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

Functional and structural plasticity co-express in a left premotor region during early bimanual skill learning

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Offline Persistence of Memory-Related Cerebral Activity during Active Wakefulness

Much remains to be discovered about the fate of recent memories in the human brain. Several studies have reported the reactivation of learning-related cerebral activity during post-training sleep, suggesting that sleep plays a role in the offline processing and consolidation of memory. However, little is known about how new information is maintained and processed during post-training wakefulness before sleep, while the brain is actively engaged in other cognitive activities. We show, using functional magnetic resonance imaging, that brain activity elicited during a new learning episode modulates brain responses to an unrelated cognitive task, during the waking period following the end of training. This post-training activity evolves in learning-related cerebral structures, in which functional connections with other brain regions are gradually established or reinforced. It also correlates with behavioral performance. These processes follow a different time course for hippocampus-dependent and hippocampus-independent memories. Our experimental approach allowed the characterization of the offline evolution of the cerebral correlates of recent memories, without the confounding effect of concurrent practice of the learned material. Results indicate that the human brain has already extensively processed recent memories during the first hours of post-training wakefulness, even when simultaneously coping with unrelated cognitive demands

Modafinil-Induced changes in functional connectivity in the cortex and cerebellum of healthy elderly subjects

In the past few years, cognitive enhancing drugs (CEDs) have gained growing interest and the focus of investigations aimed at exploring their use to potentiate the cognitive performances of healthy individuals. Most of this exploratory CED-related research has been performed on young adults. However, CEDs may also help to maintain optimal brain functioning or compensate for subtle and or subclinical deficits associated with brain aging or early-stage dementia. In this study, we assessed effects on resting state brain activity in a group of healthy elderly subjects undergoing acute administration of modafinil, a wakefulness-promoting agent. To that aim, participants (n = 24) were investigated with resting state functional Magnetic Resonance Imaging (rs-fMRI) before and after the administration of a single dose (100 mg) of modafinil. Effects were compared to age and size-matched placebo group. Rs-fMRI effects were assessed, employing a graph-based approach and Eigenvector Centrality (EC) analysis, by taking in account topological changes occurring in functional brain networks. The main finding of the study is that modafinil promotes enhanced centrality, a measure of the importance of nodes within functional networks, of the bilateral primary visual (V1) cortex. EC analysis also revealed that modafinil-treated subjects show increased functional connectivity between the V1 and specific cerebellar (Crus I, Crus II, VIIIa lobule) and frontal (right inferior frontal sulcus and left middle frontal gyrus) regions. Present findings provide functional data supporting the hypothesis that modafinil can modulate the cortico-cerebellar connectivity of the aging brai

Functional imaging in neuroenhancement

Increasingly demanding tasks, competition for competence and time pressure have lead to attempts of neuroenhancement (NE) among students and employees. NE is designed to increase cognitive abilities by modulating brain processes through the use of pharmaceutics. Substances such as methylphenidate (i.e. Ritalin®), modafinil (i.e. Vigil®) and caffeine are common candidates for enhancing cognitive abilities such as executive functions, inhibition control and memory (Wood et al., 2014). Until today, there has not been a study investigating memory enhancement in functional magnetic resonance imaging (fMRI). Using fMRI, 48 healthy participants were tested for drug effects in a single-dose, double-blind and randomized study using a declarative memory task. During memory recall, methylphenidate dependent deactivations were found in the fronto-parietal and temporal regions whereas no BOLD alterations were seen during encoding. On the behavioral level, methylphenidate enhanced subject’s judgement confidence and performance during late recall. During encoding, caffeine led to deactivations in the precentral gyrus whereas modafinil did not show any BOLD signal alterations at all. To get an overview over the existing neuroimaging literature, all published studies on the effects of the aforementioned drug agents were reviewed in addition. In line with this study, previous publications emphasized that methylphenidate seems to alter task relevant brain areas. Our main finding of task-related deactivations may point to the reduction of task-functioning distractions. Thereby, we conclude a drug-dependent increase of efficiency in data processing.Zunehmende Arbeitsbelastung, erhöhter Zeitdruck und größere Verantwortung haben dazu geführt, dass für Studenten und Arbeitnehmer das Phänomen Neuroenhancement (NE) eine zunehmende Relevanz erlangt hat. Darunter wird die Steigerung der kognitiven Leistung durch pharmazeutischen Eingriff auf zentralnervöse Prozesse verstanden. Substanzen wie z.B. Methylphenidat (Ritalin®), Modafinil (Vigil®) und Koffein gelten als aussichtsreiche Kandidaten zur Leistungssteigerung, die möglicherweise Einfluss auf kognitive Prozesse, wie z.B. Exekutive Funktionen, Inhibitionskontrolle und Gedächtnis ausüben können (Wood et al., 2014). Keine bisher publizierte Studie hat den Fokus auf neuronale Korrelate der deklarativen Gedächtnissteigerung gelegt. Aus dem Grund sind zusätzlich alle bisher veröffentlichten bildgebenden Studien zu Methylphenidat, Modafinil und Koffein zu einer strukturierten Übersicht zusammengefasst worden. Mittels funktionaler Magnetresonanztomographie (fMRT) wurden 48 gesunde Probanden, doppelt verblindet und randomisiert auf Steigerung der deklarativen Gedächtnisleistung getestet. Obwohl die Wirksamkeit der drei Substanzen ausführlich für klinische Patientenpopulationen untersucht wurde, gibt es kaum Wissen über die möglichen behavioralen und neuronalen Auswirkungen auf gesunde, erwachsene Menschen. Entgegen der Erwartung, dass die getesteten Substanzen klassische Gedächtnis assoziierte Regionen aktivieren, wurden unterschiedliche substanzspezifische Effekte gefunden. Wahrend des Abrufs von Gedächtnisinhalten deaktivierte Methylphenidat fronto-parietale und temporale Regionen. Dagegen führte die Applikation von Koffein zu einer verringerten BOLD Antwort im Gyrus Präcentralis während der Lernphase. Modafinil führte zu keiner Veränderung im Vergleich zu Placebo. Auf Verhaltensebene förderte Methylphenidat den späten Abruf von Gedächtnisinhalten, wohingegen die beiden anderen Substanzen keine Effekte hinsichtlich der Lernleistung vorwiesen. Vor dem Hintergrund bisheriger bildgebender Studien zeigt die vorliegende Arbeit, dass Neuroenhancement neben der Aktivierung leistungsrelevanter Gehirnregionen auch durch Reduzierung von störenden Einwirkungen funktionieren kann und damit womöglich die Effektivität der Informationsverarbeitung erhöht

Biophysical Modulations of Functional Connectivity

Resting-state low frequency oscillations have been detected in many functional magnetic resonance imaging (MRI) studies and appear to be synchronized between functionally related areas. Converging evidence from MRI and other imaging modalities suggest that this activity has an intrinsic neuronal origin. Multiple consistent networks have been found in large populations, and have been shown to be stable over time. Further, these patterns of functional connectivity have been shown to be altered in healthy controls under various physiological challenges. This review will present the biophysical characterization of functional connectivity, and examine the effects of physical state manipulations (such as anesthesia, fatigue, and aging) in healthy controls.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90432/1/brain-2E2011-2E0039.pd

Investigating the Cortical, Metabolic and Behavioral Effects of Transcranial Direct Current Stimulation in Preparation for Combined Rehabilitation

The goal of this thesis was to determine the cortical reorganization that occurs in patients with cervical spondylotic myelopathy (CSM) after surgical decompression and to implement this knowledge into a new rehabilitation strategy. Transcranial direct current stimulation (tDCS) is a non-invasive technique to modulate human behavior. Due to the novel electrode montage used, it was first pertinent that we determine how tDCS would modulate cortical, metabolic and motor behavior in healthy individuals. We observed the longitudinal functional adaptations that occur in patients with CSM using functional MRI. Enhanced excitation of supplementary motor area (SMA) was observed following surgical decompression and associated with increased function following surgery. This novel finding of enhanced excitation of motivated us to use a bihemispheric tDCS protocol, exciting bilateral motor areas to provide optimal motor enhancement. This novel tDCS electrode montage, targeting the SMA and primary motor cortex (M1) was implemented in healthy older adults to determine its effects on enhancing manual dexterity. Furthermore, to determine the frequency with which to apply tDCS, a single and tri session protocol was used. We observed a differential pattern of action with anti-phase and in-phase motor tasks during multisession tDCS. We used ultra-high field (7T) MRI to examined the metabolic changes that occur following tDCS. After the stimulation period we observed no significant metabolite modulation. A trend towards an increase in the NAA/tCr ratio, with a concomitant decrease in the absolute concentration of tCr was observed. Finally, we examined the functional connectivity before, during and after tDCS with the use of resting-state fMRI at 7T. We observed enhanced connectivity within right sensorimotor area after stimulation compared to during stimulation. This result confirmed that cortical modulations differ during versus after tDCS, signifying that optimal modulation of behaviour may be after the stimulation period. Furthermore, we observed an enhanced correlation between motor regions and the caudate, both during and after stimulation. In conclusion, we observed novel cortical adaptations in CSM patients after surgical decompression, which led us to believe that bihemispheric tDCS of M1-SMA network would result in optimal motor enhancement and warrants further investigation in CSM and other neurological disorders