cognitive and residual processes. One main assumption of the DDM that has undergone little empirical testing is the level of independence between cognitive and motor responses. If true, widespread incorporation of DDM estimation into applied and clinical settings could ease assessment of whether response disruption occurs due to cognitive or motor slowing. Across two experiments, we manipulated response force (motor speed) and set size to evaluate whether drift rates are independent of motor slowing or if motor slowing impacts the drift rate parameter. The hierarchical Bayesian drift diffusion model was used to quantify parameter estimates of drift rate, boundary separation, and non-decision time. Model comparison revealed changes in set size impacted the drift rate while changes in response force did not impact the drift rate, validating independence between drift rates and motor speed. Convergent validity between parameter estimates and traditional assessments of processing speed and motor function were weak or absent. Widespread application, including neurocognitive assessment where confounded changes in cognitive and motor slowing are pervasive, may provide a more process-pure measurement of information processing speed, leading to advanced disease-symptom management.

Neural correlates of extrinsic and intrinsic outcome processing during learning in individuals with TBI: a pilot investigation.

Outcome processing, the ability to learn from feedback, is an important component of adaptive behavior and rehabilitation. Evidence from healthy adults implicates the striatum and dopamine in outcome processing. Animal research shows that damage to dopaminergic pathways in the brain can lead to a disruption of dopamine tone and transmission. Such evidence thus suggests that persons with TBI experience deficits in outcome processing. However, no research has directly investigated outcome processing and associated neural mechanisms in TBI. Here, we examine outcome processing in individuals with TBI during learning. Given that TBI negatively impacts striatal and dopaminergic systems, we hypothesize that individuals with TBI exhibit deficits in learning from outcomes. To test this hypothesis, individuals with moderate-to-severe TBI and healthy adults were presented with a declarative paired-associate word learning task. Outcomes indicating performance accuracy were presented immediately during task performance and in the form of either monetary or performance-based feedback. Two types of feedback provided the opportunity to test whether extrinsic and intrinsic motivational aspects of outcome presentation play a role during learning and outcome processing. Our results show that individuals with TBI exhibited impaired learning from feedback compared to healthy participants. Additionally, individuals with TBI exhibited increased activation in the striatum during outcome processing. The results of this study suggest that outcome processing and learning from immediate outcomes is impaired in individuals with TBI and might be related to inefficient use of neural resources during task performance as reflected by increased activation of the striatum.

Ex-Gaussian analysis of simple response time as a measure of information processing speed and the relationship with brain morphometry in multiple sclerosis.

BACKGROUND: The polyfactorial nature of the widely used symbol digit modalities test (SDMT) introduces significant measurement challenges in characterizing information processing speed (IPS) deficits in multiple sclerosis (MS). Measures with high psychometric IPS-specificity and less contamination from other cognitive domains are necessary to fully understand IPS changes. OBJECTIVE: Investigate how three mathematical modeling ex-Gaussian parameter estimates (mu, sigma, tau) derived from a simple response time (RT) task (1) differentiate MS from healthy control participants and (2) correspond to structural brain changes, to evaluate a novel IPS measurement approach. METHODS: Persons with and without MS completed a two-minute behavioral simple RT task, structural MRI and the MS functional composite. RT distributions were deconvolved into ex-Gaussian parameter estimates using mathematical modeling. Group differences and brain-behavior relationships were statistically evaluated. RESULTS: Persons with MS experienced a general pattern of slowing as evidenced by a shift in the Gaussian (mu) component of the distribution. This correlated with whole brain volume and white matter specifically. Additionally, persons with MS had larger values of tau (elongated positively skewed tail) that may reflect attentional lapses. CONCLUSION: The ex-Gaussian approach is sensitive to disease-related IPS changes and provides nuanced information about IPS slowing in MS.

Pattern of thalamic nuclei atrophy in early relapse-onset multiple sclerosis.

BACKGROUND: Thalamic atrophy is prominent in multiple sclerosis; however, it is unclear which thalamic nuclei are most vulnerable, especially early in disease. INTRODUCTION: To investigate which thalamic nuclei differ between patients in early stages of relapsing-remitting multiple sclerosis (RRMS) versus healthy controls and examine the relationship between thalamic nuclei volume and T2 lesion volume. METHODS: We derived 15 thalamic subfields from high-resolution 3T magnetic resonance images in 182 patients with early RRMS (diagnosed ≤5.0 years, median 2.0 years). Independent t-tests assessed differences between patients and 35 controls across thalamic subfield volumes. Pearson correlations assessed the relationships between thalamic volumes and T2 lesion volumes. RESULTS: Patients had lower anterior and posterior nuclei volume than controls, whereas medial and ventral nuclei volumes were preserved. Higher T2 lesion volumes were disproportionately related to lower posterior subfield volumes. CONCLUSIONS: We found specific thalamic subfields were more vulnerable to early disease-related changes. We discuss potential mechanisms of differential thalamic subfield atrophy in early MS, including cortical demyelination, CSF toxicity, leptomeningeal inflammation, and iron deposition.

Can priming your self lead to punishing others?

Previous research has shown that priming the individual self can increase the accessibility of individual self-cognitions. In turn, we hypothesized that blame for immoral behaviors also would increase, leading to higher assignments of punishment, but that the size of this effect would depend on whether the behaviors violated perfect or imperfect duties. To test these hypotheses, participants assigned yearly bonus penalties to employees who had performed dishonest, disloyal, unfriendly, or uncharitable acts. As expected, the individual prime increased punishments, and this effect was accentuated for violations of perfect duties relative to violations of imperfect duties.

Global hippocampal and selective thalamic nuclei atrophy differentiate chronic TBI from Non-TBI.

Traumatic brain injury (TBI) may increase susceptibility to neurodegenerative diseases later in life. One neurobiological parallel between chronic TBI and neurodegeneration may be accelerated aging and the nature of atrophy across subcortical gray matter structures. The main aim of the present investigation is to evaluate and rank the degree that subcortical gray matter atrophy differentiates chronic moderate-severe TBI from non-TBI participants by evaluating morphometric differences between groups. Forty individuals with moderate-severe chronic TBI (9.23 yrs from injury) and 33 healthy controls (HC) underwent high resolution 3D T1-weighted structural magnetic resonance imaging. Whole brain volume was classified into white matter, cortical and subcortical gray matter structures with hippocampi and thalami further segmented into subfields and nuclei, respectively. Extensive atrophy was observed across nearly all brain regions for chronic TBI participants. A series of multivariate logistic regression models identified subcortical gray matter structures of the hippocampus and thalamus as the most sensitive to differentiating chronic TBI from non-TBI participants (McFadden R2 = .36, p < .001). Further analyses revealed the pattern of hippocampal atrophy to be global, occurring across nearly all subfields. The pattern of thalamic atrophy appeared to be much more selective and non-uniform, with largest between-group differences evident for nuclei bordering the ventricles. Subcortical gray matter was negatively correlated with time since injury (r = -.31, p = .054), while white matter and cortical gray matter were not. Cognitive ability was lower in the chronic TBI group (Cohen's d = .97, p = .003) and correlated with subcortical structures including the pallidum (r2 = .23, p = .038), thalamus (r2 = .36, p = .007) and ventral diencephalon (r2 = .23, p = .036). These data may support an accelerated aging hypothesis in chronic moderate-severe TBI that coincides with a similar neuropathological profile found in neurodegenerative diseases.

The Symbol Digit Modalities Test (SDMT) is sensitive but non-specific in MS: Lexical access speed, memory, and information processing speed independently contribute to SDMT performance.

BACKGROUND: The Symbol Digit Modalities Test (SDMT) is the most sensitive metric of neurocognitive function in multiple sclerosis (MS), and is consistently interpreted as a measure of information processing speed (IPS). OBJECTIVE: To evaluate the cognitive psychometric profile captured by the SDMT to identify whether different cognitive processes independently underlie performance. METHODS: Three samples of MS patients (total n=661; 185 research patients at MS center; 370 clinical patients at MS center; 106 persons with MS from the community) completed objective assessments of neuropsychological function across cognitive domains. Exploratory factor analysis (EFA) was used to derive latent cognitive factor scores, and operationalize cognitive domain composite scores, to understand the unique, shared and redundant contribution of different cognitive domains to SDMT performance using hierarchical multiple regression and commonality analysis. RESULTS: Across three independent samples we provide converging strong evidence that the cognitive domains of Memory, IPS and Rapid Automatized Naming (lexical access speed) jointly and uniquely contribute to SDMT performance. CONCLUSION: The SDMT measures multiple cognitive processes, which likely explains the high degree of sensitivity to cognitive change in MS. Researchers and clinicians should interpret the SDMT as a multifarious measure of general cognition rather than a specific test of IPS.

Generalizing Kant's distinction between perfect and imperfect duties to trust in different situations.

Based on previous research that violations of perfect duties cause stronger correspondent inferences than violations of imperfect ones, the authors performed four experiments to generalize this effect to trust. In Experiment 1, abstract violations of perfect duties resulted in less trust than violations of imperfect ones for specific trust scenarios. In Experiments 2 and 3, the authors experimented with different levels of abstractness of the duty violations and obtained similar effects. Experiment 4 was concerned with generalizing further--from duty violations in one situation to trust in a different situation. Although mostly consistent with the findings from Experiments 1-3, the data also demonstrated partial generalization for violations of both perfect and imperfect duties.