Brain working memory network indices as landmarks of intelligence.

Identifying the neural correlates of intelligence has long been a goal in neuroscience. Recently, the field of network neuroscience has attracted researchers' attention as a means for answering this question. In network neuroscience, the brain is considered as an integrated system whose systematic properties provide profound insights into health and behavioral outcomes. However, most network studies of intelligence have used univariate methods to investigate topological network measures, with their focus limited to a few measures. Furthermore, most studies have focused on resting state networks despite the fact that brain activation during working memory tasks has been linked to intelligence. Finally, the literature is still missing an investigation of the association between network assortativity and intelligence. To address these issues, here we employ a recently developed mixed-modeling framework for analyzing multi-task brain networks to elucidate the most critical working memory task network topological properties corresponding to individuals' intelligence differences. We used a data set of 379 subjects (22-35 y/o) from the Human Connectome Project (HCP). Each subject's data included composite intelligence scores, and fMRI during resting state and a 2-back working memory task. Following comprehensive quality control and preprocessing of the minimally preprocessed fMRI data, we extracted a set of the main topological network features, including global efficiency, degree, leverage centrality, modularity, and clustering coefficient. The estimated network features and subject's confounders were then incorporated into the multi-task mixed-modeling framework to investigate how brain network changes between working memory and resting state relate to intelligence score. Our results indicate that the general intelligence score (cognitive composite score) is associated with a change in the relationship between connection strength and multiple network topological properties, including global efficiency, leverage centrality, and degree difference during working memory as it is compared to resting state. More specifically, we observed a higher increase in the positive association between global efficiency and connection strength for the high intelligence group when they switch from resting state to working memory. The strong connections might form superhighways for a more efficient global flow of information through the brain network. Furthermore, we found an increase in the negative association between degree difference and leverage centrality with connection strength during working memory tasks for the high intelligence group. These indicate higher network resilience and assortativity along with higher circuit-specific information flow during working memory for those with a higher intelligence score. Although the exact neurobiological implications of our results are speculative at this point, our results provide evidence for the significant association of intelligence with hallmark properties of brain networks during working memory.

A mixed-modeling framework for whole-brain dynamic network analysis.

The emerging area of dynamic brain network analysis has gained considerable attention in recent years. However, development of multivariate statistical frameworks that allow for examining the associations between phenotypic traits and dynamic patterns of system-level properties of the brain, and drawing statistical inference about such associations, has largely lagged behind. To address this need we developed a mixed-modeling framework that allows for assessing the relationship between any desired phenotype and dynamic patterns of whole-brain connectivity and topology. This novel framework also allows for simulating dynamic brain networks with respect to desired covariates. Unlike current tools, which largely use data-driven methods, our model-based method enables aligning neuroscientific hypotheses with the analytic approach. We demonstrate the utility of this model in identifying the relationship between fluid intelligence and dynamic brain networks by using resting-state fMRI (rfMRI) data from 200 participants in the Human Connectome Project (HCP) study. We also demonstrate the utility of this model to simulate dynamic brain networks at both group and individual levels. To our knowledge, this approach provides the first model-based statistical method for examining dynamic patterns of system-level properties of the brain and their relationships to phenotypic traits as well as simulating dynamic brain networks.

Effects of an Allostatic Closed-Loop Neurotechnology (HIRREM) on Brain Functional Connectivity Laterality in Military-Related Traumatic Stress.

BACKGROUND AND PURPOSE: Brain asymmetries are reported in posttraumatic stress disorder, but many aspects of laterality and traumatic stress remain underexplored. This study explores lateralization changes in resting state brain network functional connectivity in a cohort with symptoms of military-related traumatic stress, associated with use of a closed-loop neurotechnology, HIRREM. METHODS: Eighteen participants (17 males, mean age 41 years [SD = 7]) received 19.5 (1.1) HIRREM sessions over 12 days. Whole brain resting magnetic resonance imaging was done pre- and post-HIRREM. Laterality of functional connectivity was assessed on a whole brain basis, and in six predefined networks or regions. Laterality of connectivity within networks or regions was assessed separately from laterality of connections between networks or regions. RESULTS: Before HIRREM, significant laterality effects of connection type (ipsilateral for either side, or contralateral in either direction) were observed for the whole brain, within networks or regions, and between networks or regions. Post-HIRREM, there were significant changes for within-network or within-region analysis in the motor network, and changes for between-network or between-region analyses for the salience network and the motor cortex. CONCLUSIONS: Among military service members and Veterans with symptoms of traumatic stress, asymmetries of network and brain region connectivity patterns were identified prior to usage of HIRREM. A variety of changes in lateralized patterns of brain connectivity were identified postintervention. These laterality findings may inform future studies of brain connectivity in traumatic stress disorders, with potential to point to mechanisms of action for successful intervention.

Graph-Theoretical Study of Functional Changes Associated with the Iowa Gambling Task.

The primary aim of this study was to examine changes in functional brain network organization from rest to the Iowa Gambling Task (IGT) using a graph-theoretical approach. Although many functional neuroimaging studies have examined task-based activations in complex-decision making tasks, changes in functional network organization during this task remain unexplored. This study used a repeated-measures approach to examine changes in functional network organization across multiple sessions of resting-state and IGT scans. The results revealed that global network organization shifted from a local, clustered organization at rest to a more global, integrated organization during the IGT. In addition, network organization was stable across sessions of rest and the IGT. Regional analyses of the Default Mode Network (DMN) and Fronto-Parietal Network (FPN) revealed differential patterns of change in regional network organization from rest to the IGT. The results of this study reveal that global and regional network organization is significantly modulated across states and fairly stable over time, and that network changes in the FPN are particularly important in the decision-making processes necessary for successful IGT performance.

Changes in brain network efficiency and working memory performance in aging.

Working memory is a complex psychological construct referring to the temporary storage and active processing of information. We used functional connectivity brain network metrics quantifying local and global efficiency of information transfer for predicting individual variability in working memory performance on an n-back task in both young (n = 14) and older (n = 15) adults. Individual differences in both local and global efficiency during the working memory task were significant predictors of working memory performance in addition to age (and an interaction between age and global efficiency). Decreases in local efficiency during the working memory task were associated with better working memory performance in both age cohorts. In contrast, increases in global efficiency were associated with much better working performance for young participants; however, increases in global efficiency were associated with a slight decrease in working memory performance for older participants. Individual differences in local and global efficiency during resting-state sessions were not significant predictors of working memory performance. Significant group whole-brain functional network decreases in local efficiency also were observed during the working memory task compared to rest, whereas no significant differences were observed in network global efficiency. These results are discussed in relation to recently developed models of age-related differences in working memory.

Changes in global and regional modularity associated with increasing working memory load.

Using graph theory measures common to complex network analyses of neuroimaging data, the objective of this study was to explore the effects of increasing working memory processing load on functional brain network topology in a cohort of young adults. Measures of modularity in complex brain networks quantify how well a network is organized into densely interconnected communities. We investigated changes in both the large-scale modular organization of the functional brain network as a whole and regional changes in modular organization as demands on working memory increased from n = 1 to n = 2 on the standard n-back task. We further investigated the relationship between modular properties across working memory load conditions and behavioral performance. Our results showed that regional modular organization within the default mode and working memory circuits significantly changed from 1-back to 2-back task conditions. However, the regional modular organization was not associated with behavioral performance. Global measures of modular organization did not change with working memory load but were associated with individual variability in behavioral performance. These findings indicate that regional and global network properties are modulated by different aspects of working memory under increasing load conditions. These findings highlight the importance of assessing multiple features of functional brain network topology at both global and regional scales rather than focusing on a single network property.

Stability of whole brain and regional network topology within and between resting and cognitive states.

BACKGROUND: Graph-theory based analyses of resting state functional Magnetic Resonance Imaging (fMRI) data have been used to map the network organization of the brain. While numerous analyses of resting state brain organization exist, many questions remain unexplored. The present study examines the stability of findings based on this approach over repeated resting state and working memory state sessions within the same individuals. This allows assessment of stability of network topology within the same state for both rest and working memory, and between rest and working memory as well. METHODOLOGY/PRINCIPAL FINDINGS: fMRI scans were performed on five participants while at rest and while performing the 2-back working memory task five times each, with task state alternating while they were in the scanner. Voxel-based whole brain network analyses were performed on the resulting data along with analyses of functional connectivity in regions associated with resting state and working memory. Network topology was fairly stable across repeated sessions of the same task, but varied significantly between rest and working memory. In the whole brain analysis, local efficiency, Eloc, differed significantly between rest and working memory. Analyses of network statistics for the precuneus and dorsolateral prefrontal cortex revealed significant differences in degree as a function of task state for both regions and in local efficiency for the precuneus. Conversely, no significant differences were observed across repeated sessions of the same state. CONCLUSIONS/SIGNIFICANCE: These findings suggest that network topology is fairly stable within individuals across time for the same state, but also fluid between states. Whole brain voxel-based network analyses may prove to be a valuable tool for exploring how functional connectivity changes in response to task demands.

Intraindividual variability in domain-specific cognition and risk of mild cognitive impairment and dementia.

Intraindividual variability among cognitive domains may predict dementia independently of interindividual differences in cognition. A multidomain cognitive battery was administered to 2305 older adult women (mean age 74 years) enrolled in an ancillary study of the Women's Health Initiative. Women were evaluated annually for probable dementia and mild cognitive impairment (MCI) for an average of 5.3 years using a standardized protocol. Proportional hazards regression showed that lower baseline domain-specific cognitive scores significantly predicted MCI (N = 74), probable dementia (N = 45), and MCI or probable dementia combined (N = 101) and that verbal and figural memory predicted each outcome independently of all other cognitive domains. The baseline intraindividual standard deviation across test scores (IAV Cognitive Domains) significantly predicted probable dementia and this effect was attenuated by interindividual differences in verbal episodic memory. Slope increases in IAV Cognitive Domains across measurement occasions (IAV Time) explained additional risk for MCI and MCI or probable dementia, beyond that accounted for by interindividual differences in multiple cognitive measures, but risk for probable dementia was attenuated by mean decreases in verbal episodic memory slope. These findings demonstrate that within-person variability across cognitive domains both at baseline and longitudinally independently accounts for risk of cognitive impairment and dementia in support of the predictive utility of within-person variability.

The locus of the benefits of repetition-lag memory training.

The repetition-lag training procedure developed by Jennings and Jacoby (2003 , Neuropsychological Rehabilitation, 14, 417) has been shown to improve older adults' performance in the recognition memory task used for training, and to improve performance in a variety of other memory and executive function tasks ( Jennings, Webster, Kleykamp, & Dagenbach, 2005 , Aging, Neuropsychology, and Cognition, 12, 278). The present study examined the effects of concurrent interference tasks during the study or test phases of training to localize the source of gains. Overall, the results suggest that training is resilient and resistant to interference, but also that the processes used during the test phases of training are more important to the gains seen in the primary task and in the transfer tasks than those used in the study phases.

Designing clinical trials for assessing the effects of cognitive training and physical activity interventions on cognitive outcomes: the Seniors Health and Activity Research Program Pilot (SHARP-P) study, a randomized controlled trial.

BACKGROUND: The efficacy of non-pharmacological intervention approaches such as physical activity, strength, and cognitive training for improving brain health has not been established. Before definitive trials are mounted, important design questions on participation/adherence, training and interventions effects must be answered to more fully inform a full-scale trial. METHODS: SHARP-P was a single-blinded randomized controlled pilot trial of a 4-month physical activity training intervention (PA) and/or cognitive training intervention (CT) in a 2 × 2 factorial design with a health education control condition in 73 community-dwelling persons, aged 70-85 years, who were at risk for cognitive decline but did not have mild cognitive impairment. RESULTS: Intervention attendance rates were higher in the CT and PACT groups: CT: 96%, PA: 76%, PACT: 90% (p=0.004), the interventions produced marked changes in cognitive and physical performance measures (p≤0.05), and retention rates exceeded 90%. There were no statistically significant differences in 4-month changes in composite scores of cognitive, executive, and episodic memory function among arms. Four-month improvements in the composite measure increased with age among participants assigned to physical activity training but decreased with age for other participants (intervention*age interaction p=0.01). Depending on the choice of outcome, two-armed full-scale trials may require fewer than 1,000 participants (continuous outcome) or 2,000 participants (categorical outcome). CONCLUSIONS: Good levels of participation, adherence, and retention appear to be achievable for participants through age 85 years. Care should be taken to ensure that an attention control condition does not attenuate intervention effects. Depending on the choice of outcome measures, the necessary sample sizes to conduct four-year trials appear to be feasible. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00688155.

Telephone interview for cognitive status (TICS) screening for clinical trials of physical activity and cognitive training: the seniors health and activity research program pilot (SHARP-P) study.

OBJECTIVE: To examine the performance of the Telephone Interview for Cognitive Status (TICS) for identifying participants appropriate for trials of physical activity and cognitive training interventions. METHODS: Volunteers (N=343), ages 70-85 years, who were being recruited for a pilot clinical trial on approaches to prevent cognitive decline, were administered TICS and required to score ≥ 31 prior to an invitation to attend clinic-based assessments. The frequencies of contraindications for physical activity and cognitive training interventions were tallied for individuals grouped by TICS scores. Relationships between TICS scores and other measures of cognitive function were described by scatterplots and correlation coefficients. RESULTS: Eligibility criteria to identify candidates who were appropriate candidates for the trial interventions excluded 51.7% of the volunteers with TICS<31. TICS scores above this range were not strongly related to cognition or attendance at screening visits, however overall enrollment yields were approximately half for participants with TICS=31 versus TICS=41, and increased in a graded fashion throughout the range of scores. CONCLUSIONS: Use of TICS to define eligibility criteria in trials of physical activity and cognitive training interventions may not be worthwhile in that many individuals with low scores would already be eliminated by intervention-specific criteria and the relationship of TICS with clinic-based tests of cognitive function among appropriate candidates for these interventions may be weak. TICS may be most useful in these trials to identify candidates for oversampling in order to obtain a balanced cohort of participants at risk for cognitive decline.

Age-related changes and the attention network task: an examination of alerting, orienting, and executive function.

The effects of aging on alerting, orienting, and executive function were examined with the use of the Attention Network Task, which combines the Posner spatial cuing task and the Eriksen flanker task into a single procedure. We found that older adults showed significantly less alerting than young adults in response to a warning cue, although there were no age differences in orienting or executive function once processing speed was taken into account. We suggest that age differences in alerting may depend in part upon the presentation duration or persistence of the warning cue.

Manipulating noise frequencies alters hemispheric contributions to decision making.

Participants listened to the Asian disease problem framed in terms of either gains or losses and chose between two plans to combat the disease. All participants heard the problem embedded in other sounds; for some it was the relatively lower-frequency information, and for others it was the relatively higher-frequency information. The classic framing effect appeared only for those participants for whom the problem was the relatively lower-frequency information (p<.05). These results suggest that mixing filtered speech signals and noise may be a way to assess the role of the left and right hemisphere in various aspects of decision making.

Recollection training and transfer effects in older adults: successful use of a repetition-lag procedure.

We examined an approach aimed at training consciously-controlled recollection, introduced by Jennings and Jacoby (2003) , for its ability to replicate and generalize. A continuous recognition task, requiring recollection to identify the occurrence of repeated items over gradually increasing lag intervals (number of intervening items between the first and second presentation of a repeated word), was given to a group of older adults twice a week for three weeks. Pre-and-post training performance was assessed on multiple measures and compared with a recognition practice and no contact control group. Recollection training proved successful; accurate identification of repeated items increased across a lag interval of 2 to 18 intervening items. Post-training gains following recollection training were found on n-back, self-ordered pointing, source discrimination and digit symbol substitution, but not with reading span or the CVLT-II. No changes were identified in the other groups. Gains from recollection training seem to transfer successfully in older adults.

Patterns of impaired verbal, spatial, and object working memory after thalamic lesions.

Working memory processes in six individuals with isolated thalamic lesions were assessed. Participants were given a verbal, spatial, and object n-back task, each at three levels of task load (1-back, 2-back, and 3-back). Relative to a control group, the patients were impaired on the verbal and spatial n-back tasks, and possibly on the object n-back task as well. None of the patients showed impaired short-term memory as measured by digit span. Group differences on trials measuring matching, sequencing, and inhibitory abilities were consistent with other reports suggesting that thalamic lesions may impair the operation of executive processes.