Perilesional and contralesional brain activations related to associative encoding of unfamiliar face-names pairs in adults with left chronic stroke with or without ischemic infarct on left inferior frontal gyrus.

The study of an Ischemic stroke infarction allows verifying how the lesion produces alterations in the neuronal networks resulting in cognitive deficits. It also allows the verification of adaptive and maladaptive cerebral reorganization related to the injury. In our previous fMRI study, we found that patients without ischemic vascular lesions in left inferior frontal gyrus showed an efficient compensation mechanism during the associative encoding of face name pairs, by the increased activation of ventrolateral and dorsolateral areas of contralesional hemisphere associated with better memory performance. While patients with ischemic vascular lesions on left inferior frontal gyrus (IFG) demonstrated worse memory performance and no signs of compensation mechanism. The present study explores more of these findings by analyzing perilesional and contralesional activations related to unfamiliar face name associative encoding in adults with chronic ischemic stroke, with or without left IFG lesion, compared to healthy controls. The main results showed that stroke survivors without lesions in IFG demonstrated increased activation in perilesional and contralesional prefrontal regions associated with better associative memory recognition, which are indicative of adaptive compensatory mechanisms. However, they also showed a negative correlation between the activation of right anterior prefrontal and inferior parietal regions and the associative memory performance, which may indicate the presence of maladaptive interhemispheric disinhibition. On the other hand, stroke survivors with IFG lesions demonstrated negative correlations in activations of the ipsilesional inferior parietal cortex and positive correlations in activations of the left middle frontal gyrus and left precentral cortex, which demonstrate the simultaneous occurrence of adaptive and maladaptive brain reorganization mechanisms in this group. However, the increase in perilesional prefrontal regions, associated with bilateral activation of the hippocampus and amygdala, was not enough to compensate for the inefficiency of associative memory performance. Finally, the differences in activation observed in stroke survivors reflect their clinical heterogeneity and demonstrate that adaptive or maladaptive compensatory mechanisms can coexist in the same group of patients. Furthermore, they reinforce the importance of the left IFG in the associative encoding of unfamiliar face name pairs and may suggest a deficit in associative memory related to injury in this region.

BDNF mediates improvement in cognitive performance after computerized cognitive training in healthy older adults.

Introduction: The often-cited mechanism linking brain-derived neurotrophic factor (BDNF) to cognitive health has received limited experimental study. There is evidence that cognitive training, physical exercise, and mindfulness meditation may improve cognition. Here, we investigated whether improvements in cognition after these three types of structured interventions are facilitated by increases in BDNF. Methods: A total of 144 heathy older adults completed a 5-week intervention involving working memory/cognitive training, physical exercise, mindfulness meditation, or an active control condition. Serum BDNF levels and Digit Symbol Test (DST) performance were measured pre- and post-intervention. Results: Linear mixed models suggested that only the cognitive training group demonstrated augmentation of BDNF and DST performance relative to the control condition. Path analysis revealed that changes in BDNF mediate intervention-related improvement in task performance. Regression analyses showed that, across all intervention conditions, increased BDNF levels were associated with increased DST scores. Discussion: This study appears to be the first to suggest that BDNF helps mediate improvements in cognition after working memory training in healthy older adults. Highlights: Older adults were randomized to physical activity, mindfulness, cognitive training (computerized cognitive training (CCT), or control.CCT, but no other condition, led to increased serum brain-derived neurotrophic factor (BDNF) levels.CCT led to improvement on the untrained Digit Symbol Test (DST) of speed/working memory.Path analysis: increases in BDNF mediate intervention-related improvement on DST.Increases in BDNF associated with improved DST across all experimental groups.

Personality-cognition associations across the adult life span and potential moderators: Results from two cohorts.

OBJECTIVE: Personality and cognitive abilities have been previously linked. However, there are inconsistencies regarding whether this relationship varies as a function of age, and a lack of evidence on whether gender contributes to this relation, particularly across the adulthood. Therefore, this study investigated the association between personality and cognition across the adult life span, accounting for age and gender. METHODS: We examined the association between personality and cognition in two large samples (Sample 1: N = 422; Sample 2: N = 549) including young, middle-aged and older adults. Participants completed personality scales and several cognitive measures related to reasoning, language, memory and speed of processing. Structural equation modeling was applied in order to investigate associations between personality and cognition, and moderation of age and gender within this relationship. We also conducted a mini-meta-analysis procedure in order to examine personality-cognition associations, combining results from the two samples. RESULTS: Openness was the main trait associated with cognitive performance; however, Extraversion, Conscientiousness, and Neuroticism were also independently associated with cognition. Age and gender did not consistently moderate personality-cognition in each sample, but the mini-metanalysis showed that gender moderated Conscientiousness-cognition associations. CONCLUSIONS: We provided robust evidence of personality-cognition associations across the adult life span, which was not consistently moderated by age, but in part by gender.

Associations between personality and whole-brain functional connectivity at rest: Evidence across the adult lifespan.

INTRODUCTION: Personality is associated with cognitive, emotional, and social functioning, and can play a role in age-related cognitive decline and dementia risk; however, little is known about the brain dynamics underlying personality characteristics, and whether they are moderated by age. METHODS: We investigated the associations between personality and resting-state functional MRI data from 365 individuals across the adult lifespan (20-80 years). Participants completed the 50-item International Personality Item Pool and a resting-state imaging protocol on a 3T MRI scanner. Within-network connectivity values were computed based on predefined networks. Regression analyzes were conducted in order to investigate personality-connectivity associations, as well as moderation by age. All models controlled for potential confounders (such as age, sex, education, IQ, and the other personality traits). RESULTS: We found that openness was positively associated with connectivity in the default-mode network, neuroticism was negatively associated with both the ventral and dorsal attention networks, and agreeableness was negatively associated with the dorsal attention network. In addition, age moderated the association between conscientiousness and the frontoparietal network, indicating that this association become stronger in older age. CONCLUSIONS: Our findings demonstrate that personality is associated with brain connectivity, which may contribute to identifying personality profiles that play a role in protection against or risk for age-related brain changes and dementia.

Training gains and transfer effects after mnemonic strategy training in mild cognitive impairment: A fMRI study.

Prior work has revealed that mnemonic strategy training (MST) can enhance memory for specific content and engages regions in the frontoparietal cognitive control network. Evidence of transfer to novel content is less clear. Here, we provide secondary analysis of functional magnetic resonance imaging (fMRI) data acquired during a randomized controlled trial that compared MST to an active education control condition in patients with amnestic mild cognitive impairment (a-MCI). In the trial, thirty participants with a-MCI were randomized to the education program (EP) or MST, where they learned to apply the technique to face-name associations during four intervening hour long training sessions. Participants underwent pre- and post-training fMRI scans, during which they encoded both the trained (i.e., those used during the four training sessions) and untrained ('novel') face-name associations. The primary cognitive outcome measures revealed significantly improved memory for both trained and novel stimuli - effects supporting near transfer of MST. Relative to pre-training, there were significant and highly similar increases in activation for both trained and novel stimuli, especially in regions associated with the frontoparietal cognitive control network bilaterally, but also in temporal areas related to social cognition and emotional processing. Critically, this pattern of activation was notably different from the EP group. Thus, the changes in activation were consistent with the strategies trained and, combined with the cognitively-based near transfer effects, suggest that MST focused on face-name association enhances performance by engaging cognitive control and social/emotional processing. Finally, our data indicated that our MST is a relevant and efficient intervention to a-MCI.

Effects of Mnemonic Strategy Training on Brain Activity and Cognitive Functioning of Left-Hemisphere Ischemic Stroke Patients.

Memory dysfunction is one of the main cognitive impairments caused by stroke, especially associative memory. Therefore, cognitive training, such as face-name mnemonic strategy training, could be an important intervention for this group of patients. The goal of this study was to evaluate the behavioral effects of face-name mnemonic strategy training, along with the neural substrate behind these effects, in the left frontoparietal lobe stroke patients. Volunteers underwent 2 sessions of functional magnetic resonance imaging (fMRI) during face-name association task: one prior and the other after the cognitive training. The fMRI followed a block design task with three active conditions: trained face-name pairs, untrained face-name pairs, and a couple of repeated face-name pairs. Prior to each fMRI session, volunteers underwent neuropsychological assessment. Training resulted in better performance on delayed memory scores of HVLT-R, and on recognition on a generalization strategy task, as well as better performance in the fMRI task. Also, trained face-name pairs presented higher activation after training in default-mode network regions, such as the posterior cingulate cortex, precuneus, and angular gyrus, as well as in lateral occipital and temporal regions. Similarly, untrained face-name pairs also showed a nonspecific training effect in the right superior parietal cortex, right supramarginal gyrus, anterior intraparietal sulcus, and lateral occipital cortex. A correlation between brain activation and task performance was also found in the angular gyrus, superior parietal cortex, anterior intraparietal sulcus, and lateral occipital cortex. In conclusion, these results suggest that face-name mnemonic strategy training has the potential to improve memory performance and to foster brain activation changes, by the recruitment of contralesional areas from default-mode, frontoparietal, and dorsal attention networks as a possible compensation mechanism.

The validity and reliability of the CAMDEX-DS for assessing dementia in adults with Down syndrome in Brazil

Objective: Alzheimer's disease occurs at a higher prevalence and an earlier age in individuals with Down syndrome (DS) than typically developing individuals. However, diagnosing dementia in individuals with intellectual disability remains a challenge due to pre-existing cognitive deficits. The aim of this study was to investigate the validity and reliability of the Brazilian version of the Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS) for individuals with DS. Methods: Two psychiatrists, working independently, evaluated 92 adults with DS ≥ 30 years of age. The concurrent validity of the CAMDEX-DS was analyzed in relation to the gold standard of established international criteria. In a subgroup of 20 subjects, the concurrent validity of the CAMDEX-DS was analyzed in relation to an independent objective assessment of cognitive decline over three years. We analyzed the inter-rater reliability of cognitive assessment. Results: The diagnostic accuracy of the CAMDEX-DS compared to the gold standard was 96.7%. CAMDEX-DS-based diagnosis was considered consistent with cognitive decline. The probability of a participant with dementia having cognitive decline was 83%. Inter-rater reliability for the participant assessment was good, with a kappa of > 0.8 for 93% of the CAMDEX-DS items. Conclusion: The CAMDEX-DS can be considered the first valid and reliable instrument for evaluating dementia in adults with DS in Brazil. Its use in such individuals could improve clinical practice and research.

The validity and reliability of the CAMDEX-DS for assessing dementia in adults with Down syndrome in Brazil.

OBJECTIVE: Alzheimer's disease occurs at a higher prevalence and an earlier age in individuals with Down syndrome (DS) than typically developing individuals. However, diagnosing dementia in individuals with intellectual disability remains a challenge due to pre-existing cognitive deficits. The aim of this study was to investigate the validity and reliability of the Brazilian version of the Cambridge Examination for Mental Disorders of Older People with Down's syndrome and Others with Intellectual Disabilities (CAMDEX-DS) for individuals with DS. METHODS: Two psychiatrists, working independently, evaluated 92 adults with DS ≥ 30 years of age. The concurrent validity of the CAMDEX-DS was analyzed in relation to the gold standard of established international criteria. In a subgroup of 20 subjects, the concurrent validity of the CAMDEX-DS was analyzed in relation to an independent objective assessment of cognitive decline over three years. We analyzed the inter-rater reliability of cognitive assessment. RESULTS: The diagnostic accuracy of the CAMDEX-DS compared to the gold standard was 96.7%. CAMDEX-DS-based diagnosis was considered consistent with cognitive decline. The probability of a participant with dementia having cognitive decline was 83%. Inter-rater reliability for the participant assessment was good, with a kappa of > 0.8 for 93% of the CAMDEX-DS items. CONCLUSION: The CAMDEX-DS can be considered the first valid and reliable instrument for evaluating dementia in adults with DS in Brazil. Its use in such individuals could improve clinical practice and research.

Resting state functional connectivity and neural correlates of face-name encoding in patients with ischemic vascular lesions with and without the involvement of the left inferior frontal gyrus.

Face-name association is a relevant ability for social interactions and involves the ventral and dorsolateral prefrontal cortices, particularly in the left hemisphere, bilateral hippocampal, fusiform gyrus and occipital regions. Previous studies demonstrated the primary role of the hippocampus for this ability in healthy subjects. However, no study has examined the participation of the left inferior frontal area, specially the left inferior frontal gyrus (LIFG) in patients with ischemic vascular lesions. In the present study we addressed this issue and investigated the neural correlates and resting state functional connectivity of face-name memory encoding in ischemic patients with LIFG or without lesions in the left IFG (nLIFG) and healthy controls (HC) using fMRI. The main results showed that the nLIFG group demonstrated efficient compensation related to encoding and performance on face-name learning and recognition memory task, in addition to similar brain areas activated during task performance compared to healthy controls. Some of these areas were more activated in nLIFG group, indicating a compensation mechanism. In contrast, the LIFG group showed worse behavior performance, and no signs of an efficient compensation mechanism. Functional connectivity analysis suggested that the left IFG region seems to be important for maintaining the connectivity of the right fusiform gyrus or, perhaps, lesion in this area is associated to maladaptive reorganization. Our findings highlight the relevant role of the left IFG in face-name learning and encoding, possibly as a primary region in addition to the bilateral hippocampal formation and fusiform gyrus.

Cognitive and Brain Activity Changes After Mnemonic Strategy Training in Amnestic Mild Cognitive Impairment: Evidence From a Randomized Controlled Trial.

Background: Mnemonic strategy training (MST) has been shown to improve cognitive performance in amnestic mild cognitive impairment (a-MCI), however, several questions remain unresolved. The goal of the present study was to replicate earlier pilot study findings using a randomized controlled design and to evaluate transfer effects and changes in brain activation. Methods: Thirty patients with a-MCI were randomized into MST or education program. At baseline, participants completed clinical and neuropsychological assessments as well as structural and functional magnetic resonance imaging (fMRI). Interventions were administered individually and comprised four sessions, over 2 weeks. MST taught patients to use a three-step process to learn and recall face-name associations. Post-treatment assessment included fMRI, a separate face-name association task, neuropsychological tests, and measures of metamemory. Behavioral (i.e., non-fMRI) measures were repeated after one and 3-months. Results: Participants in the MST condition showed greater improvement on measures of face-name memory, and increased associative strategy use; effects that were accompanied by increased fMRI activation in the left anterior temporal lobe. While all participants reported greater contentment with their everyday memory following intervention, only the MST group reported significant improvements in their memory abilities. There was no clear indication of far-transfer effects to other neuropsychological tests. Conclusion: Results demonstrate that patients with a-MCI not only show stimulus specific benefits of MST, but that they appear capable of transferring training to at least some other cognitive tasks. MST also facilitated the use of brain regions that are involved in face processing, episodic and semantic memory, and social cognition, which are consonant with the cognitive processes engaged by training.

Is Computerized Working Memory Training Effective in Healthy Older Adults? Evidence from a Multi-Site, Randomized Controlled Trial.

BACKGROUND: Developing effective interventions to attenuate age-related cognitive decline and prevent or delay the onset of dementia are major public health goals. Computerized cognitive training (CCT) has been marketed increasingly to older adults, but its efficacy remains unclear. Working memory (WM), a key determinant of higher order cognitive abilities, is susceptible to age-related decline and a relevant target for CCT in elders. OBJECTIVE: To evaluate the efficacy of CCT focused on WM compared to an active control condition in healthy older adults. METHODS: Eighty-two cognitively normal adults from two sites (USA and Sweden) were randomly assigned to Cogmed Adaptive or Non-Adaptive (active control) CCT groups. Training was performed in participants' homes, five days per week over five weeks. Changes in the performance of the Cogmed trained tasks, and in five neuropsychological tests (Trail Making Test Part A and Part B, Digit Symbol, Controlled Oral Word Association Test and Semantic Fluency) were used as outcome measures. RESULTS: The groups were comparable at baseline. The Adaptive group showed robust gains in the trained tasks, and there was a time-by-group interaction for the Digit Symbol test, with significant improvement only after Adaptive training. In addition, the magnitude of the intervention effect was similar at both sites. CONCLUSION: Home-based CCT Adaptive WM training appears more effective than Non-Adaptive training in older adults from different cultural backgrounds. We present evidence of improvement in trained tasks and on a demanding untrained task dependent upon WM and processing speed. The benefits over the active control group suggest that the Adaptive CCT gains were linked to providing a continuously challenging level of WM difficulty.

Neurophysiologic and Cognitive Changes Arising from Cognitive Training Interventions in Persons with Mild Cognitive Impairment: A Systematic Review.

Background: Previous reviews have generally reported cognitive//behavioral improvements after cognitively oriented treatments (COTs) in persons with MCI. However, comparatively little is known about the neural mechanisms associated with such cognitive improvement. Objective: The primary aim of the current review was to examine neurophysiological changes measured by functional magnetic resonance imaging (fMRI) and possible cognitive changes following COTs in those with MCI. Methods. An extensive literature search was conducted up to August 2018. Inclusion criteria were (1) studies that evaluated the effects of the COTs in patients with amnestic single- or multiple-domain MCI using fMRI, (2) the MCI patient sample having met Petersen's or Jack/Bond's criteria, (3) randomized and/or controlled trials, (4) fMRI and cognitive assessments completed pre- and post-intervention, and (5) articles available in English. Results: Amongst the 26 articles found, 7 studies were included according to the above inclusion criteria. A total of 3 studies applied rehearsal-based strategies as the primary intervention, all of which used computerized cognitive training. Four studies used fMRI to investigate the neurophysiologic and cognitive changes associated with memory strategy training. The majority of the studies included in this review showed evidence of improved objective cognitive performance associated with COTs, even in tasks similar to everyday life activities. In addition, there were significant changes in brain activation associated with interventions, in both typical and atypical brain areas and networks related to memory. Conclusions: Although additional studies are needed given the small sample size, these initial findings suggest that cognitive improvement after COTs is generally associated with both compensatory (i.e., engaging alternative brain regions or networks not "typically" engaged) and restorative (i.e., reengaging the "typical" brain regions or networks) mechanisms.

Increasing Working Memory Load Reduces Processing of Cross-Modal Task-Irrelevant Stimuli Even after Controlling for Task Difficulty and Executive Capacity.

The classic account of the load theory (LT) of attention suggests that increasing cognitive load leads to greater processing of task-irrelevant stimuli due to competition for limited executive resource that reduces the ability to actively maintain current processing priorities. Studies testing this hypothesis have yielded widely divergent outcomes. The inconsistent results may, in part, be related to variability in executive capacity (EC) and task difficulty across subjects in different studies. Here, we used a cross-modal paradigm to investigate whether augmented working memory (WM) load leads to increased early distracter processing, and controlled for the potential confounders of EC and task difficulty. Twenty-three young subjects were engaged in a primary visual WM task, under high and low load conditions, while instructed to ignore irrelevant auditory stimuli. Demands of the high load condition were individually titrated to make task difficulty comparable across subjects with differing EC. Event-related potentials (ERPs) were used to measure neural activity in response to stimuli presented in both the task relevant modality (visual) and task-irrelevant modality (auditory). Behavioral results indicate that the load manipulation and titration procedure of the primary visual task were successful. ERPs demonstrated that in response to visual target stimuli, there was a load-related increase in the posterior slow wave, an index of sustained attention and effort. Importantly, under high load, there was a decrease of the auditory N1 in response to distracters, a marker of early auditory processing. These results suggest that increased WM load is associated with enhanced attentional engagement and protection from distraction in a cross-modal setting, even after controlling for task difficulty and EC. Our findings challenge the classic LT and offer support for alternative models.