Brain enhancement through cognitive training: A new insight from brain connectome

Owing to the recent advances in neurotechnology and the progress in understanding of brain cognitive functions, improvements of cognitive performance or acceleration of learning process with brain enhancement systems is not out of our reach anymore, on the contrary, it is a tangible target of contemporary research. Although a variety of approaches have been proposed, we will mainly focus on cognitive training interventions, in which learners repeatedly perform cognitive tasks to improve their cognitive abilities. In this review article, we propose that the learning process during the cognitive training can be facilitated by an assistive system monitoring cognitive workloads using electroencephalography (EEG) biomarkers, and the brain connectome approach can provide additional valuable biomarkers for facilitating leaners' learning processes. For the purpose, we will introduce studies on the cognitive training interventions, EEG biomarkers for cognitive workload, and human brain connectome. As cognitive overload and mental fatigue would reduce or even eliminate gains of cognitive training interventions, a real-time monitoring of cognitive workload can facilitate the learning process by flexibly adjusting difficulty levels of the training task. Moreover, cognitive training interventions should have effects on brain sub-networks, not on a single brain region, and graph theoretical network metrics quantifying topological architecture of the brain network can differentiate with respect to individual cognitive states as well as to different individuals' cognitive abilities, suggesting that the connectome is a valuable approach for tracking the learning progress. Although only a few studies have exploited the connectome approach for studying alterations of the brain network induced by cognitive training interventions so far, we believe that it would be a useful technique for capturing improvements of cognitive function

Cognitive performance in healthy older adults relates to spontaneous switching between states of functional connectivity during rest

Growing evidence has shown that brain activity at rest slowly wanders through a repertoire of different states, where whole-brain functional connectivity (FC) temporarily settles into distinct FC patterns. Nevertheless, the functional role of resting-state activity remains unclear. Here, we investigate how the switching behavior of resting-state FC relates with cognitive performance in healthy older adults. We analyse resting-state fMRI data from 98 healthy adults previously categorized as being among the best or among the worst performers in a cohort study of >1000 subjects aged 50+ who underwent neuropsychological assessment. We use a novel approach focusing on the dominant FC pattern captured by the leading eigenvector of dynamic FC matrices. Recurrent FC patterns - or states - are detected and characterized in terms of lifetime, probability of occurrence and switching profiles. We find that poorer cognitive performance is associated with weaker FC temporal similarity together with altered switching between FC states. These results provide new evidence linking the switching dynamics of FC during rest with cognitive performance in later life, reinforcing the functional role of resting-state activity for effective cognitive processing.This project was financed by the Fundação Calouste Gulbenkian (Portugal) (Contract grant number: P-139977; project “Better mental health during ageing based on temporal prediction of individual brain ageing trajectories (TEMPO)”), co-financed by Portuguese North Regional Operational Program (ON.2) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER) as well as the Projecto Estratégico co-funded by FCT (PEst-C/SAU/LA0026-/2013) and the European Regional Development Fund COMPETE (FCOMP-01-0124-FEDER-037298) and under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal 2020 Partnership Agreement through the European Regional Development Fundinfo:eu-repo/semantics/publishedVersio

Effects of adverse early-life events on aggression and anti-social behaviours in animals and humans

We review the impact of early adversities on the development of violence and antisocial behaviour in humans, and present three aetiological animal models of escalated rodent aggression, each disentangling the consequences of one particular adverse early-life factor. A review of the human data, as well as those obtained with the animal models of repeated maternal separation, post-weaning social isolation and peripubertal stress, clearly shows that adverse developmental conditions strongly affect aggressive behaviour displayed in adulthood, the emotional responses to social challenges and the neuronal mechanisms activated by conflict. Although similarities between models are evident, important differences were also noted, demonstrating that the behavioural, emotional and neuronal consequences of early adversities are to a large extent dependent on aetiological factors. These findings support recent theories on human aggression, which suggest that particular developmental trajectories lead to specific forms of aggressive behaviour and brain dysfunctions. However, dissecting the roles of particular aetiological factors in humans is difficult because these occur in various combinations; in addition, the neuroscientific tools employed in humans still lack the depth of analysis of those used in animal research. We suggest that the analytical approach of the rodent models presented here may be successfully used to complement human findings and to develop integrative models of the complex relationship between early adversity, brain development and aggressive behaviour. © 2014 British Society for Neuroendocrinology

Elevated metallothionein bound cadmium concentrations in urine from bladder carcinoma patients, investigated by size exclusion chromatography inductively coupled plasma mass spectrometry

Cadmium is discussed as being involved in the development of transitional cell carcinoma of the bladder TCC and can be observed in urine of these patients. Investigations of urinary samples from bladder cancer patients and normal controls were carried out with special emphasis on metallothionein MT bound cadmium. Urines were separated by means of size exclusion chromatography and cadmium was monitored continuously with a hyphenated inductively coupled plasma mass spectrometry ICP MS system. MT bound cadmium was quantified by peak area integration, taking into account the intensity of the rhodium signal which was added continuously before ICP MS detection. The obtained results show that urinary cadmium is predominantly bound to the observed MT fraction. The average MT bound cadmium concentration in the control group was found to be 0.9 g amp; 8729;l 1 median 0.8 g amp; 8729;l 1 whereas the cancer group has an average of 4.6 g amp; 8729;l 1 median 1.8 g amp; 8729;l 1 . The variance of the data in the cancer group is much higher than in controls. However, the urinary MT bound cadmium is significantly elevated in the cancer group; Odds Ratio test 7.11 95 CI 1.89 to 26.80 , taking into account the total protein content

Aggression, DRD1 polymorphism, and lesion location in penetrating traumatic brain injury

OBJECTIVE: This study evaluated whether structural brain lesions modulate the relationship between pathological aggression and the dopaminergic system in traumatic brain injury (TBI). While converging evidence suggests that different areas of prefrontal cortex modulate dopaminergic activity, to date no evidence exists of a modulation of endogenous dopaminergic tone by lesion localization in penetrating TBI (pTBI). METHODS: This study included 141 male Caucasian veterans who suffered penetrating pTBI during their service in Vietnam and 29 healthy male Caucasian Vietnam veterans. Participants were genotyped for three functional single nucleotide polymorphisms (SNPs): dopamine receptor D1 (DRD1) rs686 and dopamine receptor D2 (DRD2) rs4648317 and catechol-o-methyltransferase (COMT) Val158Met. Patients underwent brain CT scans and were divided into medial prefrontal cortex, lateral prefrontal cortex, and posterior cortex lesion groups. Long-term aggression levels were evaluated with the agitation/aggression sub-scale of the Neuropsychiatric Inventory. RESULTS: Our data showed that carriers of more transcriptionally active DRD1 alleles compared to non-carriers demonstrated greater aggression levels due to medial prefrontal cortex lesions but reduced aggression levels due to lateral prefrontal cortex lesions independently of DRD2 rs4648317 or COMT Val158Met genotypes. CONCLUSIONS: Our results suggest that the relationship between pTBI-related aggression and the dopaminergic system is modulated by lesion location. Potentially lesion location could represent an easy-to-use, widely-available para-clinical marker to help in the development of an individualized therapeutic approach to pTBI-related pathological aggression

Differential contributions of dorso-ventral and rostro-caudal prefrontal white matter tracts to cognitive control in healthy older adults.

Prefrontal cortex mediates cognitive control by means of circuitry organized along dorso-ventral and rostro-caudal axes. Along the dorso-ventral axis, ventrolateral PFC controls semantic information, whereas dorsolateral PFC encodes task rules. Along the rostro-caudal axis, anterior prefrontal cortex encodes complex rules and relationships between stimuli, whereas posterior prefrontal cortex encodes simple relationships between stimuli and behavior. Evidence of these gradients of prefrontal cortex organization has been well documented in fMRI studies, but their functional correlates have not been examined with regard to integrity of underlying white matter tracts. We hypothesized that (a) the integrity of specific white matter tracts is related to cognitive functioning in a manner consistent with the dorso-ventral and rostro-caudal organization of the prefrontal cortex, and (b) this would be particularly evident in healthy older adults. We assessed three cognitive processes that recruit the prefrontal cortex and can distinguish white matter tracts along the dorso-ventral and rostro-caudal dimensions -episodic memory, working memory, and reasoning. Correlations between cognition and fractional anisotropy as well as fiber tractography revealed: (a) Episodic memory was related to ventral prefrontal cortex-thalamo-hippocampal fiber integrity; (b) Working memory was related to integrity of corpus callosum body fibers subserving dorsolateral prefrontal cortex; and (c) Reasoning was related to integrity of corpus callosum body fibers subserving rostral and caudal dorsolateral prefrontal cortex. These findings confirm the ventrolateral prefrontal cortex's role in semantic control and the dorsolateral prefrontal cortex's role in rule-based processing, in accordance with the dorso-ventral prefrontal cortex gradient. Reasoning-related rostral and caudal superior frontal white matter may facilitate different levels of task rule complexity. This study is the first to demonstrate dorso-ventral and rostro-caudal prefrontal cortex processing gradients in white matter integrity

Regional brain atrophy and impaired decision making on the balloon analog risk task in behavioral variant frontotemporal dementia.

OBJECTIVE: The goal of this study was 2-fold, first, to compare decision making in behavioral variant frontotemporal dementia (bvFTD) patients and healthy adults using the Balloon Analog Risk Task (BART), and, second, to identify the regions of gray matter atrophy associated with bvFTD patients' BART performance. BACKGROUND: Stimulus-reinforcement learning is required to evaluate the results of previously chosen actions to improve future decisions. Although there is a well established literature suggesting altered decision making in FTD patients and data from lesion studies suggest orbitofrontal cortex (OFC) involvement in decision making, there is very little research looking at the brain correlates of decision making in FTD populations specifically. METHOD: Twenty-seven bvFTD patients and 19 age-matched and education-matched normal controls completed the BART. Voxel-based morphometry analysis was performed on the magnetic resonance imaging scans of a subset of patients. RESULTS: Compared with healthy controls, the bvFTD patients did not learn and pumped less to inflate a balloon to receive a reward, indicating altered stimulus-reinforcement learning. The voxel-based morphometry analysis indicated that bvFTD patients' impaired BART performance was related to atrophy in the right lateral OFC. CONCLUSIONS: The right lateral OFC is crucial for stimulus-reinforcement learning required for the adjustment of behavior under changing reward contingencies