Improving effect size estimation and statistical power with multi-echo fMRI and its impact on understanding the neural systems supporting mentalizing.

Functional magnetic resonance imaging (fMRI) research is routinely criticized for being statistically underpowered due to characteristically small sample sizes and much larger sample sizes are being increasingly recommended. Additionally, various sources of artifact inherent in fMRI data can have detrimental impact on effect size estimates and statistical power. Here we show how specific removal of non-BOLD artifacts can improve effect size estimation and statistical power in task-fMRI contexts, with particular application to the social-cognitive domain of mentalizing/theory of mind. Non-BOLD variability identification and removal is achieved in a biophysical and statistically principled manner by combining multi-echo fMRI acquisition and independent components analysis (ME-ICA). Without smoothing, group-level effect size estimates on two different mentalizing tasks were enhanced by ME-ICA at a median rate of 24% in regions canonically associated with mentalizing, while much more substantial boosts (40-149%) were observed in non-canonical cerebellar areas. Effect size boosting occurs via reduction of non-BOLD noise at the subject-level and consequent reductions in between-subject variance at the group-level. Smoothing can attenuate ME-ICA-related effect size improvements in certain circumstances. Power simulations demonstrate that ME-ICA-related effect size enhancements enable much higher-powered studies at traditional sample sizes. Cerebellar effects observed after applying ME-ICA may be unobservable with conventional imaging at traditional sample sizes. Thus, ME-ICA allows for principled design-agnostic non-BOLD artifact removal that can substantially improve effect size estimates and statistical power in task-fMRI contexts. ME-ICA could mitigate some issues regarding statistical power in fMRI studies and enable novel discovery of aspects of brain organization that are currently under-appreciated and not well understood.This work was supported by a Wellcome Trust project grant to SB-C and ETB. MVL was supported by the Wellcome Trust and fellowships from Jesus College, Cambridge and the British Academy. PK was supported by the National Institutes of Health–Cambridge Scholars Program. ETB is employed half-time by the University of Cambridge and halftime by GlaxoSmithKline (GSK).This is the author accepted manuscript. It first appeared from Elseiver at http://dx.doi.org/10.1016/j.neuroimage.2016.07.022

The social neuroscience of mentalizing: challenges and recommendations

Our ability to understand and think about the mental states of other people is referred to as “mentalizing” or “theory of mind”. It features prominently in all social behavior, is essential for maintaining relationships, and shows pronounced individual differences. Here we review new approaches to study the underlying psychological mechanisms and discuss how they could best be investigated using modern tools from social neuroscience. We list key desiderata for the field, such as validity, specificity, and reproducibility, and link them to specific recommendations for the future. We also discuss new computational modeling approaches, and the application to psychopathology

The social neuroscience of mentalizing: challenges and recommendations

Our ability to understand and think about the mental states of other people is referred to as “mentalizing” or “theory of mind”. It features prominently in all social behavior, is essential for maintaining relationships, and shows pronounced individual differences. Here we review new approaches to study the underlying psychological mechanisms and discuss how they could best be investigated using modern tools from social neuroscience. We list key desiderata for the field, such as validity, specificity, and reproducibility, and link them to specific recommendations for the future. We also discuss new computational modeling approaches, and the application to psychopathology

The neural architecture of emotional intelligence.

Emotional Intelligence (EI) is a nebulous concept that permeates daily interpersonal communication. Despite prolific research into its benefits, EI subjective measurement is difficult, contributing to an enigmatic definition of its core constructs. However, neuroimaging research probing socioaffective brain mechanisms underlying putative EI constructs can add an objective perspective to existing models, thereby illuminating the nature of EI. Therefore, the primary aim of this dissertation is to identify brain networks underlying EI and examine how EI arises from the brain’s functional and structural neuroarchitecture. EI is first defined according to behavioral data, which suggests EI is made up of two core constructs: Empathy and Emotion Regulation (ER). The interaction of brain networks underlying Empathy and ER is then investigated using a novel neuroimaging analysis method: dynamic functional connectivity (dynFC). The results suggest efficient communication and (re)configuration between the CEN, DMN, SN underlie both ER and RME task dynamics, and that these temporal patterns relate to trait empathy and ER tendency. Given the demonstrated behavioral and neurobiological relationship between empathy and ER, our second aim is to examine each of these constructs individually through detailed experiments using a variety of neuroimaging methodologies. The dissertation concludes by proposing EI is an ability that arises from the effective, yet flexible communication between brain networks underlying Empathy and ER. The dissertation is divided into five chapters. Chapter I describes the foundational concept of EI as originally described by a variety of psychological figures and the lacuna that exists in terms of its neural correlates. Chapter II presents behavioral data that proposes EI is best predicted by Empathy and ER. Chapter III explores the dynamic relationship between brain networks underlying Empathy and ER, with the aim of elucidating their neurobiological associations, and investigate how such associations may combine to create EI. Chapter IV examines Empathy closely, by probing its neurobiological relationship to interoception and anxiety. Chapter V examines ER closely, by investigating whether gender plays a role in ER, and its neurobiological relationship to hormones. Chapter VI links the general findings from Chapters III, IV and V, and proposes an integrative neurocognitive EI model. The dissertation concludes by providing clinical and non-clinical applications for the model

Atypical reward-driven modulation of mimicry-related neural activity in autism

Autism spectrum disorder (ASD) is characterized by deficits in social functioning and difficulties in forming social bonds. According to the social motivation theory of ASD, people with ASD fail to attend social stimuli because they do not experience them as rewarding, resulting in deficits in social cognition. In neurotypical (NT) individuals, more rewarding faces have been shown to elicit greater spontaneous facial mimicry. This association between reward and mimicry is reduced in people with high autistic traits, suggesting that altered reward processing might explain the deficits in spontaneous facial mimicry observed in individuals with ASD. In a previous study, we observed that learned reward value of a face modulates mimicry-related neural response to it and that this modulation is reduced in people with high autistic traits. Using an identical evaluative conditioning paradigm where neutral faces were conditioned with high and low rewards, we tested the modulating effect of reward value on mimicry-related brain activity in a group of adults with and without ASD. We focused on the activity in a cluster within the inferior frontal gyrus (IFG) identified through an independent meta-analysis of 139 neuroimaging studies of mimicry, in response to passively viewing videos of the conditioned faces. The blood oxygen level dependent (BOLD) response contrast of high- vs. low-reward faces was reduced in participants with ASD compared to NT controls. The extent of reward-driven modulation was negatively correlated with autistic traits across the whole sample. Our results indicate that the mimicry-related brain response is less modulated by learned reward value in individuals with ASD when compared to NT controls. In previous studies, we found in a similar sample that being mimicked by faces was associated with less reward-related brain response in individuals ASD compared to an NT sample, suggesting that the link between reward and mimicry is affected in both directions in ASD. Together, this reduced bidirectional link between reward and mimicry can point to a potential mechanism underlying some of the social cognitive features of ASD

Neural Mechanisms Underlying Social Intelligence and Their Relationship with the Performance of Sales Managers

Identifying the drivers of salespeople’s performance, strategies and moral behavior have been under the scrutiny of marketing scholars for many years. The functioning of the drivers of salespeople’s behaviors rests on processes going on in the minds of salespeople. However, research to date has used methods based only on verbal self-reports. Advances in techniques from neuroscience such as functional Magnetic Resonance Imaging (fMRI) suggest that despite their complexity and relative inaccessibility, mental processes can be measured more directly. Theory of Mind and mirror neurons are two mechanisms that operate at an automatic or reflexive level, and are important drivers of social intelligence. We use fMRI and field studies to investigate how individual differences in de functioning of these social intelligence mechanisms relate to the job performance and ethical orientations of salespeople. In addition, we use fMRI to analyse the psychometric properties of scales. Our results show that when salespeople are presented with social stimuli during fMRI, they display individual differences in the amount of neurological processing in regions that play key roles in social intelligence, and these individual differences show associations with salespeople’s performance, strategy and ethical orientations. Implications for training, selection & recruitment of salespeople are provided. The theoretical contributions relate to the field of Marketing, Social Neuroscience, and Personality

Comparing resting state fMRI de-noising approaches using multi- and single-echo acquisitions

Artifact removal in resting state fMRI (rfMRI) data remains a serious challenge, with even subtle head motion undermining reliability and reproducibility. Here we compared some of the most popular single-echo de-noising methodsÐregression of Motion parameters, White matter and Cerebrospinal fluid signals (MWC method), FMRIB's ICA-based X-noiseifier (FIX) and ICA-based Automatic Removal Of motion Artifacts (ICA-AROMA)Ðwith a multiecho approach (ME-ICA) that exploits the linear dependency of BOLD on the echo time. Data were acquired using a clinical scanner and included 30 young, healthy participants (minimal head motion) and 30 Attention Deficit Hyperactivity Disorder patients (greater head motion). De-noising effectiveness was assessed in terms of data quality after each cleanup procedure, ability to uncouple BOLD signal and motion and preservation of default mode network (DMN) functional connectivity. Most cleaning methods showed a positive impact on data quality. However, based on the investigated metrics, ME-ICA was the most robust. It minimized the impact of motion on FC even for high motion participants and preserved DMN functional connectivity structure. The high-quality results obtained using ME-ICA suggest that using a multi-echo EPI sequence, reliable rfMRI data can be obtained in a clinical setting

Oxytocin enhances basolateral amygdala activation and functional connectivity while processing emotional faces: preliminary findings in autistic versus non-autistic women

Oxytocin is hypothesized to promote social interactions by enhancing the salience of social stimuli. While previous neuroimaging studies have reported that oxytocin enhances amygdala activation to face stimuli in autistic men, effects in autistic women remain unclear. In this study, the influence of intranasal oxytocin on activation and functional connectivity of the basolateral amygdala – the brain’s “salience detector” – while processing emotional faces vs. shapes was tested in 16 autistic and 21 non-autistic women by fMRI in a placebo-controlled, within-subjects, cross-over design. In the placebo condition, minimal activation differences were observed between autistic and non-autistic women. However, significant drug × group interactions were observed for both basolateral amygdala activation and functional connectivity. Oxytocin increased left basolateral amygdala activation among autistic women (35 voxel cluster, MNI coordinates of peak voxel= -22 -10 -28; mean change=+0.079%, t=3.159, ptukey=0.0166), but not non-autistic women (mean change =+0.003%, t=0.153, ptukey=0.999). Furthermore, oxytocin increased functional connectivity of the right basolateral amygdala with brain regions associated with socio-emotional information processing in autistic women, but not non-autistic women, attenuating group differences in the placebo condition. Taken together, these findings extend evidence of oxytocin’s effects on the amygdala to specifically include autistic women and specify the subregion of the effect.TLP was supported by the Autism Research Trust, Cambridge Trust, and Natural Sciences and Engineering Research Council of Canada. MVL was supported by an ERC Starting Grant (ERC-2017-STG; 755816). MCL was supported by a Canadian Institutes of Health Research (CIHR) Sex and Gender Science Chair (GSB 171373), the O’Brien Scholars Program within the Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children, Toronto, the Academic Scholars Award from the Department of Psychiatry, University of Toronto, the CAMH Foundation, and the Ontario Brain Institute. SBC received funding from the Wellcome Trust 214322\Z\18\Z. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. SBC also received funding from the Autism Centre of Excellence, SFARI, the Templeton World Charitable Fund, the MRC, and the National Institute for Health Research (NIHR). Any views expressed are those of the author(s) and not necessarily those of the funder. RB was supported by the MRC UK, Pinsent Darwin Trust and British Academy post-doctoral fellowship

Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women

Oxytocin may influence various human behaviors and the connectivity across subcortical and cortical networks. Previous oxytocin studies are male biased and often constrained by task-based inferences. Here, we investigate the impact of oxytocin on resting-state connectivity between subcortical and cortical networks in women. We collected resting-state functional magnetic resonance imaging (fMRI) data on 26 typically developing women 40 min following intranasal oxytocin administration using a double-blind placebo-controlled crossover design. Independent components analysis (ICA) was applied to examine connectivity between networks. An independent analysis of oxytocin receptor (OXTR) gene expression in human subcortical and cortical areas was carried out to determine plausibility of direct oxytocin effects on OXTR. In women, OXTR was highly expressed in striatal and other subcortical regions, but showed modest expression in cortical areas. Oxytocin increased connectivity between corticostriatal circuitry typically involved in reward, emotion, social communication, language and pain processing. This effect was 1.39 standard deviations above the null effect of no difference between oxytocin and placebo. This oxytocin-related effect on corticostriatal connectivity covaried with autistic traits, such that oxytocin-related increase in connectivity was stronger in individuals with higher autistic traits. In sum, oxytocin strengthened corticostriatal connectivity in women, particularly with cortical networks that are involved in social-communicative, motivational and affective processes. This effect may be important for future work on neurological and psychiatric conditions (for example, autism), particularly through highlighting how oxytocin may operate differently for subsets of individuals.During this research RB was funded by the MRC UK, the Pinsent Darwin Trust and the Cambridge Trust. M-CL is supported by the William Binks Autism Neuroscience Fellowship, Cambridge and the O’Brien Scholars Program within the Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health and The Hospital for Sick Children, Toronto. SB-C is supported by the MRC UK, the Wellcome Trust and the Autism Research Trust. The research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust