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Lisa C. Krishnamurthy

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2 papers

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YNIMG Journal 2025 Journal Article

CBF gradient and excitatory-inhibitory balance measured from pre-SMA – importance in aging and semantic fluency task difficulties

Venkatagiri Krishnamurthy
Lisa C. Krishnamurthy

In this report, we aim to systematically investigate the neural changes related to healthy aging in the presupplementary motor area (pre-SMA) and how these changes are associated with the semantic fluency task difficulty. We quantified a spatial cerebral blood flow (CBF) gradient based on previously identified task-specific subregions of the pre-SMA using pseudo-Continuous Arterial Spin Labeling, and we assessed the excitatory-inhibitory balance (EIB) using the ratio of gamma-aminobutyric acid (GABA+) to glutamate and glutamine complex (Glx) using magnetic resonance spectroscopy. We identified an ascending gradient in CBF from anterior to posterior among younger participants, which was absent in older participants. We interpret this loss of the CBF gradient in the context of neural dedifferentiation. There was a notable difference in tissue-corrected EIB between younger and older participants. Older participants exhibited a stronger inhibitory tone in the pre-SMA, driven by reduced tissue-corrected Glx in the older cohort. We interpret the increased EIB as a potential marker of under- or over-compensated synaptic scaling. Additionally, we found no relationship between neural dedifferentiation, as indicated by the CBF gradient, and synaptic scaling (EIB), suggesting that these are two distinct processes related to age-related neural changes. The tissue-corrected EIB exhibited a positive relationship with the difficulty of the semantic fluency task. However, we found no correlation between behavior and the CBF gradient. Our findings indicate that the inhibitory tone and synaptic scaling in the pre-SMA, rather than the CBF gradient and neural dedifferentiation, are crucial for managing the challenges posed by the semantic fluency task.

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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.

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