Memory Task Performance Research Articles

Right parietal cortex mediates recognition memory for melodies.

Functional brain imaging studies have highlighted the significance of right‐lateralized temporal, frontal and parietal brain areas for memory for melodies. The present study investigated the involvement of bilateral posterior parietal cortices (PPCs) for the recognition memory of melodies using transcranial direct current stimulation (tDCS). Participants performed a recognition task before and after tDCS. The task included an encoding phase (12 melodies), a retention period, as well as a recognition phase (24 melodies). Experiment 1 revealed that anodal tDCS over the right PPC led to a deterioration of overall memory performance compared with sham. Experiment 2 confirmed the results of Experiment 1 and further showed that anodal tDCS over the left PPC did not show a modulatory effect on memory task performance, indicating a right lateralization for musical memory. Furthermore, both experiments revealed that the decline in memory for melodies can be traced back to an interference of anodal stimulation on the recollection process (remember judgements) rather than to familiarity judgements. Taken together, this study revealed a causal involvement of the right PPC for memory for melodies and demonstrated a key role for this brain region in the recollection process of the memory task.

Chronic reactive gliosis following regulatory T cell depletion during acute MCMV encephalitis.

Long-term, persistent central nervous system inflammation is commonly seen following brain infection. Using a murine model of viral encephalitis (murine cytomegalovirus, MCMV) we have previously shown that post-encephalitic brains are maintained in an inflammatory state consisting of glial cell reactivity, retention of brain-infiltrating tissue-resident memory CD8+ T-cells, and long-term persistence of antibody-producing cells of the B-lineage. Here, we report that this neuroinflammation occurs concomitantly with accumulation and retention of immunosuppressive regulatory T-cells (Tregs), and is exacerbated following their ablation. However, the extent to which these Tregs function to control neuroimmune activation following MCMV encephalitis is unknown. In this study, we used Foxp3-diphtheria toxin receptor-GFP (Foxp3-DTR-GFP) transgenic mice, which upon administration of low-dose diphtheria toxin (DTx) results in the specific depletion of Tregs, to investigate their function. We found treatment with DTx during the acute phase of viral brain infection (0-4 dpi) resulted in depletion of Tregs from the brain, exacerbation of encephalitis (i.e., increased presence of CD4+ and CD8+ T-cells), and chronic reactive phenotypes of resident glial cells (i.e., elevated MHC Class II as well as PD-L1 levels, sustained microgliosis, and increased glial fibrillary acidic protein (GFAP) expression on astrocytes) versus untreated, infected animals. This chronic proinflammatory environment was associated with reduced cognitive performance in spatial learning and memory tasks (Barnes Maze) by convalescent animals. These data demonstrate that chronic glial cell activation, unremitting post-encephalitic neuroinflammation, and its associated long-term neurological sequelae in response to viral brain infection are modulated by the immunoregulatory properties of Tregs. GLIA 2015;63:1982-1996.

A commentary on "Antipsychotic-induced Parkinsonism is associated with working memory deficits in schizophrenia-spectrum disorders".

A commentary on "Antipsychotic-induced Parkinsonism is associated with working memory deficits in schizophrenia-spectrum disorders".

Memory and brain-derived neurotrophic factor after subchronic or chronic amphetamine treatment in an animal model of mania

Progression of bipolar disorder (BD) has been associated with cognitive impairment and changes in neuroplasticity, including a decrease in serum brain-derived neurotrophic factor (BDNF). However, no study could examine BDNF levels directly in different brain regions after repeated mood episodes to date. The proposed animal model was designed to mimic several manic episodes and evaluate whether the performance in memory tasks and BDNF levels in hippocampus, prefrontal cortex, and amygdala would change after repeated amphetamine (AMPH) exposure. Adult male Wistar rats were divided into subchronic (AMPH for 7 days) and chronic groups (35 days), mimicking manic episodes at early and late stages of BD, respectively. After open field habituation or inhibitory avoidance test, rats were killed, brain regions were isolated, and BDNF mRNA and protein levels were measured by quantitative real-time PCR and ELISA, respectively. AMPH impaired habituation memory in both subchronic and chronic groups, and the impairment was worse in the chronic group. This was accompanied by increased Bdnf mRNA levels in the prefrontal cortex and amygdala region, as well as reduced BDNF protein in the hippocampus. In the inhibitory avoidance, AMPH significantly decreased the change from training to test when compared to saline. No difference was observed between subchronic and chronic groups, although chronically AMPH-treated rats presented increased Bdnf mRNA levels and decreased protein levels in hippocampus when compared to the subchronic group. Our results suggest that the cognitive impairment related to BD neuroprogression may be associated with BDNF alterations in hippocampus, prefrontal cortex, and amygdala.

Limited capacity for memory tasks with multiple features within a single object

Memory for multiple features might be limited by the number of features, the number of objects, or both. To focus on the role of features, we tested memory for a variable number of features within a single object. Subjects studied a single ellipse that varied in four features: size, orientation, contrast, and position. We conducted two experiments that differed in how memory was tested. If performance is limited only by the number of objects to be remembered, there should be no effect of the number of relevant features within a single object. Instead, for both experiments, the proportion correct was lower when four features had to be remembered rather than one. The magnitude of these effects varied with the details of the two experiments. Although similar results have been reported for experiments using multiple objects, the present experiments are some of the first to have demonstrated such an effect for a single object. This result is inconsistent with theories in which visual memory has a discrete limit on the number of stored objects, and no limit on the stored features within an object. Instead, it seems likely that objects and features both play roles in limiting performance in memory tasks.

Effects of trait test anxiety and state anxiety on children's working memory task performance

This study examined the effects of (a) trait test anxiety versus state anxiety and (b) working memory load on children's mental arithmetic task performance. Participants (N=128; 11-year-olds) completed a mental arithmetic task at varying levels of working memory load under high and low situational stress conditions. Measures of task accuracy and accuracy/response time served as indicators of performance effectiveness and processing efficiency. The findings showed that trait test anxiety has a direct and detrimental effect on working memory. The effect was not mediated by state test anxiety. We also demonstrated that the adverse effects of trait test anxiety on efficiency are independent of working memory load. However, anxiety-related deficits in effectiveness occur at higher levels of working memory load. Findings are interpreted as being largely consistent with the attentional control theory.

The role of parkinson's disease-associated receptor GPR37 in the hippocampus: functional interplay with the adenosinergic system.

GPR37 is an orphan G protein-coupled receptor mostly enriched in brain areas such as the cerebellum, striatum, and hippocampus. Identified as a substrate of parkin, GPR37 has been suggested to play a role in Parkinson's disease. Distributed throughout the brain, the function of GPR37, however, remains unknown. We now provide the first mapping of GPR37 within the hippocampus, where GPR37 is widely expressed and localized at the level of the extrasynaptic plasma membrane of dendritic spines, dendritic shafts, and axon terminals. GPR37 per se does not appear to play a role in learning and memory, since knocking out GPR37 (GPR37-KO) did not alter the performance in different hippocampal-related memory tasks. This is in agreement with slice electrophysiology experiments showing no differences both in short-term plasticity paired-pulse facilitation and long-term potentiation between WT and GPR37-KO mice. However, we report a potential functional interaction between GPR37 and adenosine A2A receptors (A2 A R) in the hippocampus, with A2 A R modulating the GPR37-associated phenotype. Thus, the absence of GPR37 appeared to sensitize mice to hippocampal A2 A R-mediated signaling, as observed by the effect of the A2 A R antagonist SCH58261 increasing synaptic depotentiation, reducing novel object recognition memory and reverting the anxiolytic effect of GPR37 deletion. Collectively, these findings afford insight into the localization and role of the orphan GPR37 within the hippocampus with potential involvement in A2 A R function (i.e., A2 A R sensitization). GPR37 is an orphan G protein-coupled receptor widely expressed in the hippocampus and localized at the level of the extrasynaptic plasma membrane of dendritic spines, dendritic shafts and axon terminals. This orphan receptor per se does not appear to directly control the learning and memory processes; however knocking-out GPR37 triggers anxiolytic-like effects and sensitizes mice to hippocampal A2A R-mediated signalling.

Transcranial Direct Current Stimulation of Dorsolateral Prefrontal Cortex of Major Depression: Improving Visual Working Memory, Reducing Depressive Symptoms

Recent studies on major depression have used non-invasive brain stimulation techniques such as transcranial direct current stimulation to improve impaired emotion and cognition in MD. However, such experiments have yielded mixed results specifically with respect to cognition in MD. This study aimed to investigate whether anodal and cathodal tDCS applied over dorsolateral prefrontal cortex (DLPFC), would significantly improve visual working memory and reduce depressive symptoms in patients with MD. Thirty ( N =30) patients with major depression were randomly assigned to receive either experimental (active) or control (sham) tDCS. Participants underwent a series of visual memory neuropsychological tasks and Beck Depression Inventory (BDI) and Hamilton Depression Scale (HDRS). After 10 sessions of anodal and cathodal tDCS, patients showed improved performance in visual working memory tasks. Specifically, active stimulation improved visual memory performance for the experimental group relative to baseline, whereas sham stimulation did not differentiate performance from baseline in the control group.

Behavioural and Cognitive Assessment of Aldehyde Dehydrogenase 2 (Aldh2) Null Mice: a New, Oxidative Stress‐Based Model of Age‐Related Alzheimer's Disease (AD)

The study of AD has been hindered by the absence of animal models of late-onset/age-related AD (95% of AD cases) since current transgenic mouse models exhibit pathological changes dependent on overexpression of mutant human genes linked to early-onset, familial AD (1-5% of cases). Oxidative stress is considered a causative factor in age-related AD, and ALDH2 is important for the catabolism of toxic aldehydes (eg. 4-hydroxynonenal, HNE) associated with oxidative stress-induced lipid peroxidation. Aldh2 null mice exhibit oxidative stress, many AD-like pathologies, and importantly, age-related decreases in performance in recognition and spatial memory tasks beginning at 3 months of age and maximal at 6 months. Differences in locomotor activity and coordination, as well as behavioural phenotype using the open field test, balance beam and SHIRPA standardised battery were not observed, suggesting that diminished cognitive performance was the result of impaired memory and not due to confounding changes in motor function. Additionally, chronic administration of GT1061, a neuroprotectant that targets synaptic failure via activation of NO/cGMP/pCREB signaling, and histidine hydrazide, an HNE scavenger, reverses the progressive memory deficits and biochemical changes that occur in these mice. The presence of AD-like pathologies and the reversal of memory and biochemical deficits by pharmacological intervention, suggests that Aldh2 null mice represent a new, oxidative stress-based model of age-related cognitive impairment and AD that may prove useful both for assessing AD therapeutics and for gaining better insight into the pathogenesis of AD.

Cranial irradiation regulates CREB-BDNF signaling and variant BDNF transcript levels in the mouse hippocampus

The brain can be exposed to ionizing radiation in various ways, and such irradiation can trigger adverse effects, particularly on learning and memory. However, the precise mechanisms of cognitive impairments induced by cranial irradiation remain unknown. In the hippocampus, brain-derived neurotrophic factor (BDNF) plays roles in neurogenesis, neuronal survival, neuronal differentiation, and synaptic plasticity. The significance of BDNF transcript variants in these contexts is becoming clearer. In the present study, both object recognition memory and contextual fear conditioning task performance in adult C57BL/6 mice were assessed 1month after a single exposure to cranial irradiation (10Gy) to evaluate hippocampus-related behavioral dysfunction following such irradiation. Furthermore, changes in the levels of BDNF, the cAMP-response element binding protein (CREB) phosphorylation, and BDNF transcript variants were measured in the hippocampus 1month after cranial irradiation. On object recognition memory and contextual fear conditioning tasks, mice evaluated 1month after irradiation exhibited significant memory deficits compared to sham-irradiated controls, but no apparent change was evident in locomotor activity. Both phosphorylated CREB and BDNF protein levels were significantly downregulated after irradiation of the hippocampus. Moreover, the levels of mRNAs encoding common BDNF transcripts, and exons IIC, III, IV, VII, VIII, and IXA, were significantly downregulated after irradiation. The reductions in CREB phosphorylation and BDNF expression induced by differential regulation of BDNF hippocampal exon transcripts may be associated with the memory deficits evident in mice after cranial irradiation.

The semantic variant of primary progressive aphasia: clinical and neuroimaging evidence in single subjects.

Background/AimWe present a clinical-neuroimaging study in a series of patients with a clinical diagnosis of semantic variant of primary progressive aphasia (svPPA), with the aim to provide clinical-functional correlations of the cognitive and behavioral manifestations at the single-subject level.MethodsWe performed neuropsychological investigations, 18F-FDG-PET single-subject and group analysis, with an optimized SPM voxel-based approach, and correlation analyses. A measurement of white matter integrity by means of diffusion tensor imaging (DTI) was also available for a subgroup of patients.ResultsCognitive assessment confirmed the presence of typical semantic memory deficits in all patients, with a relative sparing of executive, attentional, visuo-constructional, and episodic memory domains. 18F-FDG-PET showed a consistent pattern of cerebral hypometabolism across all patients, which correlated with performance in semantic memory tasks. In addition, a majority of patients also presented with behavioral disturbances associated with metabolic dysfunction in limbic structures. In a subgroup of cases the DTI analysis showed FA abnormalities in the inferior longitudinal and uncinate fasciculi.DiscussionEach svPPA individual had functional derangement involving an extended, connected system within the left temporal lobe, a crucial part of the verbal semantic network, as well as an involvement of limbic structures. The latter was associated with behavioral manifestations and extended beyond the area of atrophy shown by CT scan.ConclusionSingle-subject 18F-FDG-PET analysis can account for both cognitive and behavioral alterations in svPPA. This provides useful support to the clinical diagnosis.

Role of the thalamic nucleus reuniens in mediating interactions between the hippocampus and medial prefrontal cortex during spatial working memory

Despite decades of research, the neural mechanisms of spatial working memory remain poorly understood. Although the dorsal hippocampus is known to be critical for memory-guided behavior, experimental evidence suggests that spatial working memory depends not only on the hippocampus itself, but also on the circuit comprised of the hippocampus and the medial prefrontal cortex (mPFC). Disruption of hippocampal-mPFC interactions may result in failed transfer of spatial and contextual information processed by the hippocampus to the circuitry in mPFC responsible for decision making and goal-directed behavior. Oscillatory synchrony between the hippocampus and mPFC has been shown to increase in tasks with high spatial working memory demand. However, the mechanisms and circuitry supporting hippocampal-mPFC interactions during these tasks is unknown. The midline thalamic nucleus reuniens (RE) is reciprocally connected to both the hippocampus and the mPFC and has been shown to be critical for a variety of working memory tasks. Therefore, it is likely that hippocampal-mPFC oscillatory synchrony is modulated by RE activity. This article will review the anatomical connections between the hippocampus, mPFC and RE along with the behavioral studies that have investigated the effects of RE disruption on working memory task performance. The article will conclude with suggestions for future directions aimed at identifying the specific role of the RE in regulating functional interactions between the hippocampus and the PFC and investigating the degree to which these interactions contribute to spatial working memory.

Valenced cues and contexts have different effects on event-based prospective memory.

This study examined the separate influence and joint influences on event-based prospective memory task performance due to the valence of cues and the valence of contexts. We manipulated the valence of cues and contexts with pictures from the International Affective Picture System. The participants, undergraduate students, showed higher performance when neutral compared to valenced pictures were used for cueing prospective memory. In addition, neutral pictures were more effective as cues when they occurred in a valenced context than in the context of neutral pictures, but the effectiveness of valenced cues did not vary across contexts that differed in valence. The finding of an interaction between cue and context valence indicates that their respective influence on event-based prospective memory task performance cannot be understood in isolation from each other. Our findings are not consistent with by the prevailing view which holds that the scope of attention is broadened and narrowed, respectively, by positively and negatively valenced stimuli. Instead, our findings are more supportive of the recent proposal that the scope of attention is determined by the motivational intensity associated with valenced stimuli. Consistent with this proposal, we speculate that the motivational intensity associated with different retrieval cues determines the scope of attention, that contexts with different valence values determine participants’ task engagement, and that prospective memory task performance is determined jointly by attention scope and task engagement.

Brain functional changes across the different phases of bipolar disorder.

Little is known about how functional imaging changes in bipolar disorder relate to different phases of the illness. To compare cognitive task activation in participants with bipolar disorder examined in different phases of illness. Participants with bipolar disorder in mania (n = 38), depression (n = 38) and euthymia (n = 38), as well as healthy controls (n = 38), underwent functional magnetic resonance imaging during performance of the n-back working memory task. Activations and de-activations were compared between the bipolar subgroups and the controls, and among the bipolar subgroups. All participants were also entered into a linear mixed-effects model. Compared with the controls, the mania and depression subgroups, but not the euthymia subgroup, showed reduced activation in the dorsolateral prefrontal cortex, the parietal cortex and other areas. Compared with the euthymia subgroup, the mania and depression subgroups showed hypoactivation in the parietal cortex. All three bipolar subgroups showed failure of de-activation in the ventromedial frontal cortex. Linear mixed-effects modelling revealed a further cluster of reduced activation in the left dorsolateral prefrontal cortex in the patients; this was significantly more marked in the mania than in the euthymia subgroup. Bipolar disorder is characterised by mood state-dependent hypoactivation in the parietal cortex. Reduced dorsolateral prefrontal activation is a further feature of mania and depression, which may improve partially in euthymia. Failure of de-activation in the medial frontal cortex shows trait-like characteristics.

Glutamate and GABA concentration changes in the globus pallidus internus of Parkinson’s patients during performance of implicit and declarative memory tasks: A report of two subjects

The basal ganglia, typically associated with motor function, are involved in human cognitive processes, as demonstrated in behavioral, lesion, and noninvasive functional neuroimaging studies. Here we report task-contingent changes in concentrations of the neurotransmitters glutamate (Glu) and gamma-aminobutyric acid (GABA) in the globus pallidus internus (GPi) of two patients with Parkinson’s disease undergoing deep brain stimulation surgery by utilizing in-vivo microdialysis measurements during performance of implicit and declarative memory tasks. Performance of an implicit memory task (weather prediction task–WPT) was associated with increased levels of glutamate and GABA in the GPi compared to their concentrations at baseline. On the other hand, performance of a declarative memory task (verbal learning task–VLT) was associated with decreased levels of glutamate and GABA in GPi compared to baseline during the encoding and immediate recall phase with less conclusive results during the delayed recall phase. These results are in line with hypothesized changes in these neurotransmitter levels: an increase of excitatory (Glu) input from subthalamic nucleus (STN) to GPi during implicit memory task performance and a decrease of inhibitory inputs (GABA) from globus pallidus externus (GPe) and striatum to GPi during declarative memory performance. Consistent with our previous report on in-vivo neurotransmitter changes during tasks in STN, these data provide corroborative evidence for the direct involvement of basal ganglia in cognitive functions and complements our model of the functional circuitry of basal ganglia in the healthy and Parkinson’s disease affected brain.

Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance

Studies of individuals with amnestic mild cognitive impairment (aMCI) have detected hyperactivity in the hippocampus during task-related functional magnetic resonance imaging (fMRI). Such elevated activation has been localized to the hippocampal dentate gyrus/CA3 (DG/CA3) during performance of a task designed to detect the computational contributions of those hippocampal circuits to episodic memory. The current investigation was conducted to test the hypothesis that greater hippocampal activation in aMCI represents a dysfunctional shift in the normal computational balance of the DG/CA3 regions, augmenting CA3-driven pattern completion at the expense of pattern separation mediated by the dentate gyrus. We tested this hypothesis using an intervention based on animal research demonstrating a beneficial effect on cognition by reducing excess hippocampal neural activity with low doses of the atypical anti-epileptic levetiracetam. In a within-subject design we assessed the effects of levetiracetam in three cohorts of aMCI participants, each receiving a different dose of levetiracetam. Elevated activation in the DG/CA3 region, together with impaired task performance, was detected in each aMCI cohort relative to an aged control group. We observed significant improvement in memory task performance under drug treatment relative to placebo in the aMCI cohorts at the 62.5 and 125 mg BID doses of levetiracetam. Drug treatment in those cohorts increased accuracy dependent on pattern separation processes and reduced errors attributable to an over-riding effect of pattern completion while normalizing fMRI activation in the DG/CA3 and entorhinal cortex. Similar to findings in animal studies, higher dosing at 250 mg BID had no significant benefit on either task performance or fMRI activation. Consistent with predictions based on the computational functions of the DG/CA3 elucidated in basic animal research, these data support a dysfunctional encoding mechanism detected by fMRI in individuals with aMCI and therapeutic intervention using fMRI to detect target engagement in response to treatment.

Оценка латерализации церебральной гемодинамики при выполнении вербальных мнестических заданий методом функциональной транскраниальной допплерографии

There are the preliminary results of the research of interhemispheric asymmetry of cerebral hemodynamics during the performance of auditory-verbal and visual memory tasks with the use of functional transcranial doppler ultrasound (fTCD). The fTCD is considered as a non-invasive and objective method for assessment the dominant hemisphere for verbal functions. The aim of two experiments was to analyze the effect of a) different types of verbal and nonverbal tasks and b) the conditions of the mnestic activity performance (memorize and recognize) on the changes of blood flow velocity in left and right hemispheres in 62 healthy subjects. There are preliminary results of possible application fTCD to identify the dominant hemisphere for speech functions with combination of concrete verbal cognitive tasks and condition of its presentation.

Prefrontal-Parietal Correlation during Performance of a Visuospatial Working Memory Task in Children, Adolescents and Young Adults

Development of the prefrontal cortex and its connectivity with different cortical areas has strong implications for the improvement of working memory. The aim of this research was to characterize the interhemispheric (INTER) prefrontal and hemispheric (INTRA) frontopolar-dorsolateral prefrontal and dorsolateral prefrontal-parietal correlation (r) in children, adolescents and adults during performance of a visuospatial working memory task (VSWM). INTERr and INTRAr of 36 different aged male participants (11 - 13, 18 - 20 and 26 - 30 years old) were calculated during performance of the Corsi Block-Tapping task, which assessed VSWM. On this task, children showed lower correct responses than adolescents and adults. Adults also showed lower total execution times than children and adolescents, with a more efficient performance. On the EEGs, the older groups showed both higher interfrontal correlations and left and right prefronto-parietal correlations than children. According to our results, the progressive efficiency in VSWM is related to differences in EEG patterns among children, adolescents and adults.

Associative Memory with Class I and II Izhikevich Model

Spiking neural network is a system that qualitatively reproduce the nervous system. It was shown in previous researches that the performance of associative memory task in all-to-all connected networks is higher when they are composed of Class II neurons than Class I neurons. The Izhikevich model in its Class II mode, however, does not have this performance boost. In this study, we focus on phase resetting curve as an index that reflects neuronal properties related to neuron classes in detail.

White matter disruption at the prodromal stage of Alzheimer's disease: relationships with hippocampal atrophy and episodic memory performance.

White matter tract alterations have been consistently described in Alzheimer's disease (AD). In particular, limbic fronto-temporal connections, which are critical to episodic memory function, may degenerate early in the course of the disease. However the relation between white matter tract degeneration, hippocampal atrophy and episodic memory impairment at the earliest stages of AD is still unclear. In this magnetic resonance imaging study, white matter integrity and hippocampal volumes were evaluated in patients with amnestic mild cognitive impairment due to AD (Albert et al., 2011) (n = 22) and healthy controls (n = 15). Performance in various episodic memory tasks was also evaluated in each participant. Relative to controls, patients showed a significant reduction of white matter fractional anisotropy (FA) and increase of radial diffusivity (RD) in the bilateral uncinate fasciculus, parahippocampal cingulum and fornix. Within the patient group, significant intra-hemispheric correlations were notably found between hippocampal grey matter volume and FA in the uncinate fasciculus, suggesting a relationship between atrophy and disconnection of the hippocampus. Moreover, episodic recognition scores were related with uncinate fasciculus FA across patients. These results indicate that fronto-hippocampal connectivity is reduced from the earliest pre-demential stages of AD. Disruption of fronto-hippocampal connections may occur progressively, in parallel with hippocampal atrophy, and may specifically contribute to early initial impairment in episodic memory.