fMRI Investigation Research Articles

A 7T fMRI investigation of hand and tool areas in the lateral and ventral occipitotemporal cortex.

Previous studies demonstrated the existence of hand and tool areas in lateral and ventral occipitotemporal cortex (OTC), as well as an overlap between them. We reinvestigated this organization using 7T fMRI, benefiting from a higher signal-to-noise ratio than 3T. This enabled us to include a wider array of categories to achieve a more holistic perspective, and to omit certain spatial preprocessing steps. Despite these improvements, univariate analysis confirmed the existence of hand-tool overlap across OTC, which is striking given the omission of the spatial preprocessing steps that can influence overlap. There was significantly more overlap between hands and tools, compared to other overlap types in the left hemisphere of OTC. The overlap was also larger in the left lateral OTC as compared to the right lateral OTC. We found in all hand areas a differentiation between tools and other types of objects, although they still responded more to bodies than to tools. Regarding the tool areas, we observed a differentiation between hands and other categories such as faces and non-tool objects. Left hemisphere tool areas also differentiated between hands and bodies. When excluding the overlapping voxels from the hand and tool areas, they still showed a significant response to tools or hands (compared to objects or faces) respectively. Multi-voxel pattern analysis indicated that neural representations in the hand areas showed greater similarity between hands and tools than between hands and other objects. In the tool areas, the neural representations between tools and hands and between tools and other type of objects were all equally similar. To summarize, capitalizing on the benefits of 7T fMRI, we further substantiate the evidence in favor of hand-tool overlap in several regions of occipitotemporal cortex.

Monorhinal and Birhinal Odor Processing in Humans: an fMRI investigation.

The olfactory nerve, also known as cranial nerve I, is known to have exclusive ipsilateral projections to primary olfactory cortical structures. However, the lateralization of olfactory processes is known to depend on the task and nature of stimuli. It still remains unclear whether olfactory system projections in humans also correspond to functional pathways during olfactory tasks without any trigeminal, perceptual or cognitive-motor components. Twenty young healthy subjects with a normal sense of smell took part in an olfactory functional magnetic resonance imaging (fMRI) study. We used two types of nostril specific stimulation, passive (no sniffing) and active (with sniffing), with phenyl ethyl alcohol, a pure olfactory stimulant, to investigate fMRI activity patterns in primary and secondary olfactory-related brain structures. Irrespective of the stimulated nostril and the type of stimulation, we detected symmetrical activity in primary and secondary olfactory-related brain structures such as the primary olfactory cortex, entorhinal cortex, and orbitofrontal cortex. In the absence of perceptual or cognitive-motor task demands, the perception of monorhinally presented pure odors is processed bilaterally in the brain.

The "limbic network," comprising orbitofrontal and anterior temporal cortex, is part of an extended default network: Evidence from multi-echo fMRI.

Resting-state functional magnetic resonance imaging (fMRI) investigations have provided a view of the default network (DN) as composed of a specific set of frontal, parietal, and temporal cortical regions. This spatial topography is typically defined with reference to an influential network parcellation scheme that designated the DN as one of seven large-scale networks (Yeo et al., 2011). However, the precise functional organization of the DN is still under debate, with studies arguing for varying subnetwork configurations and the inclusion of subcortical regions. In this vein, the so-called limbic network-defined as a distinct large-scale network comprising the bilateral temporal poles, ventral anterior temporal lobes, and orbitofrontal cortex-is of particular interest. A large multi-modal and multi-species literature on the anatomical, functional, and cognitive properties of these regions suggests a close relationship to the DN. Notably, these regions have poor signal quality with conventional fMRI acquisition, likely obscuring their network affiliation in most studies. Here, we leverage a multi-echo fMRI dataset with high temporal signal-to-noise and whole-brain coverage, including orbitofrontal and anterior temporal regions, to examine the large-scale network resting-state functional connectivity of these regions and assess their associations with the DN. Consistent with our hypotheses, our results support the inclusion of the majority of the orbitofrontal and anterior temporal cortex as part of the DN and reveal significant heterogeneity in their functional connectivity. We observed that left-lateralized regions within the temporal poles and ventral anterior temporal lobes, as well as medial orbitofrontal regions, exhibited the greatest resting-state functional connectivity with the DN, with heterogeneity across DN subnetworks. Overall, our findings suggest that, rather than being a functionally distinct network, the orbitofrontal and anterior temporal regions comprise part of a larger, extended default network.

The neural correlates of hearing loss-related distress: A functional magnetic resonance imaging study

Abstract Background: The objective of this study is to investigate the brain mechanisms that contribute to the experience of emotional distress related to hearing loss (HL), using functional magnetic resonance imaging (fMRI). Materials and Methods: Two groups, matched in age, and gender were recruited: one group with bilateral high-frequency HL (n = 15) and a control group with normal hearing (NH, n = 15). During the task-based phase of the experiment, participants were given instructions to rate emotional stimuli from the International Emotional Digital Sounds (IADS) database and classify them as either pleasant, unpleasant, or neutral. Results: The findings from both the fMRI investigations indicate that individuals with NH and those with HL have contrasting emotional reactions. More precisely, in the task-oriented investigation, we observed a delayed reaction to emotional sounds, but not to neutral sounds, in the group with HL in comparison to the NH group. The brain activity patterns of the NH group showed increased activation in limbic, frontal, and auditory areas, while processing emotional stimuli. Conclusions: Our results elucidate the brain mechanisms behind emotional discomfort caused by HL, paving the way for future research on therapeutic interventions to mitigate the psychological impact of HL.

Functional connectivity changes in meditators and novices during yoga nidra practice

Yoga nidra (YN) practice aims to induce a deeply relaxed state akin to sleep while maintaining heightened awareness. Despite the growing interest in its clinical applications, a comprehensive understanding of the underlying neural correlates of the practice of YN remains largely unexplored. In this fMRI investigation, we aim to discover the differences between wakeful resting states and states attained during YN practice. The study included individuals experienced in meditation and/or yogic practices, referred to as ‘meditators’ (n = 30), and novice controls (n = 31). The GLM analysis, based on audio instructions, demonstrated activation related to auditory cues without concurrent default mode network (DMN) deactivation. DMN seed based functional connectivity (FC) analysis revealed significant reductions in connectivity among meditators during YN as compared to controls. We did not find differences between the two groups during the pre and post resting state scans. Moreover, when DMN-FC was compared between the YN state and resting state, meditators showed distinct decoupling, whereas controls showed increased DMN-FC. Finally, participants exhibit a remarkable correlation between reduced DMN connectivity during YN and self-reported hours of cumulative meditation and yoga practice. Together, these results suggest a unique neural modulation of the DMN in meditators during YN which results in being restful yet aware, aligned with their subjective experience of the practice. The study deepens our understanding of the neural mechanisms of YN, revealing distinct DMN connectivity decoupling in meditators and its relationship with meditation and yoga experience. These findings have interdisciplinary implications for neuroscience, psychology, and yogic disciplines.

328. An fMRI Investigation of the Brain Circuits Involved in Religious Obsessive-Compulsive Disorder

328. An fMRI Investigation of the Brain Circuits Involved in Religious Obsessive-Compulsive Disorder

Early-Life Adversities Are Associated With Lower Expected Value Signaling in the Adult Brain

BackgroundEarly adverse experiences are assumed to affect fundamental processes of reward learning and decision making. However, computational neuroimaging studies investigating these circuits in the context of adversity are sparse and limited to studies conducted in adolescent samples, leaving the long-term effects unexplored. MethodsUsing data from a longitudinal birth cohort study (n = 156; 87 female), we investigated associations between adversities and computational markers of reward learning (i.e., expected value, prediction errors). At age 33 years, all participants completed a functional magnetic resonance imaging–based passive avoidance task. Psychopathology measures were collected at the time of functional magnetic resonance imaging investigation and during the COVID-19 pandemic. We applied a principal component analysis to capture common variations across 7 adversity measures. The resulting adversity factors (factor 1: postnatal psychosocial adversities and prenatal maternal smoking; factor 2: prenatal maternal stress and obstetric adversity; factor 3: lower maternal stimulation) were linked with psychopathology and neural responses in the core reward network using multiple regression analysis. ResultsWe found that the adversity dimension primarily informed by lower maternal stimulation was linked to lower expected value representation in the right putamen, right nucleus accumbens, and anterior cingulate cortex. Expected value encoding in the right nucleus accumbens further mediated the relationship between this adversity dimension and psychopathology and predicted higher withdrawn symptoms during the COVID-19 pandemic. ConclusionsOur results suggested that early adverse experiences in caregiver context might have a long-term disruptive effect on reward learning in reward-related brain regions, which can be associated with suboptimal decision making and thereby may increase the vulnerability of developing psychopathology.

Functional changes in brain organization after de novo audiomotor learning: An fMRI investigation

To learn to talk or play a musical instrument, the brain must acquire a “mapping” of the relationship between movements and their acoustical consequences. However, it remains unclear how this type of audiomotor learning alters the functional organization of the brain, and what neural networks support consolidation of that learning. This study used functional magnetic resonance imaging (fMRI) to measure functional changes in brain organization as a result of audiomotor learning from scratch. We used a novel paradigm in which subjects learned to move a joystick in different directions in a 2D workspace to achieve speech-like acoustical targets. At the end of each movement, subjects received auditory feedback corresponding to the sound associated with the direction that they moved in. Before and after training, we used resting-state fMRI to assess learning-related changes in functional connectivity. Behavioral results show that, over the course of practice with feedback, subjects gradually produced joystick movements with fewer errors, indicative of learning. Furthermore, some of this learning was maintained to the second day, indicating subjects started forming durable performance gains. Analyses of the fMRI data are currently underway and aimed at localizing changes in neural activity that scale with behavioral indices of audiomotor learning.

Brain functional connectivity patterns associated with symptoms of vestibular migraine.

Several functional magnetic resonance imaging (fMRI) investigations of patients with vestibular migraine (VM) have revealed abnormal functionality in different networks, indicating that VM is related to alterations in brain function. We sought to investigate the resting-state functional connectivity (FC) patterns during the interictal period in VM by combining data-driven voxel-wise degree centrality (DC) calculations and seed-based FC analyses, and thereby determine the associations between cerebral function and clinical symptoms. Thirty-eight patients with VM and 33 matched normal controls were recruited. DC was calculated and compared between the groups, and the FC of locations showing DC alterations was further tested using a seed-based technique. The participants' clinical indicators were correlated with the DC and FC values of the brain areas. In contrast to the control group, the VM group showed considerably lower DC values in the bilateral medial prefrontal cortex (mPFC) and significantly higher DC values in the right occipital lobe. In the seed-based FC analyses, patients with VM demonstrated fewer connections of the bilateral mPFC with the bilateral posterior cingulate cortex, right parahippocampus, right cerebellar posterior lobe, bilateral cuneus, and left precuneus. In addition, clinical data from patients, such as pain intensity, episode frequency, and the Dizziness Handicap Inventory score, were negatively related to these FC and DC impairments. Our findings showed changes in the default mode network and visual cortex in patients with VM, providing further insights into the complexity of the mechanisms underlying VM.

An fMRI Investigation of the Neurocognitive Processing of Measures and Strategic Objectives

A central feature of most organizations is the use of measures to represent key elements of performance across multiple strategic objectives. Prior research demonstrates a tendency for individuals to treat these measures as though they are the higher order strategic objectives the measures were intended to represent as opposed to imperfect representations of those strategic objectives—a phenomenon labeled “surrogation.” We employ an experiment to further understand this phenomenon. In this study, we capture neural activation when processing measures and when processing strategic objectives. We find that, in regions of the brain with greater (less) activation for concrete versus abstract words, brain activation is greater (less) when processing measure phrases versus when processing strategy phrases. We further find evidence that greater brain activity and longer response times are associated with less surrogation. This affirms the notion that increased cognitive involvement can reduce surrogation. This paper was accepted by Ranjani Krishnan, accounting. Funding: This work was supported by Auburn University, Brigham Young University, Utah Valley University, and an IMA Research Foundation grant from the Institute of Management Accountants. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2022.01405 .

Disentangling the neurological basis of chronic ocular pain using clinical, self-report, and brain imaging data: use of K-means clustering to explore patient phenotypes.

The factors that mediate the expression of ocular pain and the mechanisms that promote chronic ocular pain symptoms are poorly understood. Central nervous system involvement has been postulated based on observations of pain out of proportion to nociceptive stimuli in some individuals. This investigation focused on understanding functional connectivity between brain regions implicated in chronic pain in persons reporting ocular pain symptoms. We recruited a total of 53 persons divided into two cohorts: persons who reported no ocular pain, and persons who reported chronic ocular pain, irrespective of ocular surface findings. We performed a resting state fMRI investigation that was focused on subcortical brain structures including the trigeminal nucleus and performed a brief battery of ophthalmological examinations. Persons in the pain cohort reported higher levels of pain symptoms relating to neuropathic pain and ocular surface disease, as well as more abnormal tear metrics (stability and tear production). Functional connectivity analysis between groups evinced multiple connections exemplifying both increases and decreases in connectivity including regions such as the trigeminal nucleus, amygdala, and sub-regions of the thalamus. Exploratory analysis of the pain cohort integrating clinical and brain function metrics highlighted subpopulations that showed unique phenotypes providing insight into pain mechanisms. Study findings support centralized involvement in those reporting ocular-based pain and allude to mechanisms through which pain treatment services may be directed in future research.

Establishing the Roles of the Dorsal and Ventral Striatum in Humor Comprehension and Appreciation with fMRI.

Humor comprehension (i.e., getting a joke) and humor appreciation (i.e., enjoying a joke) are distinct, cognitively complex processes. Functional magnetic resonance imaging (fMRI) investigations have identified several key cortical regions but have overlooked subcortical structures that have theoretical importance in humor processing. The dorsal striatum (DS) contributes to working memory, ambiguity processing, and cognitive flexibility, cognitive functions that are required to accurately recognize humorous stimuli. The ventral striatum (VS) is critical in reward processing and enjoyment. We hypothesized that the DS and VS play important roles in humor comprehension and appreciation, respectively. We investigated the engagement of these regions in these distinct processes using fMRI. Twenty-six healthy young male and female human adults completed two humor-elicitation tasks during a 3 tesla fMRI scan consisting of a traditional behavior-based joke task and a naturalistic audiovisual sitcom paradigm (i.e., Seinfeld viewing task). Across both humor-elicitation methods, whole-brain analyses revealed cortical activation in the inferior frontal gyrus, the middle frontal gyrus, and the middle temporal gyrus for humor comprehension, and the temporal cortex for humor appreciation. Additionally, with region of interest analyses, we specifically examined whether DS and VS activation correlated with these processes. Across both tasks, we demonstrated that humor comprehension implicates both the DS and the VS, whereas humor appreciation only engages the VS. These results establish the role of the DS in humor comprehension, which has been previously overlooked, and emphasize the role of the VS in humor processing more generally.SIGNIFICANCE STATEMENT Humorous stimuli are processed by the brain in at least two distinct stages. First, humor comprehension involves understanding humorous intent through cognitive and problem-solving mechanisms. Second, humor appreciation involves enjoyment, mirth, and laughter in response to a joke. The roles of smaller subcortical brain regions in humor processing, such as the DS and VS, have been overlooked in previous investigations. However, these regions are involved in functions that support humor comprehension (e.g., working memory ambiguity resolution, and cognitive flexibility) and humor appreciation (e.g., reward processing, pleasure, and enjoyment). In this study, we used neuroimaging to demonstrate that the DS and VS play important roles in humor comprehension and appreciation, respectively, across two different humor-elicitation tasks.

Major Depression and the Perception of Affective Instrumental and Expressive Gestures: An fMRI Investigation

Major depressive disorder (MDD) is associated with biased perception of human movement. Gesture is important for communication and in this study we investigated neural correlates of gesture perception in MDD. We hypothesised different neural activity between individuals with MDD and typical individuals when viewing instrumental and expressive gestures that were negatively or positively valenced. Differences were expected in brain areas associated with gesture perception, including superior temporal, frontal, and emotion processing regions. We recruited 12 individuals with MDD and 12 typical controls matched on age, gender, and handedness. They viewed gestures displayed by stick figures while functional magnetic resonance imaging (fMRI) was performed. Results of a random effects three-way mixed ANOVA indicated that individuals with MDD had greater activity in the right claustrum compared to controls, regardless of gesture type or valence. Additionally, we observed main effects of gesture type and valence, regardless of group. Perceiving instrumental compared to expressive gestures was associated with greater activity in the left cuneus and left superior temporal gyrus, while perceiving negative compared to positive gestures was associated with greater activity in the right precuneus and right lingual gyrus. We also observed a two-way interaction between gesture type and valence in various brain regions.

Blame and Praise cross-culturally: An fMRI investigation into causal attribution and moral judgment

People from independent cultures are more likely to causally explain others’ behaviors by their disposition [vs. situation] compared to those from interdependent cultures. However, few studies have directly examined how these differences in attribution shape individuals’ moral judgment, nor the underlying neural mechanisms of this process. Aiming to address these questions, in the scanner, participants rated the blameworthiness or praiseworthiness of protagonists who did either a negative or positive behavior, respectively. These behaviors were pretested and found to be perceived as dispositionally or situationally caused to different extents on average. Regardless of their self-construal, participants showed enhanced dorsomedial prefrontal cortex (dmPFC) activity in response to the behaviors that were evaluated as more situationally caused on average. Importantly, relatively independent participants reduced their blame for the behaviors that they showed greater dmPFC activity to. Relatively interdependent participants reduced blame for the behaviors that they themselves inferred more situational causes for, but dmPFC activity did not explain their blame. These findings suggest that while dmPFC might support relatively independent participants’ effortful consideration of situational contributors to a behavior to make moral judgments, relatively interdependent participants might engage in this process automatically and relied less on dmPFC recruitment.

B - 12 fMRI Investigation of Socio-Moral Agency in Children and Adolescents.

This study investigated the neural substrate of agency in social judgments of children and adolescents. The main hypothesis was that a network of proposed "social brain" structures (the medial prefrontal cortex (mPFC), medial precuneus (mPc), temporal pole (TP), and temporoparietal junction (TPJ) would be recruited when comparing self vs. other agents in socio-moral situations. We suspected that such judgments would incur self/other referential and social cognitive processing and lead to overlapping but also distinctive neural activations in the social brain network. The developmental sample was 9-17-year-old participants (11 male, 8 female) with no medical, neurological or psychiatric history, learning disability, or medication usage. Neuropsychological functions, academic achievement, and social-emotional development were normal. Participants read brief scripts in a high field magnet and provided judgments of whether the social actions were right or wrong. Scripts were balanced for right vs. wrong behaviors, comparing the participant's own actions vs the actions of others as well as a non-social baseline condition. Data were analyzed in Matlab. Results revealed recruitment of mPFC, mPc, TP, and TPJ throughout development, linking agency to other mentalizing processes. There was overlapping recruitment of mPFC, mPc and left TPJ across the 2 conditions. Right TPJ activated only during the self-agency condition; left TP activated only during the other-agency condition. Findings support a specific network of mPFC, mPc, TP and TPJ regions associated with mediation of social agency, similar to adults, which is likely an important neural substrate for maturation of self-regulation and social cognition.

Neural Correlates of Pain-Autonomic Coupling in Patients With Complex Regional Pain Syndrome Treated by Repetitive Transcranial Magnetic Stimulation of the Motor Cortex

ObjectivesComplex regional pain syndrome (CRPS) is a chronic pain condition involving autonomic dysregulation. In this study, we report the results of an ancillary study to a larger clinical trial investigating the treatment of CRPS by neuromodulation. This ancillary study, based on functional magnetic resonance imaging (fMRI), evaluated the neural correlates of pain in patients with CRPS in relation to the sympathetic nervous system and for its potential relief after repetitive transcranial magnetic stimulation of the motor cortex. Materials and MethodsEleven patients with CRPS at one limb (six women, five men, aged 52.0 ± 9.6 years) were assessed before and one month after the end of a five-month repetitive transcranial magnetic stimulation (rTMS) therapy targeting the motor cortex contralateral to the painful limb, by means of electrochemical skin conductance (ESC) measurement, daily pain intensity scores on a visual numerical scale (VNS), and fMRI with motor tasks (alternation of finger movements and rest). The fMRI scans were analyzed voxelwise using ESC and VNS pain score as regressors to derive their neural correlates. The criterion of response to rTMS therapy was defined as ≥30% reduction in VNS pain score one month after treatment compared with baseline. ResultsAt baseline, ESC values were reduced in the affected limb vs the nonaffected limb. There was a covariance of VNS with brain activation in a small region of the primary somatosensory cortex (S1) contralateral to the painful side on fMRI investigation. After rTMS therapy on motor cortex related to the painful limb, the VNS pain scores significantly decreased by 22% on average. The criterion of response was met in six of 11 patients (55%). In these responders, at one month after treatment, ESC value increased and returned to normal in the CRPS-affected limb, and overall, the increase in ESC correlated with the decrease in VNS after motor cortex rTMS therapy. At one month after treatment, there also was a covariance of both variables (ESC and VNS) with fMRI activation of the S1 region previously mentioned. The fMRI activation of other brain regions (middle frontal gyrus and temporo-parietal junction) showed correlation with ESC values before and after treatment. Finally, we found a positive correlation at one month after treatment (not at baseline) between VNS pain score and fMRI activation in the temporo-parietal junction contralateral to painful side. ConclusionsThis study first shows a functional pain-autonomic coupling in patients with CRPS, which could involve a specific S1 region. However, the modulation of sympathetic sudomotor activities expressed by ESC changes was rather correlated with functional changes in other brain regions. Finally, the pain relief observed at one month after rTMS treatment was associated with a reduced activation of the temporo-parietal junction on the side in which rTMS was performed. These findings open perspectives to define new targets or biomarkers for using rTMS to treat CRPS-associated pain. Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT02817880.

Sex differences of the triple network model in children with autism: A resting-state fMRI investigation of effective connectivity.

Autism spectrum disorder (ASD) has a pronounced male predominance, but the underlying neurobiological basis of this sex bias remains unclear. Gender incoherence (GI) theory suggests that ASD is more neurally androgynous than same-sex controls. Given its central role, altered structures and functions, and sex-dependent network differences in ASD, the triple network model, including the central executive network (CEN), default mode network (DMN), and salience network (SN), has emerged as a candidate for characterizing this sex difference. Here, we measured the sex-related effective connectivity (EC) differences within and between these three networks in 72 children with ASD (36 females, 8-14 years) and 72 typically developing controls (TCs) (36 females, 8-14 years) from 5 sites of the Autism Brain Imaging Data Exchange repositories using a 2 × 2 analysis of covariance factorial design. We also assessed brain-behavior relationships and the effects of age on EC. We found significant diagnosis-by-sex interactions on EC: females with ASD had significantly higher EC than their male counterparts within the DMN and between the SN and CEN. The interaction pattern supported the GI theory by showing that the higher EC observed in females with ASD reflected a shift towards the higher level of EC displayed in male TCs (neural masculinization), and the lower EC seen in males with ASD reflected a shift towards the lower level of EC displayed in female TCs (neural feminization). We also found significant brain-behavior correlations and significant effects of age on EC.

A cross-cultural fMRI investigation of cannabis approach bias in individuals with cannabis use disorder

IntroductionAs cannabis policies and attitudes become more permissive, it is crucial to examine how the legal and social environment influence neurocognitive mechanisms underlying cannabis use disorder (CUD). The current study aimed to assess whether cannabis approach bias, one of the mechanisms proposed to underlie CUD, differed between environments with distinct recreational cannabis policies (Amsterdam, The Netherlands (NL) and Dallas, Texas, United States of America (TX)) and whether individual differences in cannabis attitudes affect those differences. MethodsIndividuals with CUD (NL-CUD: 64; TX-CUD: 48) and closely matched non-using controls (NL-CON: 50; TX-CON: 36) completed a cannabis approach avoidance task (CAAT) in a 3T MRI. The cannabis culture questionnaire was used to measure cannabis attitudes from three perspectives: personal, family/friends, and state/country attitudes. ResultsIndividuals with CUD demonstrated a significant behavioral cannabis-specific approach bias. Individuals with CUD exhibited higher cannabis approach bias-related activity in clusters including the paracingulate gyrus, anterior cingulate cortex, and frontal medial cortex compared to controls, which was no longer significant after controlling for gender. Site-related differences emerged in the association between cannabis use quantity and cannabis approach bias activity in the putamen, amygdala, hippocampus, and insula, with a positive association in the TX-CUD group and a negative association in the NL-CUD group. This was not explained by site differences in cannabis attitudes. ConclusionsPinpointing the underlying mechanisms of site-related differences—including, but not limited to, differences in method of administration, cannabis potency, or patterns of substance co-use—is a key challenge for future research.

Random matrix theory tools for the predictive analysis of functional magnetic resonance imaging examinations.

Random matrix theory (RMT) is an increasingly useful tool for understanding large, complex systems. Prior studies have examined functional magnetic resonance imaging (fMRI) scans using tools from RMT, with some success. However, RMT computations are highly sensitive to a number of analytic choices, and the robustness of findings involving RMT remains in question. We systematically investigate the usefulness of RMT on a wide variety of fMRI datasets using a rigorous predictive framework. We develop open-source software to efficiently compute RMT features from fMRI images and examine the cross-validated predictive potential of eigenvalue and RMT-based features ("eigenfeatures") with classic machine-learning classifiers. We systematically vary pre-processing extent, normalization procedures, RMT unfolding procedures, and feature selection and compare the impact of these analytic choices on the distributions of cross-validated prediction performance for each combination of dataset binary classification task, classifier, and feature. To deal with class imbalance, we use the area under the receiver operating characteristic curve (AUROC) as the main performance metric. Across all classification tasks and analytic choices, we find RMT- and eigenvalue-based "eigenfeatures" to have predictive utility more often than not (82.4% of median ; median AUROC range across classification tasks 0.47 to 0.64). Simple baseline reductions on source timeseries, by contrast, were less useful (58.8% of median , median AUROC range across classification tasks 0.42 to 0.62). Additionally, eigenfeature AUROC distributions were overall more right-tailed than baseline features, suggesting greater predictive potential. However, performance distributions were wide and often significantly affected by analytic choices. Eigenfeatures clearly have potential for understanding fMRI functional connectivity in a wide variety of scenarios. The utility of these features is strongly dependent on analytic decisions, suggesting caution when interpreting past and future studies applying RMT to fMRI. However, our study demonstrates that the inclusion of RMT statistics in fMRI investigations could improve prediction performances across a wide variety of phenomena.

An fMRI Investigation of Brain Reward Function in Patients with Schizophrenia and Comorbid Cannabis Use Disorder (S8.010)

<h3>Objective:</h3> The present study aims to identify neural mechanisms related to brain reward function in schizophrenia and comorbid cannabis use disorder (SCZ-CUD) by examining their fMRI activity during reward anticipation. <h3>Background:</h3> CUD is present in up to 42% of patients with SCZ. Cannabis use worsens symptoms of psychosis and disease prognosis, yet patients with SCZ-CUD continue to use the drug. Previous research has demonstrated impaired brain reward function in SCZ. We previously hypothesized that use of cannabis may remediate impaired brain reward function in this population, a form of self-medication, yet few studies have examined reward function in this comorbid group. A better understanding of the brain reward-related neural mechanisms in SCZ-CUD may support this self-medication hypothesis and lead to the development of safe and effective treatments. <h3>Design/Methods:</h3> Using fMRI, we assessed 34 abstinent patients with SCZ-CUD, 51 abstinent CUD-only patients (without SCZ), 18 SCZ-only patients (without CUD) and 28 healthy controls during a Monetary Incentive Delay task. Group differences in activity during reward anticipation were examined through voxel-wise whole-brain analyses. <h3>Results:</h3> For reward contrasts, SCZ-CUD patients showed greater task-related activity compared to healthy controls in a cluster including the right parahippocampal gyrus and the cingulate gyrus (cluster size = 1000). SCZ-CUD patients also showed increased activity compared to SCZ-only patients in a cluster consisting of the precuneus, posterior cingulate, and the limbic lobe (cluster size = 529). For reward magnitude contrasts, SCZ-CUD patients showed significantly decreased activity compared to CUD-only group in the cingulate gyrus (cluster size = 280). <h3>Conclusions:</h3> This whole-brain study presents evidence for atypical task-related activity in areas related to reward processing during reward anticipation in SCZ-CUD patients compared to healthy controls and SCZ-only patients. Future research will examine the impact of consumption of cannabis on brain reward function, which may inform the development of targeted treatments for patients with SCZ-CUD. <b>Disclosure:</b> Mr. Park has nothing to disclose. Thomas Zeffiro has nothing to disclose. Mr. Ford has received research support from NIH. Mr. Ford has received research support from the Hitchcock Foundation. Mr. Ford has received research support from National MS Society. The institution of Dr. Brunette has received research support from NIDA.