Working Memory Performance In Patients Research Articles

Altered static and dynamic cerebellar-cerebral functional connectivity in acute pontine infarction.

This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.

Dense attention network identifies EEG abnormalities during working memory performance of patients with schizophrenia.

Patients with schizophrenia typically exhibit deficits in working memory (WM) associated with abnormalities in brain activity. Alterations in the encoding, maintenance and retrieval phases of sequential WM tasks are well established. However, due to the heterogeneity of symptoms and complexity of its neurophysiological underpinnings, differential diagnosis remains a challenge. We conducted an electroencephalographic (EEG) study during a visual WM task in fifteen schizophrenia patients and fifteen healthy controls. We hypothesized that EEG abnormalities during the task could be identified, and patients successfully classified by an interpretable machine learning algorithm. We tested a custom dense attention network (DAN) machine learning model to discriminate patients from control subjects and compared its performance with simpler and more commonly used machine learning models. Additionally, we analyzed behavioral performance, event-related EEG potentials, and time-frequency representations of the evoked responses to further characterize abnormalities in patients during WM. The DAN model was significantly accurate in discriminating patients from healthy controls, ACC = 0.69, SD = 0.05. There were no significant differences between groups, conditions, or their interaction in behavioral performance or event-related potentials. However, patients showed significantly lower alpha suppression in the task preparation, memory encoding, maintenance, and retrieval phases F(1,28) = 5.93, p = 0.022, η2 = 0.149. Further analysis revealed that the two highest peaks in the attention value vector of the DAN model overlapped in time with the preparation and memory retrieval phases, as well as with two of the four significant time-frequency ROIs. These results highlight the potential utility of interpretable machine learning algorithms as an aid in diagnosis of schizophrenia and other psychiatric disorders presenting oscillatory abnormalities.

Working memory processing deficit associated with a nonlinear response pattern of the anterior cingulate cortex in first-episode and drug-naïve schizophrenia.

Impaired working memory (WM) is a core neuropsychological dysfunction of schizophrenia, however complex interactions among the information storage, information processing and attentional aspects of WM tasks make it difficult to uncover the psychophysiological mechanisms of this deficit. Thirty-six first-episode and drug-naïve schizophrenia and 29 healthy controls (HCs) were enrolled in this study. Here, we modified a WM task to isolate components of WM storage and WM processing, while also varying the difficulty level (load) of the task to study regional differences in load-specific activation using mixed effects models, and its relationship to distributed gene expression. Comparing patients with HCs, we found both attentional deficits and WM deficits, with WM processing being more impaired than WM storage in patients. In patients, but not controls, a linear modulation of brain activation was observed mainly in the frontoparietal and dorsal attention networks. In controls, an inverted U-shaped response pattern was identified in the left anterior cingulate cortex. The vertex of this inverted U-shape was lower in patients than controls, and a left-shifting axis of symmetry was associated with better WM performance in patients. Both the above linear and U-shaped modulation effects were associated with the expressions of the genes enriched in the dopamine neurotransmitter system across all cortical brain regions. These findings indicate that a WM processing deficit is evident in schizophrenia from an early stage before antipsychotic treatment, and associated with a dopamine pathway related aberration in nonlinear response pattern at the cingulate cortex when processing WM load.

Association of working memory and elevated overnight urinary norepinephrine in patients with schizophrenia

IntroductionNorepinephrine has both central and peripheral origins and is known to influence cognitive processes in attention, learning, and working memory, but the research regarding the impact of norepinephrine on cognition in schizophrenia remains sparse, and mainly focuses on centrally regulated noradrenergic effects. This study examined the relationship between cumulative overnight norepinephrine levels in the urine and working memory in patients with schizophrenia and healthy controls. MethodsUrinary catecholamines were collected overnight in patients with schizophrenia (n = 75) and healthy controls (n = 33). Working memory was assessed using the digit sequencing task. ResultsPatients showed significantly higher average levels of overnight norepinephrine (t(103.10) = −3.16, p = 0.002) and reduced working memory performance (t(90) = 3.87, p = 0.001) compared with healthy individuals. There was a significant negative correlation between norepinephrine and working memory in patients (r = −0.38, p = 0.005), but not in controls (r = 0.08, p = 0.67). After controlling for age, sex, antipsychotic medications, and serotonin-norepinephrine reuptake inhibitor-based antidepressants, the correlation remained significant (r = −0.41, p = 0.004). ConclusionsHigh peripheral overnight levels of urinary norepinephrine are associated with lower working memory performance in patients with schizophrenia. These results parallel previous studies suggesting that high levels of central norepinephrine may result in working memory impairments. As norepinephrine rapidly breaks down and usually does not pass through the blood-brain barrier, the potential effect of peripheral cumulative norepinephrine on working memory is intriguing, and needs to be further investigated.

Decreased integration of the frontoparietal network during a working memory task in major depressive disorder.

Working memory deficits are a common feature in major depressive disorder and are associated with poor functional outcomes. Intact working memory performance requires the recruitment of large-scale brain networks. However, it is unknown how the disrupted recruitment of distributed regions belonging to these large-scale networks at the whole-brain level brings about working memory impairment seen in major depressive disorder. We used graph theory to examine the functional connectomic metrics (local and global efficiency) at the whole-brain and large-scale network levels in 38 patients with major depressive disorder and 41 healthy controls during a working memory task. Altered connectomic metrics were studied in a moderation model relating to clinical symptoms and working memory accuracy in patients, and a machine learning method was employed to assess whether these metrics carry enough illness-specific information to discriminate patients from controls. Global efficiency of the frontoparietal network was reduced in major depressive disorder (false discovery rate corrected, p = 0.014); this reduction predicted worse working memory performance in patients with less severe illness burden indexed by Brief Psychiatric Rating Scale (β =-0.43, p = 0.035, t =-2.2, 95% confidence interval = [-0.043,-0.002]). We achieved a classification accuracy and area under the curve of 73.42% and 0.734, respectively, to discriminate patients from controls based on connectomic metrics, and the global efficiency of the frontoparietal network contributed most to the diagnostic classification. We report a putative mechanistic link between the global efficiency of the frontoparietal network and impaired n-back performance in major depressive disorder. This relationship is more pronounced at lower levels of symptom burden, indicating the possibility of multiple pathways to cognitive deficits in severe major depressive disorder.

Nimodipine improves cortical efficiency during working memory in healthy subjects

The L-type calcium channel gene, CACNA1C, is a validated risk gene for schizophrenia and the target of calcium channel blockers. Carriers of the risk-associated genotype (rs1006737 A allele) have increased frontal cortical activity during working memory and higher CACNA1C mRNA expression in the prefrontal cortex. The aim of this study was to determine how the brain-penetrant calcium channel blocker, nimodipine, changes brain activity during working memory and other cognitive and emotional processes. We conducted a double-blind randomized cross-over pharmacoMRI study of a single 60 mg dose of oral nimodipine solution and matching placebo in healthy men, prospectively genotyped for rs1006737. With performance unchanged, nimodipine significantly decreased frontal cortical activity by 39.1% and parietal cortical activity by 42.8% during the N-back task (2-back > 0-back contrast; PFWE < 0.05; n = 28). Higher peripheral nimodipine concentrations were correlated with a greater decrease in activation in the frontal cortex. Carriers of the risk-associated allele, A (n = 14), had a greater decrease in frontal cortical activation during working memory compared to non-risk allele carriers. No differences in brain activation were found between nimodipine and placebo for other tasks. Future studies should be conducted to test if the decreased cortical brain activity after nimodipine is associated with improved working memory performance in patients with schizophrenia, particularly those who carry the risk-associated genotype. Furthermore, changes in cortical activity during working memory may be a useful biomarker in future trials of L-type calcium channel blockers.

Task-specific Disruptions in Theta Oscillations during Working Memory for Temporal Order in People with Schizophrenia.

Prior studies demonstrated that neural oscillations are enhanced during working memory (WM) maintenance and that this activity can predict behavioral performance in healthy individuals. However, it is unclear whether the relationship holds for people with WM deficits. People with schizophrenia have marked WM deficits, and such deficits are most prominent when patients are required to process relationships between items, such as temporal order. Here, we used EEG to compare the relationship between oscillatory activity and WM performance in patients and controls. EEG was recorded as participants performed tasks requiring maintenance of complex objects ("Item") or the temporal order of objects ("Order"). In addition to testing for group differences, we examined individual differences in EEG power and WM performance across groups. Behavioral results demonstrated that patients showed impaired performance on both Item and Order trials. EEG analyses revealed that patients showed an overall reduction in alpha power, but the relationship between alpha activity and performance was preserved. In contrast, patients showed a reduction in theta power specific to Order trials, and theta power could predict performance on Order trials in controls, but not in patients. These findings demonstrate that WM impairments in patients may reflect two different processes: a general deficit in alpha oscillations and a specific deficit in theta oscillations when temporal order information must be maintained. At a broader level, the results highlight the value of characterizing brain-behavior relationships, by demonstrating that the relationship between neural oscillations and WM performance can be fundamentally disrupted in those with WM deficits.

Effects of β-hydroxybutyrate on cognition in patients with type 2 diabetes.

Cognitive impairment in type 2 diabetes is associated with cerebral glucose hypometabolism. Providing a glucose substitute such as ketone bodies might restore metabolic balance in glucose-compromised neurones and improve cognitive performance. We aimed to investigate if β-hydroxybutyrate (ketone body) infusion acutely affects cognitive performance, measured by a neuropsychological test battery, in patients with type 2 diabetes. Randomised, placebo-controlled, double-blind cross-over trial. Eighteen patients with type 2 diabetes received i.v. ketone body (β-hydroxybutyrate) and placebo (saline) infusion in a randomised order on two separate occasions. On both days of examination, blood glucose was clamped at 7.5 mmol/L and a neuropsychological test battery was used to assess global cognitive performance (primary outcome) and specialized cognitive measures of verbal memory, working memory, executive function, psychomotor speed, and sustained attention. During neurocognitive testing, β-hydroxybutyrate concentrations were 2.4 vs 0.1 mmol/L. Working memory assessed by Wechsler Adult Intelligence Scale letter-number-sequencing significantly improved by 1.6 points (95% CI: 0.7, 2.4; non-adjusted P < 0.001) corresponding to a 17% increase in performance during ketone infusion compared to placebo. There was no change for global cognitive performance or any other cognitive measure after adjusting for multiple comparisons. Blood concentrations of β-hydroxybutyrate and glycaemic status did not associate with test performance; however, insulin resistance measured by HOMA was related to improved working memory performance during ketone infusion (β = 4%; 95% CI: 1.1, 7.7; P = 0.012). Ketone infusion specifically improved working memory performance in patients with type 2 diabetes in the absence of changes in global cognition.

Altered Static and Temporal Dynamic Amplitude of Low-Frequency Fluctuations in the Background Network During Working Memory States in Mild Cognitive Impairment.

Previous studies investigating working memory performance in patients with mild cognitive impairment (MCI) have mainly focused on the neural mechanisms of alterations in activation. To date, very few studies have investigated background network alterations in the working memory state. Therefore, the present study investigated the static and temporal dynamic changes in the background network in MCI patients during a working memory task. A hybrid delayed-match-to-sample task was used to examine working memory performance in MCI patients. Functional magnetic resonance imaging (fMRI) data were collected and the marker of amplitude of low-frequency fluctuations (ALFF) was used to investigate alterations in the background network. The present study demonstrated static and dynamic alterations of ALFF in MCI patients during working memory tasks, relative to the resting state. Traditional static analysis revealed that ALFF decreased in the right ventrolateral prefrontal cortex (VLPFC), right dorsolateral PFC (DLPFC), and left supplementary motor area for normal controls (NCs) in the working memory state. However, the same regions showed increased ALFF in MCI patients. Furthermore, relative to NCs, MCI patients demonstrated altered performance-related functional connectivity (FC) patterns, with the right VLPFC and right DLPFC as ROIs. In terms of temporal dynamic analysis, the present study found that in the working memory state dynamic ALFF of bilateral thalamus regions was increased in NCs but decreased in MCI patients. Additionally, MCI patients demonstrated altered performance-related coefficient of variation patterns; the regions in MCI patients were larger and more widely distributed in the parietal and temporal lobes, relative to NCs. This is the first study to examine static and temporal dynamic alterations of ALFF in the background network of MCI patients in working memory states. The results extend previous studies by providing a new perspective on the neural mechanisms of working memory deficits in MCI patients.

Effects of reward on spatial working memory in schizophrenia.

Reward processing and cognition are disrupted in schizophrenia (SCZ), yet how these processes interface is unknown. In SCZ, deficits in reward representation may affect motivated, goal-directed behaviors. To test this, we examined the effects of monetary reward on spatial working memory (WM) performance in patients with SCZ. To capture complimentary effects, we tested biophysically grounded computational models of neuropharmacologic manipulations onto a canonical fronto-parietal association cortical microcircuit capable of WM computations. Patients with SCZ (n = 33) and healthy control subjects (HCS; n = 32) performed a spatial WM task with 2 reward manipulations: reward cues presented prior to each trial, or contextually prior to a block of trials. WM performance was compared with cortical circuit models of WM subjected to feed-forward glutamatergic excitation, feed-forward GABAergic inhibition, or recurrent modulation strengthening local connections. Results demonstrated that both groups improved WM performance to reward cues presented prior to each trial (HCS d = -0.62; SCZ d = -1.0), with percent improvement correlating with baseline WM performance (r = .472, p < .001). However, rewards presented contextually before a block of trials did not improve WM performance in patients with SCZ (d = 0.01). Modeling simulations achieved improved WM precision through strengthened local connections via neuromodulation, or feed-forward inhibition. Taken together, this work demonstrates that patients with SCZ can improve WM performance to short-term, but not longer-term rewards-thus, motivated behaviors may be limited by strength of reward representation. A potential mechanism for transiently improved WM performance may be strengthening of local fronto-parietal microcircuit connections via neuromodulation or feed-forward inhibitory drive. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Modafinil Improves Episodic Memory and Working Memory Cognition in Patients With Remitted Depression: A Double-Blind, Randomized, Placebo-Controlled Study

BackgroundCognitive dysfunction is a core feature of depression and tends to persist even after mood symptoms recover, leading to detrimental effects on clinical and functional outcomes. However, most currently available treatments have not typically addressed cognition. Modafinil has been shown to have beneficial effects on cognitive function and therefore has the potential to improve cognition in depression. The objective of this double-blind, placebo-controlled study was to investigate the effects of modafinil on cognitive functions in patients with remitted depression. MethodsIn total, 60 patients with remitted depression participated in the study. Cognitive functions were evaluated with tests of working memory, planning, attention, and episodic memory from the Cambridge Neuropsychological Test Automated Battery at the baseline session and after treatment. A double-blind, randomized, placebo-controlled, parallel groups design was used to assess the effects of single-dose (200 mg) modafinil (n = 30) or placebo (n = 30) on cognition and fatigue. The main outcome measures were neurocognitive test scores from the Cambridge Neuropsychological Test Automated Battery. Visual analogue scales for subjective feelings and fatigue were used as secondary measures. ResultsThe modafinil group had significantly better performance on tests of episodic memory (p = .01, ηp2 = .10) and working memory (p = .04, ηp2 = .06). Modafinil did not improve planning or sustained attention. ConclusionsThis study suggested that modafinil (200 mg) could improve episodic memory and working memory performance in patients with remitted depression. Modafinil may have potential as a therapeutic agent to help remitted depressed patients with persistent cognitive difficulties.

EP 112. Neurophysiological correlates of cognitive control in patients with major depressive disorder (MDD)

Affective cognitive control capacity (e.g., the ability to regulate emotions or manipulate emotional material in the service of task goals) is associated with professional and interpersonal success. Impoverished affective control, by contrast, characterizes many neuropsychiatric disorders. Resent studies already showed that patients with major depressive disorder (MDD) for example exhibit an attentional bias, meaning that they had slower reaction time for emotional valent pictures than for neutral pictures (Wolkenstein and Plewnia, 2013)? Our research group moreover discovered that emotional,in contrast to neutral valent pictures lead to an increased LPP (late positive potential) in EEGs of healthy subjects while carrying out a dual working memory task (DWM) (Faehling, 2014)? In our study we want to examine the interaction between emotion regulation,reaction time and working memory performance in patients with major depressive disorder (MDD).Therefore we used negative and neutral IAPS as distractors in a DWM and linked the task with EEG measurement. Our main hypothesis was that the late positive potential (LPP) over the prefrontal? cortex of depressed subjects, measured while watching negative pictures, increased more as in healthy subjects. Accordingly higher LPP amplitudes show higher cognitive capacity load for affective stimuli. This is in line with the discovered correlation between high LPP amplitudes and task accuracy and high LPP amplitudes and reaction time.

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex enhances working memory.

Neuroimaging and electrophysiological studies have unequivocally identified the dorsolateral prefrontal cortex (DLPFC) as a crucial structure for top-down control of working memory (WM) processes. By modulating the excitability of neurons in a targeted cortical area, transcranial magnetic stimulation (TMS) offers a unique way to modulate DLPFC function, opening the possibility of WM facilitation. Even though TMS neuromodulation effects over the left DLPFC have successfully improved WM performance in patients with depression and schizophrenia in a multitude of studies, raising the potential of TMS as a safe efficacious treatment for WM deficits, TMS interventions in healthy individuals have produced mixed and inconclusive results. Here, we stimulated the left DLPFC of healthy individuals using a high-frequency repetitive TMS protocol and evaluated behavioral performance in a battery of cognitive tasks. We found that TMS treatment enhanced WM performance in a verbal digit span and a visuospatial 2-back task.

Sternberg working memory performance following treatment with pramipexole in patients with moderate-to-severe restless legs syndrome

ObjectivesWe recently reported that the P300 amplitude related to the Sternberg working memory (WM) task was significantly lower in drug-naïve severe restless legs syndrome (RLS) patients than controls. Here, we evaluated the effects of pramipexole on the Sternberg WM task performance by event-related potential (ERP) study. MethodsThirteen drug-naïve RLS patients (52.0 ± 9.48 years) were enrolled in the study. Pramipexole was administered over a period of 12 weeks every night 1 h before bedtime. Two ERP studies were carried out: the first was performed just before giving the first dose of pramipexole and the second was conducted at 12–16 weeks after commencement of pramipexole administration. P300 amplitudes and reaction times were compared before and after treatment considering brain regions and memory load as within-subject factors. Clinical and sleep-related variables were correlated with P300 amplitude. ResultsAfter treatment with pramipexole, the International RLS Severity Scale (IRLS) score was significantly decreased. Sleep quality and depression were also significantly improved. Omission error was significantly reduced without significant change of commission error. Reaction time was significantly shortened, regardless of memory load size, following treatment with pramipexole. Parietal P300 amplitude was significantly increased after treatment with pramipexole for all memory load sizes. Increase of frontal P300 amplitude was significantly correlated with improvement of sleep duration, IRLS, Insomnia Severity Index, and Pittsburgh Sleep Quality Index score. ConclusionOur study suggested that pramipexole improves WM performance in patients with RLS in addition to improving RLS symptoms, sleep disturbance, and depression.

A controlled study on the cognitive effect of alpha neurofeedback training in patients with major depressive disorder.

Cognitive deficits are core symptoms of depression. This study aims to investigate whether neurofeedback (NF) training can improve working memory (WM) performance in patients with major depressive disorder (MDD). The NF group (n = 40) underwent eight NF sessions and was compared to a non-interventional control group (n = 20). The NF protocol aimed to increase the individual upper alpha power in the parieto-occipital area of the scalp. Main cognitive variable was WM, which was measured pre- and post- training along with other variables such as attention and executive functions. EEG was recorded in both eyes closed resting state and eyes open task-related activity, pre- and post- NF training, and pre- and post- the NF trials within each session. A power EEG analysis and an alpha asymmetry analysis were conducted at the sensor level. Frequency domain standardized low resolution tomography (sLORETA) was used to assess the effect at brain source level. Correlation analysis between the clinical/cognitive and EEG measurements was conducted at both the sensor and brain source level. The NF group showed increased performance as well as improved processing speed in a WM test after the training. The NF group showed pre-post enhancement in the upper alpha power after the training, better visible in task-related activity as compared to resting state. A current density increase appeared in the alpha band (8–12 Hz) for the NF group, localized in the subgenual anterior cingulate cortex (sgACC, BA 25). A positive correlation was found for the NF group between the improvement in processing speed and the increase of beta power at both the sensor and brain source level. These results show the effectiveness of this NF protocol in improving WM performance in patients with MDD.

Working memory encoding and false memory in schizophrenia and bipolar disorder in a spatial delayed response task.

Working memory (WM) impairment is a core feature of schizophrenia, but the contributions of different WM components are not yet specified. Here, we investigated the potential role of inefficient encoding in reduced WM performance in patients with schizophrenia (PSZ). Twenty-eight PSZ, 16 patients with bipolar disorder (PBP), 16 unaffected and unmedicated relatives of PSZ (REL), and 29 demographically matched healthy controls (HC) performed a spatial delayed response task with either low or high WM demands. The demands on attentional selection were also manipulated by presenting distractor stimuli during encoding in some of the trials. After each trial, participants rated their level of response confidence. This allowed us to analyze different types of WM responses. WM was severely impaired in PSZ compared to HC; this reduction was mainly due to an increase in the amount of false memory responses (incorrect responses that were given with high confidence) rather than an increase in the amount of incorrect and not-confident responses. Although PBP showed WM impairments, they did not have increased false memory errors. In contrast, reduced WM in REL was also accompanied by an increase in false memory errors. The presentation of distractors led to a decline in WM performance, which was comparable across groups indicating that attentional selection was intact in PSZ. These findings suggest that inefficient WM encoding is responsible for impaired WM in schizophrenia and point to differential mechanisms underlying WM impairments in PSZ and PBP.

Enhancing the Working Memory of Stroke Patients Using tDCS

We investigated whether anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex affected the working memory performance of patients after a stroke. Ten patients (mean age 47.7 yrs) with cognitive deficits after a first-ever stroke participated in this single-blind, crossover, and sham-controlled experiment. Each patient was randomly assigned to undergo two transcranial direct current stimulation sessions: anodal dorsolateral prefrontal cortex and sham stimulation within 48 hrs of a washout period. All participants performed a two-back working memory task before and after the administration of the transcranial direct current stimulation. Accuracy (correction rate), recognition accuracy (correction rate-commission error rate), and response time were measured during each experiment. Repeated-measures analysis of variance indicated a significant interaction effect of transcranial direct current stimulation type and time on the recognition accuracy. Post hoc analyses revealed a significant difference between prestimulation and poststimulation in the anodal stimulation group but not in the sham stimulation group. Regarding the accuracy, the paired t test indicated significant improvement only after anodal transcranial direct current stimulation without a significant interaction effect between the two transcranial direct current stimulation types. The response time was not significantly different in the anodal and sham stimulation groups. Our results demonstrated that anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex was associated with enhanced working memory performance as indexed by the recognition accuracy in patients after a stroke.

Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia.

We examined the status of the neural network mediating the default mode of brain function, which typically exhibits greater activation during rest than during task, in patients in the early phase of schizophrenia and in young first-degree relatives of persons with schizophrenia. During functional MRI, patients, relatives, and controls alternated between rest and performance of working memory (WM) tasks. As expected, controls exhibited task-related suppression of activation in the default network, including medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Increased task-related MPFC suppression correlated with better WM performance in patients and relatives and with less psychopathology in all 3 groups. For WM task performance, patients and relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) than controls. During rest and task, patients and relatives exhibited abnormally high functional connectivity within the default network. The magnitudes of default network connectivity during rest and task correlated with psychopathology in the patients. Further, during both rest and task, patients exhibited reduced anticorrelations between MPFC and DLPFC, a region that was hyperactivated by patients and relatives during WM performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness.

Assessment of single and bound features in a working memory task in schizophrenia

If disturbance of binding in long term memory is well established in schizophrenia, data concerning working memory maintenance are less clear. Feature binding in working memory was investigated in 19 patients with schizophrenia and 19 healthy controls. Binding was assessed by comparing two conditions in which participants had to retain four letters and four spatial locations. These features were presented either bound or separate. Results showed that both groups had better performances for bound than separate features, despite the fact that patients performed significantly worse than controls. When maintenance for isolated features was assessed, patients were severely disturbed for spatial locations but not for letters. Such a result suggests that reduced working memory performance in patients with schizophrenia for bound features is probably a consequence of a spatial deficit rather than a specific deficit of the binding process. Thus, not all form of binding are disturbed in schizophrenia.

Effect of cortisol levels on working memory performance in elderly subjects with Alzheimer's disease

Subjects with Alzheimer's disease (AD) have elevated cortisol levels as a result of hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Acute administration of hydrocortisone has been associated with working memory (WM) performance in young adults. To investigate whether cortisol levels are associated with WM performance in subjects with AD. Eighty subjects were included, comprising 40 patients with mild AD and 40 healthy elderly controls. WM was assessed using the Digit Span Backward test (DSB). Saliva samples were collected to determine cortisol levels. AD subjects had poorer performance on the DSB than controls (p=0.002) and also presented higher levels of cortisol than control group (p=0.04). No significant correlation was observed between the DSB and cortisol levels in both groups (r= -0.29). In this study, elevated cortisol levels were not associated with poorer WM performance in patients with AD or in healthy elderly subjects.