Individuals with KCNJ11 or ABCC8 mutations express over-activated KATP channels both in pancreatic beta cells as well as in the brain, and consequently exhibit a spectrum of neurodevelopmental difficulties. Even those with milder mutations exhibit more difficulty than sibling controls on a wide range of measures including executive functioning and IQ measures; but how this relates to channel dysfunction is unknown. fNIRS is a non-invasive technique increasingly used to assess brain activity as reflected by hemoglobin concentrations. fNIRS can be used to quantify fractal scaling of brain hemodynamics to estimate cognitive effort, which we hypothesized would be increased at rest or during tasks in KATP-NDM. Participants completed fNIRS assessment during a 7 minute resting state; executive function was assessed by Stroop task. Scaling phenomena may be fully described by a single Hurst exponent (H), with higher H indicating greater scale-free signal. Sixteen participants completed the resting state and Stroop task (6 affected, 10 controls, 50% female, age 7-40 years). All participants performed worse (lower accuracy and increased reaction time) on incongruent versus congruent trials of the Stroop task (accuracy: p=0.005, reaction time: p=0.02). KATP-NDM participants performed worse than controls (lower accuracy, slower reaction time), with mutation severity correlating significantly with overall accuracy (p=0.009). During resting state, affected participants had lower H than controls, possibly related to increased cognitive effort. Overall, higher H at rest corresponded to better performance on the Stroop task. Our data suggest that those with KATP-NDM experience increased cognitive effort even at rest, which may contribute to greater difficulty with task engagement and learning potential. fNIRS assessment of fractalness or other measures will help to clarify the role of KATP channel dysfunction in a range of cognitive processes.


L.R. Letourneau-Freiberg: None. K.L. Meidenbauer: None. A.M. Denson: None. P. Tian: None. K. Choe: None. M.G. Berman: None. S.W. Greeley: None.


National Institutes of Health (R01DK104942)

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