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Joseph M. Orr

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

7 papers

1 author row

YNICL Journal 2020 Journal Article

Adolescents at clinical high risk for psychosis show qualitatively altered patterns of activation during rule learning

Joseph M. Orr
Jesus Lopez
Michael J. Imburgio
Andrea Pelletier-Baldelli
Jessica A. Bernard
Vijay A. Mittal

BACKGROUND: The ability to flexibly apply rules to novel situations is a critical aspect of adaptive human behavior. While executive function deficits are known to appear early in the course of psychosis, it is unclear which specific facets are affected. Identifying whether rule learning is impacted at the early stages of psychosis is necessary for truly understanding the etiology of psychosis and may be critical for designing novel treatments. Therefore, we examined rule learning in healthy adolescents and those meeting criteria for clinical high risk (CHR) for psychosis. METHODS: 24 control and 22 CHR adolescents underwent rapid, high-resolution fMRI while performing a paradigm which required them to apply novel or practiced task rules. RESULTS: Previous work has suggested that practiced rules rely on rostrolateral prefrontal cortex (RLPFC) during rule encoding and dorsolateral prefrontal cortex (DLPFC) during task performance, while novel rules show the opposite pattern. We failed to replicate this finding, with greater activity for novel rules during performance. Comparing the HC and CHR group, there were no statistically significant effects, but an effect size analysis found that the CHR group showed less activation during encoding and greater activation during performance. This suggests the CHR group may use less efficient reactive control to retrieve task rules at the time of task performance, rather than proactively during rule encoding. CONCLUSIONS: These findings suggest that flexibility is qualitatively altered in the clinical high risk state, however, more data is needed to determine whether these deficits predict disease progression.

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YNICL Journal 2018 Journal Article

The cerebellum and learning of non-motor associations in individuals at clinical-high risk for psychosis

Jessica A. Bernard
Joseph M. Orr
Derek J. Dean
Vijay A. Mittal

The cerebello-thalamo-cortical circuit (CTCC) has been implicated in schizophrenia. However, this work has been limited to structural and functional networks, or behavior, and to date, has not been evaluated in clinical high-risk (CHR) youth, a group at elevated risk for psychosis. Here, we used an innovative learning paradigm known to activate the CTCC (while limiting potential motor confounds) to evaluate CHR and healthy control individuals during functional magnetic resonance imaging (fMRI). 20 CHR and 21 healthy control individuals performed a second-order rule learning task while undergoing fMRI. This was preceded and followed by the paradigm under dual-task conditions. In addition, all participants underwent structured clinical interviews to confirm a prodromal syndrome and assess symptom severity. The rate of learning did not differ between groups. However, the CHR group consistently performed more poorly under dual-task conditions, and exhibited a higher dual-task cost after learning. Further, learning rate in the CHR group was significantly associated with symptom severity. Both groups showed activation in regions of the CTCC. During early learning, the CHR group exhibited greater engagement of regions of the default mode network, suggesting that they were less able to engage the appropriate task positive networks. During late learning, there were qualitative differences wherein controls showed more prefrontal cortical activation. Higher order cognitive rule learning is related to symptom severity in CHR individuals. fMRI revealed that CHR individuals may not reliably disengage the default mode network, and during late learning high-risk youth may not engage the prefrontal cortex as extensively as controls.

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YNICL Journal 2017 Journal Article

Cerebello-thalamo-cortical networks predict positive symptom progression in individuals at ultra-high risk for psychosis

Jessica A. Bernard
Joseph M. Orr
Vijay A. Mittal

Prospective longitudinal evaluation of adolescents at ultra-high-risk (UHR) for the development of psychosis enables an enriched neurodevelopmental perspective of disease progression in the absence of many of the factors that typically confound research with formally psychotic patients (antipsychotic medications, drug/alcohol dependence). The cerebellum has been linked to cognitive dysfunction and symptom severity in schizophrenia and recent work from our team suggests that it is a promising target for investigation in UHR individuals as well. However, the cerebellum and cerebello-thalamo-cortical networks have not been investigated developmentally or with respect to disease progression in this critical population. Further, to date, the types of longitudinal multimodal connectivity studies that would substantially inform our understanding of this area have not yet been conducted. In the present investigation 26 UHR and 24 healthy control adolescents were administered structured clinical interviews and scanned at baseline and then again at 12-month time points to investigate both functional and structural connectivity development of cerebello-thalamo-cortical networks in conjunction with symptom progression. Our results provide evidence of abnormal functional and structural cerebellar network development in the UHR group. Crucially, we also found that cerebello-thalamo-cortical network development and connectivity at baseline are associated with positive symptom course, suggesting that cerebellar networks may be a biomarker of disease progression. Together, these findings provide support for neurodevelopmental models of psychotic disorders and suggest that the cerebellum and respective networks with the cortex may be especially important for elucidating the pathophysiology of psychosis and highlighting novel treatment targets.

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YNIMG Journal 2016 Journal Article

Differential motor and prefrontal cerebello-cortical network development: Evidence from multimodal neuroimaging

Jessica A. Bernard
Joseph M. Orr
Vijay A. Mittal

While our understanding of cerebellar structural development through adolescence and young adulthood has expanded, we still lack knowledge of the developmental patterns of cerebellar networks during this critical portion of the lifespan. Volume in lateral posterior cerebellar regions associated with cognition and the prefrontal cortex develops more slowly, reaching their peak volume in adulthood, particularly as compared to motor Lobule V. We predicted that resting state functional connectivity of the lateral posterior regions would show a similar pattern of development during adolescence and young adulthood. That is, we expected to see changes over time in Crus I and Crus II connectivity with the cortex, but no changes in Lobule V connectivity. Additionally, we were interested in how structural connectivity changes in cerebello-thalamo-cortical white matter are related to changes in functional connectivity. A sample of 23 individuals between 12 and 21years old underwent neuroimaging scans at baseline and 12months later. Functional networks of Crus I and Crus II showed significant connectivity decreases over 12months, though there were no differences in Lobule V. Furthermore, these functional connectivity changes were correlated with increases in white matter structural integrity in the corresponding cerebello-thalamo-cortical white matter tract. We suggest that these functional network changes are due to both later pruning in the prefrontal cortex as well as further development of the white matter tracts linking these brain regions.

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YNICL Journal 2016 Journal Article

Recreational marijuana use impacts white matter integrity and subcortical (but not cortical) morphometry

Joseph M. Orr
Courtnie J. Paschall
Marie T. Banich

A recent shift in legal and social attitudes toward marijuana use has also spawned a surge of interest in understanding the effects of marijuana use on the brain. There is considerable evidence that an adolescent onset of marijuana use negatively impacts white matter coherence. On the other hand, a recent well-controlled study demonstrated no effects of marijuana use on the morphometry of subcortical or cortical structures when users and non-users were matched for alcohol use. Regardless, most studies have involved small, carefully selected samples, so the ability to generalize to larger populations is limited. In an attempt to address this issue, we examined the effects of marijuana use on white matter integrity and cortical and subcortical morphometry using data from the Human Connectome Project (HCP) consortium. The HCP data consists of ultra-high resolution neuroimaging data from a large community sample, including 466 adults reporting recreational marijuana use. Rather than just contrasting two groups of individuals who vary significantly in marijuana usage as typifies prior studies, we leveraged the large sample size provided by the HCP data to examine parametric effects of recreational marijuana use. Our results indicate that the earlier the age of onset of marijuana use, the lower was white matter coherence. Age of onset also also affected the shape of the accumbens, while the number of lifetime uses impacted the shape of the amygdala and hippocampus. Marijuana use had no effect on cortical volumes. These findings suggest subtle but significant effects of recreational marijuana use on brain structure.

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YNIMG Journal 2014 Journal Article

The neural mechanisms underlying internally and externally guided task selection

Joseph M. Orr
Marie T. Banich

While some prior work suggests that medial prefrontal cortex (MFC) regions mediate freely chosen actions, other work suggests that the lateral frontal pole (LFP) is responsible for control of abstract, internal goals. The present study uses fMRI to determine whether the voluntary selection of a task in pursuit of an overall goal relies on MFC regions or the LFP. To do so, we used a modified voluntary task switching (VTS) paradigm, in which participants choose an individual task to perform on each trial (i. e. , a subgoal), under instructions to perform the tasks equally often and in a random order (i. e. the overall goal). In conjunction, we examined patterns of activation in the face of irrelevant, but task-related external stimuli that might nonetheless influence task selection. While there was some evidence that the MFC was involved in voluntary task selection, we found that the LFP and anterior insula (AI) were crucial to task selection in the pursuit of an overall goal. In addition, activation of the LFP and AI increased in the face of environmental stimuli that might serve as an interfering or conflicting external bias on voluntary task choice. These findings suggest that the LFP supports task selection according to abstract, internal goals, and leaves open the possibility that MFC may guide action selection in situations lacking in such top-down biases. As such, the current study represents a critical step towards understanding the neural underpinnings of how tasks are selected voluntarily to enable an overarching goal.

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YNICL Journal 2014 Journal Article

Widespread brain dysconnectivity associated with psychotic-like experiences in the general population

Joseph M. Orr
Jessica A. Turner
Vijay A. Mittal

It is becoming increasingly clear that psychosis occurs along a continuum. At the high end are formal psychotic disorders such as schizophrenia, and at the low-end are individuals who experience occasional psychotic symptoms, but are otherwise healthy (non-clinical psychosis, NCP). Schizophrenia has been shown to be marked by altered patterns of connectivity between brain regions, but it is not known if such dysconnectivity exists in NCP. In the current study we used functional magnetic resonance imaging (fMRI) to compare resting-state functional connectivity in NCP individuals (n =25) and healthy controls (n =27) for four brain networks of interest (fronto-parietal, cingulo-opercular, default mode, and cerebellar networks). NCP individuals showed reduced connectivity compared to controls between regions of the default mode network and frontal regions, and between regions in all of the networks and the thalamus. NCP individuals showed greater connectivity compared to controls within regions of frontal control networks. Further, positive symptom scores in NCP individuals were positively correlated with connectivity between the cingulo-opercular network and the visual cortex, and were negatively correlated with connectivity between the cerebellar network and the posterior parietal cortex and dorsal premotor cortex. Connectivity was not correlated with positive symptom scores in controls. Taken together, these findings demonstrate that a spectrum of abnormal connectivity underlies the psychosis continuum, and that individuals with sub-clinical psychotic experiences represent a key population for understanding pathogenic processes.

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