Spatial Working Memory Accuracy Research Articles

O049 Insomnia severity and cognitive performance following two weeks’ nightly supplementation with 150mg Cannabidiol (CBD) for primary insomnia

Abstract Introduction Cannabidiol (CBD) may have sleep promoting effects, but clinical dosage and safety recommendations are still lacking. This study was the first to examine whether the approved Therapeutic Goods Association (TGA) daily over-the-counter maximum dose of oral CBD oil (150mg) improved the self-rated severity of primary insomnia and explored CBD effects on higher-order cognitive performance tasks. Methods Participants (n = 30) with moderate-severe primary insomnia completed a one-week single-blind placebo-run in period followed by a 2-week double blind, parallel, randomised placebo-controlled dosing period with four assessment visits (V0-V4). Intra-group and between-group Insomnia Severity Index (ISI) (V0 and V4) and cognitive performance (ECog Pro) (V1, V2 and V4) outcomes were assessed using paired sample t-test with independent t-tests, and separate linear mixed effect models with Maximum Likelihood Estimation and independent T-tests, respectively. Results Preliminary findings showed reduced ISI for treatment (n = 5; baseline mean 16.60 to 9.60 post treatment, mean difference = -7.00, SD = 4.47) and placebo (n = 8; baseline mean 18.13 to 9.25 post treatment, mean difference = -8.88, SD = 3.68) over time (both p < .001). At conclusion, CBD did not outperform a placebo (p = .427). Numeric and spatial working memory accuracy (%) and reaction time (ms) indicated no intra-group or between-group differences at any time point (all p > 0.05). Discussion Decreased insomnia severity from moderate to subthreshold levels indicate potential clinical benefits of daily CBD supplementation as a sleep aid for primary insomnia. Preserved higher-order neurocognitive abilities suggest a good safety profile.

Reward Expectation Differentially Modulates Global and Local Spatial Working Memory Accuracy.

Although it has been suggested that reward expectation affects the performance of spatial working memory tasks, controversial results have been found in previous experiments. Hence, it is still unclear to what extent reward expectation has an effect on working memory. To clarify this question, a memory-guided saccade task was applied, in which participants were instructed to retain and reconstruct a temporospatial sequence of four locations by moving their eyes in each trial. The global- and local-level spatial working memory accuracies were calculated to determine the reward effect on the global and local level of processing in spatial working memory tasks. Although high reward expectation enhanced the encoding of spatial information, the percentage of trials in which the cued location was correctly fixated decreased with increment of reward expectation. The reconstruction of the global temporospatial sequence was enhanced by reward expectation, whereas the local reconstruction performance was not affected by reward. Furthermore, the improvements in local representations of uncued locations and local sequences were at the cost of the representation of cued locations. The results suggest that the reward effect on spatial working memory is modulated by the level of processing, which supports the flexible resource theory during maintenance.

Microstructural Changes in Higher-Order Nuclei of the Thalamus in Patients With First-Episode Psychosis

BackgroundDisruption in the thalamus, such as volume, shape, and cortical connectivity, is regarded as an important pathophysiological mechanism in schizophrenia. However, there is little evidence of nuclei-specific structural alterations in the thalamus during early-stage psychosis, mainly because of the methodological limitations of conventional structural imaging in identifying the thalamic nuclei. MethodsA total of 37 patients with first-episode psychosis and 36 matched healthy control subjects underwent diffusion tensor imaging, diffusion kurtosis imaging, and T1-weighted magnetic resonance imaging. Connectivity-based segmentation of the thalamus was performed using diffusion tensor imaging, and averages of the diffusion kurtosis values, which represent microstructural complexity, were estimated using diffusion kurtosis imaging and were compared in each thalamic nucleus between the groups. ResultsThe mean kurtosis values in the thalamic regions with strong connections to the orbitofrontal cortex (F1,70 = 8.40, p < .01) and the lateral temporal cortex (F1,70 = 8.46, p < .01) were significantly reduced in patients with first-episode psychosis compared with those of the healthy control subjects. The mean kurtosis values in the thalamic region with strong connection to the orbitofrontal cortex showed a significant correlation with spatial working memory accuracy in patients with first-episode psychosis (r = .36, p < .05), whereas no significant correlation between these variables was observed in the healthy control subjects. ConclusionsThe observed pattern of reduced microstructural complexity in the nuclei not only highlights the involvement of the thalamus but also emphasizes the role of the higher-order nuclei in the pathophysiology beginning in the early stage of schizophrenia.

Spearmint Extract Improves Working Memory in Men and Women with Age-Associated Memory Impairment.

Objective: The purpose of this study was to investigate the effects of supplementation with a spearmint (Mentha spicata L.) extract, high in polyphenols including rosmarinic acid, on cognitive performance, sleep, and mood in individuals with age-associated memory impairment (AAMI).Design: Subjects with AAMI (N = 90; 67% female; age = 59.4 ± 0.6 years) were randomly assigned (n = 30/group) to consume 900, 600, or 0 mg/day (two capsules, once daily) spearmint extract for 90 days, in this double-blind, placebo-controlled trial. Assessments were completed for cognition (days 0, 45, and 90), sleep (days 0 and 90), and mood (days 0 and 90) by using the Cognitive Drug Research (CDR) System™, Leeds Sleep Evaluation Questionnaire (LSEQ), and Profile of Mood States (POMS™), respectively.Results: Quality of working memory and spatial working memory accuracy improved after supplementation with 900 mg/day spearmint extract by 15% (p = 0.0469) and 9% (p = 0.0456), respectively, versus placebo. Subjects consuming 900 mg/day spearmint extract reported improvement in their ability to fall asleep, relative to subjects consuming placebo (p = 0.0046). Overall treatment effects were evident for vigor-activity (p = 0.0399), total mood disturbance (p = 0.0374), and alertness and behavior following wakefulness (p = 0.0415), with trends observed for improvements after spearmint supplementation relative to placebo.Conclusions: These results suggest that the distinct spearmint extract may be a beneficial nutritional intervention for cognitive health in older subjects with AAMI.

Persisting neurobehavioral effects of developmental copper exposure in wildtype and metallothionein 1 and 2 knockout mice.

BackgroundMetallothioneins (MT) are small proteins, which are crucial for the distribution of heavy and transition metals. Previously, we found in mice that knockout of MT 1 and 2 genes (MTKO) impaired spatial learning and potentiated the learning impairment caused by developmental mercury exposure. The current study examined the neurocognitive and neurochemical effects of MTKO with the developmental copper (Cu) supplementation.MethodsWildtype (WT) and MTKO mice were given supplemental Cu (0, 10 or 50 mg/l) in their drinking water during gestation and until weaning. When the mice were young adults they were trained on the win-shift 8-arm radial maze test of spatial learning and memory. After cognitive testing, their brains were analyzed for norepinepherine, dopamine and serotonin levels.ResultsIn the spatial learning test, wildtype mice showed the normal sex difference with males performing more accurately than the females. This effect was eliminated by MTKO and restored by moderate Cu supplementation during development. In neurochemical studies, MTKO caused a significant overall increase in serotonin in all of the regions studied: the frontal cortex, posterior cortex, hippocampus, striatum, midbrain, and brainstem. MTKO also caused a significant increase in norepinepherine in the brainstem and hippocampus. In wildtype mice, Cu supplementation during development caused a significant decline in dopamine and norepinepherine in the midbrain and dopamine in the frontal cortex. These effects were blocked by MTKO.ConclusionsThe normal sex difference in spatial working memory accuracy, which was eliminated by MTKO, was restored by moderate copper supplementation. MTKO increased serotonin across all brain areas studied and increased norepinepherine only in the hippocampus and brainstem. MTKO blocked copper-induced decreases in dopamine and norepinepherine in the midbrain and dopamine in the frontal cortex.

A test of the reward-value hypothesis.

Rats retain source memory (memory for the origin of information) over a retention interval of at least 1week, whereas their spatial working memory (radial maze locations) decays within approximately 1day. We have argued that different forgetting functions dissociate memory systems. However, the two tasks, in our previous work, used different reward values. The source memory task used multiple pellets of a preferred food flavor (chocolate), whereas the spatial working memory task provided access to a single pellet of standard chow-flavored food at each location. Thus, according to the reward-value hypothesis, enhanced performance in the source memory task stems from enhanced encoding/memory of a preferred reward. We tested the reward-value hypothesis by using a standard 8-arm radial maze task to compare spatial working memory accuracy of rats rewarded with either multiple chocolate or chow pellets at each location using a between-subjects design. The reward-value hypothesis predicts superior accuracy for high-valued rewards. We documented equivalent spatial memory accuracy for high- and low-value rewards. Importantly, a 24-h retention interval produced equivalent spatial working memory accuracy for both flavors. These data are inconsistent with the reward-value hypothesis and suggest that reward value does not explain our earlier findings that source memory survives unusually long retention intervals.

ID 164 – TACS over the left dorsolateral prefrontal cortex improves hit rate, but not false alarm rate, in a spatial working memory task

Objective To investigate the role of the theta activity in the left DLPFC on visual-spatial working memory. Methods Fifteen healthy right-handed volunteers (9 females, age range: 20–26 years) were participated in this randomized, placebo-controlled, crossover study. Each of them completed a 2-back match-to-sample visual-spatial memory test during transcranial alternating current stimulation (tACS; 10 min, 1 mA peak-to-baseline, 6 Hz) and sham stimulation. A focal Laplacian electrode-montage with 5 electrodes was used for stimulation (3 cm 2 each, the central electrode at AF3). Before and after each session EEG was recorded. Results We observed a significant increase of the hit rate in the memory test during stimulation (Hit control = 68.8 ± 3.2%, Hit stimulation = 73.1 ± 3.5%; p = 0.007, g = 0.33 (Paired t -test and Hedges’ g statistics)), but no effect on the false alarm rate (FA control = 19.8 ± 2.2%, FA stimulation = 18.5 ± 2.5%; p = 0.55). EEG analysis revealed an increase of the local theta band power after the stimulation ( p = 0.048, g = 0.58). Conclusions tACS at 6 Hz over the left DLPFC increases the theta power and improves the hit rate in the 2-back visual-spatial working memory test. Key message Theta oscillations in the left DLPFC affect the spatial working memory accuracy.

Lower Working Memory Performance in Overweight and Obese Adolescents Is Mediated by White Matter Microstructure.

Elevated body mass index (BMI) is associated with deficits in working memory, reduced gray matter volume in frontal and parietal lobes, as well as changes in white matter (WM) microstructure. The current study examined whether BMI was related to working memory performance and blood oxygen level dependent (BOLD) activity, as well as WM microstructure during adolescence. Linear regressions with BMI and (1) verbal working memory BOLD signal, (2) spatial working memory BOLD signal, and (3) fractional anisotropy (FA), a measure of WM microstructure, were conducted in a sample of 152 healthy adolescents ranging in BMI. BMI was inversely related to IQ and verbal and spatial working memory accuracy; however, there was no significant relationship between BMI and BOLD response for either verbal or spatial working memory. Furthermore, BMI was negatively correlated with FA in the left superior longitudinal fasciculus (SLF) and left inferior longitudinal fasciculus (ILF). ILF FA and IQ significantly mediated the relationship between BMI and verbal working memory performance, whereas SLF FA, but not IQ, significantly mediated the relationship between BMI and accuracy of both verbal and spatial working memory. These findings indicate that higher BMI is associated with decreased FA in WM fibers connecting brain regions that support working memory, and that WM microstructural deficits may underlie inferior working memory performance in youth with higher BMI. Of interest, BMI did not show the same relationship with working memory BOLD activity, which may indicate that changes in brain structure precede changes in function.

Characterization of a normal control group: Are they healthy?

We examined the health of a control group (18–81years) in our aging study, which is similar to control groups used in other neuroimaging studies. The current study was motivated by our previous results showing that one third of the elder control group had moderate to severe white matter hyperintensities and/or cortical volume loss which correlated with poor performance on memory tasks. Therefore, we predicted that cardiovascular risk factors (e.g., hypertension, high cholesterol) within the control group would account for significant variance on working memory task performance. Fifty-five participants completed 4 verbal and spatial working memory tasks, neuropsychological exams, diffusion tensor imaging (DTI), and blood tests to assess vascular risk. In addition to using a repeated measures ANOVA design, a cluster analysis was applied to the vascular risk measures as a data reduction step to characterize relationships between conjoint risk factors. The cluster groupings were used to predict working memory performance. The results show that higher levels of systolic blood pressure were associated with: 1) poor spatial working memory accuracy; and 2) lower fractional anisotropy (FA) values in multiple brain regions. In contrast, higher levels of total cholesterol corresponded with increased accuracy in verbal working memory. An association between lower FA values and higher cholesterol levels were identified in different brain regions from those associated with systolic blood pressure. The conjoint risk analysis revealed that Risk Cluster Group 3 (the group with the greatest number of risk factors) displayed: 1) the poorest performance on the spatial working memory tasks; 2) the longest reaction times across both spatial and verbal memory tasks; and 3) the lowest FA values across widespread brain regions. Our results confirm that a considerable range of vascular risk factors are present in a typical control group, even in younger individuals, which have robust effects on brain anatomy and function. These results present a new challenge to neuroimaging studies both for defining a cohort from which to characterize ‘normative’ brain circuitry and for establishing a control group to compare with other clinical populations.

The association between aerobic fitness and executive function is mediated by prefrontal cortex volume

Aging is marked by a decline in cognitive function, which is often preceded by losses in gray matter volume. Fortunately, higher cardiorespiratory fitness (CRF) levels are associated with an attenuation of age-related losses in gray matter volume and a reduced risk for cognitive impairment. Despite these links, we have only a rudimentary understanding of whether fitness-related increases in gray matter volume lead to elevated cognitive function. In this cross-sectional study, we examined whether the association between higher aerobic fitness levels and elevated executive function was mediated by greater gray matter volume in the prefrontal cortex (PFC). One hundred and forty-two older adults (mean age=66.6 years) completed structural magnetic resonance imaging (MRI) scans, CRF assessments, and performed Stroop and spatial working memory (SPWM) tasks. Gray matter volume was assessed using an optimized voxel-based morphometry approach. Consistent with our predictions, higher fitness levels were associated with: (a) better performance on both the Stroop and SPWM tasks, and (b) greater gray matter volume in several regions, including the dorsolateral PFC (DLPFC). Volume of the right inferior frontal gyrus and precentral gyrus mediated the relationship between CRF and Stroop interference while a non-overlapping set of regions bilaterally in the DLPFC mediated the association between CRF and SPWM accuracy. These results suggest that specific regions of the DLPFC differentially relate to inhibition and spatial working memory. Thus, fitness may influence cognitive function by reducing brain atrophy in targeted areas in healthy older adults.

Examining the nootropic effects of a special extract of Bacopa monniera on human cognitive functioning: 90 day double‐blind placebo‐controlled randomized trial

While Ayurvedic medicine has touted the cognitive enhancing effects of Bacopa monniera for centuries, there is a need for double-blind placebo-controlled investigations. One hundred and seven healthy participants were recruited for this double-blind placebo-controlled independent group design investigation. Sixty-two participants completed the study with 80% treatment compliance. Neuropsychological testing using the Cognitive Drug Research cognitive assessment system was conducted at baseline and after 90 days of treatment with a special extract of Bacopa monniera (2 x 150 mg KeenMind) or placebo. The Bacopa monniera product significantly improved performance on the 'Working Memory' factor, more specifically spatial working memory accuracy. The number of false-positives recorded in the Rapid visual information processing task was also reduced for the Bacopa monniera group following the treatment period. The current study provides support for the two other published studies reporting cognitive enhancing effects in healthy humans after a 90 day administration of the Bacopa monniera extract. Further studies are required to ascertain the effective dosage range, the time required to attain therapeutic levels and the effects over a longer term of administration.

Differential contributions of dopaminergic D1- and D2-like receptors to cognitive function in rhesus monkeys

Dopaminergic neurotransmission is critically involved in many aspects of complex behavior and cognition beyond reward/reinforcement and motor function. Mental and behavioral disorders associated with major disruptions of dopamine neurotransmission, including schizophrenia, attention deficit/hyperactivity disorder, Parkinson's disease, Huntington's disease, and substance abuse produce constellations of neuropsychological deficits in learning, memory, and attention in addition to other defining symptoms. To delineate the role dopaminergic D1- and D2-like receptor subtypes play in complex brain functions. Monkeys (N = 6) were trained on cognitive tests adapted from a human neuropsychological assessment battery (CAmbridge Neuropsychological Test Automated Battery). The battery included tests of spatial working memory (self-ordered spatial search task), visuo-spatial associative memory and learning (visuo-spatial paired associates learning task, vsPAL) and motivation (progressive ratio task, PR). Tests of motor function (bimanual motor skill task, BMS; rotating turntable task, RTT) were also included. The effects of the dopamine D2-like antagonist raclopride (10-56 microg/kg, i.m.) and the D1-like antagonist SCH23390 (SCH, 3.2-56 microg/kg, i.m.) on cognitive performance were then determined. Deficits on PR, RTT, and BMS performance were observed after both raclopride and SCH23390. Spatial working memory accuracy was reduced to a greater extent by raclopride than by SCH, which was unexpected, given prior reports on the involvement of D1 signaling for spatial working memory in monkeys. Deficits were observed on vsPAL performance after raclopride, but not after SCH23390. The intriguing results suggest a greater contribution of D2- over D1-like receptors to both spatial working memory and object-location associative memory.

The α 2 agonist, clonidine, improves spatial working memory performance in Parkinson's disease

Previous work has shown that the dopaminergic defect in Parkinson's disease is involved, to some extent, in the “frontal”-like impairment in spatial working memory and attentional set-shifting functions. We investigated whether an α 2 agonist, clonidine (0.5 and 2 μg/kg, per os), could alleviate spatial working memory and attentional set-shifting defect in Parkinson's disease patients. We observed that 2 μg/kg clonidine stimulated spatial working memory accuracy, but had no effect on attentional set shifting or visual recognition memory. Clonidine was also effective in stimulating spatial working memory after withdrawal of dopaminergic drugs, and when this was done, its effect was greater in severe Parkinson's disease patients. In contrast, clonidine failed to stimulate visual recognition memory. These results suggest that disrupted activation of α 2 adrenoceptors may contribute to the impairment of spatial working memory in Parkinson's disease.