Delayed Response Test Research Articles

Brain mGlu5 Is Linked to Cognition and Cigarette Smoking but Does Not Differ From Control in Early Abstinence From Chronic Methamphetamine Use.

The group-I metabotropic glutamate receptor subtype 5 (mGlu5) has been implicated in methamphetamine exposure in animals and in human cognition. Because people with methamphetamine use disorder (MUD) exhibit cognitive deficits, we evaluated mGlu5 in people with MUD and controls and tested its association with cognitive performance. Positron emission tomography was performed to measure the total VT of [18F]FPEB, a radiotracer for mGlu5, in brains of participants with MUD (abstinent from methamphetamine for at least 2 weeks, N = 14) and a control group (N = 14). Drug use history questionnaires and tests of verbal learning, spatial working memory, and executive function were administered. Associations of VT with methamphetamine use, tobacco use, and cognitive performance were tested. MUD participants did not differ from controls in global or regional VT, and measures of methamphetamine use were not correlated with VT. VT was significantly higher globally in nonsmoking vs smoking participants (main effect, P = .0041). MUD participants showed nonsignificant weakness on the Rey Auditory Verbal Learning Task and the Stroop test vs controls (P = .08 and P = .13, respectively) with moderate to large effect sizes, and significantly underperformed controls on the Spatial Capacity Delayed Response Test (P = .015). Across groups, Rey Auditory Verbal Learning Task performance correlated with VT in the dorsolateral prefrontal cortex and superior frontal gyrus. Abstinent MUD patients show no evidence of mGlu5 downregulation in brain, but association of VT in dorsolateral prefrontal cortex with verbal learning suggests that medications that target mGlu5 may improve cognitive performance.

Short-term memory, attentional control and brain size in primates.

Brain size variability in primates has been attributed to various domain-specific socio-ecological factors. A recently published large-scale study of short-term memory abilities in 41 primate species (ManyPrimates 2022 Anim. Behav. Cogn. 9, 428-516. (doi:10.26451/abc.09.04.06.2022)) did not find any correlations with 11 different proxies of external cognitive demands. Here, we found that the interspecific variation in test performance shows correlated evolution with total brain size, with the relationship becoming tighter as species with small sample sizes were successively removed, whereas it was not predicted by the often-used encephalization quotient. In a subsample, we also found that the sizes of brain regions thought to be involved in short-term memory did not predict performance better than overall brain size. The dependence on brain size suggests that domain-general cognitive processes underlie short-term memory as tested by ManyPrimates. These results support the emerging notion that comparative studies of brain size do not generally identify domain-specific cognitive adaptations but rather reveal varying selections on domain-general cognitive abilities. Finally, because attentional processes beyond short-term memory also affect test performance, we suggest that the delayed response test can be refined.

Cortical gray matter volume and working memory in a NHP model of AD‐like neuropathology

AbstractBackgroundAge‐related neurodegeneration characteristic of late‐onset Alzheimer’s disease (LOAD) begins in middle age, well before symptoms. Therefore, translational models to identify modifiable risk factors in middle‐age are needed to understand the etiology and identify early therapeutic targets for intervention. Vervet monkeys (Chlorocebus aethiops sabaeus), like humans, have complex central nervous systems and naturally develop several risk factors for LOAD with age, including obesity, prediabetes, hypertension and decline in physical function. Furthermore, aged vervets also recapitulate many of the characteristics of early AD that are associated with reduced brain volumes, including human‐like Aβ accumulation in the brain, greater Aβ plaque burden, and reduced CSF Aβ. Thus, these NHPs are ideal models for studying healthy versus neuropathological aging.MethodUsing structural magnetic resonance imaging and cognitive assessments, we examined the relationships between age, working memory, and neuroanatomy by measuring the thicknesses and volumes of AD‐signature cortical regions of interest (“meta‐ROIs”) in 46 middle‐aged to elderly female vervets (8‐29 years of age).ResultUsing linear mixed effects models with age as a fixed effect and individual as a random effect, we found that cortical gray matter volume significantly decreased with increasing age (β=‐51.94, SE=14.37; t=‐3.61; p<0.001). The thickness of the AD‐signature meta‐ROIs was not affected by age (β<0.01, SE<0.01; t=‐0.19; p=0.85), however, the volumetric meta‐ROI tended to decline with age in older animals (β=‐6.95, SE= 4.20; t=‐1.65; p= 0.098). In the precuneus, a component region of the meta‐ROI that has been shown to be reduced in preclinical AD, volume decreased with increasing age (β=‐1.69, SE=0.72; t=‐2.36; p= 0.023). In addition to these age‐related effects, the volume of the AD‐signature meta‐ROI was positively correlated with performance on the delayed response test of working memory (R= 0.235; p=0.026).ConclusionTaken together, these findings demonstrate that cortical gray matter diminishes with age in vervet monkeys in regions relevant to AD risk, and is associated with cognitive impairment. This study provides important insights about the relationships between age, neuroanatomy, and memory in vervets, and lays the groundwork for future investigations to identify at‐risk phenotypes such that therapeutic interventions may be tested in this nonhuman primate model.

Selective Loss of Thin Spines in Area 7a of the Primate Intraparietal Sulcus Predicts Age-Related Working Memory Impairment.

Brodmann area 7a of the parietal cortex is active during working memory tasks in humans and nonhuman primates, but the composition and density of dendritic spines in area 7a and their relevance both to working memory and cognitive aging remain unexplored. Aged monkeys have impaired working memory, and we have previously shown that this age-induced cognitive impairment is partially mediated by a loss of thin spines in prefrontal cortex area 46, a critical area for working memory. Because area 46 is reciprocally connected with area 7a of the parietal cortex and 7a mediates visual attention integration, we hypothesized that thin spine density in area 7a would correlate with working memory performance as well. To investigate the synaptic profile of area 7a and its relevance to working memory and cognitive aging, we investigated differences in spine type and density in layer III pyramidal cells of area 7a in young and aged, male and female rhesus macaques (Macaca mulatta) that were cognitively assessed using the delayed response test of working memory. Area 7a shows age-related loss of thin spines, and thin spine density positively correlates with delayed response performance in aged monkeys. In contrast, these cells show no age-related changes in dendritic length or branching. These changes mirror age-related changes in area 46 but are distinct from other neocortical regions, such as V1. These findings support our hypothesis that cognitive aging is driven primarily by synaptic changes, and more specifically by changes in thin spines, in key association areas.SIGNIFICANCE STATEMENT This study advances our understanding of cognitive aging by demonstrating the relevance of area 7a thin spines to working memory performance. This study is the first to look at cognitive aging in the intraparietal sulcus, and also the first to report spine or dendritic measures for area 7a in either young adult or aged nonhuman primates. These results contribute to the hypothesis that thin spines support working memory performance and confirm our prior observation that cognitive aging is driven by synaptic changes rather than changes in dendritic morphology or neuron death. Importantly, these data show that age-related working memory changes are not limited to disruptions of the prefrontal cortex but also include an association region heavily interconnected with prefrontal cortex.

Diverse Synaptic Distributions of G Protein-coupled Estrogen Receptor 1 in Monkey Prefrontal Cortex with Aging and Menopause.

Age- and menopause-related impairment in working memory mediated by the dorsolateral prefrontal cortex (dlPFC) occurs in humans and nonhuman primates. Long-term cyclic 17β-estradiol treatment rescues cognitive deficits in aged ovariectomized rhesus monkeys while restoring highly plastic synapses. Here we tested whether distributions of G protein-coupled estrogen receptor 1 (GPER1) within monkey layer III dlPFC synapses are sensitive to age and estradiol, and coupled to cognitive function. Ovariectomized young and aged monkeys administered vehicle or estradiol were first tested on a delayed response test of working memory. Then, quantitative serial section immunoelectron microscopy was used to determine the distributions of synaptic GPER1. GPER1-containing nonperforated axospinous synapse density was reduced with age, and partially restored with estrogen treatment. The majority of synapses expressed GPER1, which was predominately localized to presynaptic cytoplasm and mitochondria. GPER1 was also abundant at plasmalemmas, and within cytoplasmic and postsynaptic density (PSD) domains of dendritic spines. GPER1 levels did not differ with age or treatment, and none of the variables examined were tightly associated with cognitive function. However, greater representation of GPER1 subjacent to the PSD accompanied higher synapse density. These data suggest that GPER1 is positioned to support diverse functions key to synaptic plasticity in monkey dlPFC.

Differential effects of aging on dendritic spines in visual cortex and prefrontal cortex of the rhesus monkey

Aging decreases the density of spines and the proportion of thin spines in the non-human primate (NHP) dorsolateral prefrontal cortex (dlPFC). In this study, we used confocal imaging of dye-loaded neurons to expand upon previous results regarding the effects of aging on spine density and morphology in the NHP dlPFC and compared these results to the effects of aging on pyramidal neurons in the primary visual cortex (V1). We confirmed that spine density, and particularly the density of thin spines, decreased with age in the dlPFC of rhesus monkeys. Furthermore, the average head diameter of non-stubby spines in the dlPFC was a better predictor than chronological age of the number of trials required to reach criterion on both the delayed response test of visuospatial working memory and the delayed nonmatching-to-sample test of recognition memory. By contrast, total spine density was lower on neurons in V1 than in dlPFC, and neither total spine density, thin spine density, nor spine size in V1 was affected by aging. Our results highlight the importance and selective vulnerability of dlPFC thin spines for optimal prefrontal-mediated cognitive function. Understanding the nature of the selective vulnerability of dlPFC thin spines as compared to the resilience of thin spines in V1 may be a promising area of research in the quest to prevent or ameliorate age-related cognitive decline.

Psychostimulants Act Within the Prefrontal Cortex to Improve Cognitive Function

At low and clinically relevant doses, psychostimulants enhance cognitive and behavioral function dependent on the prefrontal cortex (PFC) and extended frontostriatal circuitry. These actions are observed in individuals with attention-deficit/hyperactivity disorder, as well as in normal human and animal subjects. Despite the widespread use of these drugs, the sites of action involved in their cognition-enhancing and therapeutic effects are poorly understood. Indirect and/or correlative evidence suggests the cognition-enhancing/therapeutic effects of psychostimulants may involve actions directly within the PFC or extended frontostriatal circuitry. The current studies examined the degree to which methylphenidate (MPH) (Ritalin) acts within distinct frontostriatal subfields to improve PFC-dependent cognition as measured in a delayed-response test of spatial working memory. Working memory performance was assessed following microinfusion of vehicle or varying doses of MPH (.03-8.0 μg/500 nL) directly into the dorsomedial PFC (dorsal prelimbic and dorsal anterior cingulate cortex), the ventromedial PFC (infralimbic), and the dorsomedial striatum of rats (n = 69). Methylphenidate infusion into the dorsomedial PFC, but not ventromedial PFC, elicited an inverted U-shaped facilitation of PFC-dependent cognition as measured in this task. The magnitude of this improvement was comparable with that seen with systemic administration. Additional studies demonstrated that although the dorsomedial striatum is necessary for accurate performance in this task, MPH infusion into this region did not affect working memory performance. These observations provide the first definitive evidence that the PFC is a site of action in the cognition-enhancing and presumably therapeutic actions of low-dose psychostimulants.

Novel study designs to investigate the placebo response

BackgroundInvestigating the size and mechanisms of the placebo response in clinical trials have relied on experimental procedures that simulate the double-blind randomized placebo-controlled design. However, as the conventional design is thought to elucidate drug rather than placebo actions, different methodological procedures are needed for the placebo response.MethodsWe reviewed the respective literature for trials designs that may be used to elucidate the size of the placebo response and the mechanisms associated with it.ResultsIn general, this can be done by either manipulation the information provided to the subjects, or by manipulation the timing of the drug applied. Two examples of each strategy are discussed: the "balanced placebo design" (BDP) and the "balanced cross-over design" (BCD) and their variants are based on false information, while the "hidden treatment" (HT) and the ""delayed response test" (DRT) are based on manipulating the time of drug action. Since most such approaches include deception or incomplete information of the subjects they are suitable for patient only with authorized deception.ConclusionBoth manipulating the information provided to subjects (BDP, DCD) or manipulating the timing of drug application (HT, DRT) allows overcoming some of the restrictions of conventional drug trials in the assessment of the placebo response, but they are feasible mostly in healthy subjects for ethical reasons.

Short-term Memory Testing in Domestic Horses: Experimental Design Plays a Role

This study investigated whether four horses could recall the location of a food objective in a two-choice delayed response test. During testing, horses stood unrestrained in a station where they observed the delivery of 30 g of grain into one of two containers. They were then released and allowed to go toward a container under the following contexts: immediate release or delayed release of 5, 10, 15, 20, or 30 seconds. Results showed that horses remembered the correct objective not only under the immediate release condition but also for all delayed release conditions tested. Observational data were also collected to determine whether the horses were indeed relying on memory to solve the delayed response problems or whether they were using orienting cues to maintain focus on the correct container. These data showed that the horses did not maintain visual contact with the objective during many of the trials; instead, they attended to an assortment of distractions in the surrounding area. Contrary to a previous report in which horses could not accurately respond in a similar situation after 10-second delays, these findings suggest that at least some horses are not as limited with respect to their ability to recall things and have an adequate spatial short-term memory. Experimental design seems to play a significant role in the outcome of this type of research.

Trial using multiple micronutrient food supplement and its effect on cognition

To test the efficacy of a multiple micronutrient food supplement (MMFS) on the nutrition status of school children and its effect on cognition. A MMFS was developed containing chelated ferrous sulphate and microencapsulated vitamin A, B2, B6, B12, folic acid, niacin, calcium pantothenate, vitamin C, vitamin E, lysine and calcium and the efficacy of the MMFS was assessed in 7-11 year old school children in Chennai, India by a pre-post test design. In the experimental group (N=51), the food in the school kitchen was cooked with the MMFS for the residential school children for a period of one year. The control group (N=72) consisted of day scholars who did not eat at the school. Hemoglobin, red blood cell count and hematocrit were measured at baseline and at the end of the study (after one year). A battery of 7 memory tests (The personal information test, the Mann-Suiter Visual memory screen for objects, The digit span forward test, The digit span backward test, The delayed response test, The Benton Visual Retention Test and The Cattells retentivity test), one test for attention and concentration (Letter cancellation test) and one test for intelligence (Ravens's coloured progressive matrices) were administered to all the children at baseline and endline. It was seen that there was a significant (P<0.05) improvement in the experimental group in hemoglobin, hematocrit and red cell count whereas in the control group there was a statistically significant decline(P<0.05) in hemoglobin and red cell count. In 5 tests out of the 7 memory tests and in the letter cancellation test for attention, the mean change in scores in the experimental group is significantly more (P<0.05) than the control group. There was no significant improvement in the overall intelligence as seen in the Ravens progressive matrices between the experimental and control groups at endline. The study shows that the MMFS is effective in improving the nutrition status and cognition in children.

Multiple micronutrient fortification of salt and its effect on cognition in Chennai school children.

To test the efficacy of a multiple micronutrient fortified salt in improving the micronutrient status and health of school children and its effect on cognition. A salt fortified with multiple micronutrients was developed containing chelated ferrous sulphate, microencapsulated vitamin A, B1, B2, B6, B12, folic acid, niacin, calcium pantothenate and iodine. The efficacy of the fortified salt was assessed in 7-11 year old school children in Chennai, India. In the experimental group (N=63), the food in the school kitchen was cooked with the fortified salt for a period of one year. The control group (N=66) consisted of day scholars who did not eat at the school. Hemoglobin, red blood cell count, hematocrit, serum vitamin A, urinary iodine and prevalence of angular stomatitis were measured at baseline and at the end of the study after one year. A battery of 7 memory tests (The personal information test, the Mann-Suiter Visual memory screen for objects, The digit span forward test, The digit span backward test, The delayed response test, The Benton Visual Retention Test and The Cattells retentivity test), one test for attention and concentration (Letter cancellation test) and one test for intelligence (Raven's coloured progressive matrices) were administered to all the children at baseline and endline. There was a significant (p<0.05) improvement in the experimental group in hemoglobin, red cell count, urinary iodine and serum vitamin A whereas in the control group there was a statistically significant decline (p<0.05) in hemoglobin, hematocrit, red cell count and urinary iodine. Angular stomatitis was eliminated from baseline 30.4% in the experimental group whereas it increased from 3.25% to 25.5% in the control group. In 4 tests out of the 7 memory tests and in the letter cancellation test for attention, the mean increment in scores in the experimental group is significantly more (p<0.05) than the control group. There was no significant improvement in overall intelligence as seen in the Ravens progressive matrices between the experimental and control groups. The study shows that the multiple micronutrient fortified salt is effective in improving multiple micronutrient status and cognition in children.

Age-related and individual differences in the performance of a delayed response task (the A-not-B task) in infant twins aged 7?12 months

The aim of the present work was to analyze the age-related dynamics and nature of interindividual differences in performing the A-not-B task, which addresses working memory in children aged 7-12 months. The cohort consisted of 150 children aged 7-12 months from mono- and dizygotic twin pairs. Working memory was assessed in terms of the maximum delay which the children could tolerate in a delayed response test (the A-not-B task). Performance of the task improved with age, such that a sharp change in the ability to tolerate the delay occurred between nine and ten months of age. Mental development as assessed using the Bayley scale showed a significant correlation with the duration of the delay in the task only after a threshold period (9-10 months of age) in the development of working memory. Analysis of intrapair correlations in mono- and dizygotic twins showed that interindividual differences in the A-not-B task delay at age 7-9 months were completely determined by individual environmental factors (including measurement errors), while at age 10-12 months the leading role in the interindividual variability in this measure was taken by the systematic environment. These results show that the abilities to tolerate delays at the beginning and end of the second six months of life are based on different mechanisms.

Cyclic Estrogen Replacement Improves Cognitive Function in Aged Ovariectomized Rhesus Monkeys

Among the identified risks and benefits of hormone-replacement therapy, the effects of treatment on cognitive function in postmenopausal women have proved difficult to define. Here we conducted a controlled, prospective analysis in a nonhuman primate model to test whether surgical menopause and estrogen replacement influence the cognitive outcome of normal aging. Sixteen aged rhesus monkeys were ovariectomized, and throughout the course of subsequent neuropsychological assessment, half received a regimen of low-dose, cyclic estradiol replacement. Hormone treatment substantially reversed the marked age-related impairment vehicle-injected monkeys exhibited on a delayed response test of spatial working memory. Modest improvement was also observed on a delayed nonmatching-to-sample recognition memory task. In contrast, ovariectomy exacerbated age-related deficits in object discrimination learning; the magnitude of this effect was equivalent among vehicle- and estrogen-treated monkeys. Together, these results demonstrate that ovarian hormone status can broadly influence normal cognitive aging in monkeys, affecting capacities mediated by multiple brain regions, including the prefrontal cortex and the medial temporal lobe memory system. The animal model established here should enable progress toward defining the neurobiological mechanisms that mediate the beneficial effects of estrogen on age-related cognitive decline in primates.

Similarities and Differences in the Neural Correlates of Episodic Memory Retrieval and Working Memory

Functional neuroimaging studies have shown that different cognitive functions activate overlapping brain regions. An activation overlap may occur because a region is involved in operations tapped by different cognitive functions or because the activated area comprises subregions differentially involved in each of the functions. To investigate these issues, we directly compared brain activity during episodic retrieval (ER) and working memory (WM) using event-related functional MRI (fMRI). ER was investigated with a word recognition test, and WM was investigated with a word delayed-response test. Two-phase trials distinguished between retrieval mode and cue-specific aspects of ER, as well as between encoding/maintenance and retrieval aspects of WM. The results revealed a common fronto-parieto-cerebellar network for ER and WM, as well as subregions differentially involved in each function. Specifically, there were two main findings. First, the results differentiated common and specific subregions within the prefrontal cortex: (i) left dorsolateral areas were recruited by both functions, possibly reflecting monitoring operations; (ii) bilateral anterior and ventrolateral areas were more activated during ER than during WM, possibly reflecting retrieval mode and cue-specific ER operations, respectively; and (iii) left posterior/ventral (Broca's area) and bilateral posterior/dorsal areas were more activated during WM than during ER, possibly reflecting phonological and generic WM operations, respectively. Second, hippocampal and parahippocampal regions were activated not only for ER but also for WM. This result suggests that indexing operations mediated by the medial temporal lobes apply to both long-term and short-term memory traces. Overall, our results show that direct cross-function comparisons are critical to understand the role of different brain regions in various cognitive functions.

Reward-dependent learning in neuronal networks for planning and decision making

Neuronal network models have been proposed for the organization of evaluation and decision processes in prefrontal circuitry and their putative neuronal and molecular bases. The models all include an implementation and simulation of an elementary reward mechanism. Their central hypothesis is that tentative rules of behavior, which are coded by clusters of active neurons in prefrontal cortex, are selected or rejected based on an evaluation by this reward signal, which may be conveyed, for instance, by the mesencephalic dopaminergic neurons with which the prefrontal cortex is densely interconnected. At the molecular level, the reward signal is postulated to be a neurotransmitter such as dopamine, which exerts a global modulatory action on prefrontal synaptic efficacies, either via volume transmission or via targeted synaptic triads. Negative reinforcement has the effect of destabilizing the currently active rule-coding clusters; subsequently, spontaneous activity varies again from one cluster to another, giving the organism the chance to discover and learn a new rule. Thus, reward signals function as effective selection signals that either maintain or suppress currently active prefrontal representations as a function of their current adequacy. Simulations of this variation-selection have successfully accounted for the main features of several major tasks that depend on prefrontal cortex integrity, such as the delayed-response test, the Wisconsin card sorting test, the Tower of London test and the Stroop test. For the more complex tasks, we have found it necessary to supplement the external reward input with a second mechanism that supplies an internal reward; it consists of an auto-evaluation loop which short-circuits the reward input from the exterior. This allows for an internal evaluation of covert motor intentions without actualizing them as behaviors, by simply testing them covertly by comparison with memorized former experiences. This element of architecture gives access to enhanced rates of learning via an elementary process of internal or covert mental simulation. We have recently applied these ideas to a new model, developed with M. Kerszberg, which hypothesizes that prefrontal cortex and its reward-related connections contribute crucially to conscious effortful tasks. This model distinguishes two main computational spaces within the human brain: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative and attentional processors. We postulate that workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice; they selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously co-activated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. This model makes predictions concerning the spatio-temporal activation patterns during brain imaging of cognitive tasks, particularly concerning the conditions of activation of dorsolateral prefrontal cortex and anterior cingulate, their relation to reward mechanisms, and their specific reaction during error processing.

Spatial, but not object, delayed response is impaired in early Parkinson's disease.

The authors hypothesized that the pathophysiology of early Parkinson's disease (PD) may selectively target structures that support visual working memory for spatial relations but leave structures that support working memory for featural characteristics of objects relatively intact. Fifteen PD and 15 normal control participants took a visual delayed-response test with a spatial condition and a (nonspatial) object condition, equating the perceptual difficulty of the tests for each participant. The stimuli were irregular polygons presented at different locations on a computer screen. Results revealed a selective impairment of spatial delayed response in PD, indicating a disruption of spatial working memory unconfounded by sensory processing difficulties. The selectivity of this deficit may reflect the circumscribed nature of pathophysiological change affecting the caudate nucleus in early PD.

Spatial, but not object, delayed response is impaired in early Parkinson's disease.

The authors hypothesized that the pathophysiology of early Parkinson's disease (PD) may selectively target structures that support visual working memory for spatial relations but leave structures that support working memory for featural characteristics of objects relatively intact. Fifteen PD and 15 normal control participants took a visual delayed-response test with a spatial condition and a (nonspatial) object condition, equating the perceptual difficulty of the tests for each participant. The stimuli were irregular polygons presented at different locations on a computer screen. Results revealed a selective impairment of spatial delayed response in PD, indicating a disruption of spatial working memory unconfounded by sensory processing difficulties. The selectivity of this deficit may reflect the circumscribed nature of pathophysiological change affecting the caudate nucleus in early PD.

The Relationship Between Vigilance Deficits and Traffic Injuries Involving Children

This study was designed to determine whether there is an increased frequency of deficits in impulse control, vigilance, or both, among child bicyclists or pedestrians who have been injured in traffic accidents, as assessed using objective measures and parent and teacher reports. This was a case-control study, in which cases were children injured as pedestrians or bicyclists (excluding those with severe head injuries) and controls were those injured as passengers or in some other manner in which the child's behavior was unlikely to be a factor. Children ages 5 to 15 years presenting to the emergency room of the Montreal Children's Hospital. For each of 286 cases, two controls were selected, making a total of 848 subjects. Among the cases, 172 were injured as pedestrians and 114 as bicyclists. Children were assessed using the Continuous Performance Task and the Delayed Response Test, both parts of a computerized test battery. Parents and teachers completed the Conners Abbreviated Symptom Questionnaire to assess hyperactivity. Cases and controls were similar on most sociodemographic and clinical measures but showed statistically significant differences in mean scores on the Continuous Performance Task measures of omissions and commissions, pointing to differences in vigilance, and on the Delayed Response Test measures of impulsivity. Mean Conners scale scores of both parent and teacher were significantly higher for cases than controls, and those of parents were higher than those of teachers. Among children whose behavior may have been a factor in the occurrence of an injury, there is subjective evidence of increased hyperactivity and objective evidence of deficits in vigilance and attention when compared with closely matched controls. These findings have important implications for prevention.

Evidence for task-dependent memory dysfunction in the aged monkey

Experimentally naive adult (9-11 years old) and aged (approximately 22-26 years old) female rhesus monkeys were evaluated on 3 neuropsychological tests of memory function. Aged monkeys were impaired in a delayed response test of visuospatial memory when the retention interval of the task was increased from 0 to 10 sec. These animals performed as well as younger subjects, however, at very short delays (0 and 1 sec), when the memory demands of the task were minimal. The same subjects were then trained in a delayed nonmatching to sample (DNMS) test of visual object recognition memory. Although they required significantly more training than the younger subjects to learn the nonmatching principle of the task, aged animals were only minimally impaired when recognition memory was tested at retention intervals ranging from 10 sec to 22 hr. In contrast to their relatively intact performance on the object recognition task, aged monkeys were dramatically impaired in a second version of DNMS that required subjects to remember the temporal order in which objects were presented. These findings support the view that certain memory functions are differentially susceptible to age-dependent deterioration. Since neuropsychological studies in young subjects demonstrate that different brain regions make relatively specific contributions to learning and memory, the task-dependent deficits observed in the aged monkey are important for determining which neural structures mediate age-dependent cognitive dysfunction. According to this perspective, aged monkeys were impaired on tasks known to be sensitive to prefrontal cortical damage, but the same animals performed well on a DNMS procedure that subjects with medial temporal lobe damage fail. These results suggest that prefrontal cortical dysfunction may mediate prominent aspects of age-dependent cognitive impairment in the monkey.

Effects of localized, chronic GABA infusions into different cortical areas of the photosensitive baboon, Papio papio

The effects of chronic (7 days) intracortical GABA infusions were investigated in both naturally photosensitive and non-photosensitive baboons. Bilateral and unilateral infusions into motor and occipital regions blocked photosensitivity, while premotor and prefrontal cortex infusions had no effect on the electro-clinical manifestations of this type of reflex epilepsy; the monkeys with prefrontal GABA infusions, however, showed selective attention deficits, detected with the delayed response test. In all cases a GABA withdrawal syndrome, appearing as epileptogenic spontaneous activity localized to the infused sites, was found at the cessation of GABA application. We conclude that GABAergic systems localizedat discrete cortical areas play an important role in photosensitivity and in the modulation of cognitive processes in the monkey.