Catecholamine Modulation of Evidence Accumulation during Perceptual Decision Formation: A Randomized Trial.

Recent behavioral modeling and pupillometry studies suggest that neuromodulatory arousal systems play a role in regulating decision formation but neurophysiological support for these observations is lacking. We employed a randomized, double-blinded, placebo-controlled, crossover design to probe the impact of pharmacological enhancement of catecholamine levels on perceptual decision-making. Catecholamine levels were manipulated using the clinically relevant drugs methylphenidate and atomoxetine, and their effects were compared with those of citalopram and placebo. Participants performed a classic EEG oddball paradigm that elicits the P3b, a centro-parietal potential that has been shown to trace evidence accumulation, under each of the four drug conditions. We found that methylphenidate and atomoxetine administration shortened RTs to the oddball targets. The neural basis of this behavioral effect was an earlier P3b peak latency, driven specifically by an increase in its buildup rate without any change in its time of onset or peak amplitude. This study provides neurophysiological evidence for the catecholaminergic enhancement of a discrete aspect of human decision-making, that is, evidence accumulation. Our results also support theoretical accounts suggesting that catecholamines may enhance cognition via increases in neural gain.

Training Working Memory in Childhood Enhances Coupling between Frontoparietal Control Network and Task-Related Regions.

UNLABELLED: Working memory is a capacity upon which many everyday tasks depend and which constrains a child's educational progress. We show that a child's working memory can be significantly enhanced by intensive computer-based training, relative to a placebo control intervention, in terms of both standardized assessments of working memory and performance on a working memory task performed in a magnetoencephalography scanner. Neurophysiologically, we identified significantly increased cross-frequency phase amplitude coupling in children who completed training. Following training, the coupling between the upper alpha rhythm (at 16 Hz), recorded in superior frontal and parietal cortex, became significantly coupled with high gamma activity (at ∼90 Hz) in inferior temporal cortex. This altered neural network activity associated with cognitive skill enhancement is consistent with a framework in which slower cortical rhythms enable the dynamic regulation of higher-frequency oscillatory activity related to task-related cognitive processes. SIGNIFICANCE STATEMENT: Whether we can enhance cognitive abilities through intensive training is one of the most controversial topics of cognitive psychology in recent years. This is particularly controversial in childhood, where aspects of cognition, such as working memory, are closely related to school success and are implicated in numerous developmental disorders. We provide the first neurophysiological account of how working memory training may enhance ability in childhood, using a brain recording technique called magnetoencephalography. We borrowed an analysis approach previously used with intracranial recordings in adults, or more typically in other animal models, called "phase amplitude coupling."

Cognitive training enhances intrinsic brain connectivity in childhood.

In human participants, the intensive practice of particular cognitive activities can induce sustained improvements in cognitive performance, which in some cases transfer to benefits on untrained activities. Despite the growing body of research examining the behavioral effects of cognitive training in children, no studies have explored directly the neural basis of these training effects in a systematic, controlled fashion. Therefore, the impact of training on brain neurophysiology in childhood, and the mechanisms by which benefits may be achieved, are unknown. Here, we apply new methods to examine dynamic neurophysiological connectivity in the context of a randomized trial of adaptive working memory training undertaken in children. After training, connectivity between frontoparietal networks and both lateral occipital complex and inferior temporal cortex was altered. Furthermore, improvements in working memory after training were associated with increased strength of neural connectivity at rest, with the magnitude of these specific neurophysiological changes being mirrored by individual gains in untrained working memory performance.

Electrophysiological measures of resting state functional connectivity and their relationship with working memory capacity in childhood.

Functional connectivity is the statistical association of neuronal activity time courses across distinct brain regions, supporting specific cognitive processes. This coordination of activity is likely to be highly important for complex aspects of cognition, such as the communication of fluctuating task goals from higher-order control regions to lower-order, functionally specific regions. Some of these functional connections are identifiable even when relevant cognitive tasks are not being performed (i.e. at rest). We used magnetoencephalographic recordings projected into source space to demonstrate that resting state networks in childhood have electrophysiological underpinnings that are evident in the spontaneous fluctuations of oscillatory brain activity. Using the temporal structure of these oscillatory patterns we were able to identify a number of functional resting state networks analogous to those reported in the adult literature. In a second analysis we fused this dynamic temporal information with the spatial information from a functional magnetic resonance imaging analysis of functional connectivity, to demonstrate that inter-subject variability in these electrophysiological measures of functional connectivity is correlated with individual differences in cognitive ability: the strength of connectivity between a fronto-parietal network and lower-level processing areas in inferior temporal cortex was associated with spatial working memory capacity, as measured outside the scanner with educationally relevant standardized assessments. This study represents the first exploration of the electrophysiological mechanisms underpinning resting state functional connectivity in source space in childhood, and the extent to which the strength of particular connections is associated with cognitive ability.

Multiple early-formed water reservoirs in the interior of Mars.

The abundance and distribution of water within Mars through time plays a fundamental role in constraining its geological evolution and habitability. The isotopic composition of martian hydrogen provides insights into the interplay between different water reservoirs on Mars. However, D/H (deuterium/hydrogen) ratios of martian rocks and of the martian atmosphere span a wide range of values. This has complicated identification of distinct water reservoirs in and on Mars within the confines of existing models that assume an isotopically homogenous mantle. Here we present D/H data collected by secondary ion mass spectrometry for two martian meteorites. These data indicate that the martian crust has been characterized by a constant D/H ratio over the last 3.9 billion years. The crust represents a reservoir with a D/H ratio that is intermediate between at least two isotopically distinct primordial water reservoirs within the martian mantle, sampled by partial melts from geochemically depleted and enriched mantle sources. From mixing calculations, we find that a subset of depleted martian basalts are consistent with isotopically light hydrogen (low D/H) in their mantle source, whereas enriched shergottites sampled a mantle source containing heavy hydrogen (high D/H). We propose that the martian mantle is chemically heterogeneous with multiple water reservoirs, indicating poor mixing within the mantle after accretion, differentiation, and its subsequent thermochemical evolution.

The Effects of Methylphenidate on the Neural Signatures of Sustained Attention.

BACKGROUND: Although it is well established that methylphenidate (MPH) enhances sustained attention, the neural mechanisms underpinning this improvement remain unclear. We examined how MPH influenced known electrophysiological precursors of lapsing attention over different time scales. METHODS: We measured the impact of MPH, compared with placebo, on behavioral and electrocortical markers while healthy adults (n = 40) performed a continuous monitoring paradigm designed to elicit attentional lapses. RESULTS: MPH led to increased rates of target detection, and electrophysiological analyses were conducted to identify the mechanisms underlying these improvements. Lapses of attention were reliably preceded by progressive increases in alpha activity that emerged over periods of several seconds. MPH led to an overall suppression of alpha activity across the entire task but also diminished the frequency of these maladaptive pretarget increases through a reduction of alpha variability. A drug-related linear increase in the amplitude of the frontal P3 event-related component was also observed in the pretarget timeframe (3 or 4 seconds). Furthermore, during immediate target processing, there was a significant increase in the parietal P3 amplitude with MPH, indicative of enhanced perceptual evidence accumulation underpinning target detection. MPH-related enhancements occurred without significant changes to early visual processing (visual P1 and 25-Hz steady-state visual evoked potential). CONCLUSIONS: MPH serves to reduce maladaptive electrophysiological precursors of lapsing attention by acting selectively on top-down endogenous mechanisms that support sustained attention and target detection with no significant effect on bottom-up sensory excitability. These findings offer candidate markers to monitor the therapeutic efficacy of psychostimulants or to predict therapeutic responses.

An asteroidal origin for water in the Moon.

The Apollo-derived tenet of an anhydrous Moon has been contested following measurement of water in several lunar samples that require water to be present in the lunar interior. However, significant uncertainties exist regarding the flux, sources and timing of water delivery to the Moon. Here we address those fundamental issues by constraining the mass of water accreted to the Moon and modelling the relative proportions of asteroidal and cometary sources for water that are consistent with measured isotopic compositions of lunar samples. We determine that a combination of carbonaceous chondrite-type materials were responsible for the majority of water (and nitrogen) delivered to the Earth-Moon system. Crucially, we conclude that comets containing water enriched in deuterium contributed significantly <20% of the water in the Moon. Therefore, our work places important constraints on the types of objects impacting the Moon ∼4.5-4.3 billion years ago and on the origin of water in the inner Solar System.

Understanding the origin and evolution of water in the Moon through lunar sample studies.

A paradigm shift has recently occurred in our knowledge and understanding of water in the lunar interior. This has transpired principally through continued analysis of returned lunar samples using modern analytical instrumentation. While these recent studies have undoubtedly measured indigenous water in lunar samples they have also highlighted our current limitations and some future challenges that need to be overcome in order to fully understand the origin, distribution and evolution of water in the lunar interior. Another exciting recent development in the field of lunar science has been the unambiguous detection of water or water ice on the surface of the Moon through instruments flown on a number of orbiting spacecraft missions. Considered together, sample-based studies and those from orbit strongly suggest that the Moon is not an anhydrous planetary body, as previously believed. New observations and measurements support the possibility of a wet lunar interior and the presence of distinct reservoirs of water on the lunar surface. Furthermore, an approach combining measurements of water abundance in lunar samples and its hydrogen isotopic composition has proved to be of vital importance to fingerprint and elucidate processes and source(s) involved in giving rise to the lunar water inventory. A number of sources are likely to have contributed to the water inventory of the Moon ranging from primordial water to meteorite-derived water ice through to the water formed during the reaction of solar wind hydrogen with the lunar soil. Perhaps two of the most striking findings from these recent studies are the revelation that at least some portions of the lunar interior are as water-rich as some Mid-Ocean Ridge Basalt source regions on Earth and that the water in the Earth and the Moon probably share a common origin.

Monoaminergic modulation of behavioural and electrophysiological indices of error processing.

RATIONALE: Error processing is a critical executive function that is impaired in a large number of clinical populations. Although the neural underpinnings of this function have been investigated for decades and critical error-related components in the human electroencephalogram (EEG), such as the error-related negativity (ERN) and the error positivity (Pe), have been characterised, our understanding of the relative contributions of key neurotransmitters to the generation of these components remains limited. OBJECTIVES: The current study sought to determine the effects of pharmacological manipulation of the dopamine, noradrenaline and serotonin neurotransmitter systems on key behavioural and event-related potential correlates of error processing. METHODS: A randomised, double-blinded, placebo-controlled, crossover design was employed. Monoamine levels were manipulated using the clinically relevant drugs methylphenidate, atomoxetine and citalopram, in comparison to placebo. Under each of the four drug conditions, participants underwent EEG recording while performing a flanker task. RESULTS: Only methylphenidate produced significant improvement in performance accuracy, which was without concomitant slowing of reaction time. Methylphenidate also increased the amplitude of an early electrophysiological index of error processing, the ERN. Citalopram increased the amplitude of the correct-response negativity, another component associated with response processing. CONCLUSIONS: The effects of methylphenidate in this study are consistent with theoretical accounts positing catecholamine modulation of error monitoring. Our data suggest that enhancing catecholamine function has the potential to remediate the error-monitoring deficits that are seen in a wide range of psychiatric conditions.

The molecular genetics of executive function: role of monoamine system genes.

Executive control processes, such as sustained attention, response inhibition, and error monitoring, allow humans to guide behavior in appropriate, flexible, and adaptive ways. The consequences of executive dysfunction for humans can be dramatic, as exemplified by the large range of both neurologic and neuropsychiatric disorders in which such deficits negatively affect outcome and quality of life. Much evidence suggests that many clinical disorders marked by executive deficits are highly heritable and that individual differences in quantitative measures of executive function are strongly driven by genetic differences. Accordingly, intense research effort has recently been directed toward mapping the genetic architecture of executive control processes in both clinical (e.g., attention-deficit/hyperactivity disorder) and nonclinical populations. Here we review the extant literature on the molecular genetic correlates of three exemplar but dissociable executive functions: sustained attention, response inhibition, and error processing. Our review focuses on monoaminergic gene variants given the strong body of evidence from cognitive neuroscience and pharmacology implicating dopamine, noradrenaline, and serotonin as neuromodulators of executive function. Associations between DNA variants of the dopamine beta hydroxylase gene and measures of sustained attention accord well with cognitive-neuroanatomical models of sustained attention. Equally, functional variants of the dopamine D2 receptor gene are reliably associated with performance monitoring, error processing, and reinforcement learning. Emerging evidence suggests that variants of the dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4) show promise for explaining significant variance in individual differences in both behavioral and neural measures of inhibitory control.