This project will seek to characterize attentional and inhibitory dysfunction in PTSD using innovative psychological and neuroimaging methods, and will focus on a central unanswered question: are increased attentional/inhibitory failures in PTSD driven by an inability to consistently engage task-positive cognitive control networks of the brain, or rather are they due to inappropriate engagement of task-negative brain networks associated with distraction? Thus, this project will identify the neural networks responsible for attentional disruption in PTSD, by using spatiotemporal patterns of brain activity to predict attentional lapses in real time, as well as to predict clinical diagnosis and severity. The proposal systematically explores sustained attention and inhibitory control in the context of fearful stimuli, as well as in more neutral, everyday contexts, using novel behavioral and fMRI methods developed by the principal investigator. This characterization of attentional and inhibitory control in PTSD will help explain difficulties that these individuals have in everyday life, and will be translatable to therapeutic augmentation and improved neurocognitive-based interventions. The project will also provide training in neuropsychological, psychiatric, and neuroimaging aspects of PTSD. This will facilitate the applicant's career goal to become a full-time, fully-funded independent investigator researching the neurocognitive injuries facing veterans, and allow the applicant to assume a leadership role as a VA scientist and to help train the next generation of researchers. The applicant is wholly committed to expanding his skills to better the lives of veterans. He intends t continue his career within the VA indefinitely. DESIGN: First, the project consists of a task-based fMRI experiment, which investigates the neural signature of sustained attention and inhibitory control deficits in individuals with PTSD. Participants (n=96) will be drawn from a RR&D TBI Center of Excellence at VA Boston- a large, extremely well-behaviorally characterized sample of OEF/OIF veterans with varying degrees of PTSD. Second, the project includes functional connectivity analyses of resting fMRI data, including multivariate pattern analyses, in an expanded set of individuals from the TBI Center. METHODS: The first set of experiments uses a novel continuous performance task and concurrent fMRI, in order to assess sustained attention and inhibitory control, and the effects of both affective and non-affective distractions. Second, an expanded cohort of participants will undergo MRI scans to examine resting state functional connectivity in core attentional and inhibitory control networks of the brain. Pattern classification (decoding) models of functional connectivity will potentially reveal neurobiological markers of PTSD. OBJECTIVES:
Aim 1. Neurally and behaviorally characterize sustained attention and inhibitory deficits in PTSD. Hypothesis 1A. Sustained attention deficits in PTSD+ vs. PTSD- will be exacerbated by distraction, and emotional distraction in particular (neutral and fearful faces). Hypothesis 1B. Sustained attention deficits in PTSD+ vs. PTSD- will be characterized by increased distraction (distraction model) as reflected by inappropriate engagement of the default mode network (mind-wandering) and face-specific brain regions associated with neutral face distractors, and in particular, fearful face distractors. Hypothesis 1C. Independent of distraction, sustained attention deficits in PTSD+ vs. PTSD- will be characterized by failure to consistently engage task- positive brain networks, including the salience and dorsal attention networks (depletion model).
Aim 2. Examine PTSD-related alterations in intrinsic functional brain connectivity, using multivariate pattern analysis (MVPA). Hypothesis 2. PTSD will be associated with abnormal connectivity in the 1) Salience network and 2) Dorsal attention network, associated with attentional, inhibitory and emotional control and 3) Default mode network, associated with mind-wandering and task-unrelated thoughts. These connectivity patterns will reliably predict the presence and severity of PTSD.

Public Health Relevance

The proposed research is directed at understanding the nature of attentional disruption in PTSD. It will systematically examine how and when individuals with PTSD fail to sustain attention and resist distraction, as well as the functional integrity of brain networks known to support these processes. Further characterizing attentional and inhibitory disruption in PTSD is critical, as attentional deficits can have profound effects on daily functioning. They often underle difficulties with memory, organization, and emotional regulation, contributing to poor social, academic, and vocational outcomes. Better appreciating the precise attentional difficulties faced by individuals with PTSD will aid development of appropriate compensatory strategies, training programs, and neurocognitive-based interventions to alleviate the impact of these cognitive deficits on everyday life. In addition, ameliorating cognitive deficits in PTSD might improve standard treatment efficacy by allowing more focused participation.

Agency
National Institute of Health (NIH)
Institute
Veterans Affairs (VA)
Type
Veterans Administration (IK2)
Project #
5IK2CX000706-05
Application #
9378096
Study Section
Mental Health and Behavioral Science A (MHBA)
Project Start
2013-10-01
Project End
2018-09-30
Budget Start
2017-10-01
Budget End
2018-09-30
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
VA Boston Health Care System
Department
Type
DUNS #
034432265
City
Boston
State
MA
Country
United States
Zip Code
02130
Kucyi, Aaron; Hove, Michael J; Esterman, Michael et al. (2017) Dynamic Brain Network Correlates of Spontaneous Fluctuations in Attention. Cereb Cortex 27:1831-1840
Esterman, Michael; Thai, Michelle; Okabe, Hidefusa et al. (2017) Network-targeted cerebellar transcranial magnetic stimulation improves attentional control. Neuroimage 156:190-198
Jor'dan, Azizah J; Poole, Victoria N; Iloputaife, Ikechukwu et al. (2017) Executive Network Activation is Linked to Walking Speed in Older Adults: Functional MRI and TCD Ultrasound Evidence From the MOBILIZE Boston Study. J Gerontol A Biol Sci Med Sci 72:1669-1675
Fortenbaugh, Francesca C; Corbo, Vincent; Poole, Victoria et al. (2017) Interpersonal early-life trauma alters amygdala connectivity and sustained attention performance. Brain Behav 7:e00684
Fortenbaugh, Francesca C; DeGutis, Joseph; Esterman, Michael (2017) Recent theoretical, neural, and clinical advances in sustained attention research. Ann N Y Acad Sci 1396:70-91
Poole, Victoria N; Robinson, Meghan E; Singleton, Omar et al. (2016) Intrinsic functional connectivity predicts individual differences in distractibility. Neuropsychologia 86:176-82
Kucyi, Aaron; Esterman, Michael; Riley, Clay S et al. (2016) Spontaneous default network activity reflects behavioral variability independent of mind-wandering. Proc Natl Acad Sci U S A 113:13899-13904
DeGutis, Joseph; Grosso, Mallory; VanVleet, Thomas et al. (2016) Sustained attention training reduces spatial bias in Parkinson's disease: a pilot case series. Neurocase 22:179-86
DeGutis, Joseph; Chiu, Christopher; Thai, Michelle et al. (2016) Trauma Sequelae are Uniquely Associated with Components of Self-Reported Sleep Dysfunction in OEF/OIF/OND Veterans. Behav Sleep Med :1-26
Esterman, Michael; Grosso, Mallory; Liu, Guanyu et al. (2016) Anticipation of Monetary Reward Can Attenuate the Vigilance Decrement. PLoS One 11:e0159741

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