Atypical Structural Connectome Organization and Cognitive Impairment in Young Survivors of Acute Lymphoblastic Leukemia

Kesler, Shelli R.; Gugel, Meike; Huston-Warren, Emily; Watson, Christa

doi:10.1089/brain.2015.0409

Cited by 59 publications

(68 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The resulting z‐score connectivity matrices were thresholded to minimum connection density and then submitted to graph theoretical analysis using our Brain Networks Toolbox (https://github.com/srkesler/bnets.git, RRID:SCR_014788) as well as Brain Connectivity Toolbox (Rubinov & Sporns, 2010) (RRID:SCR_004841) implemented in MATLAB v2014b. We focused on the clustering coefficient considering our previous findings (Bruno, Hosseini, & Kesler, 2012; Kesler, Gugel, Huston‐Warren, & Watson, 2016; Kesler et al., 2015). Clustering coefficient reflects the ratio of actual to possible connections between a node's neighbors and is therefore a measure of network segregation (Rubinov & Sporns, 2010).…”

Section: Methodsmentioning

confidence: 99%

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

et al. 2017

Self Cite

View full text Add to dashboard Cite

IntroductionSeveral previous studies have demonstrated that cancer chemotherapy is associated with brain injury and cognitive dysfunction. However, evidence suggests that cancer pathogenesis alone may play a role, even in non‐CNS cancers.MethodsUsing a multimodal neuroimaging approach, we measured structural and functional connectome topology as well as functional network dynamics in newly diagnosed patients with breast cancer. Our study involved a novel, pretreatment assessment that occurred prior to the initiation of any cancer therapies, including surgery with anesthesia. We enrolled 74 patients with breast cancer age 29–65 and 50 frequency‐matched healthy female controls who underwent anatomic and resting‐state functional MRI as well as cognitive testing.ResultsCompared to controls, patients with breast cancer demonstrated significantly lower functional network dynamics (p = .046) and cognitive functioning (p < .02, corrected). The breast cancer group also showed subtle alterations in structural local clustering and functional local clustering (p < .05, uncorrected) as well as significantly increased correlation between structural global clustering and functional global clustering compared to controls (p = .03). This hyper‐correlation between structural and functional topologies was significantly associated with cognitive dysfunction (p = .005).ConclusionsOur findings could not be accounted for by psychological distress and suggest that non‐CNS cancer may directly and/or indirectly affect the brain via mechanisms such as tumor‐induced neurogenesis, inflammation, and/or vascular changes, for example. Our results also have broader implications concerning the importance of the balance between structural and functional connectome properties as a potential biomarker of general neurologic deficit.

show abstract

Section: Methodsmentioning

confidence: 99%

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Matrices were then submitted to graph theoretical analysis using Brain Connectivity Toolbox [37] and in-house code (https://github.com/srkesler/bNets.git) implemented in Matlab v2014b (Mathworks, Inc, Natick, MA). Connectome metrics were calculated as described previously [35, 38, 39]. Specifically, efficiency is defined as the inverse of the average shortest path between nodes and is high when nodes are able to interact directly.…”

Section: Methodsmentioning

confidence: 99%

“…Since the effect of tumor volume on brain networks is unknown, models were compared with and without this variable. Nodal efficiencies were first corrected for covariates using linear regression and then group differences were measured multivariately with nonparametric permutation testing (2000 iterations) [38], FDR corrected.…”

Section: Methodsmentioning

confidence: 99%

“…Given the large number of potential predictors, small sample size and presence of categorical variables as well as our prior observations of nonlinear interactions between brain metrics and cognitive outcome [38], we explored random forest models [49] of cognitive impairment. Global efficiency, tumor volume, scanner field strength, total brain volume, network size, testing interval, education level, Karnofsky Performance Scale score, tumor region (1 = frontal, 2 = temporal, 3 = parietal), multifocal tumor (0 = no, 1 = yes) and tumor hemisphere (1 = left, 2 = right) were included as potential features.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The effect of IDH1 mutation on the structural connectome in malignant astrocytoma

et al. 2016

Self Cite

View full text Add to dashboard Cite

Mutation of the IDH1 gene is associated with differences in malignant astrocytoma growth characteristics that impact phenotypic severity, including cognitive impairment. We previously demonstrated greater cognitive impairment in patients with IDH1 wild type tumor compared to those with IDH1 mutant, and therefore we hypothesized that brain network organization would be lower in patients with wild type tumors. Volumetric, T1-weighted MRI scans were obtained retrospectively from 35 patients with IDH1 mutant and 32 patients with wild type malignant astrocytoma (mean age = 45 ± 14 years) and used to extract individual level, gray matter connectomes. Graph theoretical analysis was then applied to measure efficiency and other connectome properties for each patient. Cognitive performance was categorized as impaired or not and random forest classification was used to explore factors associated with cognitive impairment. Patients with wild type tumor demonstrated significantly lower network efficiency in several medial frontal, posterior parietal and subcortical regions (p < 0.05, corrected for multiple comparisons). Patients with wild type tumor also demonstrated significantly higher incidence of cognitive impairment (p = 0.03). Random forest analysis indicated that network efficiency was inversely, though nonlinearly associated with cognitive impairment in both groups (p < 0.0001). Cognitive reserve appeared to mediate this relationship in patients with mutant tumor suggesting greater neuroplasticity and/or benefit from neuroprotective factors. Tumor volume was the greatest contributor to cognitive impairment in patients with wild type tumor, supporting our hypothesis that greater lesion momentum between grades may cause more disconnection of core neurocircuitry and consequently lower efficiency of information processing.

show abstract

“… * p<0.05, **p<0.01. IQ estimated by the K-BIT 2 37 ; anxiety, Screen for Child Anxiety-Related Emotional Disorders 38 ; depression, Children’s Depression Inventory 39 ; PTSS [posttraumatic stress symptoms], UCLA PTSD Reaction Index for DSM-IV 36 . …”

Section: Fig1mentioning

confidence: 99%

Emotion‐related brain organization and behavioral responses to socioemotional stimuli in pediatric cancer survivors with posttraumatic stress symptoms

Marusak

Iadipaolo

Paulisin

et al. 2018

Pediatric Blood & Cancer

View full text Add to dashboard Cite

Background: Pediatric cancer is a life-changing, stressful experience for children and their families. Although most children adjust well, psychologically, a significant subset report posttraumatic stress symptoms (PTSS), with nearly 75% re-experiencing traumatic parts of cancer and/or its treatment. However, little research has examined the effects of pediatric cancer and related PTSS on emotional processing, and on functional properties of key emotional centers in the brain (e.g., amygdala). Procedure: We examined cancer-related PTSS, behavioral responses during an emotion-processing task, and resting-state functional connectivity of the amygdala in 17 pediatric cancer survivors (ages 6–11) and 17 age- and sex-matched controls. Results: Cancer survivors, relative to controls, were more likely to rate ambiguous (i.e., neutral) faces as negative (i.e., “negativity bias”). Higher re-experiencing PTSS was associated with faster responses to neutral faces. Although there were no group differences in amygdala centrality, within survivors, both higher re-experiencing PTSS and faster reaction times were associated with increased centrality of the amygdala – a functional property associated with hubs of information processing in the brain. In an exploratory mediation analysis, we found that amygdala centrality mediated the link between reaction time and PTSS, suggesting that changes in the brain may be a proximal marker of the expression of emotion-related symptomology. Conclusions: Negativity bias in cancer survivors may reflect their stressful experiences with cancer and/or its treatment. This negativity bias may represent a susceptibility to changes in emotion-related brain functioning which may, in turn, lead to PTSS.

show abstract

Atypical Structural Connectome Organization and Cognitive Impairment in Young Survivors of Acute Lymphoblastic Leukemia

Cited by 59 publications

References 51 publications

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

Disrupted brain network functional dynamics and hyper‐correlation of structural and functional connectome topology in patients with breast cancer prior to treatment

The effect of IDH1 mutation on the structural connectome in malignant astrocytoma

Emotion‐related brain organization and behavioral responses to socioemotional stimuli in pediatric cancer survivors with posttraumatic stress symptoms

Contact Info

Product

Resources

About