The sign effect in temporal discounting does not require the hippocampus.

When considering future outcomes, humans tend to discount gains more than losses. This phenomenon, referred to as the temporal discounting sign effect, is thought to result from the greater anticipated emotional impact of waiting for a negative outcome (dread) compared to waiting for a positive outcome (mixture of savoring and impatience). The impact of such anticipatory emotions has been proposed to rely on episodic future thinking. We evaluated this proposal by examining the presence and magnitude of a sign effect in the intertemporal decisions of individuals with hippocampal amnesia, who are severely impaired in their ability to engage in episodic mental simulation, and by comparing their patterns of choices to those of healthy controls. We also measured loss aversion, the tendency to assign greater value to losses compared to equivalent gains, to verify that any reduction in the sign effect in the hippocampal lesion group could not be explained by a group difference in loss aversion. Results showed that participants with hippocampal amnesia exhibited a sign effect, with less discounting of monetary losses compared to gains, that was similar in magnitude to that of controls. Loss aversion, albeit greater in the hippocampal compared to the control group, did not account for the sign effect. These results indicate that the sign effect does not depend on the integrity of hippocampally mediated episodic processes. They suggest instead that the impact of anticipatory emotions can be factored into decisions via semantic future thinking, drawing on non-contextual knowledge about oneself.

The Hippocampus Contributes to Temporal Discounting When Delays and Rewards Are Experienced in the Moment.

Temporal discounting (TD) represents the mental devaluation of rewards that are available after a delay. Whether the hippocampus is critical for TD remains unclear, with marked discrepancies between animal and human studies: although animals with discrete hippocampal lesions display impaired TD, human participants with similar lesions show intact performance on classic intertemporal choice tasks. A candidate explanation for this discrepancy is that delays and rewards are experienced in the moment in animal studies but tend to be hypothetical in human studies. We tested this hypothesis by examining the performance of amnesic participants with hippocampal lesions (one female, six males) on a novel experiential intertemporal choice task that used interesting photographs occluded by thick lines as rewards (Patt et al., 2021). Using a logistic function to model indifference points data, we compared performance to that on a classic intertemporal choice task with hypothetical outcomes. Participants with hippocampal lesions displayed impaired patterns of choices in the experiential task but not in the hypothetical task. Specifically, hippocampal lesions were associated with decreased amplitude of the delay-reward trade-off, with persistent choice of the delayed option despite delay increase. These results help explain previous discrepancies across animal and human studies, indicating that the hippocampus plays a critical role in temporal discounting when the outcomes of decisions are experienced in the moment, but not necessarily when they are hypothetical.SIGNIFICANCE STATEMENT Impaired temporal discounting (TD) has been related to maladaptive behaviors, including substance dependence and nonadherence to medical treatment. There is consensus that TD recruits the brain valuation network but whether the hippocampal memory system is additionally recruited remains unclear. This study examined TD in hippocampal amnesia, providing a unique opportunity to explore the role of the hippocampus in cognition. Whereas most human studies have used hypothetical outcomes, this study used a novel experiential task with real-time delays and rewards. Results demonstrated hippocampal involvement in the experiential task, but not in a classic hypothetical task administered for comparison. These findings elucidate previous discrepancies between animal and human TD studies. This reconciliation is critical as animals serve as models of human neurocognition.

Hippocampal Contribution to Probabilistic Feedback Learning: Modeling Observation- and Reinforcement-based Processes.

Simple probabilistic reinforcement learning is recognized as a striatum-based learning system, but in recent years, has also been associated with hippocampal involvement. This study examined whether such involvement may be attributed to observation-based learning (OL) processes, running in parallel to striatum-based reinforcement learning. A computational model of OL, mirroring classic models of reinforcement-based learning (RL), was constructed and applied to the neuroimaging data set of Palombo, Hayes, Reid, and Verfaellie [2019. Hippocampal contributions to value-based learning: Converging evidence from fMRI and amnesia. Cognitive, Affective & Behavioral Neuroscience, 19(3), 523-536]. Results suggested that OL processes may indeed take place concomitantly to reinforcement learning and involve activation of the hippocampus and central orbitofrontal cortex. However, rather than independent mechanisms running in parallel, the brain correlates of the OL and RL prediction errors indicated collaboration between systems, with direct implication of the hippocampus in computations of the discrepancy between the expected and actual reinforcing values of actions. These findings are consistent with previous accounts of a role for the hippocampus in encoding the strength of observed stimulus-outcome associations, with updating of such associations through striatal reinforcement-based computations. In addition, enhanced negative RL prediction error signaling was found in the anterior insula with greater use of OL over RL processes. This result may suggest an additional mode of collaboration between the OL and RL systems, implicating the error monitoring network.

Temporal discounting when outcomes are experienced in the moment: Validation of a novel paradigm and comparison with a classic hypothetical intertemporal choice task.

When faced with intertemporal choices, people typically devalue rewards available in the future compared to rewards more immediately available, a phenomenon known as temporal discounting. Decisions involving intertemporal choices arise daily, with critical impact on health and financial wellbeing. Although many such decisions are "experiential" in that they involve delays and rewards that are experienced in real-time and can inform subsequent choices, most studies have focused on intertemporal choices with hypothetical outcomes (or outcomes delivered after all decisions are made). The present study focused on experiential intertemporal choices. First, a novel intertemporal choice task was developed and validated, using delays experienced in real time and artistic photographs as consumable perceptual rewards. Second, performance on the experiential task was compared to performance on a classic intertemporal choice task with hypothetical outcomes. Involvement of distinct processes across tasks was probed by examining differential relations to state and trait anxiety. A two-parameter logistic function framework was proposed to fit indifference point data. This approach accounts for individual variability not only in the delay at which an individual switches from choosing the delayed to more immediate option, but also in the slope of that switch. Fit results indicated that the experiential task elicited temporal discounting, with effective trade-off between delay and perceptual reward. Comparison with the hypothetical intertemporal choice task suggested distinct mechanisms: first, temporal discounting across the two tasks was not correlated; and second, state and trait anxiety both were associated with choice behavior in the experiential task, albeit in distinct ways, whereas neither was significantly associated with choice behavior in the hypothetical task. The engagement of different processes in the experiential compared to hypothetical task may align with neural evidence for the recruitment of the hippocampus in animal but not in classic human intertemporal choice studies.

Probabilistic value learning in medial temporal lobe amnesia.

A prevailing view in cognitive neuroscience suggests that different forms of learning are mediated by dissociable memory systems, with a mesolimbic (i.e., midbrain and basal ganglia) system supporting incremental trial-and-error reinforcement learning and a hippocampal-based system supporting episodic memory. Yet, growing evidence suggests that the hippocampus may also be important for trial-and-error learning, particularly value or reward-based learning. In the present report, we use a lesion-based neuropsychological approach to clarify hippocampal contributions to such learning. Six amnesic patients with medial temporal lobe damage and a group of healthy controls were administered a simple value-based learning task involving probabilistic trial-and-error acquisition of stimulus-response-outcome (reward or none) contingencies modeled after Li et al. (Proceedings of the National Academy of Sciences , 2011, 108 (1), 55-60). As predicted, patients were significantly impaired on the task, demonstrating reduced learning of the contingencies. Our results provide further supportive evidence that the hippocampus' role in cognition extends beyond episodic memory tasks and call for further refinement of theoretical models of hippocampal functioning.

Latent Variable Modeling and Adaptive Testing for Experimental Cognitive Psychopathology Research.

The adaptation of experimental cognitive tasks into measures that can be used to quantify neurocognitive outcomes in translational studies and clinical trials has become a key component of the strategy to address psychiatric and neurological disorders. Unfortunately, while most experimental cognitive tests have strong theoretical bases, they can have poor psychometric properties, leaving them vulnerable to measurement challenges that undermine their use in applied settings. Item response theory-based computerized adaptive testing has been proposed as a solution but has been limited in experimental and translational research due to its large sample requirements. We present a generalized latent variable model that, when combined with strong parametric assumptions based on mathematical cognitive models, permits the use of adaptive testing without large samples or the need to precalibrate item parameters. The approach is demonstrated using data from a common measure of working memory-the N-back task-collected across a diverse sample of participants. After evaluating dimensionality and model fit, we conducted a simulation study to compare adaptive versus nonadaptive testing. Computerized adaptive testing either made the task 36% more efficient or score estimates 23% more precise, when compared to nonadaptive testing. This proof-of-concept study demonstrates that latent variable modeling and adaptive testing can be used in experimental cognitive testing even with relatively small samples. Adaptive testing has the potential to improve the impact and replicability of findings from translational studies and clinical trials that use experimental cognitive tasks as outcome measures.

A signal detection-item response theory model for evaluating neuropsychological measures.

INTRODUCTION: Models from signal detection theory are commonly used to score neuropsychological test data, especially tests of recognition memory. Here we show that certain item response theory models can be formulated as signal detection theory models, thus linking two complementary but distinct methodologies. We then use the approach to evaluate the validity (construct representation) of commonly used research measures, demonstrate the impact of conditional error on neuropsychological outcomes, and evaluate measurement bias. METHOD: Signal detection-item response theory (SD-IRT) models were fitted to recognition memory data for words, faces, and objects. The sample consisted of U.S. Infantry Marines and Navy Corpsmen participating in the Marine Resiliency Study. Data comprised item responses to the Penn Face Memory Test (PFMT; N = 1,338), Penn Word Memory Test (PWMT; N = 1,331), and Visual Object Learning Test (VOLT; N = 1,249), and self-report of past head injury with loss of consciousness. RESULTS: SD-IRT models adequately fitted recognition memory item data across all modalities. Error varied systematically with ability estimates, and distributions of residuals from the regression of memory discrimination onto self-report of past head injury were positively skewed towards regions of larger measurement error. Analyses of differential item functioning revealed little evidence of systematic bias by level of education. CONCLUSIONS: SD-IRT models benefit from the measurement rigor of item response theory-which permits the modeling of item difficulty and examinee ability-and from signal detection theory-which provides an interpretive framework encompassing the experimentally validated constructs of memory discrimination and response bias. We used this approach to validate the construct representation of commonly used research measures and to demonstrate how nonoptimized item parameters can lead to erroneous conclusions when interpreting neuropsychological test data. Future work might include the development of computerized adaptive tests and integration with mixture and random-effects models.

Factor Analysis of an Expanded Halstead-Reitan Battery and the Structure of Neurocognition.

OBJECTIVE: The structure of neurocognition is explored by examining the neurocognitive domains underlying comprehensive neuropsychological assessment of cognitively healthy individuals. METHOD: Exploratory factor analysis was conducted on the adult normative dataset of an expanded Halstead-Reitan Battery (eHRB), comprising Caucasian and African American participants. The factor structure contributions of the original HRB, eHRB expansion, and Wechsler intelligence scales were compared. Demographic effects were examined on composite factor scores calculated using confirmatory factor analysis. RESULTS: The full eHRB had an eight-factor structure, with latent constructs including: 'working memory', 'fluency', 'verbal episodic memory', 'visuospatial cognition' (visuospatial memory and problem solving), 'perceptual-motor speed' (speed for processing visual/tactile material and hand-motor execution), 'perceptual attention' (attention to sensory-perceptual information), 'semantic knowledge' (knowledge acquired through education and culturally-based experiences), and 'phonological decoding' (grapheme-phoneme processing essential for sounding-out words). 'Perceptual-motor speed' and 'perceptual attention' were most negatively associated with age, whereas 'semantic knowledge' and 'phonological decoding' were most resistant to aging. 'Semantic knowledge' showed the greatest dependence on demographic background, including education and ethnicity. Gender differences in cognitive performances were negligible across all domains except 'phonological decoding' with women slightly outperforming men. The original HRB contributed four neurocognitive domains, the eHRB expansion three domains, and the Wechsler scales one additional domain but with restructuring of verbal factors. CONCLUSION: Eight neurocognitive domains underlie performance of healthy cognitive individuals during comprehensive neuropsychological assessment. These domains serve as framework for understanding the constructs measured by commonly-used neuropsychological tests and may represent the structure of neurocognition.

Evidence of systematic attenuation in the measurement of cognitive deficits in schizophrenia.

Cognitive tasks that are too hard or too easy produce imprecise measurements of ability, which, in turn, attenuates group differences and can lead to inaccurate conclusions in clinical research. We aimed to illustrate this problem using a popular experimental measure of working memory-the N-back task-and to suggest corrective strategies for measuring working memory and other cognitive deficits in schizophrenia. Samples of undergraduates (n = 42), community controls (n = 25), outpatients with schizophrenia (n = 33), and inpatients with schizophrenia (n = 17) completed the N-back. Predictors of task difficulty-including load, number of word syllables, and presentation time-were experimentally manipulated. Using a methodology that combined techniques from signal detection theory and item response theory, we examined predictors of difficulty and precision on the N-back task. Load and item type were the 2 strongest predictors of difficulty. Measurement precision was associated with ability, and ability varied by group; as a result, patients were measured more precisely than controls. Although difficulty was well matched to the ability levels of impaired examinees, most task conditions were too easy for nonimpaired participants. In a simulation study, N-back tasks primarily consisting of 1- and 2-back load conditions were unreliable, and attenuated effect size (Cohen's d) by as much as 50%. The results suggest that N-back tasks, as commonly designed, may underestimate patients' cognitive deficits as a result of nonoptimized measurement properties. Overall, this cautionary study provides a template for identifying and correcting measurement problems in clinical studies of abnormal cognition. (PsycINFO Database Record

Double dissociation of a latent working memory process.

BACKGROUND: The study explored the construct validity of a computational model of working memory (WM) by determining whether model parameters manifested double dissociations of lesion laterality with type of material studied. The data set modeled involved psychometrically matched verbal and figural WM tasks on which a double dissociation between test version and lesion laterality failed to emerge when total test scores were used as the laterality marker. METHOD: This re-analysis of a previously published study involved investigating the WM performance of 15 demographically matched controls with 15 adult patients with left-hemispheric (LH) lesions and 15 adult patients with right-hemispheric (RH) lesions. Each participant was given verbal and figural versions of a continuous paired associates test (CPAT). The two versions had previously been psychometrically matched in a larger sample of healthy individuals. A WM model composed of encoding, displacement, and episodic memory parameters was fit to each individual's performance profiles for both versions of the CPAT. RESULTS: Replicating the previous results for raw scores, rank transformed values of total score performance failed to reveal a double dissociation. Nonetheless an absolute double dissociation was observed for the model's displacement parameter: RH patients demonstrated deficits on the figural but not verbal WM displacement parameter, whereas LH patients demonstrated deficits on the verbal but not figural WM displacement parameter. Additionally, both LH and RH patients were impaired on the figural encode parameter, perhaps explaining the absence of a double dissociation in total score performance. CONCLUSIONS: By combining different patterns of profile and level data into theoretically motivated model parameters, computational models of neurocognition can enhance the construct validity of interpretations of neuropsychological performance.

Measurement of latent cognitive abilities involved in concept identification learning.

INTRODUCTION: We used cognitive and psychometric modeling techniques to evaluate the construct validity and measurement precision of latent cognitive abilities measured by a test of concept identification learning: the Penn Conditional Exclusion Test (PCET). METHOD: Item response theory parameters were embedded within classic associative- and hypothesis-based Markov learning models and were fitted to 35,553 Army soldiers' PCET data from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). RESULTS: Data were consistent with a hypothesis-testing model with multiple latent abilities-abstraction and set shifting. Latent abstraction ability was positively correlated with number of concepts learned, and latent set-shifting ability was negatively correlated with number of perseverative errors, supporting the construct validity of the two parameters. Abstraction was most precisely assessed for participants with abilities ranging from 1.5 standard deviations below the mean to the mean itself. Measurement of set shifting was acceptably precise only for participants making a high number of perseverative errors. CONCLUSIONS: The PCET precisely measures latent abstraction ability in the Army STARRS sample, especially within the range of mildly impaired to average ability. This precision pattern is ideal for a test developed to measure cognitive impairment as opposed to cognitive strength. The PCET also measures latent set-shifting ability, but reliable assessment is limited to the impaired range of ability, reflecting that perseverative errors are rare among cognitively healthy adults. Integrating cognitive and psychometric models can provide information about construct validity and measurement precision within a single analytical framework.

Disentangling working memory processes during spatial span assessment: a modeling analysis of preferred eye movement strategies.

The neurocognitive processes involved during classic spatial working memory (SWM) assessment were investigated by examining naturally preferred eye movement strategies. Cognitively healthy adult volunteers were tested in a computerized version of the Corsi Block-Tapping Task--a spatial span task requiring the short term maintenance of a series of locations presented in a specific order--coupled with eye tracking. Modeling analysis was developed to characterize eye-tracking patterns across all task phases, including encoding, retention, and recall. Results revealed a natural preference for local gaze maintenance during both encoding and retention, with fewer than 40% fixated targets. These findings contrasted with the stimulus retracing pattern expected during recall as a result of task demands, with 80% fixated targets. Along with participants' self-reported strategies of mentally "making shapes," these results suggest the involvement of covert attention shifts and higher order cognitive Gestalt processes during spatial span tasks, challenging instrument validity as a single measure of SWM storage capacity.

Inhibitory deficits in euthymic bipolar disorder patients assessed in the human behavioral pattern monitor.

BACKGROUND: Bipolar disorder (BD) is associated with inhibitory deficits characterized by a reduced ability to control inappropriate actions or thoughts. While aspects of inhibition such as exaggerated novelty-seeking and perseveration are quantified in rodent exploration of novel environments, similar models are rarely applied in humans. The human Behavioral Pattern Monitor (hBPM), a cross-species exploratory paradigm, has identified a pattern of impaired inhibitory function in manic BD participants, but this phenotype has not been examined across different BD phases. The objective of this study was to determine if euthymic BD individuals demonstrate inhibitory deficits in the hBPM, supporting disinhibition as an endophenotype for the disorder. METHODS: 25 euthymic BD outpatients and 51 healthy comparison subjects were assessed in the hBPM, where activity was recorded by a concealed videocamera and an ambulatory monitoring sensor. RESULTS: Euthymic BD individuals, similar to manic subjects, demonstrated increased motor activity, greater interaction with novel objects, and more frequent perseverative behavior relative to comparison participants. The quantity of locomotion was also reduced in BD individuals treated with mood stabilizers compared to other patients. LIMITATIONS: Low sample size for treatment subgroups limits the evaluation of specific medication regimens. CONCLUSIONS: Our results suggest that BD is distinguished by both trait- and state-dependent inhibitory deficits optimally assessed with sophisticated multivariate measures. These data support the use of the hBPM as a tool to elucidate the effects of BD across various illness states, facilitate the development of BD animal models, and advance our understanding of the neurobiology underlying the disorder.