Reward anticipation-related neural activation following cued reinforcement in adults with psychotic psychopathology and biological relatives.

BACKGROUND: Schizophrenia is associated with hypoactivation of reward sensitive brain areas during reward anticipation. However, it is unclear whether these neural functions are similarly impaired in other disorders with psychotic symptomatology or individuals with genetic liability for psychosis. If abnormalities in reward sensitive brain areas are shared across individuals with psychotic psychopathology and people with heightened genetic liability for psychosis, there may be a common neural basis for symptoms of diminished pleasure and motivation. METHODS: We compared performance and neural activity in 123 people with a history of psychosis (PwP), 81 of their first-degree biological relatives, and 49 controls during a modified Monetary Incentive Delay task during fMRI. RESULTS: PwP exhibited hypoactivation of the striatum and anterior insula (AI) during cueing of potential future rewards with each diagnostic group showing hypoactivations during reward anticipation compared to controls. Despite normative task performance, relatives demonstrated caudate activation intermediate between controls and PwP, nucleus accumbens activation more similar to PwP than controls, but putamen activation on par with controls. Across diagnostic groups of PwP there was less functional connectivity between bilateral caudate and several regions of the salience network (medial frontal gyrus, anterior cingulate, AI) during reward anticipation. CONCLUSIONS: Findings implicate less activation and connectivity in reward processing brain regions across a spectrum of disorders involving psychotic psychopathology. Specifically, aberrations in striatal and insular activity during reward anticipation seen in schizophrenia are partially shared with other forms of psychotic psychopathology and associated with genetic liability for psychosis.

Conscientiousness associated with efficiency of the salience/ventral attention network: Replication in three samples using individualized parcellation.

Conscientiousness, and related constructs impulsivity and self-control, have been related to structural and functional properties of regions in the prefrontal cortex (PFC) and anterior insula. Network-based conceptions of brain function suggest that these regions belong to a single large-scale network, labeled the salience/ventral attention network (SVAN). The current study tested associations between conscientiousness and resting-state functional connectivity in this network using two community samples (N's = 244 and 239) and data from the Human Connectome Project (N = 1000). Individualized parcellation was used to improve functional localization accuracy and facilitate replication. Functional connectivity was measured using an index of network efficiency, a graph theoretical measure quantifying the capacity for parallel information transfer within a network. Efficiency of a set of parcels in the SVAN was significantly associated with conscientiousness in all samples. Findings are consistent with a theory of conscientiousness as a function of variation in neural networks underlying effective prioritization of goals.

Activation of the default network during a theory of mind task predicts individual differences in agreeableness and social cognitive ability.

Social cognitive processes, such as emotion perception and empathy, allow humans to navigate complex social landscapes and are associated with specific neural systems. In particular, theory of mind (ToM), which refers to our ability to decipher the mental states of others, is related to the dorsal medial prefrontal cortex and temporoparietal junction, which include portions of the default network. Both social cognition and the default network have been linked to the personality trait Agreeableness. We hypothesized that default network activity during a ToM task would positively predict social cognitive abilities and Agreeableness. In a 3T fMRI scanner, participants (N = 1050) completed a ToM task in which they observed triangles displaying random or social (i.e., human-like) movement. Participants also completed self-report measures of Agreeableness and tests of intelligence and social cognitive ability. In each participant, average blood oxygen level dependent responses were calculated for default network regions associated with social cognition, and structural equation modeling was used to test associations of personality and task performance with activation in those brain regions. Default network activation in the dorsal medial subsystem was greater for social versus random animations. Default network activation in response to social animations predicted better performance on social cognition tasks and, to a lesser degree, higher Agreeableness. Neural response to social stimuli in the default network may be associated with effective social processing and could have downstream effects on social interactions. We discuss theoretical and methodological implications of this work for social and personality neuroscience.

The psychosis human connectome project: An overview.

Investigations within the Human Connectome Project have expanded to include studies focusing on brain disorders. This paper describes one of the investigations focused on psychotic psychopathology: The psychosis Human Connectome Project (P-HCP). The data collected as part of this project were multimodal and derived from clinical assessments of psychopathology, cognitive assessments, instrument-based motor assessments, blood specimens, and magnetic resonance imaging (MRI) data. The dataset will be made publicly available through the NIMH Data Archive. In this report we provide specific information on how the sample of participants was obtained and characterized and describe the experimental tasks and procedures used to probe neural functions involved in psychotic disorders that may also mark genetic liability for psychotic psychopathology. Our goal in this paper is to outline the data acquisition process so that researchers intending to use these publicly available data can plan their analyses. MRI data described in this paper are limited to data acquired at 3 Tesla. A companion paper describes the study's 7 Tesla image acquisition protocol in detail, which is focused on visual perceptual functions in psychotic psychopathology.

Assessing methods for geometric distortion compensation in 7 T gradient echo functional MRI data.

Echo planar imaging (EPI) is widely used in functional and diffusion-weighted MRI, but suffers from significant geometric distortions in the phase encoding direction caused by inhomogeneities in the static magnetic field (B0 ). This is a particular challenge for EPI at very high field (≥7 T), as distortion increases with higher field strength. A number of techniques for distortion correction exist, including those based on B0 field mapping and acquiring EPI scans with opposite phase encoding directions. However, few quantitative comparisons of distortion compensation methods have been performed using human EPI data, especially at very high field. Here, we compared distortion compensation using B0 field maps and opposite phase encoding scans in two different software packages (FSL and AFNI) applied to 7 T gradient echo (GE) EPI data from 31 human participants. We assessed distortion compensation quality by quantifying alignment to anatomical reference scans using Dice coefficients and mutual information. Performance between FSL and AFNI was equivalent. In our whole-brain analyses, we found superior distortion compensation using GE scans with opposite phase encoding directions, versus B0 field maps or spin echo (SE) opposite phase encoding scans. However, SE performed better when analyses were limited to ventromedial prefrontal cortex, a region with substantial dropout. Matching the type of opposite phase encoding scans to the EPI data being corrected (e.g., SE-to-SE) also yielded better distortion correction. While the ideal distortion compensation approach likely varies depending on methodological differences across experiments, this study provides a framework for quantitative comparison of different distortion compensation methods.

Salience and central executive networks track overgeneralization of conditioned-fear in post-traumatic stress disorder.

BACKGROUND: Generalization of conditioned-fear, a core feature of post-traumatic stress disorder (PTSD), has been the focus of several recent neuroimaging studies. A striking outcome of these studies is the frequency with which neural correlates of generalization fall within hubs of well-established functional networks including salience (SN), central executive (CEN), and default networks (DN). Neural substrates of generalization found to date may thus reflect traces of large-scale brain networks that form more expansive neural representations of generalization. The present study includes the first network-based analysis of generalization and PTSD-related abnormalities therein. METHODS: fMRI responses in established intrinsic connectivity networks (ICNs) representing SN, CEN, and DN were assessed during a generalized conditioned-fear task in male combat veterans (N = 58) with wide-ranging PTSD symptom severity. The task included five rings of graded size. Extreme sizes served as conditioned danger-cues (CS+: paired with shock) and safety-cues (CS-), and the three intermediate sizes served as generalization stimuli (GSs) forming a continuum-of-size between CS+ and CS-. Generalization-gradients were assessed as behavioral and ICN response slopes from CS+, through GSs, to CS-. Increasing PTSD symptomatology was predicted to relate to less-steep slopes indicative of stronger generalization. RESULTS: SN, CEN, and DN responses fell along generalization-gradients with levels of generalization within and between SN and CEN scaling with PTSD symptom severity. CONCLUSIONS: Neural substrates of generalized conditioned-fear include large-scale networks that adhere to the functional organization of the brain. Current findings implicate levels of generalization in SN and CEN as promising neural markers of PTSD.

Cortical Correlates of Attention to Auditory Features.

Pitch and timbre are two primary features of auditory perception that are generally considered independent. However, an increase in pitch (produced by a change in fundamental frequency) can be confused with an increase in brightness (an attribute of timbre related to spectral centroid) and vice versa. Previous work indicates that pitch and timbre are processed in overlapping regions of the auditory cortex, but are separable to some extent via multivoxel pattern analysis. Here, we tested whether attention to one or other feature increases the spatial separation of their cortical representations and if attention can enhance the cortical representation of these features in the absence of any physical change in the stimulus. Ten human subjects (four female, six male) listened to pairs of tone triplets varying in pitch, timbre, or both and judged which tone triplet had the higher pitch or brighter timbre. Variations in each feature engaged common auditory regions with no clear distinctions at a univariate level. Attending to one did not improve the separability of the neural representations of pitch and timbre at the univariate level. At the multivariate level, the classifier performed above chance in distinguishing between conditions in which pitch or timbre was discriminated. The results confirm that the computations underlying pitch and timbre perception are subserved by strongly overlapping cortical regions, but reveal that attention to one or other feature leads to distinguishable activation patterns even in the absence of physical differences in the stimuli.SIGNIFICANCE STATEMENT Although pitch and timbre are generally thought of as independent auditory features of a sound, pitch height and timbral brightness can be confused for one another. This study shows that pitch and timbre variations are represented in overlapping regions of auditory cortex, but that they produce distinguishable patterns of activation. Most importantly, the patterns of activation can be distinguished based on whether subjects attended to pitch or timbre even when the stimuli remained physically identical. The results therefore show that variations in pitch and timbre are represented by overlapping neural networks, but that attention to different features of the same sound can lead to distinguishable patterns of activation.

Representations of Pitch and Timbre Variation in Human Auditory Cortex.

Pitch and timbre are two primary dimensions of auditory perception, but how they are represented in the human brain remains a matter of contention. Some animal studies of auditory cortical processing have suggested modular processing, with different brain regions preferentially coding for pitch or timbre, whereas other studies have suggested a distributed code for different attributes across the same population of neurons. This study tested whether variations in pitch and timbre elicit activity in distinct regions of the human temporal lobes. Listeners were presented with sequences of sounds that varied in either fundamental frequency (eliciting changes in pitch) or spectral centroid (eliciting changes in brightness, an important attribute of timbre), with the degree of pitch or timbre variation in each sequence parametrically manipulated. The BOLD responses from auditory cortex increased with increasing sequence variance along each perceptual dimension. The spatial extent, region, and laterality of the cortical regions most responsive to variations in pitch or timbre at the univariate level of analysis were largely overlapping. However, patterns of activation in response to pitch or timbre variations were discriminable in most subjects at an individual level using multivoxel pattern analysis, suggesting a distributed coding of the two dimensions bilaterally in human auditory cortex. SIGNIFICANCE STATEMENT: Pitch and timbre are two crucial aspects of auditory perception. Pitch governs our perception of musical melodies and harmonies, and conveys both prosodic and (in tone languages) lexical information in speech. Brightness-an aspect of timbre or sound quality-allows us to distinguish different musical instruments and speech sounds. Frequency-mapping studies have revealed tonotopic organization in primary auditory cortex, but the use of pure tones or noise bands has precluded the possibility of dissociating pitch from brightness. Our results suggest a distributed code, with no clear anatomical distinctions between auditory cortical regions responsive to changes in either pitch or timbre, but also reveal a population code that can differentiate between changes in either dimension within the same cortical regions.

Spontaneous neural activity differences in posttraumatic stress disorder: A quantitative resting-state meta-analysis and fMRI validation.

Identifying the pathophysiology of posttraumatic stress disorder (PTSD) is a critical step toward reducing its debilitating impact. Spontaneous neural activity, measured at rest using various neuroimaging techniques (e.g., regional homogeneity [ReHo], amplitude of low frequency fluctuations [ALFF]), can provide insight about baseline neurobiological factors influencing sensory, cognitive, or behavioral processes associated with PTSD. The present study used activation likelihood estimation (ALE) to conduct the largest-to-date quantitative meta-analysis of spontaneous neural activity in PTSD, including 457 PTSD cases, 292 trauma-exposed controls (TECs), and 293 non-traumatized controls (NTCs) across 22 published studies. Five regions-of-interest (ROIs) were identified where activity differed between PTSD cases and controls: one when compared to all controls (left globus pallidus), two when compared to TECs (left inferior parietal lobule [IPL] and right lingual gyrus), and two when compared to NTCs (left amygdala and right caudate head). To corroborate these results, a second analysis was conducted using resting-state functional magnetic resonance imaging on an independent sample of 205 previously-deployed US military veterans. In this analysis, converging evidence from ReHo and ALFF showed that spontaneous neural activity in the left IPL alone was positively correlated with PTSD symptom severity. This result is consistent with theoretical accounts that link left IPL activity with PTSD-relevant processes such as processing of emotional stimuli (e.g., fearful faces) and the extent that attention is captured by salient autobiographical memories. By modeling the neurobiological correlates of PTSD, we can increase our understanding of this debilitating disorder and guide the development of future clinical innovations.

Conflicting demands of abstract and specific visual object processing resolved by frontoparietal networks.

Object categorization and exemplar identification place conflicting demands on the visual system, yet humans easily perform these fundamentally contradictory tasks. Previous studies suggest the existence of dissociable visual processing subsystems to accomplish the two abilities-an abstract category (AC) subsystem that operates effectively in the left hemisphere and a specific exemplar (SE) subsystem that operates effectively in the right hemisphere. This multiple subsystems theory explains a range of visual abilities, but previous studies have not explored what mechanisms exist for coordinating the function of multiple subsystems and/or resolving the conflicts that would arise between them. We collected functional MRI data while participants performed two variants of a cue-probe working memory task that required AC or SE processing. During the maintenance phase of the task, the bilateral intraparietal sulcus (IPS) exhibited hemispheric asymmetries in functional connectivity consistent with exerting proactive control over the two visual subsystems: greater connectivity to the left hemisphere during the AC task, and greater connectivity to the right hemisphere during the SE task. Moreover, probe-evoked activation revealed activity in a broad frontoparietal network (containing IPS) associated with reactive control when the two visual subsystems were in conflict, and variations in this conflict signal across trials was related to the visual similarity of the cue-probe stimulus pairs. Although many studies have confirmed the existence of multiple visual processing subsystems, this study is the first to identify the mechanisms responsible for coordinating their operations.

Responses in early visual areas to contour integration are context dependent.

It has been shown that early visual areas are involved in contour processing. However, it is not clear how local and global context interact to influence responses in those areas, nor has the interarea coordination that yields coherent structural percepts been fully studied, especially in human observers. In this study, we used functional magnetic resonance imaging (fMRI) to measure activity in early visual cortex while observers performed a contour detection task in which alignment of Gabor elements and background clutter were manipulated. Six regions of interest (two regions, containing either the cortex representing the target or the background clutter, in each of areas V1, V2, and V3) were predefined using separate target versus background functional localizer scans. The first analysis using a general linear model showed that in the presence of background clutter, responses in V1 and V2 target regions of interest were significantly stronger to aligned than unaligned contours, whereas when background clutter was absent, no significant difference was observed. The second analysis using interarea correlations showed that with background clutter, there was an increase in V1-V2 coordination within the target regions when perceiving aligned versus unaligned contours; without clutter, however, correlations between V1 and V2 were similar no matter whether aligned contours were present or not. Both the average response magnitude and the connectivity analysis suggest different mechanisms support contour processing with or without background distractors. Coordination between V1 and V2 may play a major role in coherent structure perception, especially with complex scene organization.

The effects of orientation and attention during surround suppression of small image features: A 7 Tesla fMRI study.

Although V1 responses are driven primarily by elements within a neuron's receptive field, which subtends about 1° visual angle in parafoveal regions, previous work has shown that localized fMRI responses to visual elements reflect not only local feature encoding but also long-range pattern attributes. However, separating the response to an image feature from the response to the surrounding stimulus and studying the interactions between these two responses demands both spatial precision and signal independence, which may be challenging to attain with fMRI. The present study used 7 Tesla fMRI with 1.2-mm resolution to measure the interactions between small sinusoidal grating patches (targets) at 3° eccentricity and surrounds of various sizes and orientations to test the conditions under which localized, context-dependent fMRI responses could be predicted from either psychophysical or electrophysiological data. Targets were presented at 8%, 16%, and 32% contrast while manipulating (a) spatial extent of parallel (strongly suppressive) or orthogonal (weakly suppressive) surrounds, (b) locus of attention, (c) stimulus onset asynchrony between target and surround, and (d) blocked versus event-related design. In all experiments, the V1 fMRI signal was lower when target stimuli were flanked by parallel versus orthogonal context. Attention amplified fMRI responses to all stimuli but did not show a selective effect on central target responses or a measurable effect on orientation-dependent surround suppression. Suppression of the V1 fMRI response by parallel surrounds was stronger than predicted from psychophysics but showed a better match to previous electrophysiological reports.

DLPFC stimulation alters working memory related activations and performance: An interleaved TMS-fMRI study.

BACKGROUND: Findings from correlative neuroimaging studies link increased frontoparietal network (FPN) activation and default mode network (DMN) deactivation to enhanced high cognitive demand processing. To causally investigate FPN-DMN contributions to high cognitive demand processing, the current interleaved TMS-fMRI study simultaneously manipulated and indexed neural activity while tracking cognitive performance during high and low cognitive load conditions. METHODS: Twenty participants completed an n-back task consisting of four conditions (0-back, 0-backTMS, 2-back, 2-backTMS) while undergoing interleaved TMS-fMRI. During TMS concurrent with n-back blocks, TMS single pulses were delivered to the left DLPFC at 100% motor-threshold every 2.4s. RESULTS: TMS delivered during high cognitive load strengthened cognitive processing. FPN node activations and DMN node deactivations were increased in the high versus low cognitive load TMS condition. Contrary to our hypothesis, TMS did not increase high load related activation in FPN nodes. However, as hypothesized, increased DMN node deactivations emerged as a function of TMS during high load (right angular gyrus) and from interactions between cognitive load and TMS (right middle temporal gyrus). Load and TMS combined to dampen activation within the DMN at trend level (p = .058). Deactivation in a dorsomedial DMN node was associated with TMS driven improvements in high load cognitive processing. CONCLUSIONS: Exogenous perturbation of the DLPFC via single pulse TMS amplified DMN node deactivations and enhanced high cognitive demand processing. Neurobehavioral findings linking these effects hint at a promising, albeit preliminary, cognitive control substrate requiring replication in higher-powered studies that use control stimulation.

"Better the devil you know": a preliminary study of the differential modulating effects of reputation on reward processing for boys with and without externalizing behavior problems.

Very little is known about the neurobiological correlates of reward processing during social decision-making in the developing brain and whether prior social and moral information (reputations) modulates reward responses in youth as has been demonstrated in adults. Moreover, although externalizing behavior problems in youth are associated with deficits in reward processing and social cognition, a real-life social interaction paradigm using functional neuroimaging (fMRI) has not yet been applied to probe reward processing in such youth. Functional neuroimaging was used to examine the neural correlates of reward-related decision-making during a trust task in two samples of age-matched 11 to 16-year-old boys: with (n = 10) and without (n = 10) externalizing behavior problems. The task required subjects to decide whether to share or keep monetary rewards from partners they themselves identified during a real-life peer sociometric procedure as interpersonally aggressive or kind (vs. neutral). Results supported the notion that prior social and moral information (reputations) modulated reward responses in the adolescent brain. Moreover, boys with externalizing problems showed differential activation in the bilateral insula during the decision phase of the game as well as the caudate and anterior insula during the outcome phase of the game. Similar activation in adolescents in response to reward related stimuli as found in adults suggests some developmental continuity in corticostriatal circuits. Group differences are interpreted with caution given the small group sizes in the current study. Notwithstanding this limitation, the study provides preliminary evidence for anomalous reward responses in boys with externalizing behavior problems, thereby providing a possible biological correlate of well-established social-cognitive and reward-related theories of externalizing behavior disorders.

Aberrant Cortical Connectivity During Ambiguous Object Recognition Is Associated With Schizophrenia.

BACKGROUND: Dysfunctional connectivity within the perceptual hierarchy is proposed to be an integral component of psychosis. The fragmented ambiguous object task was implemented to investigate neural connectivity during object recognition in patients with schizophrenia (SCZ) and bipolar disorder and first-degree relatives of patients with SCZ (SREL). METHODS: We analyzed 3T functional magnetic resonance imaging data collected from 27 patients with SCZ, 23 patients with bipolar disorder, 24 control subjects, and 19 SREL during the administration of the fragmented ambiguous object task. Fragmented ambiguous object task stimuli were line-segmented versions of objects and matched across a number of low-level features. Images were categorized as meaningful or meaningless based on ratings assigned by the participants. RESULTS: An a priori region of interest was defined in the primary visual cortex (V1). In addition, the lateral occipital complex/ventral visual areas, intraparietal sulcus (IPS), and middle frontal gyrus (MFG) were identified functionally via the contrast of cortical responses to stimuli judged as meaningful or meaningless. SCZ was associated with altered neural activations at V1, IPS, and MFG. Psychophysiological interaction analyses revealed negative connectivity between V1 and MFG in patient groups and altered modulation of connectivity between conditions from right IPS to left IPS and right IPS to left MFG in patients with SCZ and SREL. CONCLUSIONS: Results provide evidence that SCZ is associated with inefficient processing of ambiguous visual objects at V1, which is likely attributable to altered feedback from higher-level visual areas. We also observed distinct patterns of aberrant connectivity among low-level, mid-level, and high-level visual areas in patients with SCZ, patients with bipolar disorder, and SREL.

The neurobiology of human fear generalization: meta-analysis and working neural model.

Fear generalization to stimuli resembling a conditioned danger-cue (CS+) is a fundamental dynamic of classical fear-conditioning. Despite the ubiquity of fear generalization in human experience and its known pathogenic contribution to clinical anxiety, neural investigations of human generalization have only recently begun. The present work provides the first meta-analysis of this growing literature to delineate brain substrates of conditioned fear-generalization and formulate a working neural model. Included studies (K = 6, N = 176) reported whole-brain fMRI results and applied generalization-gradient methodology to identify brain activations that gradually strengthen (positive generalization) or weaken (negative generalization) as presented stimuli increase in CS+ resemblance. Positive generalization was instantiated in cingulo-opercular, frontoparietal, striatal-thalamic, and midbrain regions (locus coeruleus, periaqueductal grey, ventral tegmental area), while negative generalization was implemented in default-mode network nodes (ventromedial prefrontal cortex, hippocampus, middle temporal gyrus, angular gyrus) and amygdala. Findings are integrated within an updated neural account of generalization centering on the hippocampus, its modulation by locus coeruleus and basolateral amygdala, and the excitation of threat- or safety-related loci by the hippocampus.

Posttraumatic stress symptomatology and abnormal neural responding during emotion regulation under cognitive demands: mediating effects of personality.

Posttraumatic stress disorder (PTSD) is often complicated by the after-effects of mild traumatic brain injury (mTBI). The mixture of brain conditions results in abnormal affective and cognitive functioning, as well as maladaptive behavior. To better understand how brain activity explains cognitive and emotional processes in these conditions, we used an emotional N-back task and functional magnetic resonance imaging (fMRI) to study neural responses in US military veterans after deployments to Iraq and Afghanistan. Additionally, we sought to examine whether hierarchical dimensional models of maladaptive personality could account for the relationship between combat-related brain conditions and fMRI responses under cognitive and affective challenge. FMRI data, measures of PTSD symptomatology (PTSS), blast-induced mTBI (bmTBI) severity, and maladaptive personality (MMPI-2-RF) were gathered from 93 veterans. Brain regions central to emotion regulation were selected for analysis, and consisted of bilateral amygdala, bilateral dorsolateral prefrontal (dlPFC), and ventromedial prefrontal/subgenual anterior cingulate (vmPFC-sgACC). Cognitive load increased activity in dlPFC and reduced activity in emotional responding brain regions. However, individuals with greater PTSS showed blunted deactivations in bilateral amygdala and vmPFC-sgACC, and weaker responses in right dlPFC. Additionally, we found that elevated emotional/internalizing dysfunction (EID), specifically low positive emotionality (RC2), accounted for PTSS-related changes in bilateral amygdala under increased cognitive load. Findings suggest that PTSS might result in amygdala and vmPFC-sgACC activity resistant to moderation by cognitive demands, reflecting emotion dysregulation despite a need to marshal cognitive resources. Anhedonia may be an important target for interventions that improve the affective and cognitive functioning of individuals with PTSD.

Converging functional magnetic resonance imaging evidence for a role of the left inferior frontal lobe in semantic retention during language comprehension.

Increasing evidence supports dissociable short-term memory (STM) capacities for semantic and phonological representations. Cognitive neuropsychological data suggest that damage to the left inferior and middle frontal gyri are associated with deficits of semantic STM, while damage to inferior parietal areas is associated with deficits of phonological STM. Patients identified as having semantic STM deficits are also impaired on a number of language comprehension and production paradigms. We used one such comprehension task derived from cognitive neuropsychological data to test predictions with functional magnetic resonance imaging (fMRI) using healthy participants. Using a task that required participants to make semantic anomaly judgements, we found significantly greater activation in areas of the left inferior frontal and middle frontal gyri for phrases that required maintenance of multiple words for eventual integration with a subsequent noun or verb. These data are consistent with our previous patient studies (Hanten & Martin, 2000; R. C. Martin & He, 2004; R. C. Martin & Romani, 1994 ) that suggest that semantic STM is associated with the left inferior and middle frontal gyri and that deficits of semantic STM have particular consequences for comprehension tasks that require maintenance of several word meanings in unintegrated form.

Fragmented ambiguous objects: Stimuli with stable low-level features for object recognition tasks.

Visual object recognition is a complex skill that relies on the interaction of many spatially distinct and specialized visual areas in the human brain. One tool that can help us better understand these specializations and interactions is a set of visual stimuli that do not differ along low-level dimensions (e.g., orientation, contrast) but do differ along high-level dimensions, such as whether a real-world object can be detected. The present work creates a set of line segment-based images that are matched for luminance, contrast, and orientation distribution (both for single elements and for pair-wise combinations) but result in a range of object and non-object percepts. Image generation started with images of isolated objects taken from publicly available databases and then progressed through 3-stages: a computer algorithm generating 718 candidate images, expert observers selecting 217 for further consideration, and naïve observers performing final ratings. This process identified a set of 100 images that all have the same low-level properties but cover a range of recognizability (proportion of naïve observers (N = 120) who indicated that the stimulus "contained a known object") and semantic stability (consistency across the categories of living, non-living/manipulable, and non-living/non-manipulable when the same observers named "known" objects). Stimuli are available at https://github.com/caolman/FAOT.git.

Functional Magnetic Resonance Imaging and Oculomotor Dysfunction in Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is a significant cause of disability, especially when symptoms become chronic. This chronicity is often linked to oculomotor dysfunction (OMD). To our knowledge, this is the first prospective study to localize aberrations in brain function between mTBI cohorts, by comparing patients with mTBI with OMD with an mTBI control group without OMD, using task and resting-state functional magnetic resonance imaging (fMRI). Ten subjects with mTBI who had OMD (OMD group) were compared with nine subjects with mTBI who had no findings of OMD (control group). These groups were determined by a developmental optometrist using objective testing for OMD. The (convergence) task fMRI data demonstrated significantly decreased brain activity, measured as decreases in the blood oxygen level dependent (BOLD) signal, in the OMD group compared with the control group in three brain regions: the left posterior lingual gyrus, the bilateral anterior lingual gyrus and cuneus, and the parahippocampal gyrus. When doing a seed-based resting state fMRI analysis in the lingual/parahippocampal region, a large cluster covering the left middle frontal gyrus and the dorsolateral pre-frontal cortex (Brodmann areas 9 and 10), with decreased functional correlation in the OMD group, was identified. Together these observations provide evidence for neural networks of interactions involving the control of eye movement for visual processing, reading comprehension, spatial localization and navigation, and spatial working memory that appear to be decreased in mTBI patients with OMD compared with mTBI patients without OMD. The clinical symptomatology associated with post-traumatic OMD correlates well with these MRI findings.