Group-level Results Research Articles

Isolating the sources of pipeline-variability in group-level task-fMRI results.

Task‐fMRI researchers have great flexibility as to how they analyze their data, with multiple methodological options to choose from at each stage of the analysis workflow. While the development of tools and techniques has broadened our horizons for comprehending the complexities of the human brain, a growing body of research has highlighted the pitfalls of such methodological plurality. In a recent study, we found that the choice of software package used to run the analysis pipeline can have a considerable impact on the final group‐level results of a task‐fMRI investigation (Bowring et al., 2019, BMN). Here we revisit our work, seeking to identify the stages of the pipeline where the greatest variation between analysis software is induced. We carry out further analyses on the three datasets evaluated in BMN, employing a common processing strategy across parts of the analysis workflow and then utilizing procedures from three software packages (AFNI, FSL, and SPM) across the remaining steps of the pipeline. We use quantitative methods to compare the statistical maps and isolate the main stages of the workflow where the three packages diverge. Across all datasets, we find that variation between the packages' results is largely attributable to a handful of individual analysis stages, and that these sources of variability were heterogeneous across the datasets (e.g., choice of first‐level signal model had the most impact for the balloon analog risk task dataset, while first‐level noise model and group‐level model were more influential for the false belief and antisaccade task datasets, respectively). We also observe areas of the analysis workflow where changing the software package causes minimal differences in the final results, finding that the group‐level results were largely unaffected by which software package was used to model the low‐frequency fMRI drifts.

Group‐guided individual functional parcellation of the hippocampus and application to normal aging

Aging is closely associated with cognitive decline affecting attention, memory and executive functions. The hippocampus is the core brain area for human memory, learning, and cognition processing. To delineate the individual functional patterns of hippocampus is pivotal to reveal the neural basis of aging. In this study, we developed a group‐guided individual parcellation approach based on semisupervised affinity propagation clustering using the resting‐state functional magnetic resonance imaging to identify individual functional subregions of hippocampus and to identify the functional patterns of each subregion during aging. A three‐way group parcellation was yielded and was taken as prior information to guide individual parcellation of hippocampus into head, body, and tail in each subject. The superiority of individual parcellation of hippocampus is validated by higher intraregional functional similarities by compared to group‐level parcellation results. The individual variations of hippocampus were associated with coactivation patterns of three typical functions of hippocampus. Moreover, the individual functional connectivities of hippocampus subregions with predefined target regions could better predict age than group‐level functional connectivities. Our study provides a novel framework for individual brain functional parcellations, which may facilitate the future individual researches for brain cognitions and brain disorders and directing accurate neuromodulation.

Where is the Trouble in Pseudo-empirical Research?

Smedslund (Psychol Inq 2(4):325-338, 1991) has demonstrated that much of the experimental research in psychology is pseudo-empirical-empirically testing what can be determined a priori based on the meanings of everyday psychological terminology. The present article shows how Smedslund's general perspective is consistent with certain aspects of a theoretical model of the narrative form, and how the latter provides a useful lens for making sense of pseudo-empiricism. This raises a paradox: While something along the lines of the narrative element of 'trouble' is required as a premise for research, trouble is not possible in the context of questions of the general relation between everyday psychological concepts. This paradox is resolved by showing how certain methodological and discursive characteristics of research-specifically, the reification and abstraction of psychological terminology, quantification, and the statistical analysis of group-level results function to obscure the absence (and impossibility) of trouble and/or to create the illusion of its presence.

Implicit Visuomotor Adaptation Remains Limited after Several Days of Training.

Learning in sensorimotor adaptation tasks has been viewed as an implicit learning phenomenon. The implicit process affords recalibration of existing motor skills so that the system can adjust to changes in the body or environment without relearning from scratch. However, recent findings suggest that the implicit process is heavily constrained, calling into question its utility in motor learning and the theoretical framework of sensorimotor adaptation paradigms. These inferences have been based mainly on results from single bouts of training, where explicit compensation strategies, such as explicitly re-aiming the intended movement direction, contribute a significant proportion of adaptive learning. It is possible, however, that the implicit process supersedes explicit compensation strategies over repeated practice sessions. We tested this by dissociating the contributions of explicit re-aiming strategies and the implicit process in human participants over five consecutive days of training. Despite a substantially longer duration of training, the implicit process still plateaued at a value far short of complete learning and, as has been observed in previous studies, was inappropriate for a mirror-reversal task. Notably, we find significant between subject differences that call into question traditional interpretation of these group-level results.

Improved normalization of lesioned brains via cohort-specific templates.

In MRI studies, spatial normalization is required to infer results at the group level. In the presence of a brain lesion, such as in stroke patients, the normalization process can be affected by tissue loss, spatial deformations, signal intensity changes, and other stroke sequelae that introduce confounds into the group analysis results. Previously, most neuroimaging studies with lesioned brains have used normalization methods optimized for intact brains, raising potential concerns about the accuracy of the resulting transformations and, in turn, their reported group level results. In this study, we demonstrate the benefits of creating an intermediate, cohort‐specific template in conjunction with diffeomorphism‐based methods to normalize structural MRI images in stroke patients. We show that including this cohort‐specific template improves accuracy compared to standard methods for normalizing lesioned brains. Critically, this method reduces overall differences in normalization accuracy between stroke patients and healthy controls, and may improve the localization and connectivity of BOLD signal in functional neuroimaging data.

The role of race, religion, and partisanship in misperceptions about COVID-19

Concerns about misperceptions among the public are rampant. Yet, little work explores the correlates of misperceptions in varying contexts – that is, how do factors such as group affiliations, media exposure, and lived experiences correlate with the number of misperceptions people hold? We address these questions by investigating misperceptions about COVID-19, focusing on the role of racial/ethnic, religious, and partisan groups. Using a large survey, we find the number of correct beliefs held by individuals far dwarfs the number of misperceptions. When it comes to misperceptions, we find that minorities, those with high levels of religiosity, and those with strong partisan identities – across parties – hold a substantially greater number of misperceptions than those with contrasting group affiliations. Moreover, we show other variables (e.g., social media usage, number of COVID-19 cases in one’s county) do not have such strong relationships with misperceptions, and the group-level results do not reflect acquiescence to believing any information regardless of its truth value. Our results accentuate the importance of studying group-level misperceptions on other scientific and political issues and developing targeted interventions for these groups.

An empirical investigation of the benefit of increasing the temporal resolution of task-evoked fMRI data with multi-band imaging

ObjectiveThere is a tendency for reducing TR in MRI experiments with multi-band imaging. We empirically investigate its benefit for the group-level statistical outcome in task-evoked fMRI.MethodsThree visual fMRI data sets were collected from 17 healthy adult participants. Multi-band acquisition helped vary the TR (2000/1000/410 ms, respectively). Because these data sets capture different temporal aspects of the haemodynamic response (HRF), we tested several HRF models. We computed a composite descriptive statistic, H, from β’s of each first-level model fit and carried it to the group-level analysis. The number of activated voxels and the t value of the group-level analysis as well as a goodness-of-fit measure were used as surrogate markers of data quality for comparison.ResultsIncreasing the temporal sampling rate did not provide a universal improvement in the group-level statistical outcome. Rather, both the voxel-wise and ROI-averaged group-level results varied widely with anatomical location, choice of HRF and the setting of the TR. Correspondingly, the goodness-of-fit of HRFs became worse with increasing the sampling frequency.ConclusionRather than universally increasing the temporal sampling rate in cognitive fMRI experiments, these results advocate the performance of a pilot study for the specific ROIs of interest to identify the appropriate temporal sampling rate for the acquisition and the correspondingly suitable HRF for the analysis of the data.

A Bayesian optimization approach for rapidly mapping residual network function in stroke.

Post-stroke cognitive and linguistic impairments are debilitating conditions, with limited therapeutic options. Domain-general brain networks play an important role in stroke recovery and characterizing their residual function with functional MRI has the potential to yield biomarkers capable of guiding patient-specific rehabilitation. However, this is challenging as such detailed characterization requires testing patients on multitudes of cognitive tasks in the scanner, rendering experimental sessions unfeasibly lengthy. Thus, the current status quo in clinical neuroimaging research involves testing patients on a very limited number of tasks, in the hope that it will reveal a useful neuroimaging biomarker for the whole cohort. Given the great heterogeneity among stroke patients and the volume of possible tasks this approach is unsustainable. Advancing task-based functional MRI biomarker discovery requires a paradigm shift in order to be able to swiftly characterize residual network activity in individual patients using a diverse range of cognitive tasks. Here, we overcome this problem by leveraging neuroadaptive Bayesian optimization, an approach combining real-time functional MRI with machine-learning, by intelligently searching across many tasks, this approach rapidly maps out patient-specific profiles of residual domain-general network function. We used this technique in a cross-sectional study with 11 left-hemispheric stroke patients with chronic aphasia (four female, age ± standard deviation: 59 ± 10.9 years) and 14 healthy, age-matched control subjects (eight female, age ± standard deviation: 55.6 ± 6.8 years). To assess intra-subject reliability of the functional profiles obtained, we conducted two independent runs per subject, for which the algorithm was entirely reinitialized. Our results demonstrate that this technique is both feasible and robust, yielding reliable patient-specific functional profiles. Moreover, we show that group-level results are not representative of patient-specific results. Whereas controls have highly similar profiles, patients show idiosyncratic profiles of network abnormalities that are associated with behavioural performance. In summary, our study highlights the importance of moving beyond traditional ‘one-size-fits-all’ approaches where patients are treated as one group and single tasks are used. Our approach can be extended to diverse brain networks and combined with brain stimulation or other therapeutics, thereby opening new avenues for precision medicine targeting a diverse range of neurological and psychiatric conditions.

Establishing anchor-based minimally important differences for the EORTC QLQ-C30 in glioma patients.

BackgroundMinimally important differences (MIDs) allow interpretation of the clinical relevance of health-related quality of life (HRQOL) results. This study aimed to estimate MIDs for all European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) scales for interpreting group-level results in brain tumor patients.MethodsClinical and HRQOL data from three glioma trials were used. Clinical anchors were selected for each EORTC QLQ-C30 scale, based on correlation (>0.30) and clinical plausibility of association. Changes in both HRQOL and the anchors were calculated, and for each scale and time period, patients were categorized into one of the three clinical change groups: deteriorated by one anchor category, no change, or improved by one anchor category. Mean change method and linear regression were applied to estimate MIDs for interpreting within-group change and between-group differences in change over time, respectively. Distribution-based methods were applied to generate supportive evidence.ResultsA total of 1687 patients were enrolled in the three trials. The retained anchors were performance status and eight Common Terminology Criteria for Adverse Events (CTCAE) scales. MIDs for interpreting within-group change ranged from 4 to 12 points for improvement and −4 to −14 points for deterioration. MIDs for between-group difference in change ranged from 4 to 9 for improvement and −4 to −16 for deterioration. Most anchor-based MIDs were closest to the 0.3 SD distribution-based estimates (range: 3-10).ConclusionsMIDs for the EORTC QLQ-C30 scales generally ranged between 4 and 11 points for both within-group mean change and between-group mean difference in change. These results can be used to interpret QLQ-C30 results from glioma trials.

Effects of Presentation Level on Spatial Hearing With and Without Bone-Conduction Amplification in Congenital Unilateral Aural Atresia.

This study assessed the effect of ipsilateral bone-conduction amplification on spatial hearing abilities in subjects with congenital unilateral aural atresia (CUAA). Twelve patients with unilateral conductive hearing loss secondary to CUAA and normal hearing in the contralateral ear were tested. Most (75%) had limited experience with a bone-conduction hearing aid (BCHA). Performance was evaluated with and without a BCHA fitted acutely on a softband. Spatial hearing abilities were evaluated in two paradigms. Spatial release from masking was evaluated by comparing masked sentence recognition with a target and two speech maskers either colocated at 0 degree or with the maskers separated at +90 degrees and -90 degrees. Sound source localization was evaluated in a 180 degrees arc of loudspeakers on the horizontal plane. Performance was evaluated at 50 and 75 dB SPL, and results were compared for patients tested with and without a BCHA. Group level results indicate similar spatial release from masking in the aided and unaided conditions at both presentation levels. Localization at 50 dB SPL was similar aided and unaided, but at 75 dB SPL the root mean square error was lower unaided than aided (17.2 degrees vs 41.3 degrees; p = 0.010). Use of a BCHA in patients with CUAA may interfere with auditory cues required for sound source localization when the signal level is intense enough to overcome the patient's conductive hearing loss. These findings have potential clinical implications in fitting of BCHAs to support optimal spatial hearing in patients with CUAA.

Affect and Personality: Ramifications of Modeling (Non-)Directionality in Dynamic Network Models.

The use of dynamic network models has grown in recent years. These models allow researchers to capture both lagged and contemporaneous effects in longitudinal data typically as variations, reformulations, or extensions of the standard vector autoregressive (VAR) models. To date, many of these dynamic networks have not been explicitly compared to one another. We compare three popular dynamic network approaches-GIMME, uSEM, and LASSO gVAR-in terms of their differences in modeling assumptions, estimation procedures, statistical properties based on a Monte Carlo simulation, and implications for affect and personality researchers. We found that all three approaches dynamic networks provided yielded group-level empirical results in partial support of affect and personality theories. However, individual-level results revealed a great deal of heterogeneity across approaches and participants. Reasons for discrepancies are discussed alongside these approaches' respective strengths and limitations.

Mapping language function with task-based vs. resting-state functional MRI.

BackgroundUse of functional MRI (fMRI) in pre-surgical planning is a non-invasive method for pre-operative functional mapping for patients with brain tumors, especially tumors located near eloquent cortex. Currently, this practice predominantly involves task-based fMRI (T-fMRI). Resting state fMRI (RS-fMRI) offers an alternative with several methodological advantages. Here, we compare group-level analyses of RS-fMRI vs. T-fMRI as methods for language localization.PurposeTo contrast RS-fMRI vs. T-fMRI as techniques for localization of language function.MethodsWe analyzed data obtained in 35 patients who had both T-fMRI and RS-fMRI scans during the course of pre-surgical evaluation. The RS-fMRI data were analyzed using a previously trained resting-state network classifier. The T-fMRI data were analyzed using conventional techniques. Group-level results obtained by both methods were evaluated in terms of two outcome measures: (1) inter-subject variability of response magnitude and (2) sensitivity/specificity analysis of response topography, taking as ground truth previously reported maps of the language system based on intraoperative cortical mapping as well as meta-analytic maps of language task fMRI responses.ResultsBoth fMRI methods localized major components of the language system (areas of Broca and Wernicke) although not with equal inter-subject consistency. Word-stem completion T-fMRI strongly activated Broca's area but also several task-general areas not specific to language. RS-fMRI provided a more specific representation of the language system.ConclusionWe demonstrate several advantages of classifier-based mapping of language representation in the brain. Language T-fMRI activated task-general (i.e., not language-specific) functional systems in addition to areas of Broca and Wernicke. In contrast, classifier-based analysis of RS-fMRI data generated maps confined to language-specific regions of the brain.

Modulatory difference due to injury pattern in the moderate-TBI brain: Effective connectivity of working memory from preliminary findings

Traumatic brain injury could cause cognitive deficits due to brain network disruption. The present study examined the effective connectivity of working memory in a group of moderate-TBI participants and making comparison with healthy controls. Group-level results of the n-back task with four levels of cognitive load (0-, 1-, 2-, and 3-back) identified activation in regions that corresponded with past literature of working memory, including the bilateral inferior occipital gyri, superior parietal lobules, and superior frontal gyri that were specified as regions of interest for subsequent dynamic causal model specification. The modulatory inputs were differentially defined in six models for every participant. Bayesian model selection directed to different winning models between the groups based on injury patterns. The moderate-TBI group with left hemisphere injury favoured connectivity involving a bottom-up left-to-right modulation, whereas the healthy group and TBI group with injuries involving both hemispheres preferred the connectivity model with a bottom-up modulation that is bilateral and bidirectional. The left-lateralized modulatory pattern reported in the moderate-TBI participants implies the role of the left hemisphere in attending to cognitively demanding tasks, especially in individuals with a disrupted neural network. Future studies could work on expanding the connectivity analyses based on the current finding.

Predictive Analytics and the Return of "Research" Information to Participants.

The World Health Organization (WHO) estimates older adults aged 60+ will double by 2050 with 80% living in low to moderate income countries. As remote research studies supported by digital devices increase separation between researchers and participants, it is important to maintain participant trust. Research participants have expressed an interest in accessing both group and individual level results, which are not readily available. To bridge this gap, we engaged residents of a local continuing care senior housing community (CCSHC) to co-design documents used to convey information about study results. The process informed the refinement of informational materials for communicating scientific research that the CCSHC community considers accessible and meaningful.

Fronto-parietal engagement in response inhibition is inversely scaled with attention-deficit/hyperactivity disorder symptom severity.

Impaired response inhibition is one of the most consistent findings in attention deficit hyperactivity disorder (ADHD). However, the underlying brain mechanisms are not clear. This study aimed to underpin atypical inhibition-related brain activation and connectivity patterns in ADHD using a novel Go/No-go task design, and to determine its association with clinical symptoms of the disorder. Forty-eight adults with ADHD performed a Go/No-go task in which target frequency was manipulated during functional MRI. Specific inhibition-related brain activation was correlated with ADHD symptom severity, to assess the relationship of individual differences in engagement of inhibition-related brain circuits with the magnitude of every-day functioning impairments. Finally, generalized psychophysical interaction analyses were carried out to examine whether not only engagement but also functional connectivity between regions implicated in response inhibition is related to symptom severity. We found no evidence for the expected parietal modulation by increased demand for inhibition at the group-level results. However, this lack of modulation was mediated by individual differences in ADHD symptom severity - increased engagement of the intraparietal sulcus (IPS) in inhibition-demanding events was evident in individuals with less severe symptoms but dissipated with increase in symptomatology. Similarly, functional connectivity between the IPS and the right inferior frontal gyrus (rIFG) was elevated under high inhibitory demand conditions, but this effect diminished with increased symptom severity. The results highlight the importance of IPS engagement in response inhibition and suggest that IPS modulation may be driven by top-down control from the IFG. Moreover, the current findings force the point of treating ADHD as a continuum whereby brain correlates are scaled with severity of the disorder, and point to the potential use of individual differences in the modulation of IPS activation and connectivity as a neuromarker of ADHD.

A nation-wide initiative for brain imaging and clinical phenotype data federation in Swiss university memory centres.

The goal of our nation-wide initiative is to provide clinicians intuitive and robust tools for accurate diagnosis, therapy monitoring and prognosis of cognitive decline that is based on large-scale multidomain data. We describe a federation framework that allows for statistical analysis of aggregated brain imaging and clinical phenotyping data across memory clinics in Switzerland. The adaptation and deployment of readily available data capturing and federation modules is paralleled by developments in ontology, quality and regulatory control of brain imaging data. Our initiative incentivizes data sharing through the common resource in a way that provides individual researcher with access to large-scale data that surpasses the data acquisition capacity of a single centre. Clinicians benefit from fine-grained epidemiological characterization of own data compared with the rest additional to intuitive tools allowing for computer-based diagnosis of dementia. Finally, our concept aims at closing the loop between group-level results based on aggregate data and individual diagnosis by providing disease models, that is, classifiers for neurocognitive disorders that will enable the computer-based diagnosis of individual patients. The obtained results will inform recommendations on best clinical practice in all relevant fields focusing on standardization and interoperability of acquired data, privacy protection framework and ethical consideration in the context of evolutive pathology.

Subject-specific responses to an adaptive ankle prosthesis during incline walking

Individuals with lower-limb amputation often have difficulty walking on slopes, in part due to limitations of conventional prosthetic feet. Conventional prostheses have fixed ankle set-point angles and cannot fully replicate able-bodied ankle dynamics. Microprocessor-controlled ankles have been developed to help overcome these limitations. The objective of this study was to characterize how the slope adaptation feature of a microprocessor-controlled ankle affected individual prosthesis user gait biomechanics during sloped walking. Previous studies on similar microprocessor-controlled ankles have focused on group-level results (inter-subject mean), but did not report individual subject results. Our study builds upon prior work and provides new insight by presenting subject-specific results and investigating to what extent individual responses agree with the group-level results. We performed gait analysis on seven individuals with unilateral transtibial amputation while they walked on a 7.5° incline with a recently redesigned microprocessor-controlled ankle that adjusts ankle set-point angle to the slope. We computed gait kinematics and kinetics, and compared how users walked with vs. without this set-point adjustment. The microprocessor-controlled ankle increased minimum toe clearance for all subjects. Despite the microprocessor-controlled ankle behaving similarly for each user, we observed marked differences in individual responses. For instance, two users switched from a forefoot landing pattern with the microprocessor-controlled ankle locked at neutral angle to rearfoot landing when the microprocessor-controlled ankle adapted to the slope, while two maintained a forefoot and three maintained a rearfoot landing pattern across conditions. Changes in knee angle and moment were also subject-specific. Individual user responses were often not well represented by inter-subject mean. Although the prevailing experimental paradigm in prosthetic gait analysis studies is to focus on group-level analysis, our findings call attention to the high inter-subject variability which may necessitate alternative experimental approaches to assess prosthetic interventions.

The Influence of Daily Stress on Sedentary Behavior: Group and Person (N of 1) Level Results of a 1-Year Observational Study.

The purpose of this study, which used mobile technologies to continuously collect data for 1 year, was to examine the association of psychological stress with objectively measured sedentary behavior in adults at both the group (e.g., nomothetic approach) and individual (e.g., idiographic approach) level. Data were collected in an observational study of healthy adults (n = 79) residing in the New York City metro area who were studied for 365 days from 2014 to 2015. Sedentary behavior was objectively measured via accelerometry. A smartphone-based electronic diary was used to assess level of stress ("Overall, how stressful was your day?" 0-10 scale) and sources of stress. The end-of-day stress rating was not associated with total sedentary time (B = -1.34, p = .767) at the group level. When specific sources of stress were evaluated at the group level, argument-related stress was associated with increased sedentariness, whereas running late- and work-related stress were associated with decreased sedentariness. There was a substantial degree of interindividual variability in the relationship of stress with sedentary behavior. Both the level and sources of stress were associated with increased sedentariness for some, decreased sedentariness for others, and had no effect for many (within-person variance p < .001). These findings suggest that the influence of stress on sedentary behavior varies by source of stress and from person to person. A precision medicine approach may be warranted to target reductions in sedentary time, although further studies are needed to confirm the observed findings in light of study limitations including a small sample size and enrollment of participants from a single, urban metropolitan area.

Clinical subcategorization of minimally conscious state according to resting functional connectivity.

Patients in minimally conscious state (MCS) have been subcategorized in MCS plus and MCS minus, based on command-following, intelligible verbalization or intentional communication. We here aimed to better characterize the functional neuroanatomy of MCS based on this clinical subcategorization by means of resting state functional magnetic resonance imaging (fMRI). Resting state fMRI was acquired in 292 MCS patients and a seed-based analysis was conducted on a convenience sample of 10 MCS plus patients, 9 MCS minus patients and 35 healthy subjects. We investigated the left and right frontoparietal networks (FPN), auditory network, default mode network (DMN), thalamocortical connectivity and DMN between-network anticorrelations. We also employed an analysis based on regions of interest (ROI) to examine interhemispheric connectivity and investigated intergroup differences in gray/white matter volume by means of voxel-based morphometry. We found a higher connectivity in MCS plus as compared to MCS minus in the left FPN, specifically between the left dorso-lateral prefrontal cortex and left temporo-occipital fusiform cortex. No differences between patient groups were observed in the auditory network, right FPN, DMN, thalamocortical and interhemispheric connectivity, between-network anticorrelations and gray/white matter volume. Our preliminary group-level results suggest that the clinical subcategorization of MCS may involve functional connectivity differences in a language-related executive control network. MCS plus and minus patients are seemingly not differentiated by networks associated to auditory processing, perception of surroundings and internal awareness/self-mentation, nor by interhemispheric integration and structural brain damage.

Reward circuitry activation reflects social preferences in the face of cognitive effort

Research at the intersection of social neuroscience and cognitive effort is an interesting new area for exploration. There is great potential to broaden our understanding of how social context and cognitive effort processes, currently addressed in disparate literatures, interact with one another. In this paper, we briefly review the literature on cognitive effort, focusing on effort-linked valuation and the gap in the literature regarding cognitive effort in the social domain. Next, we present a study designed to explore valuation processes linked to cognitive effort within the social context of an inequality manipulation. More specifically, we created monetary inequality among the participant (SELF, endowed with $50) and two confederates: one also endowed with $50 (OTHER HIGH) and another with only $5 (OTHER LOW). We then scanned participants using fMRI as they attempted to earn bonus payments for themselves and others through a cognitively effortful feedback-based learning task. Positive feedback produced significantly greater activation than negative feedback in key valuation regions, the ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC), both when participants were performing the task on their own behalf and when earning rewards for others. While reward-related activity in the VS was exaggerated for SELF compared to OTHER HIGH for both positive and negative feedback, activity in the vmPFC did not distinguish between recipients in the group-level results. Furthermore, participants naturally fell into two groups: those most engaged when playing for themselves and those who reported engagement for others. While Self-Engaged participants showed differences between the SELF and both OTHER conditions in the VS and vmPFC, Other-Engaged participants only showed an attenuated response to negative feedback for OTHER HIGH compared to SELF in the VS and no differences between recipient conditions in the vmPFC. Together, this work shows the importance of individual differences and the fragility of advantageous inequality aversion in the face of cognitive effort, highlighting the need to study cognitive effort in the social domain.