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Our ability to remember past events requires not only storing enduring engrams or memory traces of these events, but also successfully reactivating these latent traces in response to appropriate cues at the time of retrieval—a process that has been termed ecphory. However, relatively little is known about the processes that facilitate the dynamic interactions between retrieval cues and stored memory traces that are critical for successful recognition and recollection. Recently, an intriguing link between pupil dilation and recognition memory has been identified, with studied items eliciting greater pupil dilation than unstudied items during retrieval. However, the processes contributing to this "pupillary old/new effect" remain unresolved, with current explanations suggesting that it reflects the strength of the underlying memory trace. Here, we explore the novel hypothesis that the pupillary old/new effect does not index memory strength alone, but rather reflects the facilitation of cue–trace interactions during episodic memory retrieval that may be supported by activity within the pupil‐linked locus coeruleus‐noradrenergic (LC‐NA) arousal system. First, we show that the magnitude of pupil dilation is influenced by the degree of overlap between cue and trace information. Second, we find that the magnitude of pupil dilation reflects the amount of study contextual information reinstated during retrieval. These findings provide a novel framework for understanding the pupillary old/new effect, and identify a potential role for the LC‐NA system in recognition memory retrieval. Our findings support the novel hypothesis that synergistic interactions between retrieval cues and memory trace information during episodic memory retrieval trigger activity within the pupil‐linked arousal system that in turn facilitates contextual retrieval. These findings serve to resolve conflicting theories of the pupillary old/new effect and provide a framework for understanding the role of the LC‐NA system in episodic memory. [ABSTRACT FROM AUTHOR]

Background: Pathological changes of Alzheimer's disease (AD) occur in the locus coeruleus (LC) years before clinical symptoms. This may affect LC activity that can be indexed by changes in pupil dilation. AD also disrupts connections between related but functionally distinct cortical areas leading to visual feature binding deficits. Thus, feature binding in individuals with preclinical AD may require additional cognitive effort that engages LC activity. Pupil dilation during conjunctive visual search may therefore be a particularly sensitive marker of preclinical AD. Method: Sixty‐three cognitively unimpaired older adults from the UCSD Alzheimer's Disease Research Center (51% men; overall mean age = 78.4 years, education = 17.5 years, and MoCA score = 25.9), performed a conjunctive visual search task while their pupil diameter was continuously recorded. There were 108 trials in which the participant searched for a target stimulus (a black dot moving up‐and‐down) among distractor stimuli that shared target features (white dots moving up‐and‐down and black dots moving left‐and‐right). Search displays contained 1, 3, or 5 stimuli with a target present on half of the trials. Reaction time and accuracy in detecting presence of a target were recorded. Plasma levels of the AD biomarker pTau181 were determined by the National Centralized Repository for Alzheimer's Disease using Quanterix (v2). Plasma pTau181>4.09 pg/mL was considered AD positive. Result: AD positive (n = 19) and AD negative (n = 44) groups did not differ on age, education, sex, or MoCA scores. Despite similar behavioral performance in visual search, the groups displayed striking differences in pupillary responses across conditions. Both groups showed more pupil dilation with increasing display size, consistent with the application of cognitive effort. However, only the AD‐positive group showed significantly greater pupil dilation in the target‐present than target‐absent condition. This selective pupil modulation in the AD‐positive group may reflect greater demands associated with maintaining the search template in working memory or with performing template‐matching processes to guide attention. Conclusion: Results suggest early functional changes in the LC noradrenergic system are detectable in biomarker‐positive cognitively healthy older adults. Pupillary responsivity under task‐induced conjunction search conditions may serve as a particularly sensitive marker of preclinical AD. [ABSTRACT FROM AUTHOR]

Objective. To investigate the behavioral and neural effects of rule-based knowledge on motor sequence learning. Methods. The authors developed a novel 2-dimensional variant of the serial reaction time (SRT) task [...]

Objective: PD patients commonly exhibit executive dysfunction early in the disease course which may or may not predict further cognitive decline over time. Early emergence of visuospatial and memory impairments, in contrast, are more consistent predictors of an evolving dementia syndrome. Most prior studies using fMRI have focused on mechanisms of executive dysfunction and have demonstrated that PD patients exhibit hyperactivation that is dependent on the degree of cognitive impairment, suggestive of compensatory strategies. No study has evaluated whether PD patients with normal cognition (PD-NC) and PD patients with Mild Cognitive Impairment (PD-MCI) exhibit compensatory activation patterns during visuospatial task performance. Participants and Methods: 10 PD-NC, 12 PD-MCI, and 14 age and sex-matched healthy controls (HC) participated in the study. PD participants were diagnosed with MCI based on the Movement Disorders Society Task Force, Level II assessment (comprehensive assessment). Functional magnetic resonance imaging (fMRI) was performed during a motion discrimination task that required participants to identify the direction of horizontal global coherent motion embedded within dynamic visual noise under Low and High coherence conditions. Behavioral accuracy and functional activation were evaluated using 3 * 2 analyses of covariance (ANCOVAs) (group [HC, PD-NC, PD-MCI] * Coherence [High vs. Low]) accounting for age, sex, and education. Analyses were performed in R (v4.1.2(Team, 2013)). Results: PD-MCI (0.702± 0.269) patients exhibited significantly lower accuracy on the motion discrimination task than HC (0.853 ± 0.241; p = 0.033) and PD-NC (0.880 ± 0.208; p =0.039). A Group * Coherence interaction was identified in which several regions, including orbitofrontal, posterior parietal and occipital cortex, showed increased activation during High relative to Low coherence trials in the PD patient groups but not in the HC group. HC showed default mode deactivation and frontal-parietal activation during Low relative to High coherence trials that was not evident in the patient groups. Conclusions: PD-MCI patients exhibited worse visuospatial performance on a motion discrimination task than PD-NC and HC participants and exhibited hyperactivation of the posterior parietal and occipital regions during motion discrimination, suggesting possible compensatory activation. [ABSTRACT FROM AUTHOR]

Objective: Repetition priming is a form of implicit memory in which prior exposure to a stimulus facilitates the subsequent processing of that stimulus. While explicit memory has consistently been shown to decline with age, the effect of age on implicit memory remains unresolved. Most studies examining age-related effects on priming have utilized words or pictures of real objects with pre-existing representations that may differentially involve implicit and explicit memory processes across age groups. Repetition priming may also be influenced by attentional processes during encoding that are differentially affected by age. In a previous study using word-stem completion, we found that individual differences in cortical arousal, but not spatial attention, influenced the magnitude and temporal dynamics of conceptual priming in healthy older adults. The objective of this study is to investigate whether cortical arousal and spatial attention play differential roles in the magnitude and temporal dynamics of repetition priming in young and older adults using novel shapes that do not have pre-existing representations within memory. Participants and Methods: Healthy young (n=25, M age=19.4) and older adults (n=54, M age=70.0) completed a perceptual repetition priming task that was followed by a recognition memory test and an alerting/spatial orienting task from which behavioral measures of cortical arousal and spatial attention were derived. Older adults also completed a battery of neuropsychological tests. In the perceptual priming task, participants made a speeded judgment on whether novel nonverbal shapes had "closed" or "open" perimeters. Each shape was presented twice: half following the first presentation (immediate repetition) and half after three intervening items (delayed repetition). Participants were then shown closed and open versions of each shape and asked to identify which version was presented in the previous task. In the alerting/orienting task, participants made a speeded response to the location of a visual target; on a subset of trials, either nonspatial alerting or spatial orienting cues were presented 300ms prior to the target. Results: Response times were slower and judgment accuracy greater in older adults (p s<0.05). However, the groups showed comparable levels of immediate and delayed repetition priming along with chance levels of recognition memory accuracy. Cortical arousal was reduced (p <0.001) and costs associated with spatial attention were larger (p <0.01) in the older adults. Despite comparable priming, cortical arousal and spatial attention were differentially related to priming across groups. In the young group, lower cortical arousal was associated with greater delayed priming (r=-.47, p =0.017) and slower decay rate (r=.44, p =0.03). In the older group, higher cost of spatial orienting was associated with greater immediate priming (r=.40, p =0.003) and faster decay rate (r=.29, p =0.03). Better category fluency performance was also associated with greater immediate priming (r=.32, p =0.035) and faster decay rate (r=.34, p =0.025) in older adults. Conclusions: These findings suggest that different attentional systems support repetition priming across age groups. Priming is modulated by the efficiency of cortical arousal in young adults, but by the costs of spatial attention in older adults with reduced cortical arousal, consistent with a shift from bottom-up to top-down attentional processes and broader attentional scope with age. [ABSTRACT FROM AUTHOR]

Introduction: During the clinical assessment of episodic memory, encoding ability is typically inferred from immediate recall performance. This dependency on effortful retrieval may not be optimal for estimating encoding, particularly in the presence of executive dysfunction. We examined whether a test of immediate recognition memory could meaningfully supplement recall in estimating encoding and provide unique information about memory retention. Method: Fifty older adult outpatients were administered a neuropsychological test battery including original and revised versions of the Hopkins Verbal Learning Test; the former (HVLT) assesses recognition memory immediately after learning trials, while the latter (HVLT-R) assesses only delayed recognition. Hierarchical regressions evaluated the incremental value of immediate recognition in predicting both delayed verbal and visual recognition. ANCOVA was performed on subgroups defined by the number of impaired performances on executive functioning tests (EF-intact, EF-1, EF-2) to examine the influence of executive impairment on measures of immediate recall and recognition. Recall- and recognition-based estimates of verbal memory retention were also compared across groups to determine whether they yield distinct patterns of memory consolidation. Results: Immediate verbal recognition accounted for significant variance in both delayed verbal and visual recognition beyond immediate recall, age, and education. Although subgroups were demographically similar, EF-1 and EF-2 performed significantly worse than EF-intact across verbal and visual memory recall. Contrastingly, there were no group differences in immediate recognition. Subgroups attained similar scores on a conventional, recall-based memory retention measure, but EF-2 showed relatively greater forgetting on a recognition-based retention measure. Conclusions: Immediate verbal recognition is an independent determinant of delayed memory performance but is not captured in current test paradigms. Study results provide proof-of-concept that recognition testing at learning can provide a more comprehensive index of encoding ability than recall alone, may facilitate disentangling memory functions from executive deficits, and could have important downstream implications for estimating memory consolidation. [ABSTRACT FROM AUTHOR]

Background: Previous epidemiologic studies have reported adverse neurodevelopmental sequelae following prenatal infectious exposure, yet long-term effects estimated from these observational studies are often subject to biases due to confounding and loss to follow-up.Objectives: We demonstrate the joint use of inverse probability (IP) treatment and censoring weights when evaluating neurotoxic effects of prenatal bacterial infection.Methods: We applied IP weighting for both treatment and censoring to estimate the effects of maternal bacterial infection during pregnancy on mean intelligence quotient (IQ) scores measured at age 7 using the Wechsler Intelligence Scale for Children. Participants were members of a population-based pregnancy cohort recruited in the Boston and Providence sites of the Collaborative Perinatal Project between 1959 and 1966 (n = 11 984). We calculated average treatment effects (ATE) and average treatment effects on the treated (ATT) using IP weights estimated via generalized boosted models.Results: ATE- and ATT-weighted mean IQ scores were lowest among offspring exposed to multi-systemic bacterial infection during pregnancy and highest for those unexposed. The effects of prenatal bacterial infection were greater among male offspring, particularly on performance IQ scores. Offspring who were exposed to multi-systemic bacterial infection in the third trimester displayed the largest reduction in mean full-scale, verbal, and performance IQ scores at age 7 compared to those unexposed or exposed in earlier trimesters.Conclusions: We find that prenatal bacterial infection is associated with cognitive impairments at age 7. Associations are strongest for more severe infections, that occur in the third trimester, and among males. Public health intervention targeting bacterial infection in pregnant women may help enhance the cognitive development of offspring. [ABSTRACT FROM AUTHOR]

The Hick-Hyman law states that choice response time (RT) increases linearly with increasing information uncertainty. Neuroimaging studies suggest that the representation of uncertainty in support of response generation is mediated by the cognitive control network (CCN), which is disrupted in Alzheimer's disease (AD). Thus, we predicted that patients with AD would be sensitive to increased uncertainty particularly under conditions that place demands on the internal representation of uncertainty, and that choice RT performance under these conditions would be associated with performance on tests of executive function. Cognitively normal older adults (CN) and patients with AD completed card-sorting tasks that separately manipulated either externally cued uncertainty (i.e., number of sorting piles with a fixed probability of each stimulus type) or more internally driven uncertainty (i.e., the probability of each stimulus type with a fixed number of sorting piles). Consistent with our predictions, AD patients were impaired relative to CN particularly on the internally driven uncertainty task, and RT in this task was associated with performance on neuropsychological measures of executive functioning but not episodic memory. We suggest that this pattern of findings is consistent with presumed disruptions to the CCN in AD and provides neuropsychological evidence in support of the role of the CCN in the representation of uncertainty. [ABSTRACT FROM AUTHOR]

Objectives: Patients with Alzheimer’s disease (AD) demonstrate deficits in cross-cortical feature binding distinct from age-related changes in selective attention. This may have consequences for driving performance given its demands on multisensory integration. We examined the relationship of visuospatial search and binding to driving in patients with early AD and elderly controls (EC). Methods: Participants (42 AD; 37 EC) completed search tasks requiring either luminance-motion (L-M) or color-motion (C-M) binding, analogs of within and across visual processing stream binding, respectively. Standardized road test (RIRT) and naturalistic driving data (CDAS) were collected alongside clinical screening measures. Results: Patients performed worse than controls on most cognitive and driving indices. Visual search and clinical measures were differentially related to driving behavior across groups. L-M search and Trail Making Test (TMT-B) were associated with RIRT performance in controls, while C-M binding, TMT-B errors, and Clock Drawing correlated with CDAS performance in patients. After controlling for demographic and clinical predictors, L-M reaction time significantly predicted RIRT performance in controls. In patients, C-M binding made significant contributions to CDAS above and beyond demographic and clinical predictors. RIRT and C-M binding measures accounted for 51% of variance in CDAS performance in patients. Conclusions: Whereas selective attention is associated with driving behavior in EC, cross-cortical binding appears most sensitive to driving in AD. This latter relationship may emerge only in naturalistic settings, which better reflect patients’ driving behavior. Visual integration may offer distinct insights into driving behavior, and thus has important implications for assessing driving competency in early AD. (JINS, 2018, 24, 486–497) [ABSTRACT FROM AUTHOR]

Effective audiovisual sensory integration involves dynamic changes in functional connectivity between superior temporal sulcus and primary sensory areas. This study examined whether disrupted connectivity in early Alzheimer's disease (AD) produces impaired audiovisual integration under conditions requiring greater corticocortical interactions. Audiovisual speech integration was examined in healthy young adult controls (YC), healthy elderly controls (EC), and patients with amnestic mild cognitive impairment (MCI) using McGurk-type stimuli (providing either congruent or incongruent audiovisual speech information) under conditions differing in the strength of bottom-up support and the degree of top-down lexical asymmetry. All groups accurately identified auditory speech under congruent audiovisual conditions, and displayed high levels of visual bias under strong bottom-up incongruent conditions. Under weak bottom-up incongruent conditions, however, EC and amnestic MCI groups displayed opposite patterns of performance, with enhanced visual bias in the EC group and reduced visual bias in the MCI group relative to the YC group. Moreover, there was no overlap between the EC and MCI groups in individual visual bias scores reflecting the change in audiovisual integration from the strong to the weak stimulus conditions. Top-down lexicality influences on visual biasing were observed only in the MCI patients under weaker bottom-up conditions. Results support a deficit in bottom-up audiovisual integration in early AD attributable to disruptions in corticocortical connectivity. Given that this deficit is not simply an exacerbation of changes associated with healthy aging, tests of audiovisual speech integration may serve as sensitive and specific markers of the earliest cognitive change associated with AD. [ABSTRACT FROM AUTHOR]

Background: Cognitive tasks that require conjunctive binding – i.e., the integration of distinct features into a coherent representation – are sensitive to AD even in the preclinical stage. To further explore the sensitivity and utility of conjunctive binding tasks, we examined the association of visual sensory binding with novel CSF biomarkers of neurodegeneration in cognitively healthy older adults. Method: Two versions of a visual search paradigm were used to compare sensory conjunctive binding under conditions that differ in terms of the demands placed on cross‐cortical interactions. In these tasks, the binding of motion direction (up/down or left/right) must be integrated with either luminance contrast (black or white; within stream binding) or isoluminant color (red or green; across‐stream binding). We examined the association of cross‐cortical sensory binding efficiency (the difference in overall median response time between the color and luminance conditions) with CSF biomarkers of AD pathology (Aß42/Aß40 and p‐tau 181) and synapse function (neurogranin, NPTX2, and SNAP25) in N = 32 cognitively healthy older adults (mean age = 74.6, SD = 5.5; mean Dementia Rating Scale score (max score: 144) = 139.9, SD = 2.9). Result: Bivariate correlations revealed that cross‐cortical sensory binding efficiency was significantly associated with neurogranin (r =.36; p<.05) but not with Aß42 (r =.08; p =.68), p‐tau 181 (r =.25; p =.17), NPTX2 (r =.04; p =.82), or SNAP25 (r =.16; p =.41). In multiple regression analyses, neurogranin remained significantly associated with binding efficiency (ß =.46; p =.02) after controlling for age (ß =.03; p =.87), sex/gender (ß =.17; p =.33), and Aß42/Aß40 (ß =.30; p =.14). The addition of p‐tau 181 (ß =.45; p =.12) to this model slightly attenuated the association between neurogranin and binding (ß =.27; p =.24). Conclusion: In cognitively healthy older adults, efficiency of cross‐cortical conjunctive binding on a visual search task was significantly associated with CSF neurogranin, a post‐synaptic protein that is abundant in dendritic spines. Increased CSF neurogranin signifies synaptic degeneration and is specific to AD. Results suggest that visual sensory binding is a cognitive marker that is sensitive to changes in synaptic function in older adults who perform normally on traditional neuropsychological measures. Follow‐up investigation will determine if visual sensory binding efficiency is predictive of cognitive decline and subsequent dementia. [ABSTRACT FROM AUTHOR]

Previous findings that older drivers engage in strategic self-regulatory behaviors to minimize perceived safety risks are primarily based on survey reports rather than actual behavior. This study analyzed in-car video recording of naturalistic driving of 18 patients with Alzheimer disease (AD) and 20 age-matched controls in order to (1) characterize self-regulatory behaviors engaged by older drivers and (2) assess how behaviors change with cognitive impairment. Only participants who were rated “safe” on a prior standardized road test were selected for this study. Both groups drove primarily in environments that minimized the demands on driving skill and that incurred the least risk for involvement in major crashes. Patients with AD displayed further restrictions of driving behavior beyond those of healthy elderly individuals, suggesting additional regulation on the basis of cognitive status. These data provide critical empirical support for findings from previous survey studies indicating an overall reduction in driving mobility among older drivers with cognitive impairment. [ABSTRACT FROM PUBLISHER]

A battery of standard neuropsychological tests examining various features of executive function, attention, and visual perception was administered to 27 subjects with questionable to mild dementia and compared to a 4-point caregiver rating scale of driving ability. Based on the results of this study, a computerized maze task, employing 10 mazes, was administered to a second sample of 40 normal elders and questionable to moderately demented drivers. Comparison was made to the same caregiver rating scale as well as to crash frequency. In the first study of neuropsychological tests, errors on Porteus Mazes emerged as the only significant predictor of driving ability in a stepwise regression analysis. In the follow-up study employing the computerized mazes, all 10 mazes were significantly related to driving ability ratings. Computerized tests of maze performance offer promise as a screening tool to identify potential driving impairment among cognitively impaired elderly and demented drivers. [ABSTRACT FROM AUTHOR]

An attempt was made to construct and validate a questionnaire measure of hypnotic-like experiences based on Shor's (1979) 8-dimension phenomenological analysis of hypnosis. Separate item pools were developed to measure each disposition: Trance, Nonconscious Involvement, Archaic Involvement, Drowsiness, Relaxation, Vividness of Imagery, Absorption, and Access to the Unconscious. Based on preliminary testing (totel N = 856), a final questionnaire was produced containing 5 items measuring normal, everyday experiences in each domain. Results from a standardization sample (N = 468) showed that each of the subscales, except for Archaic Involvement, possessed satisfactory levels of internal consistency and test-retest reliability. Factor analysis indicated that 6 subscales loaded highly on a common factor similar to the absorption construct (Tellegen & Atkinson, 1974), while items pertaining to Relaxation and Archaic Involvement formed separate factors. Validation testing on 4 samples receiving the Harvard Group Scale of Hypnotic Susceptibility, Form A (HGSHS:A) of Shor and E. Orne (1962) (total N = 1855) showed that the Absorption and Trance dimensions correlated most strongly with HGSHS:A; the correlations with Drowsiness, Relaxation, and Nonconscious Involvement approached 0. The scales derived from Shor's analysis, however, did not improve the prediction of hypnotizability over that obtained with the absorption scale (Tellegen & Atkinson, 1974). [ABSTRACT FROM PUBLISHER]