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Cameron S. Carter

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13 papers
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13

YNICL Journal 2022 Journal Article

Data augmentation with Mixup: Enhancing performance of a functional neuroimaging-based prognostic deep learning classifier in recent onset psychosis

  • Jason Smucny
  • Ge Shi
  • Tyler A. Lesh
  • Cameron S. Carter
  • Ian Davidson

Although deep learning holds great promise as a prognostic tool in psychiatry, a limitation of the method is that it requires large training sample sizes to achieve replicable accuracy. This is problematic for fMRI datasets as they are typically small due to the considerable time, cost, and resources necessary to obtain them. A recently developed self-supervised learning method called Mixup may help overcome this challenge. In Mixup, the learner combines pairs of training instances to produce a virtual third instance that is a linear combination of the two instances and their labels. This procedure is also well-suited to the coregistered images typically found in fMRI datasets. Here we compared performance of a task fMRI-based deep learner with Mixup vs without Mixup on predicting response to treatment in recent onset psychosis. Whole brain fMRI time series data were extracted from a cognitive control task in 82 patients with recent onset psychosis and used to predict "Improver" (n = 47) vs "Non-Improver" (n = 35) status, with Improver defined as showing a 20 % reduction in total Brief Psychiatric Rating Scale score after 1 year of treatment. Mixup significantly improved performance (accuracy without Mixup: 76.5 % [95 % CI: 75.9-77.1 %]; accuracy with Mixup: 80.1 % [95 % CI: 79.4-80.8 %]). Ablation showed the improvement was due to improvement in both Improvers and Non-Improvers. These results suggest that using Mixup may significantly improve performance and reduce overfitting of fMRI-based prognostic deep learners and may also help overcome the small sample size challenge inherent to many neuroimaging datasets.

YNICL Journal 2019 Journal Article

A multicenter study of ketamine effects on functional connectivity: Large scale network relationships, hubs and symptom mechanisms

  • Leah M. Fleming
  • Daniel C. Javitt
  • Cameron S. Carter
  • Joshua T. Kantrowitz
  • Ragy R. Girgis
  • Lawrence S. Kegeles
  • John D. Ragland
  • Richard J. Maddock

Ketamine is an uncompetitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist. It induces effects in healthy individuals that mimic symptoms associated with schizophrenia. We sought to root these experiences in altered brain function, specifically aberrant resting state functional connectivity (rsfMRI). In the present study, we acquired rsfMRI data under ketamine and placebo in a between-subjects design and analyzed seed-based measures of rsfMRI using large-scale networks, dorsolateral prefrontal cortex (DLPFC) and sub-nuclei of the thalamus. We found ketamine-induced alterations in rsfMRI connectivity similar to those seen in patients with schizophrenia, some changes that may be more comparable to early stages of schizophrenia, and other connectivity signatures seen in patients that ketamine did not recreate. We do not find any circuits from our regions of interest that correlates with positive symptoms of schizophrenia in our sample, although we find that DLPFC connectivity with ACC does correlate with a mood measure. These results provide support for ketamine's use as a model of certain biomarkers of schizophrenia, particularly for early or at-risk patients.

YNICL Journal 2017 Journal Article

Functional network changes and cognitive control in schizophrenia

  • Kimberly L. Ray
  • Tyler A. Lesh
  • Amber M. Howell
  • Taylor P. Salo
  • J. Daniel Ragland
  • Angus W. MacDonald
  • James M. Gold
  • Steven M. Silverstein

Cognitive control is a cognitive and neural mechanism that contributes to managing the complex demands of day-to-day life. Studies have suggested that functional impairments in cognitive control associated brain circuitry contribute to a broad range of higher cognitive deficits in schizophrenia. To examine this issue, we assessed functional connectivity networks in healthy adults and individuals with schizophrenia performing tasks from two distinct cognitive domains that varied in demands for cognitive control, the RiSE episodic memory task and DPX goal maintenance task. We characterized general and cognitive control-specific effects of schizophrenia on functional connectivity within an expanded frontal parietal network (FPN) and quantified network topology properties using graph analysis. Using the network based statistic (NBS), we observed greater network functional connectivity in cognitive control demanding conditions during both tasks in both groups in the FPN, and demonstrated cognitive control FPN specificity against a task independent auditory network. NBS analyses also revealed widespread connectivity deficits in schizophrenia patients across all tasks. Furthermore, quantitative changes in network topology associated with diagnostic status and task demand were observed. The present findings, in an analysis that was limited to correct trials only, ensuring that subjects are on task, provide critical insights into network connections crucial for cognitive control and the manner in which brain networks reorganize to support such control. Impairments in this mechanism are present in schizophrenia and these results highlight how cognitive control deficits contribute to the pathophysiology of this illness.

YNICL Journal 2013 Journal Article

Proactive and reactive cognitive control and dorsolateral prefrontal cortex dysfunction in first episode schizophrenia

  • Tyler A. Lesh
  • Andrew J. Westphal
  • Tara A. Niendam
  • Jong H. Yoon
  • Michael J. Minzenberg
  • J. Daniel Ragland
  • Marjorie Solomon
  • Cameron S. Carter

Cognitive control deficits have been consistently documented in patients with schizophrenia. Recent work in cognitive neuroscience has hypothesized a distinction between two theoretically separable modes of cognitive control-reactive and proactive. However, it remains unclear the extent to which these processes are uniquely associated with dysfunctional neural recruitment in individuals with schizophrenia. This functional magnetic resonance imaging (fMRI) study utilized the color word Stroop task and AX Continuous Performance Task (AX-CPT) to tap reactive and proactive control processes, respectively, in a sample of 54 healthy controls and 43 patients with first episode schizophrenia. Healthy controls demonstrated robust dorsolateral prefrontal, anterior cingulate, and parietal cortex activity on both tasks. In contrast, patients with schizophrenia did not show any significant activation during proactive control, while showing activation similar to control subjects during reactive control. Critically, an interaction analysis showed that the degree to which prefrontal activity was reduced in patients versus controls depended on the type of control process engaged. Controls showed increased dorsolateral prefrontal cortex (DLPFC) and parietal activity in the proactive compared to the reactive control task, whereas patients with schizophrenia did not demonstrate this increase. Additionally, patients' DLPFC activity and performance during proactive control was associated with disorganization symptoms, while no reactive control measures showed this association. Proactive control processes and concomitant dysfunctional recruitment of DLPFC represent robust features of schizophrenia that are also directly associated with symptoms of disorganization.

YNIMG Journal 2012 Journal Article

Neural correlates of relational and item-specific encoding during working and long-term memory in schizophrenia

  • John D. Ragland
  • Robert S. Blumenfeld
  • Ian S. Ramsay
  • Andrew Yonelinas
  • Jong Yoon
  • Marjorie Solomon
  • Cameron S. Carter
  • Charan Ranganath

Successful long-term memory (LTM) depends upon effective control of information in working memory (WM), and there is evidence that both WM and LTM are impaired by schizophrenia. This study tests the hypothesis that LTM deficits in schizophrenia may result from impaired control of relational processing in WM due to dorsolateral prefrontal cortex (DLPFC) dysfunction. fMRI was performed on 19 healthy controls and 20 patients with schizophrenia during WM tasks emphasizing relational (reorder trials) versus item-specific (rehearse trials) processing. WM activity was also examined with respect to LTM recognition on a task administered outside the scanner. Receiver operator characteristic analysis assessed familiarity and recollection components of LTM. Patients showed a disproportionate familiarity deficit for reorder versus rehearse trials against a background of generalized LTM impairments. Relational processing during WM led to DLPFC activation in both groups. However, this activation was less focal in patients than in controls, and patients with more severe negative symptoms showed less of a DLPFC increase. fMRI analysis of subsequent recognition performance revealed a group by condition interaction. High LTM for reorder versus rehearse trials was associated with bilateral DLPFC activation in controls, but not in patients who activated the left middle temporal and inferior occipital gyrus. Results indicate that although patients can activate the DLPFC on a structured relational WM task, this activation is less focal and does not translate to high retrieval success, suggesting a disruption in the interaction between WM and LTM processes in schizophrenia.

YNIMG Journal 2007 Journal Article

Optimum template selection for atlas-based segmentation

  • Minjie Wu
  • Caterina Rosano
  • Pilar Lopez-Garcia
  • Cameron S. Carter
  • Howard J. Aizenstein

Atlas-based segmentation of MR brain images typically uses a single atlas (e. g. , MNI Colin27) for region identification. Normal individual variations in human brain structures present a significant challenge for atlas selection. Previous researches mainly focused on how to create a specific template for different requirements (e. g. , for a certain population). We address atlas selection with a different approach: instead of choosing a fixed brain atlas, we use a family of brain templates for atlas-based segmentation. For each subject and each region, the template selection method automatically chooses the ‘best’ template with the highest local registration accuracy, based on normalized mutual information. The region classification performances of the template selection method and the single template method were quantified by the overlap ratios (ORs) and intraclass correlation coefficients (ICCs) between the manual tracings and the respective automated labeled results. Two groups of brain images and multiple regions of interest (ROIs), including the right anterior cingulate cortex (ACC) and several subcortical structures, were tested for both methods. We found that the template selection method produced significantly higher ORs than did the single template method across all of the 13 analyzed ROIs (two-tailed paired t-test, right ACC at t(8)=4. 353, p =0. 0024; right amygdala, matched paired t test t(8)>3. 175, p <0. 013; for the remaining ROIs, t(8)=4. 36, p <0. 002). The template selection method also provided more reliable volume estimates than the single template method with increased ICCs. Moreover, the improved accuracy of atlas-based segmentation using optimum templates approaches the accuracy of manual tracing, and thus is valid for automated brain imaging analyses.

YNIMG Journal 2005 Journal Article

An information-processing model of three cortical regions: evidence in episodic memory retrieval

  • Myeong-Ho Sohn
  • Adam Goode
  • V. Andrew Stenger
  • Kwan-Jin Jung
  • Cameron S. Carter
  • John R. Anderson

ACT-R (Anderson, J. R. , et al. , 2003. An information-processing model of the BOLD response in symbol manipulation tasks. Psychon. Bull. Rev. 10, 241–261) relates the inferior dorso-lateral prefrontal cortex to a retrieval buffer that holds information retrieved from memory and the posterior parietal cortex to an imaginal buffer that holds problem representations. Because the number of changes in a problem representation is not necessarily correlated with retrieval difficulties, it is possible to dissociate prefrontal–parietal activations. In two fMRI experiments, we examined this dissociation using the fan effect paradigm. Experiment 1 compared a recognition task, in which representation requirement remains the same regardless of retrieval difficulty, with a recall task, in which both representation and retrieval loads increase with retrieval difficulty. In the recognition task, the prefrontal activation revealed a fan effect but not the parietal activation. In the recall task, both regions revealed fan effects. In Experiment 2, we compared visually presented stimuli and aurally presented stimuli using the recognition task. While only the prefrontal region revealed the fan effect, the activation patterns in the prefrontal and the parietal region did not differ by stimulus presentation modality. In general, these results provide support for the prefrontal–parietal dissociation in terms of retrieval and representation and the modality-independent nature of the information processed by these regions. Using ACT-R, we also provide computational models that explain patterns of fMRI responses in these two areas during recognition and recall.

YNIMG Journal 2005 Journal Article

Separating semantic conflict and response conflict in the Stroop task: A functional MRI study

  • Vincent van Veen
  • Cameron S. Carter

Attentive behavior requires the ability to perform in the face of distraction. Distracting information can cause conflict at any level along the information processing stream. However, it is not yet known whether the brain has distinct subsystems dedicated to detecting and resolving these different forms of distraction. Although previous studies have localized brain activity during semantic and response conflict, no prior study has specifically determined whether these activations occur in distinct or overlapping regions. We used a modified version of the Stroop color-word task, by which we were able to separate semantic from response conflict. Behavioral data indicate that these two kinds of conflict both contribute to the overall Stroop interference effect, while fMRI data indicate that they elicit non-overlapping activation in anterior cingulate, prefrontal, and parietal brain regions. These results suggest that the brain has distinct but parallel attentional mechanisms for resolving these different forms of cognitive interference.

YNIMG Journal 2001 Journal Article

Anterior Cingulate Cortex, Conflict Monitoring, and Levels of Processing

  • Vincent van Veen
  • Jonathan D. Cohen
  • Matthew M. Botvinick
  • V.Andrew Stenger
  • Cameron S. Carter

It has been hypothesized that the anterior cingulate cortex (ACC) contributes to cognition by detecting conflicts that might occur during information processing, to signal the need to engage top–down attentional processes. The present study was designed to investigate which levels of processing are being monitored by the ACC for the presence of conflict. Event-related fMRI was used to measure the response of the ACC during an interference task in which distracting information could be congruent, conflicting at the level of stimulus identification, or conflicting at the response level. Although both types of conflict caused reaction time interference, the fMRI data showed that the ACC is responsive only to response conflict, even when controlling for reaction times. These results suggest a highly specific contribution of the ACC to executive functions, through the detection of conflicts occurring at later or response-related levels of processing.

YNIMG Journal 1999 Journal Article

A Study of Injected Dose for Brain Mapping on the ECAT HR+: Activation Maps for a Parametric Verbal Working Memory Task

  • Roberto A. Isoardi
  • David W. Townsend
  • Cameron S. Carter
  • Amy Herbster
  • Marsha A. Dachille
  • Carolyn Cidis Meltzer

The success of the15O-water PET technique to localize statistically significant changes in regional cerebral blood flow is dependent on factors such as the activity level injected and the magnitude of the flow change. Undetectable changes may occur if insufficient activity is injected leading to high levels of statistical noise or the task performed results in only small changes in blood flow. To explore the relationship between injected activity and statistical significance, we performed a series of studies with the ECAT EXACT HR+, a high resolution PET tomograph. A parametric verbal working memory task (theN-back task) was selected to examine the relationship between regional cerebral blood flow and working memory load across a range of injected doses of15O-water. At each activity level the volunteers were required to perform four different levels of theN-back task, a task in which a letter displayed on a monitor is matched with the letter displayedNletters previously. With increasingN, this task places increased load on working memory. For this study, 5, 10, and 15 mCi of15O-water were injected into nine normal volunteers. The complete sequence of four tasks (N =0, 1, 2, and 3) at three activity levels was repeated twice, for a total of 24 injections of15O-water. We show that the peak count rate performance for the HR+ is approached at injected activity levels of15O-water around 15 mCi. For this particular choice ofN-back task, robust activation maps can nevertheless be obtained with as little as 5 mCi injected dose.

YNIMG Journal 1999 Journal Article

Overt Verbal Responding during fMRI Scanning: Empirical Investigations of Problems and Potential Solutions

  • Deanna M. Barch
  • Fred W. Sabb
  • Cameron S. Carter
  • Todd S. Braver
  • Douglas C. Noll
  • Jonathan D. Cohen

This paper presents a pair of studies designed to empirically explore the severity of potential artifacts associated with overt verbal responding during fMRI scanning and to examine several different solutions to these artifacts. In Study One, we compared susceptibility artifacts, signal-to-noise ratios, and activation patterns when overt versus covert verbal responses were elicited during fMRI scanning, using both individual and group analyses. The results indicated that different patterns of brain activation were elicited during covert as compared to overt verbal responses. This suggests that covert responses cannot be used as a simple substitute for overt verbal responses. Further, the results suggested that the use of overt verbal responses during fMRI scanning can produce interpretable results if: (1) the primary comparison is between two conditions that both use overt verbal responses, and (2) analyses are conducted on pooled group data rather than individual participant data. In Study Two, we evaluated the feasibility and validity of a method for acquiring participants' overt responses during fMRI scanning. The results indicated that our method was very accurate in acquiring the content of participant's responses. Further, inspection of the responses demonstrated that participants do not always comply with task instructions and highlighted the importance of obtaining behavioral performance measures during fMRI scanning.

YNIMG Journal 1995 Journal Article

Interference and Facilitation Effects during Selective Attention: An H215O PET Study of Stroop Task Performance

  • Cameron S. Carter
  • Mark Mintun
  • Jonathan D. Cohen

To investigate the functional anatomy of interference and facilitation during selective attention, we studied 15 normal subjects using the H2 15O positron emission tomography technique and a computer presented single-trial Stroop task for cognitive activation. Increases in regional cerebral blood flow (rCBF) were observed in a network of structures that have been previously associated with selective attention, including the anterior cingulate gyrus, the frontal polar cortex, the inferior parietal lobule, and the thalamus, as well as the lingual gyrus. Furthermore rCBF decreases (compared to control states) were observed in lateral extra-striate cortex. rCBF changes in prefrontal and extra-striate regions varied with differences in the need to modulate the influence of word and color information while subjects responded to either incongruent or congruent Stroop stimuli. These results indicate the utility of Stroop procedures for investigating the functional anatomy of selective attention. Given recent interest regarding the role of the anterior cingulate gyrus in the pathophysiology of neuropsychiatric disorders, our results also suggest that the Stroop task can serve as a reliable neurobehavioral probe for this region. The significance of these results for understanding processing mechanisms underlying selective attention is discussed within the framework of a parallel distributed processing model of Stroop task performance.

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