An Event-Related fMRI Study of Phonological Verbal Working Memory in Schizophrenia

Background

While much is known about the role of prefrontal cortex (PFC) in working memory (WM) deficits of schizophrenia, the nature of the relationship between cognitive components of WM and brain activation patterns remains unclear. We aimed to elucidate the neural correlates of the maintenance component of verbal WM by examining correct and error trials with event-related fMRI.

Methodology/Findings

Twelve schizophrenia patients (SZ) and thirteen healthy control participants (CO) performed a phonological delayed-matching-to-sample-task in which a memory set of three nonsense words was presented, followed by a 6-seconds delay after which a probe nonsense word appeared. Participants decided whether the probe matched one of the targets, and rated the confidence of their decision. Blood-oxygen-level-dependent (BOLD) activity during WM maintenance was analyzed in relation to performance (correct/error) and confidence ratings. Frontal and parietal regions exhibited increased activation on correct trials for both groups. Correct and error trials were further segregated into true memory, false memory, guess, and true error trials. True memory trials were associated with increased bilateral activation of frontal and parietal regions in both groups but only CO showed deactivation in PFC. There was very little maintenance-related cortical activity during guess trials. False memory was associated with increased left frontal and parietal activation in both groups.

Conclusion

These findings suggest that a wider network of frontal and parietal regions support WM maintenance in correct trials compared with error trials in both groups. Furthermore, a more extensive and dynamic pattern of recruitment of the frontal and parietal networks for true memory was observed in healthy controls compared with schizophrenia patients. These results underscore the value of parsing the sources of memory errors in fMRI studies because of the non-linear nature of the brain-behavior relationship, and suggest that group comparisons need to be interpreted in more specific behavioral contexts.     

A Working Memory Deficit among Dyslexic Readers with No Phonological Impairment as Measured Using the N-Back Task: An fNIR Study

Data indicated that dyslexic individuals exhibited difficulties on tasks involving Working Memory (WM). Previous studies have suggested that these deficits stem from impaired processing in the Phonological Loop (PL). The PL impairment was connected to poor phonological processing. However, recent data has pointed to the Central Executive (CE) system as another source of WM deficit in dyslexic readers. This opened a debate whether the WM deficit stems solely from PL or can also be seen as an outcome of poor CE processing. In an attempt to verify this question, the current study compared adult skilled and compensated dyslexic readers with no impairment of phonological skills. The participants’ PL and CE processing were tested by using the fNIR device attached to the frontal lobe and measured the changes in brain oxygen values when performing N-back task. As it was previously suggested, the N = 0 represented PL and N = 1 to 3 represent CE processing. It was hypothesized that dyslexic readers who show non-impaired phonological skills will exhibit deficits mainly in the CE subsystem and to a lesser extent in the PL. Results indicated that the two reading level groups did not differ in their accuracy and reaction times in any of the N-Back conditions. However, the dyslexic readers demonstrated significant lower maximum oxyHb values in the upper left frontal lobe, mainly caused due to a significant lower activity under the N = 1 condition. Significant task effects were found in the medial left hemisphere, and the high medial right hemisphere. In addition, significant correlations between fNIR-features, reading performance and speed of processing were found. The higher oxyHb values, the better reading and speed of processing performance obtained. The results of the current study support the hypothesis that at least for the group of dyslexics with non-impaired PL, WM deficit stems from poor CE activity.     

Reduced Functional Reserve in Patients with Age-Related White Matter Changes: A Preliminary fMRI Study of Working Memory

Subcortical age-related white matter changes (ARWMC) are a frequent finding in healthy elderly people suggested to cause secondary tissue changes and possibly affecting cognitive processes. We aimed to determine the influence of the extent of ARWMC load on attention and working memory processes in healthy elderly individuals. Fourteen healthy elderly subjects (MMSE >26; age 55–80 years) performed three fMRI tasks with increasing difficulty assessing alertness, attention (0-back), and working memory (2-back). We compared activation patterns in those with only minimal ARWMC (Fazekas 0–1) to those with moderate to severe ARWMC (Fazekas 2–3). During the fMRI experiments, the study population showed activation in brain areas typically involved in attention and working memory with a recruitment of cortical areas with increasing task difficulty. Subjects with higher lesion load showed a higher activation at all task levels with only sparse increase of signal with increasing complexity. In the lower lesion load group, rising task difficulty lead to a significant and widely distributed increase of activation. Although the number of patients included in the study is small, these findings suggest that even clinically silent ARWMC may affect cognitive processing and lead to compensatory activation during cognitive tasks. This can be interpreted as a reduction of functional reserve and may pose a risk for cognitive decline in these patients.     

Dual N-Back Working Memory Training in Healthy Adults: A Randomized Comparison to Processing Speed Training

Enhancing cognitive ability is an attractive concept, particularly for middle-aged adults interested in maintaining cognitive functioning and preventing age-related declines. Computerized working memory training has been investigated as a safe method of cognitive enhancement in younger and older adults, although few studies have considered the potential impact of working memory training on middle-aged adults. This study investigated dual n-back working memory training in healthy adults aged 30–60. Fifty-seven adults completed measures of working memory, processing speed, and fluid intelligence before and after a 5-week web-based dual n-back or active control (processing speed) training program. Results: Repeated measures multivariate analysis of variance failed to identify improvements across the three cognitive composites, working memory, processing speed, and fluid intelligence, after training. Follow-up Bayesian analyses supported null findings for training effects for each individual composite. Findings suggest that dual n-back working memory training may not benefit working memory or fluid intelligence in healthy adults. Further investigation is necessary to clarify if other forms of working memory training may be beneficial, and what factors impact training-related benefits, should they occur, in this population.     

Functional Activation during the Rapid Visual Information Processing Task in a Middle Aged Cohort: An fMRI Study

The Rapid Visual Information Processing (RVIP) task, a serial discrimination task where task performance believed to reflect sustained attention capabilities, is widely used in behavioural research and increasingly in neuroimaging studies. To date, functional neuroimaging research into the RVIP has been undertaken using block analyses, reflecting the sustained processing involved in the task, but not necessarily the transient processes associated with individual trial performance. Furthermore, this research has been limited to young cohorts. This study assessed the behavioural and functional magnetic resonance imaging (fMRI) outcomes of the RVIP task using both block and event-related analyses in a healthy middle aged cohort (mean age = 53.56 years, n = 16). The results show that the version of the RVIP used here is sensitive to changes in attentional demand processes with participants achieving a 43% accuracy hit rate in the experimental task compared with 96% accuracy in the control task. As shown by previous research, the block analysis revealed an increase in activation in a network of frontal, parietal, occipital and cerebellar regions. The event related analysis showed a similar network of activation, seemingly omitting regions involved in the processing of the task (as shown in the block analysis), such as occipital areas and the thalamus, providing an indication of a network of regions involved in correct trial performance. Frontal (superior and inferior frontal gryi), parietal (precuenus, inferior parietal lobe) and cerebellar regions were shown to be active in both the block and event-related analyses, suggesting their importance in sustained attention/vigilance. These networks and the differences between them are discussed in detail, as well as implications for future research in middle aged cohorts.     

The Default Mode Network and the Working Memory Network Are Not Anti-Correlated during All Phases of a Working Memory Task

Introduction

The default mode network and the working memory network are known to be anti-correlated during sustained cognitive processing, in a load-dependent manner. We hypothesized that functional connectivity among nodes of the two networks could be dynamically modulated by task phases across time.

Methods

To address the dynamic links between default mode network and the working memory network, we used a delayed visuo-spatial working memory paradigm, which allowed us to separate three different phases of working memory (encoding, maintenance, and retrieval), and analyzed the functional connectivity during each phase within and between the default mode network and the working memory network networks.

Results

We found that the two networks are anti-correlated only during the maintenance phase of working memory, i.e. when attention is focused on a memorized stimulus in the absence of external input. Conversely, during the encoding and retrieval phases, when the external stimulation is present, the default mode network is positively coupled with the working memory network, suggesting the existence of a dynamically switching of functional connectivity between “task-positive” and “task-negative” brain networks.

Conclusions

Our results demonstrate that the well-established dichotomy of the human brain (anti-correlated networks during rest and balanced activation-deactivation during cognition) has a more nuanced organization than previously thought and engages in different patterns of correlation and anti-correlation during specific sub-phases of a cognitive task. This nuanced organization reinforces the hypothesis of a direct involvement of the default mode network in cognitive functions, as represented by a dynamic rather than static interaction with specific task-positive networks, such as the working memory network.     

Simultaneous EEG-fMRI during a Working Memory Task: Modulations in Low and High Frequency Bands

Background

EEG studies of working memory (WM) have demonstrated load dependent frequency band modulations. FMRI studies have localized load modulated activity to the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and posterior parietal cortex (PPC). Recently, an EEG-fMRI study found that low frequency band (theta and alpha) activity negatively correlated with the BOLD signal during the retention phase of a WM task. However, the coupling of higher (beta and gamma) frequencies with the BOLD signal during WM is unknown.

Methodology

In 16 healthy adult subjects, we first investigated EEG-BOLD signal correlations for theta (5–7 Hz), alpha1 (8–10), alpha2 (10–12 Hz), beta1 (13–20), beta2 (20–30 Hz), and gamma (30–40 Hz) during the retention period of a WM task with set size 2 and 5. Secondly, we investigated whether load sensitive brain regions are characterised by effects that relate frequency bands to BOLD signals effects.

Principal Findings

We found negative theta-BOLD signal correlations in the MPFC, PPC, and cingulate cortex (ACC and PCC). For alpha1 positive correlations with the BOLD signal were found in ACC, MPFC, and PCC; negative correlations were observed in DLPFC, PPC, and inferior frontal gyrus (IFG). Negative alpha2-BOLD signal correlations were observed in parieto-occipital regions. Beta1-BOLD signal correlations were positive in ACC and negative in precentral and superior temporal gyrus. Beta2 and gamma showed only positive correlations with BOLD, e.g., in DLPFC, MPFC (gamma) and IFG (beta2/gamma). The load analysis revealed that theta and—with one exception—beta and gamma demonstrated exclusively positive load effects, while alpha1 showed only negative effects.

Conclusions

We conclude that the directions of EEG-BOLD signal correlations vary across brain regions and EEG frequency bands. In addition, some brain regions show both load sensitive BOLD and frequency band effects. Our data indicate that lower as well as higher frequency brain oscillations are linked to neurovascular processes during WM.     

Increased Cortical Activity in Binge Drinkers during Working Memory Task: A Preliminary Assessment through a Functional Magnetic Resonance Imaging Study

Background

Cerebral dysfunction is a common feature of both chronic alcohol abusers and binge drinkers. Here, we aimed to study whether, at equated behavioral performance levels, binge drinkers exhibited increased neural activity while performing simple cognitive tasks.

Methods

Thirty-two participants (16 binge drinkers and 16 matched controls) were scanned using functional magnetic resonance imaging (fMRI) while performing an n-back working memory task. In the control zero-back (N0) condition, subjects were required to press a button with the right hand when the number “2″ was displayed. In the two-back (N2) condition, subjects had to press a button when the displayed number was identical to the number shown two trials before.

Results

fMRI analyses revealed higher bilateral activity in the pre-supplementary motor area in binge drinkers than matched controls, even though behavioral performances were similar. Moreover, binge drinkers showed specific positive correlations between the number of alcohol doses consumed per occasion and higher activity in the dorsomedial prefrontal cortex, as well as between the number of drinking occasions per week and higher activity in cerebellum, thalamus and insula while performing the N2 memory task.

Conclusions

Binge alcohol consumption leads to possible compensatory cerebral changes in binge drinkers that facilitate normal behavioral performance. These changes in cerebral responses may be considered as vulnerability factors for developing adult substance use disorders.     

Prospective Memory Performance in Non-Psychotic First-Degree Relatives of Patients with Schizophrenia: A Controlled Study

Objective

We aimed at investigating prospective memory and its socio-demographic and neurocognitive correlates in non-psychotic, first-degree relatives (FDRs) of patients with schizophrenia compared to patients with first episode schizophrenia (FES), and healthy controls (HCs).

Methods

Forty-seven FES patients, 50 non-psychotic FDRs (23 offspring and 27 siblings) of patients with chronic schizophrenia (unrelated to the FES group) and 51 HCs were studied. The Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT) was used to measure time-based prospective memory (TBPM) and event-based prospective memory (EBPM) performance. Other cognitive functions (involving respective memory and executive functions) were evaluated with standardized tests.

Results

After controlling for basic demographic characteristics including age, gender and educational level, there was a significant difference between FDRs, FES and HCs with respect to both TBPM (F_(2,142) = 10.4, p<0.001) and EBPM (F_(2,142) = 10.8, p<0.001). Multiple linear regression analyses revealed that lower scores of the Hopkins Verbal Learning Test-Revised (HVLT-R) and the STROOP Word-Color Test (SWCT) contributed to TBPM impairment, while lower educational level and higher scores of the Color Trails Test-2 (CTT-2) contributed to EBPM deficit in FDRs.

Conclusions

FDRs share similar but attenuated prospective memory impairments with schizophrenia patients, suggesting that prospective memory deficits may represent an endophenotype of schizophrenia.     

Evidence for Anomalous Network Connectivity during Working Memory Encoding in Schizophrenia: An ICA Based Analysis

Background

Numerous neuroimaging studies report abnormal regional brain activity during working memory performance in schizophrenia, but few have examined brain network integration as determined by “functional connectivity” analyses.

Methodology/Principal Findings

We used independent component analysis (ICA) to identify and characterize dysfunctional spatiotemporal networks in schizophrenia engaged during the different stages (encoding and recognition) of a Sternberg working memory fMRI paradigm. 37 chronic schizophrenia and 54 healthy age/gender-matched participants performed a modified Sternberg Item Recognition fMRI task. Time series images preprocessed with SPM2 were analyzed using ICA. Schizophrenia patients showed relatively less engagement of several distinct “normal” encoding-related working memory networks compared to controls. These encoding networks comprised 1) left posterior parietal-left dorsal/ventrolateral prefrontal cortex, cingulate, basal ganglia, 2) right posterior parietal, right dorsolateral prefrontal cortex and 3) default mode network. In addition, the left fronto-parietal network demonstrated a load-dependent functional response during encoding. Network engagement that differed between groups during recognition comprised the posterior cingulate, cuneus and hippocampus/parahippocampus. As expected, working memory task accuracy differed between groups (p<0.0001) and was associated with degree of network engagement. Functional connectivity within all three encoding-associated functional networks correlated significantly with task accuracy, which further underscores the relevance of abnormal network integration to well-described schizophrenia working memory impairment. No network was significantly associated with task accuracy during the recognition phase.

Conclusions/Significance

This study extends the results of numerous previous schizophrenia studies that identified isolated dysfunctional brain regions by providing evidence of disrupted schizophrenia functional connectivity using ICA within widely-distributed neural networks engaged for working memory cognition.     

Timing over Tuning: Overcoming the Shortcomings of a Line Attractor during a Working Memory Task

How the brain stores information about a sensory stimulus in working memory is not completely known. Clues about the mechanisms responsible for working memory can be gleaned by recording from neurons during the performance of a delayed response task. I focus on the data recorded during such an experiment, a classic tactile discrimination task. I describe how the observed variability in the firing rate during a trial suggests that the type of attractor that is responsible for holding the stimulus information is not a fixed-point type attractor. I propose an alternate mechanism to a line attractor that allows the network to hold the value of an analog stimulus variable for the duration of the delay period, but rather than maintain a constant level of activity, the cells'' firing rate varies throughout the delay period. I describe how my proposed mechanism offers a substantial advantage over a line attractor: The tuning requirements of cell to cell connections are greatly eased from that of a line attractor. To accommodate a change in the length of the delay period, I show that the network can be altered by changing a single parameter - the timing of an executive signal that originates outside of the network. To demonstrate the mechanism, as well as the tuning benefits, I use a well known model of propagation in neuronal networks.     

Working Memory in the Processing of the Iowa Gambling Task: An Individual Differences Approach

The Iowa Gambling Task (IGT) is a sequential learning task in which participants develop a tendency towards advantageous options arising from the outcomes associated with their previous decisions. The role of working memory in this complex task has been largely debated in the literature. On one hand, low working memory resources lead to a decrease in the number of advantageous decisions and make a significant part of participants unable to report explicitly which options are the most profitable. On the other hand, several studies have shown no contribution of working memory to the IGT decision patterns. In order to investigate this apparent incompatibility of results, we used an individual differences approach, which has proven an effective method to investigate the role of working memory in cognition. We compared the IGT decision patterns of participants as a function of their working memory capacity (WMC). As expected, contrary to low WMC participants, high WMC participants developed a tendency towards advantageous decisions. These findings lead us to discuss the role of WMC in decision making tasks.     

Patterns of Brain Activation when Mothers View Their Own Child and Dog: An fMRI Study

Neural substrates underlying the human-pet relationship are largely unknown. We examined fMRI brain activation patterns as mothers viewed images of their own child and dog and an unfamiliar child and dog. There was a common network of brain regions involved in emotion, reward, affiliation, visual processing and social cognition when mothers viewed images of both their child and dog. Viewing images of their child resulted in brain activity in the midbrain (ventral tegmental area/substantia nigra involved in reward/affiliation), while a more posterior cortical brain activation pattern involving fusiform gyrus (visual processing of faces and social cognition) characterized a mother''s response to her dog. Mothers also rated images of their child and dog as eliciting similar levels of excitement (arousal) and pleasantness (valence), although the difference in the own vs. unfamiliar child comparison was larger than the own vs. unfamiliar dog comparison for arousal. Valence ratings of their dog were also positively correlated with ratings of the attachment to their dog. Although there are similarities in the perceived emotional experience and brain function associated with the mother-child and mother-dog bond, there are also key differences that may reflect variance in the evolutionary course and function of these relationships.     

Aberrant Function of Learning and Cognitive Control Networks Underlie Inefficient Cognitive Flexibility in Anorexia Nervosa: A Cross-Sectional fMRI Study

ObjectivesPeople with Anorexia Nervosa exhibit difficulties flexibly adjusting behaviour in response to environmental changes. This has previously been attributed to problematic behavioural shifting, characterised by a decrease in fronto-striatal activity. Additionally, alterations of instrumental learning, which relies on fronto-striatal networks, may contribute to the observation of inflexible behaviour. The authors sought to investigate the neural correlates of cognitive flexibility and learning in Anorexia Nervosa.MethodThirty-two adult females with Anorexia Nervosa and thirty-two age-matched female control participants completed the Wisconsin Card Sorting Task whilst undergoing functional magnetic resonance imaging. Event-related analysis permitted the comparison of cognitive shift trials against those requiring maintenance of rule-sets and allowed assessment of trials representing learning.ResultsAlthough both groups performed similarly, we found significant interactions in the left middle frontal gyrus, precuneus and superior parietal lobule whereby blood-oxygenated-level dependent response was higher in Anorexia Nervosa patients during shifting but lower when maintaining rule-sets, as compared to healthy controls. During learning, posterior cingulate cortex activity in healthy controls decreased whilst increasing in the Anorexia Nervosa group, whereas the right precuneus exhibited the opposite pattern. Furthermore, learning was associated with lower blood-oxygenated-level dependent response in the caudate body, as compared to healthy controls.ConclusionsPeople with Anorexia Nervosa display widespread changes in executive function. Whilst cognitive flexibility appears to be associated with aberrant functioning of the fronto-parietal control network that mediates between internally and externally directed cognition, fronto-striatal alterations, particularly within the caudate body, were associated with instrumental learning. Together, this shows how perseverative tendencies could be a substrate of multiple high-order processes that may contribute to the maintenance of Anorexia Nervosa.     

Psychotic Experiences and Working Memory: A Population-Based Study Using Signal-Detection Analysis

Psychotic Experiences (PEs) during adolescence index increased risk for psychotic disorders and schizophrenia in adult life. Working memory (WM) deficits are a core feature of these disorders. Our objective was to examine the relationship between PEs and WM in a general population sample of young people in a case control study. 4744 individuals of age 17–18 from Bristol and surrounding areas (UK) were analyzed in a cross-sectional study nested within the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort study. The dependent variable was PEs, assessed using the semi-structured Psychosis-Like Symptom Interview (PLIKSi). The independent variable was performance on a computerized numerical n-back working memory task. Signal-Detection Theory indices, including standardized hits rate, false alarms rate, discriminability index (d’) and response bias (c) from 2-Back and 3-Back tasks were calculated. 3576 and 3527 individuals had complete data for 2-Back and 3-Back respectively. Suspected/definite PEs prevalence was 7.9% (N = 374). Strongest evidence of association was seen between PEs and false alarms on the 2-Back, (odds ratio (OR) = 1.17 [95% confidence intervals (CI) 1.01, 1.35]) and 3-back (OR = 1.35 [1.18, 1.54]) and with c (OR = 1.59 [1.09, 2.34]), and lower d’ (OR = 0.76 [0.65, 0.89]), on the 3-Back. Adjustment for several potential confounders, including general IQ, drug exposure and different psycho-social factors, and subsequent multiple imputation of missing data did not materially alter the results. WM is impaired in young people with PEs in the general population. False alarms, rather than poor accuracy, are more closely related to PEs. Such impairment is consistent with different neuropsychological models of psychosis focusing on signal-to-noise discrimination, probabilistic reasoning and impaired reality monitoring as a basis of psychotic symptoms.     

The Association between Intelligence Scores and Family History of Psychiatric Disorder in Schizophrenia Patients,Their Siblings and Healthy Controls

Background

The degree of intellectual impairment in schizophrenia patients and their relatives has been suggested to be associated with the degree of familial loading for schizophrenia. Since other psychiatric disorders are also more present in relatives of schizophrenia patients, the definition of family history should be broadened. The association between family history for psychiatric disorder and intelligence scores was investigated in patients with non-affective psychosis, their unaffected siblings and controls.

Methods

A sample of 712 schizophrenia proband families (696 patients and 766 siblings) and 427 healthy control families (517 subjects) participated in this study. Family history of psychiatric disorder was determined while excluding the data of the participating schizophrenia patient. A dichotomous division was made between families with no first- or second degree relative with psychiatric disorder and families with one or more affected relatives. Total intelligence scores were estimated by admission of the short form of the Wechsler Adult Intelligence Scale III.

Results

A significant interaction was found between family history of psychiatric disorder and clinical status (F(2,1086.87)= 4.17; p=.016). Patients with a positive family history of psychiatric disorder obtained higher intelligence scores compared to patients with no family history (mean IQ scores are 95.52 and 92.72) with an opposite effect in controls (mean IQ scores are 108.71 and 111.19). No significant difference was found between siblings of schizophrenia patients with or without a positive family history (mean IQ scores are 102.98 and 103.24).

Conclusion

In patients with schizophrenia, a negative family history of psychiatric disorder was associated with relatively low IQ suggesting that the etiology in these patients may involve environmental or genetic factors which are unique to the patient and are not observed in other relatives. Possible factors include severe environmental stressors containing premature birth or brain injury and genetic factors (e.g de novo Copy Number Variants).     

Working Memory Training in Post-Secondary Students with ADHD: A Randomized Controlled Study

Objectives

To determine whether standard-length computerized training enhances working memory (WM), transfers to other cognitive domains and shows sustained effects, when controlling for motivation, engagement, and expectancy.

Methods

97 post-secondary students (59.8% female) aged 18–35 years with Attention-Deficit/Hyperactivity Disorder, were randomized into standard-length adaptive Cogmed WM training (CWMT; 45-min/session), a shortened-length adaptive version of CWMT (15 min/session) that controlled for motivation, engagement and expectancy of change, or into a no training group (waitlist-control group). All three groups received weekly telephone calls from trained coaches, who supervised the CWMT and were independent from the research team. All were evaluated before and 3 weeks post-training; those in the two CWMT groups were also assessed 3 months post-training. Untrained outcome measures of WM included the WAIS-IV Digit Span (auditory-verbal WM), CANTAB Spatial Span (visual-spatial WM) and WRAML Finger Windows (visual-spatial WM). Transfer-of-training effects included measures of short-term memory, cognitive speed, math and reading fluency, complex reasoning, and ADHD symptoms.

Results

Performance on 5/7 criterion measures indicated that shortened-length CWMT conferred as much benefit on WM performance as did standard-length training, with both CWMT groups improving more than the waitlist-control group. Only 2 of these findings remained robust after correcting for multiple comparisons. Follow-up analyses revealed that post-training improvements on WM performance were maintained for at least three months. There was no evidence of any transfer effects but the standard-length group showed improvement in task-specific strategy use.

Conclusions

This study failed to find robust evidence of benefits of standard-length CWMT for improving WM in college students with ADHD and the overall pattern of findings raise questions about the specificity of training effects.

Trial Registration

ClinicalTrials.gov NCT01657721     

The Effects of CPAP Treatment on Task Positive and Default Mode Networks in Obstructive Sleep Apnea Patients: An fMRI Study

Introduction

Functional magnetic resonance imaging studies enable the investigation of neural correlates underlying behavioral performance. We investigate the effect of active and sham Continuous Positive Airway Pressure (CPAP) treatment on working memory function of patients with Obstructive Sleep Apnea Syndrome (OSAS) considering Task Positive and Default Mode networks (TPN and DMN).

Methods

An experiment with 4 levels of visuospatial n-back task was used to investigate the pattern of cortical activation in 17 men with moderate or severe OSAS before and after 2 months of therapeutic (active) or sub-therapeutic (sham) CPAP treatment.

Results

Patients with untreated OSAS had significantly less deactivation in the temporal regions of the DMN as compared to healthy controls, but activation within TPN regions was comparatively relatively preserved. After 2 months of treatment, active and sham CPAP groups exhibited opposite trends of cerebral activation and deactivation. After treatment, the active CPAP group demonstrated an increase of cerebral activation in the TPN at all task levels and of task-related cerebral deactivation in the anterior midline and medial temporal regions of the DMN at the 3-back level, associated with a significant improvement of behavioral performance, whereas the sham CPAP group exhibited less deactivation in the temporal regions of Default Mode Network and less Task Positive Network activation associated to longer response times at the 3-back.

Conclusion

OSAS has a significant negative impact primarily on task-related DMN deactivation, particularly in the medial temporal regions, possibly due to nocturnal hypoxemia, as well as TPN activation, particularly in the right ventral fronto-parietal network. After 2 months of active nasal CPAP treatment a positive response was noted in both TPN and DMN but without compete recovery of existing behavioral and neuronal deficits. Initiation of CPAP treatment early in the course of the disease may prevent or slow down the occurrence of irreversible impairment.     

A Neuropsychological and Neurophysiological Study of Memory Impairments in Patients with Left-Hemispheric Stroke during Rehabilitation

The informative and prognostic value of assessing the brain functional state and memory functions with neurophysiological, electrophysiological, and clinical methods was demonstrated in patients with consequences of ischemic stroke. The character and degree of memory impairments were associated with the localization and extent of the postischemic lesion and correlated with the markedness of pathological signs in the bioelectrical activity of the brain. This allowed identification of predictors of an adverse outcome and yielded valuable information for neurorehabilitation of poststroke patients.