Specialized late cingulo-opercular network activation elucidates the mechanisms underlying decisions about ambiguity.

Cortical task control networks, including the cingulo-opercular (CO) network play a key role in decision-making across a variety of functional domains. In particular, the CO network functions in a performance reporting capacity that supports successful task performance, especially in response to errors and ambiguity. In two studies testing the contribution of the CO network to ambiguity processing, we presented a valence bias task in which masked clearly and ambiguously valenced emotional expressions were slowly revealed over several seconds. This slow reveal task design provides a window into the decision-making mechanisms as they unfold over the course of a trial. In the main study, the slow reveal task was administered to 32 young adults in the fMRI environment and BOLD time courses were extracted from regions of interest in three control networks. In a follow-up study, the task was administered to a larger, online sample (n = 81) using a more extended slow reveal design with additional unmasking frames. Positive judgments of surprised faces were uniquely accompanied by slower response times and strong, late activation in the CO network. These results support the initial negativity hypothesis, which posits that the default response to ambiguity is negative and positive judgments are associated with a more effortful controlled process, and additionally suggest that this controlled process is mediated by the CO network. Moreover, ambiguous trials were characterized by a second CO response at the end of the trial, firmly placing CO function late in the decision-making process.

Explicit and Implicit Emotion Processing in the Cerebellum: A Meta-analysis and Systematic Review.

The cerebellum's role in affective processing is increasingly recognized in the literature, but remains poorly understood, despite abundant clinical evidence for affective disruptions following cerebellar damage. To improve the characterization of emotion processing and investigate how attention allocation impacts this processing, we conducted a meta-analysis on task activation foci using GingerALE software. Eighty human neuroimaging studies of emotion including 2761 participants identified through Web of Science and ProQuest databases were analyzed collectively and then divided into two categories based on the focus of attention during the task: explicit or implicit emotion processing. The results examining the explicit emotion tasks identified clusters within the posterior cerebellar hemispheres (bilateral lobule VI/Crus I/II), the vermis, and left lobule V/VI that were likely to be activated across studies, while implicit tasks activated clusters including bilateral lobules VI/Crus I/II, right Crus II/lobule VIII, anterior lobule VI, and lobules I-IV/V. A direct comparison between these categories revealed five overlapping clusters in right lobules VI/Crus I/Crus II and left lobules V/VI/Crus I of the cerebellum common to both the explicit and implicit task contrasts. There were also three clusters activated significantly more for explicit emotion tasks compared to implicit tasks (right lobule VI, left lobule VI/vermis), and one cluster activated more for implicit than explicit tasks (left lobule VI). These findings support previous studies indicating affective processing activates both the lateral hemispheric lobules and the vermis of the cerebellum. The common and distinct activation of posterior cerebellar regions by tasks with explicit and implicit attention demonstrates the supportive role of this structure in recognizing, appraising, and reacting to emotional stimuli.

Affective flexibility as a developmental building block of cognitive reappraisal: An fMRI study.

Cognitive reappraisal is a form of emotion regulation that involves reinterpreting the meaning of a stimulus, often to downregulate one's negative affect. Reappraisal typically recruits distributed regions of prefrontal and parietal cortex to generate new appraisals and downregulate the emotional response in the amygdala. In the current study, we compared reappraisal ability in an fMRI task with affective flexibility in a sample of children and adolescents (ages 6-17, N = 76). Affective flexibility was defined as variability in valence interpretations of ambiguous (surprised) facial expressions from a second behavioral task. Results demonstrated that age and affective flexibility predicted reappraisal ability, with an interaction indicating that flexibility in children (but not adolescents) supports reappraisal success. Using a region of interest-based analysis of participants' BOLD time courses, we also found dissociable reappraisal-related brain mechanisms that support reappraisal success and affective flexibility. Specifically, late increases in middle prefrontal cortex activity supported reappraisal success and late decreases in amygdala activity supported flexibility. Together, these results suggest that our novel measure of affective flexibility - the ability to see multiple interpretations of an ambiguous emotional cue - may represent part of the developmental building blocks of cognitive reappraisal ability.

Task-irrelevant emotional faces impact BOLD responses more for prosaccades than antisaccades in a mixed saccade fMRI task.

Cognitive control allows individuals to flexibly and efficiently perform tasks by attending to relevant stimuli while inhibiting distraction from irrelevant stimuli. The antisaccade task assesses cognitive control by requiring participants to inhibit a prepotent glance towards a peripheral stimulus and generate an eye movement to the mirror image location. This task can be administered with various contextual manipulations to investigate how factors such as trial timing or emotional content interact with cognitive control. In the current study, 26 healthy adults completed a mixed antisaccade and prosaccade fMRI task that included task irrelevant emotional faces and gap/overlap timing. The results showed typical antisaccade and gap behavioral effects with greater BOLD activation in frontal and parietal brain regions for antisaccade and overlap trials. Conversely, there were no differences in behavior based on the emotion of the task irrelevant face, but trials with neutral faces had greater activation in widespread visual regions than trials with angry faces, particularly for prosaccade and overlap trials. Together, these effects suggest that a high level of cognitive control and inhibition was required throughout the task, minimizing the impact of the face presentation on saccade behavior, but leading to increased attention to the neutral faces on overlap prosaccade trials when both the task cue (look towards) and emotion stimulus (neutral, non-threatening) facilitated disinhibition of visual processing.

Reward-Based Learning and Emotional Habit Formation in the Cerebellum.

There is growing evidence of the cerebellum's contribution to emotion processing from neuroimaging studies of healthy function and clinical studies of cerebellar patients. As demonstrated initially in the motor domain, one of the cerebellum's functions is to construct internal models of an individual's state and make predictions about how future behaviors will impact that state. By utilizing widespread connections with neocortex and subcortical regions such as the basal ganglia, the cerebellum can monitor and modulate precisely timed patterns of events using prediction and reward-based error feedback in a diverse range of tasks including auditory emotion prosody recognition. In coordination with a broader affective network, the cerebellum helps to select and refine emotional responses that are the most rewarded in a particular context, strengthening neural activity in relevant regions to form a representational chunk. This chunked set of affective stimuli, cognitive evaluations, and physiological responses subsequently can be enacted as a unitary response (i.e., an emotional habit) more quickly and with less attentional control than for a novel stimulus or goal-oriented action. Such emotional habits can allow for efficient, automatic, stimulus-triggered responses while maintaining the flexibility to adapt output when prediction errors signal a renewed need for cerebellar modification of cortical activity, or, conversely, may lead to behavioral or mood disorders when habitual responses persist despite negative consequences.

Reappraisal-related downregulation of amygdala BOLD activation occurs only during the late trial window.

During cognitive reappraisal, an individual reinterprets the meaning of an emotional stimulus to regulate the intensity of their emotional response. Prefrontal cortex activity has been found to support reappraisal and is putatively thought to downregulate the amygdala response to these stimuli. The timing of these regulation-related responses during the course of a trial, however, remains poorly understood. In the current fMRI study, participants were instructed to view or reappraise negative images and then rate how negative they felt following each image. The hemodynamic response function was estimated in 11 regions of interest for the entire time course of the trial including image viewing and rating. Notably, within the amygdala there was no evidence of downregulation in the early (picture viewing) window of the trial, only in the late (rating) window, which also correlated with a behavioral measure of reappraisal success. With respect to the prefrontal regions, some (e.g., inferior frontal gyrus) showed reappraisal-related activation in the early window, whereas others (e.g., middle frontal gyrus) showed increased activation primarily in the late window. These results highlight the temporal dynamics of different brain regions during emotion regulation and suggest that the amygdala response to negative images need not be immediately dampened to achieve successful cognitive reappraisal.

A novel computerized assessment of manual spatial exploration in unilateral spatial neglect.

Unilateral spatial neglect is a neuropsychological syndrome commonly observed after stroke and defined by the inability to attend or respond to contralesional stimuli. Typically, symptoms are assessed using clinical tests that rely upon visual/perceptual abilities. However, neglect may affect high-level representations controlling attention in other modalities as well. Here we developed a novel manual exploration test using a touch screen computer to quantify spatial search behaviour without visual input. Twelve chronic stroke patients with left neglect and 27 patients without neglect (based on clinical tests) completed our task. Four of the 12 "neglect" patients exhibited clear signs of neglect on our task as compared to "non-neglect" patients and healthy controls, and six other patients (from both groups) also demonstrated signs of neglect compared to healthy controls only. While some patients made asymmetrical responses on only one task, generally, patients with the strongest neglect performed poorly on multiple tasks. This suggests that representations associated with different modalities may be affected separately, but that severe forms of neglect are more likely related to damage in a common underlying representation. Our manual exploration task is easy to administer and can be added to standard neglect screenings to better measure symptom severity.

Real-time fMRI and EEG neurofeedback: A perspective on applications for the rehabilitation of spatial neglect.

Spatial neglect is a neuropsychological syndrome characterized by a failure to orient, perceive, and act toward the contralesional side of the space after brain injury. Neglect is one of the most frequent and disabling neuropsychological syndromes following right-hemisphere damage, often persisting in the chronic phase and responsible for a poor functional outcome at hospital discharge. Different rehabilitation approaches have been proposed over the past 60 years, with a variable degree of effectiveness. In this point-of-view article, we describe a new rehabilitation technique for spatial neglect that directly targets brain activity and pathological physiological processes: namely, neurofeedback (NFB) with real-time brain imaging methodologies. In recent proof-of-principle studies, we have demonstrated the potential of this rehabilitation technique. Using real-time functional MRI (rt-fMRI) NFB in chronic neglect, we demonstrated that patients are able to upregulate their right visual cortex activity, a response that is otherwise reduced due to losses in top-down attentional signals. Using real-time electroencephalography NFB in patients with acute or chronic condition, we showed successful regulation with partial restoration of brain rhythm dynamics over the damaged hemisphere. Both approaches were followed by mild, but encouraging, improvement in neglect symptoms. NFB techniques, by training endogenous top-down modulation of attentional control on sensory processing, might induce sustained changes at both the neural and behavioral levels, while being non-invasive and safe. However, more properly powered clinical studies with control groups and longer follow-up are needed to fully establish the effectiveness of the techniques, identify the most suitable candidates, and determine how the techniques can be optimized or combined in the context of rehabilitation.

The basal ganglia and the cerebellum in human emotion.

The basal ganglia (BG) and the cerebellum historically have been relegated to a functional role in producing or modulating motor output. Recent research, however, has emphasized the importance of these subcortical structures in multiple functional domains, including affective processes such as emotion recognition, subjective feeling elicitation and reward valuation. The pathways through the thalamus that connect the BG and cerebellum directly to each other and with extensive regions of the cortex provide a structural basis for their combined influence on limbic function. By regulating cortical oscillations to guide learning and strengthening rewarded behaviors or thought patterns to achieve a desired goal state, these regions can shape the way an individual processes emotional stimuli. This review will discuss the basic structure and function of the BG and cerebellum and propose an updated view of their functional role in human affective processing.

Differential parietal activations for spatial remapping and saccadic control in a visual memory task.

Remapping is a process that updates visual information in internal spatial representations across eye movements, allowing for stable perception of the environment. Previous work has demonstrated visual remapping activity in parietal cortex during saccades, but it remains unclear whether remapping is triggered by overt saccades only (or by attentional shifts also), and whether it engages parietal areas only (or other cortical areas). Here, we used fMRI to investigate spatial remapping during two visuospatial memory tasks requiring either overt (accompanied by a saccade) or covert (with central fixation) attention shifts to peripheral distracters. Participants had to remember the position and color of a lateralized dot during a saccade or attention shift, requiring them to update the dot position in memory, and then indicate if a second dot matched the first. Differential activation patterns were observed within parietal cortex as a function of the different visual, motor, and interhemispheric remapping demands in the saccade task, presumably mediating the maintenance of spatial position in perceptual and motor maps. Remapping engaged parietal areas adjacent to, but not overlapping with, those activated by saccade execution, while it did not engage the frontal eye fields, pointing to distinct neural substrates for ocular motor and spatial updating processes. No differential activation related to remapping was found during the covert attention shift task, suggesting that this condition did not necessitate the same remapping as the saccade condition. Overall these results further elucidate the mechanisms of spatial remapping in human parietal cortex and their relationship with attention processing and ocular motor behavior, with implications for understanding visuospatial attention deficits in hemispatial neglect.

Regularized aggregation of statistical parametric maps.

Combining statistical parametric maps (SPM) from individual subjects is the goal in some types of group-level analyses of functional magnetic resonance imaging data. Brain maps are usually combined using a simple average across subjects, making them susceptible to subjects with outlying values. Furthermore, t tests are prone to false positives and false negatives when outlying values are observed. We propose a regularized unsupervised aggregation method for SPMs to find an optimal weight for aggregation, which aids in detecting and mitigating the effect of outlying subjects. We also present a bootstrap-based weighted t test using the optimal weights to construct an activation map robust to outlying subjects. We validate the performance of the proposed aggregation method and test using simulated and real data examples. Results show that the regularized aggregation approach can effectively detect outlying subjects, lower their weights, and produce robust SPMs.

Microstructural differences in visual white matter tracts in people with aniridia.

Aniridia is a panocular disorder characterized chiefly by iris hypoplasia. Most cases result from mutations of the PAX6 gene, which is important in both eye and brain development. In addition to ocular alterations, differences in global brain volume and functional connectivity have been reported in humans with aniridia. Understanding neural alterations in aniridia may require examination of possible differences in white matter structure, as few studies have assessed white matter in this population. The current study utilized diffusion-weighted imaging to assess white matter structure in 11 people with aniridia and 11 healthy comparison participants, matched for sex and age. A map of the local connectome was calculated to compare quantitative anisotropy (QA), an index of white matter tract density, in all white matter voxels, revealing subcomponents of white matter tracts with differing QA between people with aniridia and healthy comparisons. The analysis indicated that QA was lower for people with aniridia in portions of bilateral optic tract [t(20)=-4.23, P=0.001, d=-1.80], bilateral optic radiation [t(20)=-4.06, P=0.001, d=-1.73], forceps major [t(20)=-3.65, P=0.002, d=-1.55], bilateral superior longitudinal fasciculus [left: t(20)=-3.15, P=0.005, d=-1.34; right, t(20)=-4.28, P<0.001, d=-1.83], and right posterior corona radiata [t(20)=-3.19, P=0.006, d=-1.36]. These differences demonstrate that white matter structure is altered in people with aniridia in both visual tracts and associated posterior visual pathways.

Evaluating the Specificity of Cognitive Control Deficits in Schizophrenia Using Antisaccades, Functional Magnetic Resonance Imaging, and Healthy Individuals With Poor Cognitive Control.

Cognitive control impairments in schizophrenia (SZ) can be evaluated using antisaccade tasks and functional magnetic resonance imaging (fMRI). Studies, however, often compare people with SZ to high performing healthy people, making it unclear if antisaccade-related disruptions are specific to the disease or due to generalized deficits in cognitive control. We included two healthy comparison groups in addition to people with SZ: healthy people with high cognitive control (HCC), who represent a more typical comparison group, and healthy people with low cognitive control (LCC), who perform similarly on antisaccade measures as people with SZ. Using two healthy comparison groups may help determine which antisaccade-related deficits are specific to SZ (distinguish SZ from LCC and HCC groups) and which are due to poor cognitive control (distinguish the LCC and SZ groups from the HCC group). People with SZ and healthy people with HCC or LCC performed an antisaccade task during fMRI acquisition. LCC and SZ groups showed under-activation of saccade circuitry. SZ-specific disruptions were observed in the left superior temporal gyrus and insula during error trials (suppression of activation in the SZ group compared to the LCC and HCC group). Differences related to antisaccade errors may distinguish people with SZ from healthy people with LCC.

Structural brain abnormalities in 12 persons with aniridia.

Background: Aniridia is a disorder predominately caused by heterozygous loss-of-function mutations of the PAX6 gene, which is a transcriptional regulator necessary for normal eye and brain development.  The ocular abnormalities of aniridia have been well characterized, but mounting evidence has implicated brain-related phenotypes as a prominent feature of this disorder as well.  Investigations using neuroimaging in aniridia patients have shown reductions in discrete brain structures and changes in global grey and white matter.  However, limited sample sizes and substantive heterogeneity of structural phenotypes in the brain remain a challenge.  Methods: Here, we examined brain structure in a new population sample in an effort to add to the collective understanding of anatomical abnormalities in aniridia.  The current study used 3T magnetic resonance imaging to acquire high-resolution structural data in 12 persons with aniridia and 12 healthy demographically matched comparison subjects.  Results: We examined five major structures: the anterior commissure, the posterior commissure, the pineal gland, the corpus callosum, and the optic chiasm.  The most consistent reductions were found in the anterior commissure and the pineal gland; however, abnormalities in all of other structures examined were present in at least one individual.  Conclusions: Our results indicate that the anatomical abnormalities in aniridia are variable and largely individual-specific.  These findings suggest that future studies investigate this heterogeneity further, and that normal population variation should be considered when evaluating structural abnormalities.

White matter fiber integrity of the saccadic eye movement network differs between schizophrenia and healthy groups.

Recent diffusion tensor imaging (DTI) studies suggest that altered white matter fiber integrity is a pathophysiological feature of schizophrenia. Lower white matter integrity is associated with poor cognitive control, a characteristic of schizophrenia that can be measured using antisaccade tasks. Although the functional neural correlates of poor antisaccade performance have been well documented, fewer studies have investigated the extent to which white matter fibers connecting the functional nodes of this network contribute to antisaccade performance. The aim of the present study was to assess the white matter structural integrity of fibers connecting two functional nodes (putamen and medial frontal eye fields) of the saccadic eye movement network implicated in poor antisaccade performance in schizophrenia. To evaluate white matter integrity, DTI was acquired on subjects with schizophrenia and two comparison groups: (a) behaviorally matched healthy comparison subjects with low levels of cognitive control (LCC group), and (b) healthy subjects with high levels of cognitive control (HCC group). White matter fibers were tracked between functional regions of interest generated from antisaccade fMRI activation maps, and measures of diffusivity were quantified. The results demonstrated lower white matter integrity in the schizophrenia group than in the HCC group, but not the LCC group who showed similarly poor cognitive control performance. Overall, the results suggest that these alterations are not specific to the disease process of schizophrenia, but may rather be a function of uncontrolled cognitive factors that are concomitant with the disease but also observed in some healthy people.

Contextual effects on cognitive control and BOLD activation in single versus mixed saccade tasks.

The context or trial history of a task influences response efficiency in mixed paradigms based on cognitive control demands for task set selection. In the current study, the impact of context on prosaccade and antisaccade trials in single and mixed tasks was investigated with BOLD fMRI. Prosaccades require a look towards a newly appearing target, while antisaccades require cognitive control for prepotent response inhibition and generation of a saccade to the opposite location. Results indicated slower prosaccade reaction times and more antisaccade errors for switched than repeated or single trials, and slower antisaccade reaction times for single than mixed trials. BOLD activation was greater for the mixed than the single context in frontal eye fields and precuneus, while switch trials had greater activation than repeat trials in posterior parietal and middle occipital cortex. Greater antisaccade activation was observed overall in saccade circuitry, although effects were evident primarily for the mixed task when considered separately. Finally, an interaction was observed in superior frontal cortex, precuneus, anterior cingulate, and thalamus with strong responses for antisaccade switch trials in the latter two regions. Altogether this response pattern demonstrated the sensitivity of cognitive control to changing task conditions, especially due to task switching costs. Such context-specific differences highlight the importance of trial history when assessing cognitive control.

Reduced Cognitive Control Demands after Practice of Saccade Tasks in a Trial Type Probability Manipulation.

Cognitive control is engaged to facilitate stimulus-response mappings for novel, complex tasks and supervise performance in unfamiliar, challenging contexts-processes supported by pFC, ACC, and posterior parietal cortex. With repeated task practice, however, the appropriate task set can be selected in a more automatic fashion with less need for top-down cognitive control and weaker activation in these brain regions. One model system for investigating cognitive control is the ocular motor circuitry underlying saccade production, with basic prosaccade trials (look toward a stimulus) and complex antisaccade trials (look to the mirror image location) representing low and high levels of cognitive control, respectively. Previous studies have shown behavioral improvements on saccade tasks after practice with contradictory results regarding the direction of functional MRI BOLD signal change. The current study presented healthy young adults with prosaccade and antisaccade trials in five mixed blocks with varying probability of each trial type (0%, 25%, 50%, 75%, or 100% anti vs. pro) at baseline and posttest MRI sessions. Between the scans, participants practiced either the specific probability blocks used during testing or only a general 100% antisaccade block. Results indicated an overall reduction in BOLD activation within pFC, ACC, and posterior parietal cortex and across saccade circuitry for antisaccade trials. The specific practice group showed additional regions including ACC, insula, and thalamus with an activation decrease after practice, whereas the general practice group showed a little change from baseline in those clusters. These findings demonstrate that cognitive control regions recruited to support novel task behaviors were engaged less after practice, especially with exposure to mixed task contexts rather than a novel task in isolation.

Effects of preparation time and trial type probability on performance of anti- and pro-saccades.

Cognitive control optimizes responses to relevant task conditions by balancing bottom-up stimulus processing with top-down goal pursuit. It can be investigated using the ocular motor system by contrasting basic prosaccades (look toward a stimulus) with complex antisaccades (look away from a stimulus). Furthermore, the amount of time allotted between trials, the need to switch task sets, and the time allowed to prepare for an upcoming saccade all impact performance. In this study the relative probabilities of anti- and pro-saccades were manipulated across five blocks of interleaved trials, while the inter-trial interval and trial type cue duration were varied across subjects. Results indicated that inter-trial interval had no significant effect on error rates or reaction times (RTs), while a shorter trial type cue led to more antisaccade errors and faster overall RTs. Responses following a shorter cue duration also showed a stronger effect of trial type probability, with more antisaccade errors in blocks with a low antisaccade probability and slower RTs for each saccade task when its trial type was unlikely. A longer cue duration yielded fewer errors and slower RTs, with a larger switch cost for errors compared to a short cue duration. Findings demonstrated that when the trial type cue duration was shorter, visual motor responsiveness was faster and subjects relied upon the implicit trial probability context to improve performance. When the cue duration was longer, increased fixation-related activity may have delayed saccade motor preparation and slowed responses, guiding subjects to respond in a controlled manner regardless of trial type probability.

Modulation of cognitive control levels via manipulation of saccade trial-type probability assessed with event-related BOLD fMRI.

Cognitive control supports flexible behavior adapted to meet current goals and can be modeled through investigation of saccade tasks with varying cognitive demands. Basic prosaccades (rapid glances toward a newly appearing stimulus) are supported by neural circuitry, including occipital and posterior parietal cortex, frontal and supplementary eye fields, and basal ganglia. These trials can be contrasted with complex antisaccades (glances toward the mirror image location of a stimulus), which are characterized by greater functional magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) signal in the aforementioned regions and recruitment of additional regions such as dorsolateral prefrontal cortex. The current study manipulated the cognitive demands of these saccade tasks by presenting three rapid event-related runs of mixed saccades with a varying probability of antisaccade vs. prosaccade trials (25, 50, or 75%). Behavioral results showed an effect of trial-type probability on reaction time, with slower responses in runs with a high antisaccade probability. Imaging results exhibited an effect of probability in bilateral pre- and postcentral gyrus, bilateral superior temporal gyrus, and medial frontal gyrus. Additionally, the interaction between saccade trial type and probability revealed a strong probability effect for prosaccade trials, showing a linear increase in activation parallel to antisaccade probability in bilateral temporal/occipital, posterior parietal, medial frontal, and lateral prefrontal cortex. In contrast, antisaccade trials showed elevated activation across all runs. Overall, this study demonstrated that improbable performance of a typically simple prosaccade task led to augmented BOLD signal to support changing cognitive control demands, resulting in activation levels similar to the more complex antisaccade task.

White matter structural integrity differs between people with schizophrenia and healthy groups as a function of cognitive control.

A behavioral hallmark of schizophrenia is poor cognitive control. Recent evidence suggests that problems with cognitive control in schizophrenia are related to disconnectivity along major white matter fibers. Although deficits of cognitive control are common in schizophrenia, a proportion of otherwise healthy subjects show poor cognitive control performance. The present study sought to address this potential confound by comparing white matter integrity between a group with schizophrenia and otherwise healthy individuals with either high or low levels of cognitive control (based on working memory span performance). Diffusion tensor imaging was used to evaluate white matter integrity in 24 participants with schizophrenia, 24 healthy participants with high cognitive control (HCC), and 25 healthy participants with low cognitive control (LCC). To test for differences in fractional anisotropy (FA) across major white matter fiber tracts, a voxelwise region of interest analysis was conducted in standardized brain space. In a separate analysis, regions of interest were manually drawn in native brain space to isolate superior longitudinal fasciculus (SLF), a tract implicated in cognitive control performance. The voxelwise analysis demonstrated widespread lower FA in the schizophrenia group compared to the HCC group. With a high degree of concordance, the manual ROI analysis revealed lower FA in the schizophrenia group compared to the HCC group. Taken together, these results provide evidence to suggest that structural differences identified between healthy groups and schizophrenia may not be entirely specific to the disease process and can vary as a function of cognitive control capacity in the comparison group.