Power-up: a reanalysis of 'power failure' in neuroscience using mixture modelling

Evidence for endemically low statistical power has recently cast neuroscience findings into doubt. If low statistical power plagues neuroscience, this reduces confidence in reported effects. However, if statistical power is not uniformly low, such blanket mistrust might not be warranted. Here, we provide a different perspective on this issue, analysing data from an influential paper reporting a median power of 21% across 49 meta-analyses (Button et al., 2013). We demonstrate, using Gaussian mixture modelling, that the sample of 730 studies included in that analysis comprises several subcomponents; therefore the use of a single summary statistic is insufficient to characterise the nature of the distribution. We find that statistical power is extremely low for studies included in meta-analyses that reported a null result; and that it varies substantially across subfields of neuroscience, with particularly low power in candidate gene association studies. Thus, while power in neuroscience remains a critical issue, the notion that studies are systematically underpowered is not the full story: low power is far from a universal problem. SIGNIFICANCE STATEMENT: Recently, researchers across the biomedical and psychological sciences have become concerned with the reliability of results. One marker for reliability is statistical power: the probability of finding a statistically significant result, given that the effect exists. Previous evidence suggests that statistical power is low across the field of neuroscience. Our results present a more comprehensive picture of statistical power in neuroscience: on average, studies are indeed underpowered-some very seriously so-but many studies show acceptable or even exemplary statistical power. We show that this heterogeneity in statistical power is common across most subfields in neuroscience (psychology, neuroimaging, etc.). This new, more nuanced picture of statistical power in neuroscience could affect not only scientific understanding, but potentially policy and funding decisions for neuroscience research

Non-invasive direct current brain stimulation: the evidence behind the hype

The leading global cause of disability is major depression, affecting over 350 million people worldwide. Pharmacological and psychological therapies for depression have changed very little in the past thirty years, despite extensive research for new treatment targets. The most common antidepressant drugs are effective for about 58% of depressed patients in primary care, while 45% respond to placebo. The difficulty in developing new treatments arises in part because depression is a disorder of unknown aetiology. The neurobiological correlates of depression, on the other hand, are not entirely unknown: neuroscience research has identified several brain circuits that operate abnormally in depression. Recently, this knowledge has contributed to the development of experimental treatments, including those that stimulate the brain directly in a targeted manner. Among these novel treatments is a form of painless, noninvasive brain stimulation termed transcranial direct current stimulation (tDCS), commonly applied to the dorsolateral prefrontal cortex (DLPFC) in trials for depression. The practical advantages of tDCS are many: tDCS is comparatively inexpensive, portable, and safe. In this article we discuss the evidence that tDCS is effective in depression, and the neural and cognitive mechanisms that may drive its putative antidepressant effect. We also outline the importance of mechanistic studies of DLPFC tDCS to clarify its effects on the brain, and optimize its potential for clinical use

Resting state connectivity of the human habenula at ultra-high field

The habenula, a portion of the epithalamus, is implicated in the pathophysiology of depression, anxiety and addiction disorders. Its small size and connection to other small regions prevent standard human imaging from delineating its structure and connectivity with confidence. Resting state functional connectivity is an established method for mapping connections across the brain from a seed region of interest. The present study takes advantage of 7T fMRI to map, for the first time, the habenula resting state network with very high spatial resolution in 32 healthy human participants. Results show novel functional connections in humans, including functional connectivity with the septum and bed nucleus of the stria terminalis (BNST). Results also show many habenula connections previously described only in animal research, such as with the nucleus basalis of Meynert, dorsal raphe, ventral tegmental area (VTA), and periaqueductal grey (PAG). Connectivity with caudate, thalamus and cortical regions such as the anterior cingulate, retrosplenial cortex and auditory cortex are also reported. This work, which demonstrates the power of ultra-high field for mapping human functional connections, is a valuable step toward elucidating subcortical and cortical regions of the habenula network

Harnessing electric potential: DLPFC tDCS induces widespread brain perfusion changes.

A commentary on widespread modulation of cerebral perfusion induced during and after transcranial direct current stimulation applied to the left dorsolateral prefrontal corte

The neural basis of hot and cold cognition in depressed patients, unaffected relatives, and low -risk healthy controls: An fMRI investigation

BACKGROUND: Modern cognitive neuropsychological models of depression posit that negatively biased emotional (“hot”) processing confers risk for depression, while preserved executive function (“cold”) cognition promotes resilience. METHODS: We compared neural responses during hot and cold cognitive tasks in 99 individuals: those at familial risk for depression (N = 30 unaffected first-degree relatives of depressed individuals) and those currently experiencing a major depressive episode (N = 39 unmedicated depressed patients) with low-risk healthy controls (N = 30). Primary analyses assessed neural activation on two functional magnetic resonance imaging tasks previously associated with depression: dorsolateral prefrontal cortex (DLPFC) responsivity during the n-back working memory task; and amygdala and subgenual anterior cingulate cortex (sgACC) responsivity during incidental emotional face processing. RESULTS: Depressed patients exhibited significantly attenuated working memory-related DLPFC activation, compared to low-risk controls and unaffected relatives; unaffected relatives did not differ from low-risk controls. We did not observe a complementary pattern during emotion processing. However, we found preliminary support that greater DLPFC activation was associated with lower amygdala response during emotion processing. LIMITATIONS: These findings require confirmation in a longitudinal study to observe each individual's risk of developing depression; without this, we cannot identify the true risk level of the first-degree relative or low-risk control group. CONCLUSIONS: These findings have implications for understanding the neural mechanisms of risk and resilience in depression: they are consistent with the suggestion that preserved executive function might confer resilience to developing depression in first-degree relatives of depressed patients

Does excitatory fronto-extracerebral tDCS lead to improved working memory performance?

Evidence suggests that excitatory transcranial direct current stimulation (tDCS) may improve performance on a wide variety of cognitive tasks. Due to the non-invasive and inexpensive nature of the method, harnessing its potential could be particularly useful for the treatment of neuropsychiatric illnesses involving cognitive dysfunction. However, questions remain regarding the efficacious stimulation parameters. Here, using a double-blind between-subjects design, we explored whether 1 mA excitatory (anodal) left dorsolateral prefrontal cortex stimulation with a contralateral extracerebral reference electrode, leads to enhanced working memory performance across two days, relative to sham stimulation. Participants performed the 3-back, a test of working memory, at baseline, and during and immediately following stimulation on two days, separated by 24-48 hours. Active stimulation did not significantly enhance performance versus sham over the course of the experiment. However, exploratory comparisons did reveal a significant effect of stimulation group on performance during the first stimulation phase only, with active stimulation recipients performing better than sham. While these results do not support the hypothesis that dorsolateral prefrontal cortex tDCS boosts working memory, they raise the possibility that its effects may be greatest during early learning stages

Depression is associated with enhanced aversive Pavlovian control over instrumental behaviour.

The dynamic modulation of instrumental behaviour by conditioned Pavlovian cues is an important process in decision-making. Patients with major depressive disorder (MDD) are known to exhibit mood-congruent biases in information processing, which may occur due to Pavlovian influences, but this hypothesis has never been tested directly in an unmedicated sample. To address this we tested unmedicated MDD patients and healthy volunteers on a computerized Pavlovian-Instrumental Transfer (PIT) task designed to separately examine instrumental approach and withdrawal actions in the context of Pavlovian appetitive and aversive cues. This design allowed us to directly measure the degree to which Pavlovian cues influence instrumental responding. Depressed patients were profoundly influenced by aversive Pavlovian stimuli, to a significantly greater degree than healthy volunteers. This was the case for instrumental behaviour both in the approach condition (in which aversive Pavlovian cues inhibited 'go' responses), and in the withdrawal condition (in which aversive Pavlovian cues facilitated 'go' responses). Exaggerated aversive PIT provides a potential cognitive mechanism for biased emotion processing in major depression. This finding also has wider significance for the understanding of disrupted motivational processing in neuropsychiatric disorders.This work was supported by a Medical Research Council project grant (G0901275) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre

Unreliability of putative fMRI biomarkers during emotional face processing

There is considerable need to develop tailored approaches to psychiatric treatment. Numerous researchers have proposed using functional magnetic resonance imaging (fMRI) biomarkers to predict therapeutic response, in particular by measuring task-evoked subgenual anterior cingulate (sgACC) and amygdala activation in mood and anxiety disorders. Translating this to the clinic relies on the assumption that blood-oxygen-level dependent (BOLD) responses in these regions are stable within individuals. To test this assumption, we scanned a group of 29 volunteers twice (mean test-retest interval=14.3 days) and calculated the within-subject reliability of the amplitude of the amygdalae and sgACC BOLD responses to emotional faces using three paradigms: emotion identification; emotion matching; and gender classification. We also calculated the reliability of activation in a control region, the right fusiform face area (FFA). All three tasks elicited robust group activations in the amygdalae and sgACC (which changed little on average over scanning sessions), but within-subject reliability was surprisingly low, despite excellent reliability in the control right FFA region. Our findings demonstrate low statistical reliability of two important putative treatment biomarkers in mood and anxiety disorders

The effect of frontoparietal paired associative stimulation on decision-making and working memory

Previous single-site neurostimulation experiments have unsuccessfully attempted to shift decision-making away from habitual control, a fast, inflexible cognitive strategy, towards goal-directed control, a flexible, though computationally expensive strategy. We employed a dual-target neurostimulation approach in 30 healthy participants, using cortico-cortical paired associative stimulation (ccPAS) to target two key nodes: lateral prefrontal cortex (LPFC) and intraparietal sulcus (IPS), to test whether decision-making can be artificially shifted from habitual toward goal-directed control. Participants received three active stimulations, delivered at least six days apart (each involving 100 paired pulses over the IPS and LPFC, varying the interstimulus interval): two interventional, time-relevant ccPAS (10 msec interval) and one control, non-time-relevant ccPAS (100 msec interval). Following stimulation, participants completed a sequential learning task, measuring goal-directed/habitual control, and a working memory task. IPS→LPFC ccPAS (stimulating IPS, then LPFC with a 10 msec interval) shifted decision-making from habitual toward goal-directed control, compared to control ccPAS. There was no effect of LPFC→IPS ccPAS, nor an effect of any PAS condition on working memory. Previous studies have shown ccPAS effects outside the motor domain targeting prefrontal regions on response inhibition, attentional bias, and alpha asymmetry. The present study measures the behavioural effects of parietal-prefrontal PAS, focusing on a highly complex decision-making task and working memory. If confirmed in larger studies, this would be the first instance of neurostimulation successfully shifting decision-making from habitual to goal-directed control, putatively via inducing long-term potentiation between the IPS and LPFC. However, we found no effect in the other direction (LPFC→IPS ccPAS), and no effect on working memory overall. PAS is a relatively new neuromodulatory technique in the cognitive arsenal, and this study could help guide future approaches in healthy and disordered decision-making

Children's very low food security is associated with increased dietary intakes in energy, fat, and added sugar among Mexican-origin children (6-11 y) in Texas border Colonias

<p>Abstract</p> <p>Background</p> <p>Food insecurity among Mexican-origin and Hispanic households is a critical nutritional health issue of national importance. At the same time, nutrition-related health conditions, such as obesity and type 2 diabetes, are increasing in Mexican-origin youth. Risk factors for obesity and type 2 diabetes are more common in Mexican-origin children and include increased intakes of energy-dense and nutrient-poor foods. This study assessed the relationship between children's experience of food insecurity and nutrient intake from food and beverages among Mexican-origin children (age 6-11 y) who resided in Texas border <it>colonias</it>.</p> <p>Methods</p> <p>Baseline data from 50 Mexican-origin children were collected in the home by trained <it>promotora</it>-researchers. All survey (demographics and nine-item child food security measure) and 24-hour dietary recall data were collected in Spanish. Dietary data were collected in person on three occasions using a multiple-pass approach; nutrient intakes were calculated with NDS-R software. Separate multiple regression models were individually fitted for total energy, protein, dietary fiber, calcium, vitamin D, potassium, sodium, Vitamin C, and percentage of calories from fat and added sugars.</p> <p>Results</p> <p>Thirty-two children (64%) reported low or very low food security. Few children met the recommendations for calcium, dietary fiber, and sodium; and none for potassium or vitamin D. Weekend intake was lower than weekday for calcium, vitamin D, potassium, and vitamin C; and higher for percent of calories from fat. Three-day average dietary intakes of total calories, protein, and percent of calories from added sugars increased with declining food security status. Very low food security was associated with greater intakes of total energy, calcium, and percentage of calories from fat and added sugar.</p> <p>Conclusions</p> <p>This paper not only emphasizes the alarming rates of food insecurity for this Hispanic subgroup, but describes the associations for food insecurity and diet among this sample of Mexican-origin children. Child-reported food insecurity situations could serve as a screen for nutrition problems in children. Further, the National School Lunch and School Breakfast Programs, which play a major beneficial role in children's weekday intakes, may not be enough to keep pace with the nutritional needs of low and very low food secure Mexican-origin children.</p