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Josef Ling

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YNICL Journal 2025 Journal Article

A one year longitudinal study of cortical myelination changes following pediatric mild traumatic brain injury

  • Jessica R. McQuaid
  • Tracey V. Wick
  • Josef Ling
  • Andrew B. Dodd
  • Divyasree Sasi Kumar
  • Upasana Nathaniel
  • Samuel D. Miller
  • Vadim Zotev

The impact of pediatric mild traumatic brain injury (pmTBI) on cortical (i. e. , grey matter) myelination is not yet understood, especially for interactions with neurodevelopment. The current study examined the impact of pmTBI on cortical myelination relative to healthy controls (HC) by estimating myelin content using the T1w/T2w ratio method. Data were obtained from pmTBI (N = 217) participants at approximately 7 days (Visit 1 [V1]), 4 months (Visit 2 [V2]), and 1 year (Visit 3 [V3]) post-injury, with equivalent sampling points for age and sex-matched HC (N = 180). Clinical results suggested only partial recovery from post-concussive symptoms from V1 to V3, with similar incomplete recovery of sleep, functional outcomes, behavior, and long-term memory. Myelin content increased with chronological age and as a function of individual aging across study visits in a hemisphere specific fashion (left > right), most visibly within the posterior parietal lobe. Myelin content was also greater for females relative to males. There was evidence of both a reduction in myelination within the posterior parietal cortex for the pmTBI group at 4 months post-injury, as well as evidence of increased myelination within the left prefrontal cortex at one-year post-injury. However, neither of these findings survived various sensitivity analyses, suggesting that there were minimal effects of pmTBI on cortical myelin content in general. In summary, although rapid changes in myelin content existed as a function of neurodevelopment, there was little evidence to suggest that pmTBI permanently altered cortical myelin development trajectories.

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YNICL Journal 2020 Journal Article

Brain activation and subjective anxiety during an anticipatory anxiety task is related to clinical outcome during prazosin treatment for alcohol use disorder

  • Claire E. Wilcox
  • Bryon Adinoff
  • Joshua Clifford
  • Josef Ling
  • Katie Witkiewitz
  • Andrew R. Mayer
  • Kylar M. Boggs
  • Matthew Eck

BACKGROUND: Higher levels of anxiety, negative affect, and impaired emotion regulation are associated with alcohol use disorder (AUD) and contribute to relapse and worse treatment outcomes. Prazosin, while typically used to treat post-traumatic stress disorder (PTSD) and other anxiety disorders, has shown promise for treating AUD. In order to better understand these underlying neural processes in individuals with AUD, our aims in this study were to measure brain activation during an anticipatory anxiety task before treatment to determine whether observed patterns supported previous work. We then aimed to measure the effects of prazosin on patients with AUD and explore whether greater baseline anticipatory anxiety (as measured by subjective and neural measures) predicts better treatment outcomes. METHODS: Thirty-four individuals seeking treatment for AUD participated in a six-week placebo-controlled study of prazosin and underwent an anticipatory anxiety task during fMRI scans at baseline and three weeks. Alcohol use over six weeks was measured. RESULTS: Greater levels of subjective anxiety and deactivation in posterior cingulate cortex (PCC) and ventromedial prefrontal cortex (vmPFC) were observed during high-threat stimuli compared to low-threat stimuli. Compared to placebo, prazosin reduced subjective anxiety to high-threat stimuli but there were no observed significant effects of prazosin on brain activation during the task. However, AUD patients with greater vmPFC deactivation during high threat relative to low threat and patients with low baseline anticipatory anxiety during the task had worse clinical outcomes on prazosin. CONCLUSIONS: Deactivation in PCC and vmPFC to high-threat stimuli replicated previous work and shows promise for further study as a marker for AUD. Although prazosin did not affect brain activation in the regions of interest during the anticipatory anxiety task, subjective levels of anxiety and brain activation in vmPFC predicted treatment outcomes in individuals with AUD undergoing treatment with prazosin, highlighting individuals more likely to benefit from prazosin than others.

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