Effects of prenatal bacterial infection on cognitive performance in early childhood.

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.

What underlies visual selective attention development? Evidence that age-related improvements in visual feature integration influence visual selective attention performance.

Visual selective attention (VSA) improves across childhood. Conjunction search tasks require integrating multiple visual features in order to find a target among distractors and are often used to measure VSA. Motivated by the visual system's architecture and developmental changes in neural connectivity, we predicted that feature integration across separate visual pathways (e.g., color and motion) should develop later than feature integration within the same visual pathways (e.g., luminance and motion). A total of 89 4- to 10-year-old children completed a visual search task that manipulated whether feature integration was between separate parallel visual pathways or within the same visual pathway. We first examined whether color-motion integration was associated with a performance cost relative to luminance-motion integration across childhood. We found that color-motion integration was worse than luminance-motion integration in early childhood but that this difference decreased with age. We also examined whether luminance-motion and color-motion visual search performance developed differently across childhood. Reaction time (RT) visual search slopes for the luminance-motion condition were both stable across childhood and steeper overall than those for the color-motion condition. In contrast, RT search slopes for the color-motion condition became steeperincrease across childhood. Finally, we found that age-related improvements in color-motion integration, relative to luminance-motion integration, were associated with longer color-motion search rates across childhood. These data suggest that age-related improvements in color-motion feature integration may increase competition between color-motion targets and distractors, thereby increasing the amount of time needed to process distractors as nontargets during the selection process.

Differential Contributions of Selective Attention and Sensory Integration to Driving Performance in Healthy Aging and Alzheimer's Disease.

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).

Effects of aging on externally cued and internally driven uncertainty representations.

OBJECTIVE: The Hick-Hyman law states that response time (RT) increases linearly with increasing information uncertainty. The effects of aging on uncertainty representations in choice RT paradigms remain unclear, including whether aging differentially affects processes mediating externally cued versus internally driven uncertainty. This study sought to characterize age-related differences in uncertainty representations using a card-sorting task. METHOD: The task separately manipulated internally driven uncertainty (i.e., probability of each stimulus type with fixed number of response piles) and externally cued uncertainty (i.e., number of response piles with fixed probability of each stimulus type). RESULTS: Older adults (OA) showed greater RT slowing than younger adults in response to uncertainty load, an effect that was stronger in the externally cued than internally driven condition. While both age groups showed lower accuracy and greater RTs in response to unexpected (surprising) stimuli in the internally driven condition at low uncertainty loads, OA were unable to distinguish between expected and nonexpected stimuli at higher uncertainty loads when the probability of each stimulus type was close to equal. Among OA, better performance on the internally driven, but not externally cued, condition was associated with better global cognitive performance and verbal fluency. CONCLUSIONS: Collectively, these findings provide behavioral evidence of age-related disruptions to bottom-up (externally cued) and top-down (supporting internally driven mental representations) resources to process uncertainty and coordinate task-relevant action. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effect of cognitive status on self-regulatory driving behavior in older adults: an assessment of naturalistic driving using in-car video recordings.

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.

Age-related enhancement in visuomotor learning by a dual-task.

Many daily activities require performance of multiple tasks integrating cognitive and motor processes. While the fact that both processes go through deterioration and changes with aging has been generally accepted, not much is known about how aging interacts with stages of motor skill acquisition under a cognitively demanding situation. To address this question, we combined a visuomotor adaptation task with a secondary cognitive task. We made two primary findings beyond the expected age-related performance deterioration. First, while young adults showed classical dual-task cost in the early motor learning phase dominated by explicit processes, older adults instead strikingly displayed enhanced performance in the later stage, dominated by implicit processes. For older adults, the secondary task may have facilitated a shift to their relatively intact implicit learning processes that reduced reliance on their already-deficient explicit processes during visuomotor adaptation. Second, we demonstrated that consistently performing the secondary task in learning and re-learning phases can operate as an internal task-context and facilitate visuomotor memory retrieval later regardless of age groups. Therefore, our study demonstrated age-related similarities and differences in integrating concurrent cognitive load with motor skill acquisition which, may in turn, contributes to the understanding of a shift in balance across multiple systems.

Effects of cholinesterase inhibitors on visual attention in drivers with Alzheimer disease.

OBJECTIVE: We conducted a combined observational cohort and case-control study in patients with Alzheimer disease (AD) to assess the effects of acetylcholinesterase inhibitor (ChEI) treatment on cognitive functions important for driving. METHODS: Performance of 24 outpatients with newly diagnosed (untreated) early-stage AD was compared before beginning ChEI (pre-ChEI) and after 3 months of therapy (post-ChEI) on a set of computerized tests of visual attention and executive function administered under both single-task and dual-task conditions. To address the limitation of a lack of an untreated control group in this observational cohort study, performance of 35 outpatients with newly diagnosed (untreated) early-stage AD (ChEI nonusers) were also compared with a demographically matched group of AD patients treated with stable doses of a ChEI (ChEI users) on these tasks. RESULTS: Performance was consistently worse under dual-task than single-task conditions regardless of ChEI treatment status. However, ChEI treatment consistently affected specific components of attention within each test across both sets of comparisons: ChEI treatment enhanced simulated driving accuracy and was associated with significantly better visual search target detection accuracy and response time in both pre-ChEI-post-ChEI and users-nonusers treatment comparisons. Cholinesterase inhibitor treatment also improved overall time to complete a set of mazes while not affecting accuracy of completion. CONCLUSIONS: Cholinesterase inhibitor treatment was associated with improvements in tests of executive function and visual attention. These findings could have important implications for patients who continue to drive in the early stages of AD.

Forward to the past: Revisiting the role of immediate recognition in the assessment of episodic memory.

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.

Phasic alerting enhances spatial orienting in healthy aging but not in mild cognitive impairment.

OBJECTIVE: Previous studies in young adults have demonstrated strong functional links between phasic alerting and exogenous orienting. The present study examined changes in the dynamic interaction between these attentional networks in healthy aging and in amnestic mild cognitive impairment. METHOD: Healthy young adults, healthy older adults, and patients with amnestic mild cognitive impairment (MCI) were asked to identify as quickly as possible the color of a target stimulus that appeared within one of 2 peripheral boxes. Orienting was manipulated by a brief flashing of the same (valid cue) or opposite (invalid cue) box in which the target subsequently appeared. Alerting was manipulated by presenting an auditory white noise burst simultaneously with the visual orienting cue on half of the trials. RESULTS: All 3 groups displayed significant alerting and orienting effects but differed in the nature of the interaction between alerting and orienting. As expected, young adults displayed increased orienting under high alerting conditions through a selective enhancement of validly cued targets. While older adults displayed a greater effect of alerting on orienting compared to young adults, MCI patients did not display a significant interaction between attentional networks. CONCLUSIONS: Results provide support for the presence of increased compensatory interactions between attentional networks in healthy aging that may be no longer effective with the emergence of clinical symptoms in MCI. The demonstration of qualitatively distinct effects of healthy aging and MCI suggests that behavioral tests of attentional network interactions may serve as cognitive markers in individuals at increased risk for developing AD. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Age-related changes in the neural dynamics of bottom-up and top-down processing during visual object recognition: an electrophysiological investigation.

When recognizing objects in our environments, we rely on both what we see and what we know. While older adults often display increased sensitivity to top-down influences of contextual information during object recognition, the locus of this increased sensitivity remains unresolved. To examine the effects of aging on the neural dynamics of bottom-up and top-down visual processing during rapid object recognition, we probed the differential effects of object perceptual ambiguity and scene context congruity on specific EEG event-related potential components indexing dissociable processes along the visual processing stream. Older adults displayed larger behavioral scene congruity effects than young adults. Older adults' larger visual P2 amplitudes to object perceptual ambiguity (as opposed to the scene congruity P2 effects in young adults) suggest continued resolution of perceptual ambiguity that interfered with scene congruity processing, while post-perceptual semantic integration (as indexed by N400) remained largely intact. These findings suggest that compromised bottom-up perceptual processing in healthy aging leads to an increased involvement of top-down processes to resolve greater perceptual ambiguity during object recognition.

Age-related changes in the functional integrity of the phasic alerting system: a pupillometric investigation.

Enhanced processing following a warning cue is thought to be mediated by a phasic alerting response involving the locus coeruleus-noradrenergic (LC-NA) system. We examined the effect of aging on phasic alerting using pupil dilation as a marker of LC-NA activity in conjunction with a novel assessment of task-evoked pupil dilation. While both young and older adults displayed behavioral and pupillary alerting effects, reflected in decreased RT and increased pupillary response under high (tone) versus low (no tone) alerting conditions, older adults displayed a weaker pupillary response that benefited more from the alerting tone. The strong association between dilation and speed displayed by older adults in both alerting conditions was reduced in young adults in the high alerting condition, suggesting that in young (but not older) adults the tone conferred relatively little behavioral benefit beyond that provided by the alerting effect elicited by the target. These findings suggest a functioning but deficient LC-NA alerting system in older adults, and help reconcile previous results concerning the effects of aging on phasic alerting.

Impaired integration of object feature knowledge in amnestic mild cognitive impairment.

OBJECTIVE: Accessing semantic representations of real-world objects requires integration of multimodal perceptual features that are represented across relevant neocortical areas. Early Alzheimer's disease (AD) neuropathology, including neurofibrillary tangles in the perirhinal cortex as well as disrupted cortico-cortical connectivity, would be expected to disrupt the integration of object features. This integration deficit may underlie AD patients' semantic memory deficits and would be predicted to be more prominent for living objects, which tend to be more defined by sensory features compared with nonliving objects. METHOD: Two experiments were conducted to assess feature integration in cognitively healthy older adults and patients with amnestic mild cognitive impairment (MCI). In both experiments, pictures of real-world objects were presented in congruent or incongruent colors. Participants were instructed to make a speeded color congruency judgment (Experiment 1) or name the presented surface color (Experiment 2). RESULTS: Across experiments, MCI patients showed a selective integration deficit for living, but not nonliving, objects across both experimental paradigms that was consistent with a deterioration in semantic structural representations rather than a deficit in controlled semantic retrieval. Planned secondary analyses with a subset of patients (Experiment 1) for whom PET imaging was available indicated that the degree of impairment was associated with the magnitude of cortical amyloid burden. CONCLUSIONS: These findings suggest that early AD pathology leads to impaired integration of distributed semantic object representations. The development of integration tasks as sensitive markers of early AD pathology may lead to more effective diagnostic tools for early detection and intervention. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Alzheimer's disease and the processing of uncertainty during choice task performance: Executive dysfunction within the Hick-Hyman law.

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.

Computerized maze navigation and on-road performance by drivers with dementia.

This study examined the ability of computerized maze test performance to predict the road test performance of cognitively impaired and normal older drivers. The authors examined 133 older drivers, including 65 with probable Alzheimer disease, 23 with possible Alzheimer disease, and 45 control subjects without cognitive impairment. Subjects completed 5 computerized maze tasks employing a touch screen and pointer as well as a battery of standard neuropsychological tests. Parameters measured for mazes included errors, planning time, drawing time, and total time. Within 2 weeks, subjects were examined by a professional driving instructor on a standardized road test modeled after the Washington University Road Test. Road test total score was significantly correlated with total time across the 5 mazes. This maze score was significant for both Alzheimer disease subjects and control subjects. One maze in particular, requiring less than 2 minutes to complete, was highly correlated with driving performance. For the standard neuropsychological tests, highest correlations were seen with Trail Making A (TrailsA) and the Hopkins Verbal Learning Tests Trial 1 (HVLT1). Multiple regression models for road test score using stepwise subtraction of maze and neuropsychological test variables revealed significant independent contributions for total maze time, HVLT1, and TrailsA for the entire group; total maze time and HVLT1 for Alzheimer disease subjects; and TrailsA for normal subjects. As a visual analog of driving, a brief computerized test of maze navigation time compares well to standard neuropsychological tests of psychomotor speed, scanning, attention, and working memory as a predictor of driving performance by persons with early Alzheimer disease and normal elders. Measurement of maze task performance appears to be useful in the assessment of older drivers at risk for hazardous driving.

Change in retinal structural anatomy during the preclinical stage of Alzheimer's disease.

INTRODUCTION: We conducted a 27-month longitudinal study of mid-life adults with preclinical Alzheimer's disease (AD), using spectral domain optical coherence tomography to compare changes in volume and thickness in all retinal neuronal layers to those of age-matched healthy control subjects. METHODS: Fifty-six older adults (mean age = 65.36 years) with multiple risk factors for AD completed spectral domain optical coherence tomography retinal imaging and cognitive testing at baseline. Twenty-seven months later, they completed the same examinations and an 18F-florbetapir positron emission tomography imaging study. RESULTS: Compared to healthy control subjects, those in the preclinical stage of AD showed a significant decrease in macular retinal nerve fiber layer (mRNFL) volume, over a 27-month follow-up interval period, as well as a decrease in outer nuclear layer and inner plexiform layer volumes and thickness in the inferior quadrant. However, only the mRNFL volume was linearly related to neocortical positron emission tomography amyloid standardized uptake value ratio after controlling for any main effects of age (R2 = 0.103; ρ = 0.017). Furthermore, the magnitude of mRNFL volume reduction was significantly correlated with performance on a task of participants' abilities to efficiently integrate visual and auditory speech information (McGurk effect). DISCUSSION: We observed a decrease in mRNFL, outer nuclear layer, and inner plexiform layer volumes, in preclinical AD relative to controls. Moreover, the largely myelinated axonal loss in the RNFL is related to increased neocortical amyloid-ß accumulation after controlling for age. Volume loss in the RNFL, during the preclinical stage, is not related to performance on measures of episodic memory or problem solving. However, this retinal change does appear to be modestly related to relative decrements in performance on a measure of audiovisual integration efficiency that has been recently advanced as a possible early cognitive marker of mild cognitive impairment.

Deterioration of visual-perceptual organization ability in Alzheimer's disease.

Although deterioration of higher-order visual information processing abilities occurs in Alzheimer's disease (AD), few cross-sectional or longitudinal studies have systematically examined this deficit. The performance of 135 patients with probable AD and 97 matched normal control (NC) participants were compared on a structured test of perceptual organization ability, the Hooper Visual Organization Test (VOT). Both the standard VOT score and a derived score that corrected for anomia were significantly lower for AD patients than for NC participants, but neither score was particularly effective at distinguishing between the groups. The derived VOT score proved to be a more effective measure of visuospatial functioning than the standard VOT score as it loaded with other visuospatial tests in a principal components analysis while the standard score loaded with language tests. The VOT was sensitive to severity of dementia in the AD patients. Longitudinal assessment of 37 of the AD patients and 46 NC participants revealed significant decline over one year in the VOT scores of AD patients, but not in those of NC participants. These results indicate that higher-order visual information processing is impaired in patients with AD and gradually deteriorates with disease progression. This deficit may not be a particularly salient early marker of the disease, but it may be useful in tracking disease course.

Dissociable Effects of Aging and Mild Cognitive Impairment on Bottom-Up Audiovisual Integration.

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.

Considering phasic alerting in Alzheimer's disease: comment on Tales et al. (2006).

A. Tales, R. J. Snowden, M. Brown, and G. Wilcock (2006) have questioned the authors' view of a possible interdependence between attentional systems mediating exogenous spatial orienting and phasic alerting as well as the authors' suggestion that phasic alerting deficits in patients with Alzheimer's disease (AD) may be influencing their performance on tests of spatial orienting. Consistent with this possibility, both laboratories have previously demonstrated increased spatial orienting and decreased phasic alerting in patients with AD. In Tales et al.'s current study, however, they have instead suggested that their results provide evidence for functional independence between these attentional systems in AD. In this commentary, the authors address the misinterpretations of their study and evaluate the degree to which Tales et al.'s study addresses the issues that they raise. Given Tales et al.'s difficulty performing analyses on response time data because of variance issues, the presence of a reduced (although not significant) alerting effect in Tales et al.'s AD group (consistent with the authors' previous findings), and a potential floor effect in their measure of alerting, the authors question the validity of Tales et al.'s conclusions and reaffirm their position that not considering interactions among attentional systems can lead to inaccurate characterizations of the mechanisms by which they operate.

Conditional associative learning of spatial and object information in children with attention deficit/hyperactivity disorder.

The present study assessed frontostriatal mediated memory functions in children with ADHD (N=12) and healthy control participants (N=12) using two tests of conditional associative learning (i.e., object and spatial) that shared similar stimulus-response association structures but that differed in terms of the demands placed upon strategic processes. Children with ADHD displayed normal performance on the object learning task but were impaired on the spatial learning task that placed greater demands on internally derived strategic processes. Secondary analyses further indicated that this strategic processing impairment cannot be attributed specifically to perseverative or working memory errors but rather appears to be related to a more general inability to maintain a high degree of consistency in responding across trials. Although the results of this study must be interpreted in light of the small sample sizes, they suggest that ADHD does not produce a basic deficit in acquiring stimulus-response associations previously shown to be associated with basal ganglia dysfunction. Rather, these findings suggest that the impaired conditional associative learning performance of children with ADHD is attributable to deficits in strategic processes previously been found to be dependent upon the integrity of the prefrontal cortex.

Learning motor sequences with and without knowledge of governing rules.

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 to test the effect of prior, verbalizable rule knowledge on motor learning behavior. To examine neurophysiological effects, they also performed functional magnetic resonance imaging on a small cohort of subjects while performing the same task. RESULTS: Behavioral data demonstrated that instruction on sequence-governing rules enhanced behavioral performance in both learning magnitudes and rates. The neuroimaging data revealed substantially different, but partially overlapping, learning-related activation patterns with and without prior rule instruction. Direct comparison of these 2 conditions revealed significantly different involvement of bilateral superior and anterior prefrontal cortex (Brodmann areas 8 and 10, respectively), right superior temporal cortex (BA 38/21), and left cerebellum. CONCLUSIONS: These behavioral findings demonstrate an advantage of teaching governing rules prior to 2D-SRT task performance. While these neuroimaging findings remain to be replicated in a larger cohort of subjects, results suggest that substantially different-though partially overlapping-brain regions subserve learning in these 2 rehabilitation-relevant conditions. Thus, appropriate choice of pretraining may benefit, for example, rehabilitation populations, at least in motor skill acquisition that requires sequencing.