Interactions of cognitive reserve with regional brain anatomy and brain function during a working memory task in healthy elders

Cognitive reserve (CR) defines the capacity of the adult brain to cope with pathology in order to minimize symptomatology. Relevant lifetime social, cognitive and leisure activities represent measurable proxies of cognitive CR but its underlying structural and functional brain mechanisms remain poorly understood. We investigated the relationship between CR and regional gray matter volumes and brain activity (fMRI) during a working memory task in a sample of healthy elders. Participants with higher CR had larger gray matter volumes in frontal and parietal regions. Conversely, a negative correlation was observed between CR and fMRI signal in the right inferior frontal cortex, suggesting increased neural efficiency for higher CR individuals. This latter association however disappeared after adjusting for gray matter images in a voxel-based manner. Altogether, present results may reflect both general and specific anatomofunctional correlates of CR in the healthy elders. Thus, whereas heteromodal anterior and posterior gray matter regions correspond to passive (i.e. morphological) correlates of CR unrelated to functional brain activation during this particular cognitive task, the right inferior frontal area reveals interactions between active and passive components of CR related to the cognitive functions tested in the fMRI study.     

Effects of chewing in working memory processing

It has been generally suggested that chewing produces an enhancing effect on cognitive performance-related aspects of memory by the test battery. Furthermore, recent studies have shown that chewing is associated with activation of various brain regions, including the prefrontal cortex. However, little is known about the relation between cognitive performances affected by chewing and the neuronal activity in specified regions in the brain. We therefore examined the effects of chewing on neuronal activities in the brain during a working memory task using fMRI. The subjects chewed gum, without odor and taste components, between continuously performed two- or three-back (n-back) working memory tasks. Chewing increased the BOLD signals in the middle frontal gyrus (Brodmann's areas 9 and 46) in the dorsolateral prefrontal cortex during the n-back tasks. Furthermore, there were more prominent activations in the right premotor cortex, precuneus, thalamus, hippocampus and inferior parietal lobe during the n-back tasks after the chewing trial. These results suggest that chewing may accelerate or recover the process of working memory besides inducing improvement in the arousal level by the chewing motion.     

Midlife memory ability accounts for brain activity differences in healthy aging

Cross-sectional neuroimaging studies suggest that hippocampal and prefrontal cortex functions underlie individual differences in memory ability in older individuals, but it is unclear how individual differences in cognitive ability in youth contribute to cognitive and neuroimaging measures in older age. Here, we investigated the relative influences of midlife memory ability and age-related memory change on memory-related BOLD-signal variability at one time point, using a sample from a longitudinal population-based aging study (N = 203, aged 55–80 years). Hierarchical regression analyses showed that midlife memory ability, assessed 15–20 years earlier, explained at least as much variance as memory change in clusters in the left inferior prefrontal cortex and the bilateral hippocampus, during memory encoding. Furthermore, memory change estimates demonstrated higher sensitivity than current memory levels in identifying distinct frontal regions where activity was selectively related to age-related memory change, as opposed to midlife memory. These findings highlight challenges in interpreting individual differences in neurocognitive measures as age-related changes in the absence of longitudinal data and also demonstrate the improved sensitivity of longitudinal measures.     

Verbal episodic memory deficits in remitted bipolar patients: A combined behavioural and fMRI study

Background

Episodic memory deficits affect the majority of patients with bipolar disorder (BD).

Aims

The study investigates episodic memory performance through different approaches, including behavioural measures, physiological parameters, and the underlying functional activation patterns with functional neuroimaging (fMRI).

Methods

26 Remitted BD patients and a matched group of healthy controls underwent a verbal episodic memory test together with monitored autonomic response, psychopathological ratings and functional magnetic resonance imaging (fMRI) during the verbal episodic memory test.

Results

Compared to healthy controls, BD patients performed significantly worse during the episodic memory task. The results further indicate that verbal episodic memory deficits in BD are associated with abnormal functional activity patterns in frontal, occipital and limbic regions, and an increase in stress parameters.

Limitations

We aimed to minimise sample heterogeneity by setting clear criteria for remission, based on the scores of a depression (BDI II) and mania scale (BRMAS) and on the DSM IV criteria. However, our patients were not symptom-free and scored higher on BDI II scores than the control group.

Conclusions

The results are of interest for the treatment of cognitive symptoms in BD patients, as persistent cognitive impairment may hamper full rehabilitation.     

Interaction of threat and verbal working memory in adolescents

Threat induces a state of sustained anxiety that can disrupt cognitive processing, and, reciprocally, cognitive processing can modulate an anxiety response to threat. These effects depend on the level of cognitive engagement, which itself varies as a function of task difficulty. In adults, we recently showed that induced anxiety impaired working memory accuracy at low and medium but not high load. Conversely, increasing the task load reduced the physiological correlates of anxiety (anxiety‐potentiated startle). The present work examines such threat‐cognition interactions as a function of age. We expected threat to more strongly impact working memory in younger individuals by virtue of putatively restricted cognitive resources and weaker emotion regulation. This was tested by examining the influence of age on the interaction of anxiety and working memory in 25 adolescents (10 to 17 years) and 25 adults (22 to 46 years). Working memory load was manipulated using a verbal n‐back task. Anxiety was induced using the threat of an aversive loud scream and measured via eyeblink startle. Findings revealed that, in both age groups, accuracy was lower during threat than safe conditions at low and medium but not high load, and reaction times were faster during threat than safe conditions at high load but did not differ at other loads. Additionally, anxiety‐potentiated startle was greater during low and medium than high load. Thus, the interactions of anxiety with working memory appear similar in adolescents and adults. Whether these similarities reflect common neural mechanisms would need to be assessed using functional neuroimaging.     

Adrenocortical stress responses and altered working memory performance

This study examined stress cortisol responses and cognitive performance. We initially measured cortisol responses of 40 right-handed healthy male volunteers to counterbalanced mental arithmetic and public speaking stressors. We then examined the relationship between cortisol reactivity and dichotic listening and mental arithmetic performance. High cortisol responders made more errors and completed fewer mental arithmetic items than low reactors. On dichotic listening, high responders tended toward better performance in all conditions and to both ears. High responders showed better performance to the right ear in the forced right than in the nonforced condition, whereas no difference between these conditions was found in low responders. High cortisol responders may have an increased focus on sensory stimuli and a decreased allocation of resources to working memory tasks.     

Motivation enhances visual working memory capacity through the modulation of central cognitive processes

Motivation is well known to enhance working memory (WM) capacity, but the mechanism underlying this effect remains unclear. The WM process can be divided into encoding, maintenance, and retrieval, and in a change detection visual WM paradigm, the encoding and retrieval processes can be subdivided into perceptual and central processing. To clarify which of these segments are most influenced by motivation, we measured ERPs in a change detection task with differential monetary rewards. The results showed that the enhancement of WM capacity under high motivation was accompanied by modulations of late central components but not those reflecting attentional control on perceptual inputs across all stages of WM. We conclude that the “state‐dependent” shift of motivation impacted the central, rather than the perceptual functions in order to achieve better behavioral performances.     

KIBRA gene variants are associated with episodic memory performance in subjective memory complaints

The KIBRA gene encodes a cytoplasmatic protein, a member of the signal transduction protein family, expressed mainly in the brain. Recent studies have implicated the involvement of a genetic variation in the KIBRA gene (T allele) in human memory in normal subjects and in the risk of developing Alzheimer's disease (AD). We report here the distribution of the KIBRA genetic variant and the Apolipoprotein E (ApoE) epsilon4 allele and their association with neuropsychological measures in older adults reporting problems with everyday memory (subjective memory complaints, SMC). We found that SMC subjects with the CT/TT genotype performed more poorly than those with the CC genotype on long-term memory tests. Thus, in our opinion, these data suggest that the KIBRA genotype could affect memory performance in a different way in those that complain of memory deficits compared to those that do not.     

Individual differences in working memory moderate the relationship between prosaccade latency and antisaccade error rate

Cognitive control is required for flexible responses in changing environments and can be assessed by measuring antisaccade error rate. Considerable variance in antisaccade error rate is observed in healthy participants, which motivated the current study to explore the cognitive factors affecting antisaccade performance. Relationships exist between prosaccade latency and antisaccade error rate, with faster prosaccade latencies linked to more antisaccade errors. Individual differences in working memory also impact saccadic performance. The current study tested the relationships among prosaccade latency, antisaccade error rate, and working memory in 153 healthy participants. Correlation and multiple regression analyses demonstrated that prosaccade latency predicted antisaccade error rate, and working memory moderated this relationship. These results may help elucidate individual differences in cognitive control among healthy individuals.     

The emotional startle effect is disrupted by a concurrent working memory task

Working memory (WM) processes are often thought to play an important role in the cognitive regulation of negative emotions. However, little is known about how they influence emotional processing. We report two experiments that tested whether a concurrent working memory task could modulate the emotional startle eyeblink effect, a well‐known index of emotional processing. In both experiments, emotionally negative and neutral pictures were viewed in two conditions: a “cognitive load” (CL) condition, in which participants had to actively maintain information in working memory (WM) while viewing the pictures, and a control “no load” (NL) condition. Picture‐viewing instructions were identical across CL and NL. In both experiments, results showed a significant reduction of the emotional modulation of the startle eyeblink reflex in the CL condition compared to the NL condition. These findings suggest that a concurrent WM task disrupts emotional processing even when participants are directing visual focus on emotionally relevant information.     

Distinct alterations in value-based decision-making and cognitive control in suicide attempters: Toward a dual neurocognitive model

Objective

The literature suggests that many suicide attempters show impairment in both decision-making and cognitive control. However, it is not clear if these deficits are linked to each other, and if they may be related to more basic alterations in attention. This is a relevant question in the perspective of future interventions targeting cognitive deficits to prevent suicidal acts.

Method

Two different populations of patients with histories of suicide attempts were assessed (N=142 and 119). The Iowa Gambling Task (IGT) was used to measure decision-making in both populations. We used a D2 cancellation task and a verbal working memory task in population 1; the Stroop test, the N-Back task, the Trail Making Test, and the Hayling Sentence Completion test in population 2.

Results

Regarding decision-making, we only found a small negative correlation between the Hayling test error score (r=−0.24; p=0.01), and the net score from the second half of the IGT. In contrast, working memory, cognitive flexibility and cognitive inhibition measures were largely inter-correlated.

Limitation

Most patients were medicated. Only patients with mood disorders.

Conclusion

These results add to previous findings suggesting that the neurocognitive vulnerability to suicidal behavior may rely on impairments in two distinct anatomical systems, one processing value-based decision-making (associated with ventral prefrontal cortex, among others) and one underlying cognitive control (associated with more dorsal prefrontal regions). This distinction may result in tailored-made cognitive interventions.     

Gynaecological history, complaints and examinations in a middle-aged population

A sample of women aged 40–56 years (n = 1349) was selected at random from the Census Register of Göteborg, Sweden. Altogether, 1095 (81%) filled out a questionnaire concerning gynaecological data. A control group (n = 170) was established and 135 women from this group (79%) underwent an extensive personal interview and pelvic examination. One aim was to investigate the representativity of the control group for the initial random sample and to compare the information obtained from the questionnaire with the information acquired by personal interview. An additional aim was to obtain information related to pelvic examination and FSH concentrations in the serum of middle-aged women. In general there was a good agreement between information from questionnaires and from personal interviews.The pelvic examination revealed that 53% of the post-menopausal women showed signs of genital atrophy and this condition was more common in sexually inactive than active women. Weakness of the pelvic floor was encountered in 16%. The uterus was of normal size in 94%, anteflexed in 76%, mid-positioned in 8% and retroflexed in 16%. There was a positive correlation between a pathological smear and cervical ectopy. Serum FSH values in menstruating women ranged from 6.4 to 47 IU/I. A cut-off value of 50 IU/I gave a complete separation between menstruating and post-menopausal subjects.     

Factors associated with menopausal symptom severity in middle-aged Brazilian women from the Brazilian Western Amazon

Objective

To determine the frequency and severity of menopausal symptoms and associated factors in middle-aged Brazilian women.

Methods

A cross-sectional study was carried out involving 1415 women aged 35–65 years attended at the Outpatient unit of the Clinicas Hospital of Rio Branco, Acre state, Brazil. The Menopause Rating Scale (MRS) was used to assess the severity of menopause symptoms. The Stata 10 statistical package was used for all data analysis whereas Pearson's x² nonparametric association test was used for bivariate analysis, adopting a level of statistical significance of 5%. On the multivariate analysis, independent variables positively associated with the dependent model were retained in the final model (p < 0.005).

Results

Overall, 54.1% of participants were premenopausal, 10.1% perimenopausal, and 35.8% postmenopausal. Irritability was the most frequent symptom (78.3%), followed by joint and muscular discomfort (74.8%), and anxiety (72.7%). Mean total MRS score was 15.6 + 8.8 (median 15). After adjusting for confounding factors, the logistic regression analysis found low educational level (OR:1.53; [95% CI:1.21–1.95]; p < 0.001); self-perceived poor/very poor health (OR:4.48; [95% CI: 3.53–5.69]; p < 0.001), and menopausal transition phase (OR:1.73; [95% CI:1.18–2.53]; p = 0.005) to be statistically significantly associated with more severe menopausal symptoms.

Conclusion

Among Brazilian women, atypical symptoms of the menopause were the most frequently reported. Severe menopausal symptoms were more likely in women with low educational level, self-perceived poor health and at the menopausal transition phase.     

Electrophysiological evidence for different effects of working memory load on interference control in adolescents than adults

The present study investigated how the development of interference control is influenced by the development of working memory (WM) capacity during adolescence. In a dual-task, 17 adolescents (12-16 years) and 19 adults (18-48 years) performed a gender word-face Stroop task, while WM-capacity was manipulated by a concurrently performed N-back task. Behavior (reaction times, % errors and % misses) and event-related potentials associated with the detection (N450) of the Stroop conflict and response selection (sustained positivity; SP) were measured without or with a concurrent WM load. Adolescents had lower accuracy on N-back and Stroop trials than adults. N450 results showed Stroop conflict above temporal-occipital cortex which was suggested to be caused by processing of distracter faces. This N450 conflict response was smaller in adults and only present when holding a simultaneous WM-load, whereas adolescents' N450 conflict responses were already present without a concurrent WM-load and did not further increase with load. These N450 results indicate poorer distracter suppression in adolescence which is suggested to be due to insufficient attentional resources for top-down control. Irrespective of WM-load, adolescents also had larger parietal SP conflict responses than adults, suggesting inefficient response selection in case of activation of two conflicting responses. The main conclusion is that adolescents have worse distracter suppression than adults, caused by lower availability of resources for top-down control.     

Involvement of prefrontal cortex in visual search

Visual search for target items embedded within a set of distracting items has consistently been shown to engage regions of occipital and parietal cortex, but the contribution of different regions of prefrontal cortex remains unclear. Here, we used fMRI to compare brain activity in 12 healthy participants performing efficient and inefficient search tasks in which target discriminability and the number of distractor items were manipulated. Matched baseline conditions were incorporated to control for visual and motor components of the tasks, allowing cortical activity associated with each type of search to be isolated. Region of interest analysis was applied to critical regions of prefrontal cortex to determine whether their involvement was common to both efficient and inefficient search, or unique to inefficient search alone. We found regions of the inferior and middle frontal cortex were only active during inefficient search, whereas an area in the superior frontal cortex (in the region of FEF) was active for both efficient and inefficient search. Thus, regions of ventral as well as dorsal prefrontal cortex are recruited during inefficient search, and we propose that this activity is related to processes that guide, control and monitor the allocation of selective attention.     

Visual contrast sensitivity in Alzheimer’s disease,mild cognitive impairment,and older adults with cognitive complaints

Deficits in contrast sensitivity (CS) have been reported in Alzheimer’s disease (AD). However, the extent of these deficits in prodromal AD stages, including mild cognitive impairment (MCI) or even earlier, has not been investigated. In this study, CS was assessed using frequency doubling technology in older adults with AD (n = 10), amnestic MCI (n = 28), cognitive complaints without performance deficits (CC; n = 20), and healthy controls (HC; n = 29). The association between CS and cognition was also evaluated. Finally, the accuracy of CS measures for classifying MCI versus HC was evaluated. CS deficits were found in AD and MCI, while CC showed intermediate performance between MCI and HC. Upper right visual field CS showed the most significant difference among groups. CS was also associated with cognitive performance. Finally, CS measures accurately classified MCI versus HC. The CS deficits in AD and MCI, and intermediate performance in CC, indicate that these measures are sensitive to early AD-associated changes. Therefore, frequency doubling technology-based measures of CS may have promise as a novel AD biomarker.     

Validity and reliability of a rating scale on subjective cognitive deficits in bipolar disorder (COBRA)

Background

Discrepancies between bipolar patients' reports and neuropsychological testing have been described and replicated. Unfortunately, no valid, specific, user-friendly, brief instrument is available to measure cognitive deficits as reported by these patients. The main aim of this study was to validate a novel instrument named the “cognitive complaints in bipolar disorder rating assessment” (COBRA). Second, we investigated the relationship between the COBRA, objective cognitive measures and illness course variables.

Method

The total sample (N=215) included 91 bipolar disorder patients and 124 healthy controls. The psychometric properties of the COBRA (e.g. internal consistency, concurrent validity, discriminative validity, factorial analyses, ROC curve and feasibility) were analyzed. A complete neuropsychological battery was used as objective cognitive assessment.

Results

The COBRA had one-factor structure with very high internal consistency (Cronbach's alpha=0.913). A high convergent validity was indicated by a strong correlation with the Frankfurt Complaint Questionnaire (ro=0.888, p<0.001). Bipolar patients experienced greater cognitive complaints compared to control group suggesting a discriminative validity of the instrument. Significant correlations were found between the COBRA and some objective cognitive measures. Furthermore, higher COBRA scores were associated with bipolar II subtype, residual depressive symptoms, hypomanic episodes and total episodes.

Limitations

The cross-sectional design of the study, the influence of medication and severity of patients included.

Conclusions

The COBRA showed to be a useful instrument to assess overall cognitive complaints in bipolar disorder with very satisfactory psychometric properties. Cognitive complaints were partially correlated with memory and executive function measures and with issues that may increase the subjective perception of cognitive deficits, such as subthreshold depressive symptoms and number of episodes.     

Maintenance of real objects and their verbal designations in working memory

The present study investigated the neural correlates of working memory maintenance for real objects in contrast to their verbal designations. For this purpose we employed a delayed match-to-sample task using functional magnetic resonance imaging. The conjunction of load effects for objects and for words revealed a common bilateral network with main foci in the ventrolateral prefrontal cortex and the intraparietal sulcus. Load effect for objects in comparison to load effect for words revealed stronger activation of bilateral precuneus, which suggests the use of mental imagery of objects and object features. The opposite comparison load words versus load objects showed premotor and auditory areas to be activated in association with phonological rehearsal. The bilateral common activation indicates overlapping codes for real-world objects and their verbal designations. Importantly, there is also a dissociation between maintenance of words and objects, which indicates that phonological rehearsal and mental imagery are employed to different degrees.     

Climacteric symptoms in middle-aged women with chronic somatic diseases

ObjectivesChronic diseases may aggravate or simulate climacteric symptoms. Although acknowledged in clinical practice, there is a lack of research systematically analysing the association between chronic diseases and climacteric symptoms.Study design and main outcome measuresOur study was a cross-sectional population-based study, which included 3421 women, aged 41–54 years. Climacteric symptoms were evaluated using the Women’s Health Questionnaire (WHQ), of which we included seven symptom domains (vasomotor, sleep, depressive, anxiety/fears, cognitive, sexual, and menstrual) and a question concerning whether the women were worried about growing old. The occurrence of various diseases (cardiovascular, neurological, sensory organ, bronchopulmonary, musculoskeletal, gastrointestinal, urological, dermatological, and thyroid disease, diabetes, and cancer) was recorded. The associations between the diseases and symptoms were defined with multivariable analyses, adjusting for various confounding factors.ResultsThe women with the diseases had more symptoms. Vasomotor symptoms and sleep problems were associated only with gastrointestinal diseases, and lower sexual functioning only with diabetes. The remaining symptoms were associated with several diseases, except being worried about growing old, which was not associated with any.ConclusionsMany symptoms connected to the climacteric may manifest also due to chronic diseases. Thus, health-care professionals should consider the origin of the symptoms when treating middle-aged women with chronic diseases.