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Tricia Z. King

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YNICL Journal 2022 Journal Article

White matter hyperintensities relate to executive dysfunction, apathy, but not disinhibition in long-term adult survivors of pediatric cerebellar tumor

  • Olivia C. Haller
  • Holly A. Aleksonis
  • Lisa C. Krishnamurthy
  • Tricia Z. King

White matter hyperintensities (WMHs) have been related to executive dysfunction, apathy and disinhibition in a wide range of neurological populations. However, this relationship has not been examined in survivors of pediatric brain tumor. The goal of this study was to investigate how executive dysfunction, apathy, and disinhibition relate to WMHs in 31 long-term survivors of pediatric cerebellar brain tumor and 58 controls, using informant-report data from the Frontal Systems Behavior Scale. Total WMH volume was quantified using the Lesion Growth Algorithm. Further, periventricular, and subcortical volumes were identified based on proximity to custom ventricle masks generated in FSL. A ratio of WMH volume to whole brain volume was used to obtain normalized WMH volumes. Additionally, a multivariate regression analysis was performed. On average, informant-report scores were within normal limits and only executive dysfunction was significantly higher in survivors compared to controls (t(47.9) = -2.4, p=.023). Informants reported clinically significant levels of apathy in 32.3% of survivors. Informants also reported clinically significant executive dysfunction in 19.4 % of survivors and clinically significant disinhibition in, again, 19.4 % of survivors. Increased volume of WMHs was positively correlated with executive dysfunction (r = 0.33, p = 0.02) and apathy (r = 0.23, p = .04). Similarly, multivariate regression demonstrated correlations with executive dysfunction (p=.05, FDR corrected) and apathy (p=.05, FDR corrected). Exploratory analysis demonstrated an interaction wherein the relationship between total WMHs and executive dysfunction and apathy depends on whether the participant was a survivor. The current findings indicate that increased WMH volumes are associated with higher ratings of apathy and executive dysfunction, and that these results are likely unique to cerebellar brain tumor survivors. WMH burden may serve as a useful marker to identify survivors at risk of executive dysfunction or increased apathy.

YNICL Journal 2019 Journal Article

Neuroimaging of the component white matter connections and structures within the cerebellar-frontal pathway in posterior fossa tumor survivors

  • Alyssa S. Ailion
  • Simone Renée Roberts
  • Bruce Crosson
  • Tricia Z. King

INTRODUCTION: In posterior fossa tumor survivors, lower white matter integrity (WMI) in the right cerebellar-left frontal pathway has been well documented and appears to be related to proximity to the cerebellum, radiation treatment, as well as time since treatment in both cranial radiation and surgery-only treatment groups. The current study investigated theories of transneural degeneration following cerebellar tumor resection that may underlie or relate to reductions in WMI and regional brain volumes using correlations. We hypothesized a positive relationship between the volume of the right cerebellum and known white matter output pathways, as well as with the volume of structures that receive cerebellar projections along the pathway. METHODS: Adult survivors of childhood brain tumors were recruited (n = 29; age, M = 22 years, SD = 5; 45% female). Age- and gender-matched controls were also included (n = 29). Participants completed 3 T diffusion-weighted and T1 MPRAGE MRI scans. Brain structure volume relative to intracranial vault served as regional volumetric measures. Fractional anisotropy (FA) and radial diffusivity (RD) served as WMI measures. In the survivor group, partial correlations between WMI and regional volume included controlling for disease severity. RESULTS: In posterior fossa tumor survivors, the volumes of the cerebellum, thalamus, and frontal lobe were correlated with WMI of the thalamic-frontal segment of the cerebellar-frontal pathway (r = 0.41-0.49, p .05; RD, r = 0.53, p < .01). In the no-radiation survivor group, the regional volume of each structure along the pathway was associated with WMI in the cerebellar-rubral segment. In the radiation survivor group, significant correlations were found between the regional brain volume of each structure and the thalamic-frontal segment of the pathway. DISCUSSION: The results of this multimodal neuroimaging study provide correlational evidence that the mechanism of injury subsequent to brain tumor treatment may be different depending on type of treatment(s). Without radiation, the primary mechanism of injury is cerebellar tumor growth, resection, and hydrocephalus. Therefore, the most proximal connection to that injury (cerebellar-rubral pathway) was correlated with reductions in volume along the pathway. In contrast, the survivor group treated with radiation may have had possible radiation-induced demyelination of the thalamic-frontal portion of the pathway, based on a strong correlation with volume loss in the cerebellum, red nucleus, thalamus, and frontal lobe.

YNICL Journal 2018 Journal Article

White matter network topology relates to cognitive flexibility and cumulative neurological risk in adult survivors of pediatric brain tumors

  • Sabrina Na
  • Longchuan Li
  • Bruce Crosson
  • Vonetta Dotson
  • Tobey J. MacDonald
  • Hui Mao
  • Tricia Z. King

Adult survivors of pediatric brain tumors exhibit deficits in executive functioning. Given that brain tumors and medical treatments for brain tumors result in disruptions to white matter, a network analysis was used to explore the topological properties of white matter networks. This study used diffusion tensor imaging and deterministic tractography in 38 adult survivors of pediatric brain tumors (mean age in years = 23.11 (SD = 4.96), 54% female, mean years post diagnosis = 14.09 (SD = 6.19)) and 38 healthy peers matched by age, gender, handedness, and socioeconomic status. Nodes were defined using the Automated Anatomical Labeling (AAL) parcellation scheme, and edges were defined as the mean fractional anisotropy of streamlines that connected each node pair. Global efficiency and average clustering coefficient were reduced in survivors compared to healthy peers with preferential impact to hub regions. Global efficiency mediated differences in cognitive flexibility between survivors and healthy peers, as well as the relationship between cumulative neurological risk and cognitive flexibility. These results suggest that adult survivors of pediatric brain tumors, on average one and a half decades post brain tumor diagnosis and treatment, exhibit altered white matter topology in the form of suboptimal integration and segregation of large scale networks, and that disrupted topology may underlie executive functioning impairments. Network based studies provided important topographic insights on network organization in long-term survivors of pediatric brain tumor.

YNIMG Journal 2017 Journal Article

Intranasal oxytocin reduces social perception in women: Neural activation and individual variation

  • Erin E. Hecht
  • Diana L. Robins
  • Pritam Gautam
  • Tricia Z. King

Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females’ responses can differ substantially from males’. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were “friends” or “not friends. ” Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were “friends” or “not friends, ” and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin.

YNICL Journal 2016 Journal Article

Increased frontal functional networks in adult survivors of childhood brain tumors

  • Hongbo Chen
  • Liya Wang
  • Tricia Z. King
  • Hui Mao

Childhood brain tumors and associated treatment have been shown to affect brain development and cognitive outcomes. Understanding the functional connectivity of brain many years after diagnosis and treatment may inform the development of interventions to improve the long-term outcomes of adult survivors of childhood brain tumors. This work investigated the frontal region functional connectivity of 16 adult survivors of childhood cerebellar tumors after an average of 14.9 years from diagnosis and 16 demographically-matched controls using resting state functional MRI (rs-fMRI). Independent component analysis (ICA) was applied to identify the resting state activity from rs-fMRI data and to select the specific regions associated with executive functions, followed by the secondary analysis of the functional networks connecting these regions. It was found that survivors exhibited differences in the functional connectivity in executive control network (ECN), default mode network (DMN) and salience network (SN) compared to demographically-matched controls. More specifically, the number of functional connectivity observed in the survivors is higher than that in the controls, and with increased strength, or stronger correlation coefficient between paired seeds, in survivors compared to the controls. Observed hyperconnectivity in the selected frontal functional network thus is consistent with findings in patients with other neurological injuries and diseases.

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