The Temporal Dynamics of Brain Plasticity in Aging.

Cognitive training has been suggested as a possible remediation of decline in brain structure with older age. However, it is unknown whether training effects are transient or enduring, as no studies have examined training-induced plasticity relative to decline in older adults across extended periods with multiple intervention phases. We investigated the temporal dynamics of brain plasticity across periods on and off memory training, hypothesizing that (1) a decline in white matter (WM) microstructure would be observed across the duration of the study and (2) that periods of memory training would moderate the WM microstructural decline. In total, 107 older adults followed a 40-week program, including 2 training periods separated by periods with no intervention. The general decline in WM microstructure observed across the duration of the study was moderated following the training periods, demonstrating that cognitive training may mitigate age-related brain deterioration. The training-related improvements were estimated to subside over time, indicating that continuous training may be a premise for the enduring attenuation of neural decline. Memory improvements were largely maintained after the initial training period, and may thus not rely on continuous training to the same degree as WM microstructure.

Neurodevelopmental origins of lifespan changes in brain and cognition.

Neurodevelopmental origins of functional variation in older age are increasingly being acknowledged, but identification of how early factors impact human brain and cognition throughout life has remained challenging. Much focus has been on age-specific mechanisms affecting neural foundations of cognition and their change. In contrast to this approach, we tested whether cerebral correlates of general cognitive ability (GCA) in development could be extended to the rest of the lifespan, and whether early factors traceable to prenatal stages, such as birth weight and parental education, may exert continuous influences. We measured the area of the cerebral cortex in a longitudinal sample of 974 individuals aged 4-88 y (1,633 observations). An extensive cortical region was identified wherein area related positively to GCA in development. By tracking area of the cortical region identified in the child sample throughout the lifespan, we showed that the cortical change trajectories of higher and lower GCA groups were parallel through life, suggesting continued influences of early life factors. Birth weight and parental education obtained from the Norwegian Mother-Child Cohort study were identified as such early factors of possible life-long influence. Support for a genetic component was obtained in a separate twin sample (Vietnam Era Twin Study of Aging), but birth weight in the child sample had an effect on cortical area also when controlling for possible genetic differences in terms of parental height. Our results provide novel evidence for stability in brain-cognition relationships throughout life, and indicate that early life factors impact brain and cognition for the entire life course.

Multimodal cortical and hippocampal prediction of episodic-memory plasticity in young and older adults.

Episodic memory can be trained in both early and late adulthood, but there is considerable variation in cognitive improvement across individuals. Which brain characteristics make some individuals benefit more than others? We used a multimodal approach to investigate whether volumetric magnetic resonance imaging (MRI) and resting-state functional MRI characteristics of the cortex and hippocampus, brain regions involved in episodic-memory function, were predictive of cognitive improvement after memory training. We hypothesized that these brain characteristics would differentially predict memory improvement in young and older adults, given the vulnerability of cortical regions as well as the hippocampus to healthy aging. Following structural and resting-state activity magnetic resonance scans, 50 young and 76 older participants completed 10 weeks of strategic episodic-memory training. Both age groups improved their memory performance, but the young adults more so than the older. Vertex-wise analyses of cortical volume showed no significant relation to memory benefit. When analyzing the two age groups separately, hippocampal volume was predictive of memory improvement in the group of older participants only. In this age group, the lower resting-state activity of the hippocampus was also predictive of memory improvement. Both volumetric and resting-state characteristics of the hippocampus explained unique variance of the improvement in the older participants suggesting that a multimodal imaging approach is valuable for the understanding of mechanisms underlying memory plasticity in aging.

Development and aging of cortical thickness correspond to genetic organization patterns.

There is a growing realization that early life influences have lasting impact on brain function and structure. Recent research has demonstrated that genetic relationships in adults can be used to parcellate the cortex into regions of maximal shared genetic influence, and a major hypothesis is that genetically programmed neurodevelopmental events cause a lasting impact on the organization of the cerebral cortex observable decades later. Here we tested how developmental and lifespan changes in cortical thickness fit the underlying genetic organizational principles of cortical thickness in a longitudinal sample of 974 participants between 4.1 and 88.5 y of age with a total of 1,633 scans, including 773 scans from children below 12 y. Genetic clustering of cortical thickness was based on an independent dataset of 406 adult twins. Developmental and adult age-related changes in cortical thickness followed closely the genetic organization of the cerebral cortex, with change rates varying as a function of genetic similarity between regions. Cortical regions with overlapping genetic architecture showed correlated developmental and adult age change trajectories and vice versa for regions with low genetic overlap. Thus, effects of genes on regional variations in cortical thickness in middle age can be traced to regional differences in neurodevelopmental change rates and extrapolated to further adult aging-related cortical thinning. This finding suggests that genetic factors contribute to cortical changes through life and calls for a lifespan perspective in research aimed at identifying the genetic and environmental determinants of cortical development and aging.

The effects of memory training on behavioral and microstructural plasticity in young and older adults.

Age differences in human brain plasticity are assumed, but have not been systematically investigated. In this longitudinal study, we investigated changes in white matter (WM) microstructure in response to memory training relative to passive and active control conditions in 183 young and older adults. We hypothesized that (i) only the training group would show improved memory performance and microstructural alterations, (ii) the young adults would show larger memory improvement and a higher degree of microstructural alterations as compared to the older adults, and (iii) changes in memory performance would relate to microstructural alterations. The results showed that memory improvement was specific to the training group, and that both the young and older participants improved their performance. The young group improved their memory to a larger extent compared to the older group. In the older sample, the training group showed less age-related decline in WM microstructure compared to the control groups, in areas overlapping the corpus callosum, the cortico-spinal tract, the cingulum bundle, the superior longitudinal fasciculus, and the anterior thalamic radiation. Less microstructural decline was related to a higher degree of memory improvement. Despite individual adaptation securing sufficient task difficulty, no training-related group differences in microstructure were found in the young adults. The observed divergence of behavioral and microstructural responses to memory training with age is discussed within a supply-demand framework. The results demonstrate that plasticity is preserved into older age, and that microstructural alterations may be part of a neurobiological substrate for behavioral improvements in older adults. Hum Brain Mapp 38:5666-5680, 2017. © 2017 Wiley Periodicals, Inc.

Selective increase in posterior corpus callosum thickness between the age of 4 and 11years.

Establishing an efficient functional and structural connectivity between the two cerebral hemispheres is an important developmental task during childhood, and alterations in this development have accordingly been linked to a series of neurodevelopmental and pediatric disorders. The corpus callosum, the major white-matter structure connecting the hemispheres, has been shown to increase in size throughout the three first decades of life. However, behavioral studies indicate that adult-like performance levels of functional hemispheric interaction are already reached during middle and late childhood. Thus, here we specifically examine the structural development of the corpus callosum during the functionally relevant time period by for the first time (a) selectively addressing prospective childhood development and (b) analyzing a sample in which also younger children are well represented. Corpus callosum anatomy was assessed from 732 T1-weighted MRI datasets acquired from 428 children (213 boys, 215 girls) aged of 4.1 and 10.9years, of which 304 were scanned at two time points. Regional callosal thickness was determined from an outline-based segmentation of the mid-sagittal cross-sectional surface area. Linear-mixed model analyses revealed a significant increase in thickness with age (effect size: up to 15% explained variance) equivalent to a growth in callosal thickness of up to 0.19mm per year in the posterior corpus callosum. The age effect was found to be stronger in posterior segments (i.e., splenium) than in other callosal subregions. Also, the age effect was found to be comparable between boys and girls, and was detected irrespective of whether developmental or individual differences in overall brain size where accounted for or not. Our results demonstrate a selective increase in posterior corpus-callosum thickness during middle and late childhood. Since axons crossing the midline in the splenium mainly connect occipital and parietal cortices, the accentuated posterior growth might reflect the onset of a posterior-to-anterior moving maturation wave in cortical development known to take place in the same time period.

Accelerated longitudinal gray/white matter contrast decline in aging in lightly myelinated cortical regions.

Highly myelinated cortical regions seem to develop early and are more robust to age-related decline. By use of different magnetic resonance imaging (MRI) measures such as contrast between T1- and T2-weighted MRI scans (T1w/T2w) it is now possible to assess correlates of myelin content in vivo. Further, previous studies indicate that gray/white matter contrast (GWC) become blurred as individuals' age, apparently reflecting age-related changes in myelin structure. Here we address whether longitudinal changes in GWC are dependent on initial myelin content within tissue as defined by baseline T1w/T2w contrast, and hypothesize that lightly myelinated regions undergo more decline longitudinally. A sample of 207 healthy adult participants (range: 20-84 years) was scanned twice (interscan interval: 3.6 years). Results showed widespread longitudinal reductions of GWC throughout the cortical surface, especially in the frontal cortices, mainly driven by intensity decay in the white matter. Annual rate of GWC blurring showed acceleration with age in temporal and medial prefrontal regions. Moreover, the anatomical distribution of increased rate of GWC decline with advancing age was strongly related to baseline levels of intracortical myelin. This study provides a first evidence of accelerated regional GWC blurring with advancing age, relates GWC patterns to cortical myeloarchitectonics and supports the hypothesis of increased age-related vulnerability of lightly myelinated areas. Hum Brain Mapp 37:3669-3684, 2016. © 2016 Wiley Periodicals, Inc.

Correlations Between Objective Behavioral Features Collected From Mobile and Wearable Devices and Depressive Mood Symptoms in Patients With Affective Disorders: Systematic Review.

BACKGROUND: Several studies have recently reported on the correlation between objective behavioral features collected via mobile and wearable devices and depressive mood symptoms in patients with affective disorders (unipolar and bipolar disorders). However, individual studies have reported on different and sometimes contradicting results, and no quantitative systematic review of the correlation between objective behavioral features and depressive mood symptoms has been published. OBJECTIVE: The objectives of this systematic review were to (1) provide an overview of the correlations between objective behavioral features and depressive mood symptoms reported in the literature and (2) investigate the strength and statistical significance of these correlations across studies. The answers to these questions could potentially help identify which objective features have shown most promising results across studies. METHODS: We conducted a systematic review of the scientific literature, reported according to the preferred reporting items for systematic reviews and meta-analyses guidelines. IEEE Xplore, ACM Digital Library, Web of Sciences, PsychINFO, PubMed, DBLP computer science bibliography, HTA, DARE, Scopus, and Science Direct were searched and supplemented by hand examination of reference lists. The search ended on April 27, 2017, and was limited to studies published between 2007 and 2017. RESULTS: A total of 46 studies were eligible for the review. These studies identified and investigated 85 unique objective behavioral features, covering 17 various sensor data inputs. These features were divided into 7 categories. Several features were found to have statistically significant and consistent correlation directionality with mood assessment (eg, the amount of home stay, sleep duration, and vigorous activity), while others showed directionality discrepancies across the studies (eg, amount of text messages [short message service] sent, time spent between locations, and frequency of mobile phone screen activity). CONCLUSIONS: Several studies showed consistent and statistically significant correlations between objective behavioral features collected via mobile and wearable devices and depressive mood symptoms. Hence, continuous and everyday monitoring of behavioral aspects in affective disorders could be a promising supplementary objective measure for estimating depressive mood symptoms. However, the evidence is limited by methodological issues in individual studies and by a lack of standardization of (1) the collected objective features, (2) the mood assessment methodology, and (3) the statistical methods applied. Therefore, consistency in data collection and analysis in future studies is needed, making replication studies as well as meta-analyses possible.

A longitudinal study of computerized cognitive training in stroke patients - effects on cognitive function and white matter.

Background Computerized cognitive training is suggested to enhance attention and working memory functioning following stroke, but effects on brain and behavior are not sufficiently studied and longitudinal studies assessing brain and behavior relationships are scarce. Objective The study objectives were to investigate relations between neuropsychological performance post-stroke and white matter microstructure measures derived from diffusion tensor imaging (DTI), including changes after 6 weeks of working memory training. Methods In this experimental training study, 26 stroke patients underwent DTI and neuropsychological tests at 3 time points - before and after a passive phase of 6 weeks, and again after 6 weeks of working memory training (Cogmed QM). Fractional anisotropy (FA) was extracted from stroke-free brain areas to assess the white matter microstructure. Twenty-two participants completed the majority of training (≥18/25 sessions) and were entered into longitudinal analyses. Results Significant correlations between FA and baseline cognitive functions were observed (r = 0.58, p = 0.004), however, no evidence was found of generally improved cognitive functions following training or of changes in white matter microstructure. Conclusions While white matter microstructure related to baseline cognitive function in stroke patients, the study revealed no effect on cognitive functions or microstructural changes in white matter in relation to computerized working memory training.

The corpus callosum as anatomical marker of intelligence? A critical examination in a large-scale developmental study.

Intellectual abilities are supported by a large-scale fronto-parietal brain network distributed across both cerebral hemispheres. This bihemispheric network suggests a functional relevance of inter-hemispheric coordination, a notion which is supported by a series of recent structural magnetic resonance imaging (MRI) studies demonstrating correlations between intelligence scores (IQ) and corpus-callosum anatomy. However, these studies also reveal an age-related dissociation: mostly positive associations are reported in adult samples, while negative associations are found in developing samples. In the present study, we re-examine the association between corpus callosum and intelligence measures in a large (734 datasets from 495 participants) developmental mixed cross-sectional and longitudinal sample (6.4-21.9 years) using raw test scores rather than deviation IQ measures to account for the ongoing cognitive development in this age period. Analyzing mid-sagittal measures of regional callosal thickness, a positive association in the splenium of the corpus callosum was found for both verbal and performance raw test scores. This association was not present when the participants' age was considered in the analysis. Thus, we did not reveal any association that cannot be explained by a temporal co-occurrence of overall developmental trends in intellectual abilities and corpus callosum maturation in the present developing sample.

White matter integrity as a marker for cognitive plasticity in aging.

Age-related differences in white matter (WM) integrity are substantial, but it is unknown whether between-subject variability in WM integrity influences the capacity for cognitive improvement. We investigated the effects of memory training related to active and passive control conditions in older adults and tested whether WM integrity at baseline was predictive of training benefits. We hypothesized that (1) memory improvement would be restricted to the training group, (2) widespread areas would show greater mean diffusivity (MD) and lower fractional anisotropy in older adults relative to young adults, and (3) within these areas, variability in WM microstructure in the older group would be predictive of training gains. The results showed that only the group receiving training improved their memory. Significant age differences in MD and fractional anisotropy were found in widespread areas. Within these areas, voxelwise analyses showed a negative relationship between MD and memory improvement in 3 clusters, indicating that WM integrity could serve as a marker for the ability to adapt in response to cognitive challenges in aging.

BCI using imaginary movements: the simulator.

Over the past two decades, much progress has been made in the rapidly evolving field of Brain Computer Interface (BCI). This paper presents a novel concept: a BCI-simulator, which has been developed for the Hex-O-Spell interface, using the sensory motor rhythms (SMR) paradigm. With the simulator, it is possible to evaluate how the model parameters such as error classifications, delay between classifications and success rate affect the communication rate. Another advantage of the simulator is that it allows us to study for more classes than most online BCI systems which are limited to only two classes. Results show that the BCI simulator is able to give a deeper understanding of the feedback systems. We also find that a 3-class system is more efficient than a 2-class system if it obtains a success rate of at least 55% of the 2-class system.