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

Effects of Methylphenidate on Memory and Attention in Healthy Adults

Methylphenidate (MPH) is the most prescribed medicinal drug for people diagnosed with attention deficit/hyperactivity disorder. However, the off-label use by healthy adults has increased over the last year due to the potential beneficial effects on cognitive performance. It causes augmented catecholaminergic neurotransmission by blocking dopamine and norepinephrine’s reuptake mainly in prefrontal cortex and striatum. The aim of this review was to examine the effects of MPH on memory and attention in healthy adults. The results were ambiguous, however, MPH’s beneficial effects on memory were found more consistently than effects on attention. In addition, individuals whose baseline performance was lower than average benefitted more than others. Optimal dosing seems to be dependent on the task and cognitive domain tested. The controversy about cognitive enhancing drugs arises when taking side effects, as well as ethical aspects, into consideration. Common adverse effects are insomnia and appetite loss. In conclusion, despite the positive effects of MPH on memory and attention, the use of MPH as cognitive enhancer in healthy adults is not recommended based on the lack of longitudinal studies and the risks of adverse effects. MPH self-medication is not recommended

Task-related default mode network modulation and inhibitory control in ADHD: effects of motivation and methylphenidate

Background: Deficits characteristic of Attention Deficit/Hyperactivity Disorder (ADHD), including poor attention and inhibitory control, are at least partially alleviated by factors that increase engagement of attention, suggesting a hypodopaminergic reward deficit. Lapses of attention are associated with attenuated deactivation of the Default Mode Network (DMN), a distributed brain system normally deactivated during tasks requiring attention to the external world. Task-related DMN deactivation has been shown to be attenuated in ADHD relative to controls. We hypothesised that motivational incentives to balance speed against restraint would increase task engagement during an inhibitory control task, enhancing DMN deactivation in ADHD. We also hypothesised that methylphenidate, an indirect dopamine agonist, would tend to normalise abnormal patterns of DMN deactivation. Method: We obtained functional magnetic resonance images from eighteen methylphenidate-responsive children with ADHD (DSM-IV combined subtype) and 18 pairwise-matched typically developing children aged 9-15 years while they performed a paced Go/No-go task. We manipulated motivational incentive to balance response speed against inhibitory control, and tested children with ADHD both on and off methylphenidate. Results: When children with ADHD were off-methylphenidate and task incentive was low, event-related DMN deactivation was significantly attenuated compared to controls, but the two groups did not differ under high motivational incentives. The modulation of DMN deactivation by incentive in the children with ADHD, off- methylphenidate, was statistically significant, and significantly greater than in typically developing children. When children with ADHD were on-methylphenidate, motivational modulation of event-related DMN deactivation was abolished, and no attenuation relative to their typically developing peers was apparent in either motivational condition. Conclusions: During an inhibitory control task, children with ADHD exhibit a raised motivational threshold at which task-relevant stimuli become sufficiently salient to deactivate the DMN. Treatment with methylphenidate normalises this threshold, rendering their pattern of task-related DMN deactivation indistinguishable from that of typically developing children

The pill and the will : pharmacological and psychological modulation of cognitive and affective processes

Background: Impairments in cognition are components of practically all psychiatric disorders and in that sense transdiagnostic factors. In both clinical and non-clinical populations, ‘hot’ and ‘cold’ cognitive control, i.e., in emotional context and non-emotional context, is strongly associated with daily functioning and physical and mental well-being. The paradigm shift that the National Institute of Mental Health (NIMH) Research Domain Criteria initiative (RDoC) has introduced, signifies that targeting the underlying biological and behavioural endophenotypes that determine mental health and illness might be more fruitful than simply focusing on symptom based diagnostic categories. Yet, little is known on how pharmacological interventions such as selective serotonin reuptake inhibitors (SSRI) and psychostimulants (CS), that are routinely used in everyday clinical praxis, affect cognitive and emotional processes beyond the symptoms they are supposed to treat. Aim: The aim of this thesis was to compare induction and regulation of fear and disgust in healthy subjects, and to investigate how SSRI affect these processes. This basic design was expanded to also include the effect of stimulant medication on the induction and regulation of negative emotions in healthy controls and patients with ADHD. A parallel aim was to compare pharmacological emotion regulation (SSRI and CS) with psychological emotion regulation (reappraisal) and emotion regulation with skills training/ exposure (task repetition). Methods: A multimodal approach was used to explore (i) subjective rating of emotion intensity and objective measures of performance at the behavioural level, (ii) neural underpinnings in the CNS with functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM) and (iii) physiological components of the sympathetic nervous system (electrodermal activity), which were all evaluated in the absence and presence of pharmacological and psychological interventions, during emotion induction, emotion regulation, cognitive Stroop and emotional Stroop paradigms. Results: Study I and IV demonstrated that emotion regulation with reappraisal is an effective strategy with robust effects on subjective emotional experience and electrodermal activity. Study II and III showed that task repetition improved performance during both cognitive and emotional Stroop tasks, and reduced electrodermal activity during cognitive Stroop, without significantly modifying emotion induction or emotion regulation. Study II and III showed significant effects of single dose escitalopram in reducing subjective emotional experience, improving task performance during affective interference of an ongoing cognitive process, altering prefrontal activity in a task-specific manner, and blurring the differences in the electrodermal activity between fear and disgust seen at baseline. Study IV showed that single dose CS reduced emotion induction, and that emotion regulation with reappraisal was significantly more effective in reducing subjective emotional experience compared to pharmacological emotion regulation with CS. Lastly, Study IV revealed aberrant emotion processing in patients with ADHD both at the behavioural and CNS levels, with patients reporting lower emotion induction and regulation scores, accompanied by less activation of dorsolateral prefrontal cortex, less deactivation of the default mode network and instead greater deactivation of the dorsal attention network, during emotion regulation compared to healthy controls. Structurally (VBM), less gray matter volume was found in limbic and paralimbic areas in patients with ADHD compared to healthy controls. Conclusions and implications: Dimensional approach using behavioural endophenotypes is a fruitful framework for studying normal physiology and diagnostic and treatment aspects of psychiatric disorders. In this thesis, it is demonstrated that emotional and non-emotional cognitive processes, although part of a continuum, likely respond differentially to psychological and pharmacological interventions and skills training with task repetition. Ultimately, improved knowledge in this field will help formulate hypothesisdriven and science-informed frameworks that will guide diagnosis and treatment plans, and usher a shift in psychiatric praxis

Catecholamines and cognition after traumatic brain injury

Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person’s catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ‘networks’ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner

The Effects of Methylphenidate on Cognitive Control in Active Methamphetamine Dependence Using Functional Magnetic Resonance Imaging

Methamphetamine (MA) dependence is associated with cognitive deficits. Methylphenidate (MPH) has been shown to improve inhibitory control in healthy and cocaine-dependent subjects. This study aimed to understand the neurophysiological effects before and after acute MPH administration in active MA-dependent and control subjects. Fifteen MA-dependent and 18 control subjects aged 18–46 years were scanned using functional magnetic resonance imaging before and after either a single oral dose of MPH (18 mg) or placebo while performing a color-word Stroop task. Baseline accuracy was lower (p = 0.026) and response time (RT) was longer (p < 0.0001) for the incongruent compared to congruent condition, demonstrating the task probed cognitive control. Increased activation of the dorsolateral prefrontal cortex (DLPFC) and parietal cortex during the incongruent and Stroop effect conditions, respectively was observed in MA-dependent compared to control subjects (p < 0.05), suggesting the need to recruit neural resources within these regions for conflict resolution. Post- compared to pre-MPH treatment, increased RT and DLPFC activation for the Stroop effect were observed in MA-dependent subjects (p < 0.05). In comparison to MPH-treated controls and placebo-treated MA-dependent subjects, MPH-treated MA-dependent subjects showed decreased activation of parietal and occipital regions during the incongruent and Stroop effect conditions (p < 0.05). These findings suggest that in MA-dependent subjects, MPH facilitated increased recruitment of the DLPFC for Stroop conflict resolution, and a decreased need for recruitment of neural resources in parietal and occipital regions compared to the other groups, while maintaining a comparable level of task performance to that achieved pre-drug administration. Due to the small sample size, the results from this study are preliminary; however, they inform us about the effects of MPH on the neural correlates of cognitive control in active MA-dependent subjects

Comparing Auditory Noise Treatment with Stimulant Medication on Cognitive Task Performance in Children with Attention Deficit Hyperactivity Disorder: Results from a Pilot Study

Background: Recent research has shown that acoustic white noise (80 dB) can improve task performance in people with attention deficits and/or Attention Deficit Hyperactivity Disorder (ADHD). This is attributed to the phenomenon of stochastic resonance in which a certain amount of noise can improve performance in a brain that is not working at its optimum. We compare here the effect of noise exposure with the effect of stimulant medication on cognitive task performance in ADHD. The aim of the present study was to compare the effects of auditory noise exposure with stimulant medication for ADHD children on a cognitive test battery. A group of typically developed children (TDC) took the same tests as a comparison. Methods: Twenty children with ADHD of combined or inattentive subtypes and twenty TDC matched for age and gender performed three different tests (word recall, spanboard and n-back task) during exposure to white noise (80 dB) and in a silent condition. The ADHD children were tested with and without central stimulant medication. Results: In the spanboard- and the word recall tasks, but not in the 2-back task, white noise exposure led to significant improvements for both non-medicated and medicated ADHD children. No significant effects of medication were found on any of the three tasks. Conclusion: This pilot study shows that exposure to white noise resulted in a task improvement that was larger than the one with stimulant medication thus opening up the possibility of using auditory noise as an alternative, non-pharmacological treatment of cognitive ADHD symptoms