Impaired Visuospatial Working Memory Research Articles

Visuospatial working memory in behavioural variant frontotemporal dementia: a comparative analysis with Alzheimer's disease using the box task.

This study investigated the visuospatial working memory profiles of behavioural variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) using a novel computerised test of visuospatial working memory: the Box Task. Twenty-eight bvFTD and 28 AD patients, as well as 32 age-matched control participants were recruited. All participants completed the Box Task and conventional neuropsychological tests of working memory, episodic memory, and visuospatial function. Both the bvFTD and AD groups exhibited significantly more Box Task between-search errors than the control group across all set sizes. Notably, the AD group demonstrated a significantly higher error rate compared to the bvFTD group. Regression analysis revealed that whilst episodic memory impairment significantly predicted Box Task error performance in AD, this was not the case for bvFTD. Additionally, a noticeable trend was observed for attention in predicting Box Task errors in both bvFTD and AD groups. The Box Task demonstrated high utility in differentiating between bvFTD and AD, with a decision tree correctly classifying 82.1% of bvFTD patients and 75% of AD patients. Our findings reveal significant visuospatial working memory impairments in bvFTD, albeit of lesser severity compared to disease-matched AD patients. The Box Task, a novel measure of visuospatial working memory, proved effective in differentiating between bvFTD and AD, outperforming many traditional neuropsychological measures. Overall, our findings highlight the utility of assessing visuospatial memory when differentiating between bvFTD and AD in the clinical setting.

Differential resting-state neurophysiological activity associated with game usage patterns and genres in Internet gaming disorder.

We investigated differences in quantitative electroencephalogram (EEG) patterns associated with game usage patterns and genre among patients with Internet gaming disorder (IGD). Data from 140 participants (76 IGD patients and 64 healthy controls) were analysed. The IGD group was divided into subgroups based on game usage patterns (single game [SG] or multiple games [MGs]) and genre (multiplayer online battle arena, first-person shooter [FPS], or massively multiplayer online role-playing game [MMORPG; hereafter, MMG]). A resting-state, eye-closed quantitative EEG was recorded, and the absolute power and coherence of brain waves were analysed. IGD patients who played SGs showed increased beta activity compared with those who played MGs and controls. Increased absolute beta power was significantly associated with higher tendencies towards behavioural inhibition compared with controls. FPS gamers showed increased delta power in the frontal region compared with controls, which was related to the severity of IGD. Furthermore, decreased intrahemispheric coherence in the left frontoparietal region was observed in the MMG and FPS groups compared with controls. This decreased coherence was observed in the theta (MMG and FPS), delta (MMG), and beta (FPS) bands. These features were related to impairment in visuospatial working memory. Unique neurophysiological features related to preoccupation with an SG may be associated with the inhibition of behavioural changes. The present study suggests that the underlying neurophysiological networks in IGD differ according to game usage patterns and genre.

Disruption in Surface-Based Functional Connectivity in the Right Posterior Hippocampal CA3 Subfield: A Probable Neural Basis of Visuospatial Working Memory Impairment in Patients With Right Temporal Lobe Epilepsy.

Visuospatial working memory (VSWM) impairment is common in patients with right temporal lobe epilepsy (rTLE). The posterior hippocampus is critical for spatial memory, but the contributions of the different subfields to VSWM deficits remain unclear. Forty-six rTLE patients and 42 healthy controls (HCs) were recruited. Resting-state fMRI (rsfMRI) and structural MRI scans were administered, followed by a VSWM_Nback test. The right posterior hippocampus was automatically segmented, and the surface-based functional connectivity (SBFC) of the subiculum (Sub), CA1, CA3, dentate gyrus (DG), hippocampal tail, and right entorhinal cortex (EC) were compared between groups. Correlation analysis was performed between the altered SBFC and VSWM_Nback scores for rTLE patients. The results showed that rTLE patients underperformed in the VSWM_Nback test, with longer mean reaction time of accurate response (ACCmeanRT) in 0back and 2back condition, lower hit rate (HR) and higher false alarm rate (FAR) in 2back condition. Compared with HCs, the rCA3 in the rTLE group exhibited decreased SBFC with inferior parietal cortex (IPC), temporal lateral cortex (TLC), and posterior visual cortex (PVC) in the right hemisphere as well as the bilateral dorsolateral prefrontal cortex (DLPFC). The SBFC of the rEC and right anterior cingulate cortex (rACC) increased in the rTLE group. Within the rTLE group, the decreased SBFC of the rCA3-rIPC and rCA3-rLTC were correlated with worse VSWM performance. Therefore, the decreased SBFC of the rCA3-rIPC and rCA3-rLTC might be the critical aberrant FC pattern reflecting VSWM impairment in rTLE patients. The mechanism might involve functional disruption between the core subsystem and the medial temporal subsystem of the default mode network (DMN).

Naturally FIV-infected cats exhibit a higher risk of age-related visuospatial working memory impairment compared with cats without FIV disease

Visuospatial working memory performance was examined in a cohort of twenty naturally infected cats with feline immunodeficiency virus (FIV) and twenty uninfected controls. We used a simple object permanence task where cats needed to recall the encoded spatial information from their working memory after a limited period to locate the indicated container. After the exclusion criteria, the cats were grouped based on their age and FIV status and the total number of correct choices was recorded for each participant. The groups were then compared with each other on the basis of median group performance to evaluate any notable difference in the median number of correct choices between groups. Results of the present study revealed a significant difference in median group performance between the young and the old FIV-infected group (P = 0.002) as well as the young FIV-negative compared with the old FIV-negative group (P = 0.003). Similarly, the old FIV-negative group performed better than the old FIV-positive group (P = 0.048). Nevertheless, the young FIV-positive and -negative cats did not appear to be any different in their median group performance (P = 0.29). Collectively, these findings suggest that FIV infection is associated with an age-related decrement in visuospatial working memory efficiency of naturally infected cats. However, an evaluation of different cognitive domains in a larger study population is needed to see whether FIV infection is likely to accelerate age-related cognitive impairments in naturally FIV-infected cats or not.

Memory and language impairments are associated with anxiety disorder severity in childhood.

Introduction Children with anxiety disorders have been suggested to possess deficits in verbal fluency, shifting and attention, with inconsistent results regarding working memory and its subcomponents. This study extends previous findings by analyzing the performance of children with anxiety disorders in a wide range of neuropsychological functions. Methods We evaluated 54 children with a primary diagnosis of an anxiety disorder according to diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) using subtests of a neuropsychological battery. The severity of anxiety disorders was assessed using the Pediatric Anxiety Rating Scale (PARS). We calculated the frequency of neuropsychological impairments (-1.5 standard deviation of the normative sample). Comparisons between groups were performed based on the severity of anxiety symptoms, as well as in the presence of one vs. more diagnoses of anxiety disorder. Results We found higher impairment in visuospatial working memory (23.1%), semantic memory (27.8%), oral language (35.4%) and word writing (44.4%) in anxious children. Moreover, children with higher anxiety severity presented lower performance in visuospatial working memory, inferential processing, word reading, writing comprehension, copied writing, and semantic verbal fluency (d = 0.49 to 0.96 [Cohen's d]). The higher the number of anxiety diagnoses, the lower the performance in episodic memory and oral and written language (d = 0.56 to 0.77). Conclusion Our data suggested the presence of memory (visuospatial working memory and semantic memory) and language deficits (oral and writing) in some children with an anxiety disorder. Severity and number of anxiety diagnoses were associated with lower performance in memory and language domains in childhood.

Numeric input operation on electronic devices among individuals with visuospatial working memory impairment

ABSTRACT In human–computer interactions, higher-level visuospatial function is likely needed to effectively use the interface. The aim of this study is to clarify whether individuals with visuospatial defects can use electronic devices effectively. We quantitatively and qualitatively analyzed the ability of seven individuals with Bálint syndrome and seven individuals with left-unilateral spatial neglect (USN) to input a digit sequence into a flat touch interface. Control groups consisted of seven individuals with memory deficits and 11 healthy individuals. Participants with Bálint syndrome took longer and had more hesitations than the USN group and the two control groups to input numerical sequences (Steel-Dwass test, p < .01). In addition, participants with Bálint syndrome had a high percentage of hesitations for exploration of the button array on the interface relative to USN and the memory deficit group (Fisher’s exact test, p < .05). Regarding neuropsychological data, participants with Bálint syndrome had a lower score for visuospatial working memory than participants with USN and the memory deficits control group (Steel-Dwass test, p < .01). The results shed some light on the relation between visuospatial working memory deficits and the spatial perception of interface layouts and spatial control during electronic device operation.

Abnormal distraction and load-specific connectivity during working memory in cognitively normal Parkinson's disease.

Visuospatial working memory impairments are common in Parkinson's disease (PD), yet the underlying neural mechanisms are poorly understood. The present study investigated abnormalities in context‐dependent functional connectivity of working memory hubs in PD. Cognitively normal PD and control participants underwent fMRI while performing a visuospatial working memory task. To identify sources of dysfunction, distraction, and load‐modulated connectivity were disentangled for encoding and retrieval phases of the task. Despite normal working memory performance in PD, two features of abnormal connectivity were observed, one due to a loss in normal context‐related connectivity and another related to upregulated connectivity of hubs for which the controls did not exhibit context‐dependent connectivity. During encoding, striatal‐prefrontal coupling was lost in PD, both during distraction and high memory loads. However, long‐range connectivity of prefrontal, medial temporal and occipital hubs was upregulated in a context‐specific manner. Memory retrieval was characterized by different aberrant connectivity patterns, wherein precuneus connectivity was upregulated during distraction, whereas prefrontal couplings were lost as memory load approached capacity limits. Features of abnormal functional connectivity in PD had pathological and compensatory influences as they correlated with poorer working memory or better visuospatial skills. The results offer new insights into working memory‐related signatures of aberrant cortico–cortical and corticostriatal functional connections, which may portend future declines in different facets of working memory.

Atomoxetine prevents working memory loss in hyperactive rats, mediating plastic changes in prefrontal cortex pyramidal neurons

Attention Deficit Hyperactivity Disorder (ADHD) causes impaired visuospatial working memory (VWM), which primarily maps to the prefrontal cortex. However, little is known about the synaptic processes underlying cognitive loss in ADHD, or those ultimately involved in the preventive effect observed through the clinical use of Atomoxetine (ATX). To investigate the plasticity underlying ADHD related cognitive loss, and that potentially involved in the preventive action of Atomoxetine, allocentric VWM was assessed, as well as the dendritic spine number and proportional density on pyramidal neurons in the prefrontal cerebral cortex layer III of neonatal 6-hydroxydopamine-lesioned rats. The effect of acute ATX treatment was also assessed at 28 days of age. 6-OHDA induced lesions produced increased motor activity and a loss of VWM, concomitant with a reduction in thin spine density. ATX administration reversed cognitive loss, in conjunction with a decrease in thin spines and an increase in mushroom spines. A reduction in the proportion of spines involved in learning in hyperactive animals could account for the loss in cognitive function observed. Considering thin spine density was also reduced after ATX administration, we hypothesized that the restoration in cognitive function recorded could be brought about by an increase in memory related mushroom spines.

Visuospatial working memory assessment using a digital tablet in adolescents with attention deficit hyperactivity disorder

Background and objectiveAttention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder hypothesized to involve impaired visuospatial working memory (VSWM). However, there are few studies utilizing neuropsychological tests to measure VSWM in ADHD adolescents. The Rey–Osterrieth complex figure test (ROCF) is commonly used as a neuropsychological test to assess visuospatial working memory for individuals with ADHD. We assessed working memory using the ROCF test on a digital Galaxy tablet with the technically new Gaussian filter method. MethodsThirty adolescents with ADHD and 30 healthy control adolescents were recruited for participation in the current study. All adolescents were assessed with K-WISC-IV, Children's depression inventory, and the Korean ADHD rating scale. All adolescents were asked to copy the ROCF from paper onto a Galaxy tablet screen using a wireless pen. ResultsThere was a significant difference in representative value of the deviation of the original images from template images (R-value) in copy and delayed recall between ADHD adolescents and healthy adolescents. There was no significant difference in R-value of immediate recall between ADHD adolescents and healthy adolescents. In all adolescents (ADHD and healthy) and ADHD adolescents, the R-value of copy was negatively correlated with visuospatial index and working memory index, and the R-value of delayed recall was negatively correlated with WMI. The R-value of copy and delayed recall was positively correlated with K-ARS in all adolescents and ADHD adolescents. ConclusionsADHD adolescents showed differences in the R-values of copy and delayed recall in the digital ROCF version compared to healthy adolescents. The digital ROCF assessment tool can represent different patterns of visuospatial working memory abilities in ADHD adolescents compared to healthy adolescents.

Noncredible cognitive performance at clinical evaluation of adult ADHD: An embedded validity indicator in a visuospatial working memory test.

The assessment of performance validity is an essential part of the neuropsychological evaluation of adults with attention-deficit/hyperactivity disorder (ADHD). Most available tools, however, are inaccurate regarding the identification of noncredible performance. This study describes the development of a visuospatial working memory test, including a validity indicator for noncredible cognitive performance of adults with ADHD. Visuospatial working memory of adults with ADHD (n = 48) was first compared to the test performance of healthy individuals (n = 48). Furthermore, a simulation design was performed including 252 individuals who were randomly assigned to either a control group (n = 48) or to 1 of 3 simulation groups who were requested to feign ADHD (n = 204). Additional samples of 27 adults with ADHD and 69 instructed simulators were included to cross-validate findings from the first samples. Adults with ADHD showed impaired visuospatial working memory performance of medium size as compared to healthy individuals. Simulation groups committed significantly more errors and had shorter response times as compared to patients with ADHD. Moreover, binary logistic regression analysis was carried out to derive a validity index that optimally differentiates between true and feigned ADHD. ROC analysis demonstrated high classification rates of the validity index, as shown in excellent specificity (95.8%) and adequate sensitivity (60.3%). The visuospatial working memory test as presented in this study therefore appears sensitive in indicating cognitive impairment of adults with ADHD. Furthermore, the embedded validity index revealed promising results concerning the detection of noncredible cognitive performance of adults with ADHD. (PsycINFO Database Record

Working Memory Impairments in Chromosome 22q11.2 Deletion Syndrome: The Roles of Anxiety and Stress Physiology.

Stress and anxiety have a negative impact on working memory systems by competing for executive resources and attention. Broad memory deficits, anxiety, and elevated stress have been reported in individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS). We investigated anxiety and physiological stress reactivity in relation to visuospatial working memory impairments in 20 children with 22q11.2DS and 32 typically developing (TD) children ages 7 to 16. Children with 22q11.2DS demonstrated poorer working memory, reduced post-stress respiratory sinus arrhythmia recovery, and overall increased levels of cortisol in comparison to TD children. Anxiety, but not physiological stress responsivity, mediated the relationship between 22q11.2DS diagnosis and visuospatial working memory impairment. Findings indicate that anxiety exacerbates impaired working memory in children with 22q11.2DS.

Brain Connectivity Changes in Autosomal Recessive Parkinson Disease: A Model for the Sporadic Form.

Biallelic genetic mutations in the Park2 and PINK1 genes are frequent causes of autosomal recessive PD. Carriers of single heterozygous mutations may manifest subtle signs of disease, thus providing a unique model of preclinical PD. One emerging hypothesis suggests that non-motor symptom of PD, such as cognitive impairment may be due to a distributed functional disruption of various neuronal circuits. Using resting-state functional MRI (RS-fMRI), we tested the hypothesis that abnormal connectivity within and between brain networks may account for the patients’ cognitive status. Eight homozygous and 12 heterozygous carriers of either PINK1 or Park2 mutation and 22 healthy controls underwent RS-fMRI and cognitive assessment. RS-fMRI data underwent independent component analysis to identify five networks of interest: default-mode network, salience network, executive network, right and left fronto-parietal networks. Functional connectivity within and between each network was assessed and compared between groups. All mutation carriers were cognitively impaired, with the homozygous group reporting a more prominent impairment in visuo-spatial working memory. Changes in functional connectivity were evident within all networks between homozygous carriers and controls. Also heterozygotes reported areas of reduced connectivity when compared to controls within two networks. Additionally, increased inter-network connectivity was observed in both groups of mutation carriers, which correlated with their spatial working memory performance, and could thus be interpreted as compensatory. We conclude that both homozygous and heterozygous carriers exhibit pathophysiological changes unveiled by RS-fMRI, which can account for the presence/severity of cognitive symptoms.

Impaired executive functions in experimental model of temporal lobe epilepsy.

The present study aimed to investigate cognitive and behavioural changes consistent with attention deficit hyperactivity disorder (ADHD -like behavior in male Wistar rats with temporal lobe epilepsy (TLE). Male Wistar rats at 25 day of age were submitted to animal model of TLE by pilocarpine injection (350 mg/kg, ip) and a control group received saline 0.9%. The animals were continuously video monitored up to the end of experiments. The behavioural tests (open field, elevated plus maze and operant conditioning box) started from 60 days postnatal. Animals with TLE exhibited elevated locomotor activity, reduced level of anxiety-related behavior, impulsivity and impaired visuospatial working memory. Taken as a whole, we concluded that animals with TLE exhibited some cognitive and behavioural changes consistent with ADHD-like behavior.

Neural correlates of visuospatial working memory in attention-deficit/hyperactivity disorder and healthy controls

Impaired visuospatial working memory (VSWM) is suggested to be a core neurocognitive deficit in attention-deficit/hyperactivity disorder (ADHD), yet the underlying neural activation patterns are poorly understood. Furthermore, it is unclear to what extent age and gender effects may play a role in VSWM-related brain abnormalities in ADHD. Functional magnetic resonance imaging (fMRI) data were collected from 109 individuals with ADHD (60% male) and 103 controls (53% male), aged 8–25 years, during a spatial span working memory task. VSWM-related brain activation was found in a widespread network, which was more widespread compared with N-back tasks used in the previous literature. Higher brain activation was associated with higher age and male gender. In comparison with controls, individuals with ADHD showed greater activation in the left inferior frontal gyrus (IFG) and the lateral frontal pole during memory load increase, effects explained by reduced activation on the low memory load in the IFG pars triangularis and increased activation during high load in the IFG pars opercularis. Age and gender effects did not differ between controls and individuals with ADHD. Results indicate that individuals with ADHD have difficulty in efficiently and sufficiently recruiting left inferior frontal brain regions with increasing task difficulty.

Support for distinct subcomponents of spatial working memory: A double dissociation between spatial–simultaneous and spatial–sequential performance in unilateral neglect

Over the last decade, many studies have demonstrated that visuospatial working memory (VSWM) can be divided into separate subsystems dedicated to the retention of visual patterns and their serial order. Impaired VSWM has been suggested to exacerbate left visual neglect in right-brain-damaged individuals. The aim of this study was to investigate the segregation between spatial–sequential and spatial–simultaneous working memory in individuals with neglect. We demonstrated that patterns of results on these VSWM tasks can be dissociated. Spatial–simultaneous and sequential aspects of VSWM can be selectively impaired in unilateral neglect. Our results support the hypothesis of multiple VSWM subsystems, which should be taken into account to better understand neglect-related deficits.

Reduced Prefrontal Efficiency for Visuospatial Working Memory in Attention-Deficit/Hyperactivity Disorder

Visuospatial working memory impairments have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, most ADHD research has focused on the neural correlates of nonspatial mnemonic processes. This study examined brain activation and functional connectivity for visuospatial working memory in youth with and without ADHD. Twenty-four youth with ADHD and 21 age- and sex-matched healthy controls were scanned with functional magnetic resonance imaging while performing an N-back test of working memory for spatial position. Block-design analyses contrasted activation and functional connectivity separately for high (2-back) and low (1-back) working memory load conditions versus the control condition (0-back). The effect of working memory load was modeled with linear contrasts. The 2 groups performed comparably on the task and demonstrated similar patterns of frontoparietal activation, with no differences in linear gains in activation as working memory load increased. However, youth with ADHD showed greater activation in the left dorsolateral prefrontal cortex (DLPFC) and left posterior cingulate cortex (PCC), greater functional connectivity between the left DLPFC and left intraparietal sulcus, and reduced left DLPFC connectivity with left midcingulate cortex and PCC for the high load contrast compared to controls (p < .01; k > 100 voxels). Reanalysis using a more conservative statistical approach (p < .001; k > 100 voxels) yielded group differences in PCC activation and DLPFC-midcingulate connectivity. Youth with ADHD show decreased efficiency of DLPFC for high-load visuospatial working memory and greater reliance on posterior spatial attention circuits to store and update spatial position than healthy control youth. Findings should be replicated in larger samples.

Alteration of functional connectivity within visuospatial working memory-related brain network in patients with right temporal lobe epilepsy: A resting-state fMRI study

PurposeThis study aimed to investigate the resting-state brain network related to visuospatial working memory (VSWM) in patients with right temporal lobe epilepsy (rTLE). The functional mechanism underlying the cognitive impairment in VSWM was also determined. MethodFifteen patients with rTLE and 16 healthy controls matched for age, gender, and handedness underwent a 6-min resting-state functional MRI session and a neuropsychological test using VSWM_Nback. The VSWM-related brain network at rest was extracted using multiple independent component analysis; the spatial distribution and the functional connectivity (FC) parameters of the cerebral network were compared between groups. Behavioral data were subsequently correlated with the mean Z-value in voxels showing significant FC difference during intergroup comparison. ResultsThe distribution of the VSWM-related resting-state network (RSN) in the group with rTLE was virtually consistent with that in the healthy controls. The distribution involved the dorsolateral prefrontal lobe and parietal lobe in the right hemisphere and the partial inferior parietal lobe and posterior lobe of the cerebellum in the left hemisphere (p<0.05, AlphaSim corrected). Between-group differences suggest that the group with rTLE had a decreased FC within the right superior frontal lobe (BA8), right middle frontal lobe, and right ventromedial prefrontal lobe compared with the controls (p<0.05, AlphaSim corrected). The regions of increased FC in rTLE were localized within the right superior frontal lobe (BA11), right superior parietal lobe, and left posterior lobe of the cerebellum (p<0.05, AlphaSim corrected). Moreover, patients with rTLE performed worse than controls in the VSWM_Nback test, and there were negative correlations between ACCmeanRT (2-back) and the mean Z-value in the voxels showing decreased or increased FC in rTLE (p<0.05). ConclusionThe results suggest that the alteration of the VSWM-related RSN might underpin the VSWM impairment in patients with rTLE and possibly implies a functional compensation by enlarging the FC within the ipsilateral cerebral network.

Visuospatial Working Memory in ADHD Patients, Unaffected Siblings, and Healthy Controls

Objective: The aim of this study was to (a) test the usefulness of visuospatial working memory (VSWM) as an endophenotype for ADHD and (b) study the developmental trajectory of VSWM in ADHD. Method: A total of 110 ADHD patients, 60 unaffected siblings, and 109 controls, aged 8 to 29 years, were assessed on VSWM functioning. Multilevel analyses were carried out to account for the correlation between measurements within families. Results: ADHD patients showed impaired VSWM performance compared with unaffected siblings and controls, with comparable performance between unaffected siblings and controls. Impaired VSWM in ADHD patients was not more pronounced on higher memory loads, signifying executive rather than storage deficits as an underlying mechanism. ADHD patients, unaffected siblings, and controls showed parallel developmental trajectories of VSWM. Conclusion: Current findings question the usefulness of VSWM as a neurocognitive endophenotype for ADHD and provide unique insights into the developmental trajectory of VSWM in ADHD.

Visual Working Memory Impairment in Premanifest Gene-Carriers and Early Huntington's Disease.

Working memory deficits have been found in Huntington's disease (HD) and in a small group of premanifest (PreHD) gene-carriers. However, the nature and extent of these deficits are unknown. In a large cross-sectional study, we aimed to determine the degree of visuospatial working memory dysfunction across multiple stages of HD. Specifically, visuospatial working memory capacity and response times across various degrees of difficulty were examined, as well as the relationship between visuospatial working memory and motor dysfunction. We examined 62 PreHD-A gene-carriers (>10.8 years from estimated disease onset), 58 PreHD-B gene-carriers (<10.8 years from estimated disease onset), 77 stage-1 HD patients (HD1), 44 stage-2 HD patients (HD2), and 122 healthy controls. Participants viewed coloured squares (in sets of 3, 5 and 7) on a screen and were to decide whether on a subsequent screen the encircled square has changed colour. Accuracy and response times were recorded. Compared to controls, significant group differences in visuospatial working memory capacity (accuracy) were seen in PreHD-B, HD1 and HD2 groups across the difficulty levels. Significant group differences on response times were found for all groups (PreHD-A to HD2) compared to controls; the most difficult level producing the only group difference in speed between PreHD-A and controls. Accuracy and speed were positively correlated only in the HD groups. These findings suggest that visuospatial working memory impairments are detectable in both premanifest and manifest HD; the manifest HD showed evidence for a "worse-worse phenomenon" whereby reductions were present in both motor speed and accuracy.

Visuospatial working memory deficits in remitted patients with bipolar disorder: susceptibility to the effects of GABAergic agonists

Visuospatial working memory (VSWM) deficit under high working memory (WM) load deserves further investigation as a potential trait marker for bipolar disorder (BPD). However, VSWM performances may depend on basic neurocognitive processes and are possibly compromised by neurocognitive effects of psychotropic medications. A total of 32 remitted BPD patients and 39 healthy controls undertook parametric VSWM tasks and assessments for selective attention, sustained attention, psychomotor speed, mental flexibility, and Wechsler Adult Intelligence Scale-III full IQ. Using a multivariate model and trend analysis and controlling for other basic neurocognitive ability, the effects of mood stabilizers, antipsychotics, GABAergic agonists, and anticholinergics on VSWM performances were explored by post-hoc analysis comparing performances across WM loads between healthy controls and patients treated and not treated with a specific medication. Remitted BPD patients showed more pronounced performance declines in VSWM performances as WM loads increased, indicating inefficient VSWM processing. The VSWM deficits of remitted patients were independent of their impairments in attentional processes or psychomotor speed. Among the medications, only GABAergic agonists were associated with impaired VSWM performances. Remitted BPD patients had WM-load-dependent VSWM processing deficits after controlling for neurocognitive performances. As these deficits were associated with the use of GABAergic agonists, altered GABAergic neurotransmission might be involved with the underlying mechanisms of the impaired VSWM processing of BPD. Since GABAergic agonist use is often continued from the acute to the remitted phase in BPD and might potentially affect the functional recovery, clinicians should be aware of these neurocognitive side effects, even at low dosages. Close monitoring and timely discontinuation of GABAergic agonists is of utmost importance for clinical practice.