Three approaches to investigating functional compromise to the default mode network after traumatic axonal injury

Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Brain Imaging and Behavior (Impact Factor: 4.6). 07/2012; 8(3). DOI: 10.1007/s11682-012-9191-2
Source: PubMed

ABSTRACT The default mode network (DMN) is a reliably elicited functional neural network with potential clinical implications. Its discriminant and prognostic utility following traumatic axonal injury (TAI) have not been previously investigated. The present study used three approaches to analyze DMN functional connectedness, including a whole-brain analysis [A1], network-specific analysis [A2], and between-node (edge) analysis [A3]. The purpose was to identify the utility of each method in distinguishing between healthy and brain-injured individuals, and determine whether observed differences have clinical significance. Resting-state fMRI was acquired from 25 patients with TAI and 17 healthy controls. Patients were scanned 6-11 months post-injury, and functional and neurocognitive outcomes were assessed the same day. Using all three approaches, TAI subjects revealed significantly weaker functional connectivity (FC) than controls, and binary logistic regressions demonstrated all three approaches have discriminant value. Clinical outcomes were not correlated with FC using any approach. Results suggest that compromise to the functional connectedness of the DMN after TAI can be identified using resting-state FC; however, the degree of functional compromise to this network, as measured in this study, may not have clinical implications in chronic TAI.

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    • "Emerging evidence suggests that dynamic brain functional connectivity may index changes in neural activity patterns underlying critical aspects of cognition or clinically relevant information (Allen et al. 2014; Calhoun et al. 2014; Hutchison et al. 2013a; Kucyi and Davis 2015; Park and Friston 2013; Tagliazucchi and Laufs 2014; Tagliazucchi et al. 2012). Furthermore, understanding the relationship between static and dynamic DMN functional connectivity with brain behavior will be critical to elucidate more fully the role of DMN signals in both healthy cognition and mental illness (Arenivas et al. 2014; Tam et al. 2014). Despite the number of studies focusing on DMN static and dynamic functional connectivity and mental state, to date, some previous studies have suggested that DMN functional connectivity is associated with brain cognitive function (Bonnelle et al. 2012; Buckner et al. 2008; Kucyi and Davis 2014). "
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    ABSTRACT: Characterization of the default mode network (DMN) as a complex network of functionally interacting dynamic systems has received great interest for the study of DMN neural mechanisms. In particular, understanding the relationship of intrinsic resting-state DMN brain network with cognitive behaviors is an important issue in healthy cognition and mental disorders. However, it is still unclear how DMN functional connectivity links to cognitive behaviors during resting-state. In this study, we hypothesize that static and dynamic DMN nodal topology is associated with upcoming cognitive task performance. We used graph theory analysis in order to understand better the relationship between the DMN functional connectivity and cognitive behavior during resting-state and task performance. Nodal degree of the DMN was calculated as a metric of network topology. We found that the static and dynamic posterior cingulate cortex (PCC) nodal degree within the DMN was associated with task performance (Reaction Time). Our results show that the core node PCC nodal degree within the DMN was significantly correlated with reaction time, which suggests that the PCC plays a key role in supporting cognitive function.
    Brain Imaging and Behavior 04/2015; DOI:10.1007/s11682-015-9384-6 · 4.60 Impact Factor
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    • "Previously, it has been shown the greater activation in the prefontal cortex is related to better working memory , though this relationship was not found in the current study (Desposito et al., 1995). However, Cohen et al. (1997) showed that greater activation in parietal regions as well as the prefrontal cortex were related to better maintenance of working memory and executive functions; these regions are critical for the default mode network and are likely disrupted in TBI, playing a role in reduced working memory (Arenivas et al., 2012; Bonnelle et al., 2011; Bonnelle et al., 2012; Mayer et al., 2012). Moreover, studies show that individuals with temporal lobe lesions also perform more poorly on measure of working memory (Morris, Miotto, Feigenbaum , Bullock, & Polkey, 1997), though some have found this association only with greater task difficulty (Owen, Morris, Sahakian, Polkey, & Robbins, 1996). "
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    ABSTRACT: There has been limited examination of the effect of brain pathology on subsequent function. The current study examined the relationships between regional variation in grey matter volume, age and cognitive impairment using a semi-automated image analysis tool. This study included 69 individuals with mild-to-severe TBI, 41 of whom also completed neuropsychological tests of attention, working memory, processing speed, memory and executive functions. A widespread reduction in grey matter volume was associated with increasing age. Regional volumes that were affected also related to the severity of injury, whereby the most severe TBI participants displayed the most significant pathology. Poorer retention of newly learned material was associated with reduced cortical volume in frontal, parietal, and occipital brain regions. In addition, poorer working memory and executive control performance was found for individuals with lower cortical volume in temporal, parietal, and occipital regions. These findings are largely in line with previous literature, which suggests that frontal, temporal, and parietal regions are integral for the encoding of memories into long-term storage, memory retrieval, and working memory. The present study suggests that automated image analysis methods may be used to explore the relationships between regional variation in grey matter volume and cognitive function following TBI.
    Brain and Cognition 07/2013; 83(1):34-44. DOI:10.1016/j.bandc.2013.06.007 · 2.48 Impact Factor
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    ABSTRACT: IMPORTANCE The study of brain activity and connectivity at rest provides a unique opportunity for the investigation of the brain substrates of cognitive outcome after traumatic axonal injury. This knowledge may contribute to improve clinical management and rehabilitation programs. OBJECTIVE To study functional magnetic resonance imaging abnormalities in signal amplitude and brain connectivity at rest and their relationship to cognitive outcome in patients with chronic and severe traumatic axonal injury. DESIGN Observational study. SETTING University of Barcelona and Hospital Clinic de Barcelona, Barcelona, and Institut Guttmann-Neurorehabilitation Hospital, Badalona, Spain. PARTICIPANTS Twenty patients with traumatic brain injury (TBI) were studied, along with 17 matched healthy volunteers. INTERVENTIONS Resting-state functional magnetic resonance imaging and diffusion tensor imaging data were acquired. After exploring group differences in amplitude of low-frequency fluctuations (ALFF), we studied functional connectivity within the default mode network (DMN) by means of independent component analysis, followed by a dual regression approach and seed-based connectivity analyses. Finally, we performed probabilistic tractography between the frontal and posterior nodes of the DMN. MAIN OUTCOMES AND MEASURES Signal amplitude and functional connectivity during the resting state, tractography related to DMN, and the association between signal amplitudes and cognitive outcome. RESULTS Patients had greater ALFF in frontal regions, which was correlated with cognitive performance. Within the DMN, patients showed increased connectivity in the frontal lobes. Seed-based connectivity analyses revealed augmented connectivity within surrounding areas of the frontal and left parietal nodes of the DMN. Fractional anisotropy of the cingulate tract was correlated with increased connectivity of the frontal node of the DMN in patients with TBI. CONCLUSIONS AND RELEVANCE Increased ALFF is related to better cognitive performance in chronic TBI. The loss of structural connectivity produced by damage to the cingulum tract explained the compensatory increases in functional connectivity within the frontal node of the DMN.
    05/2013; 70(7):1-7. DOI:10.1001/jamaneurol.2013.38
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