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Selective neuronal lapses precede human cognitive lapses following sleep deprivation

Abstract

Sleep deprivation is a major source of morbidity with widespread health effects, including increased risk of hypertension, diabetes, obesity, heart attack, and stroke1. Moreover, sleep deprivation brings about vehicle accidents and medical errors2,3,4 and is therefore an urgent topic of investigation. During sleep deprivation, homeostatic and circadian processes interact to build up sleep pressure5, which results in slow behavioral performance (cognitive lapses) typically attributed to attentional thalamic and frontoparietal circuits6,7,8,9,10,11,12,13,14, but the underlying mechanisms remain unclear3,15. Recently, through study of electroencephalograms (EEGs) in humans16,17 and local field potentials (LFPs) in nonhuman primates18 and rodents19 it was found that, during sleep deprivation, regional 'sleep-like' slow and theta (slow/theta) waves co-occur with impaired behavioral performance during wakefulness. Here we used intracranial electrodes to record single-neuron activities and LFPs in human neurosurgical patients performing a face/nonface categorization psychomotor vigilance task (PVT)20,21,22,23,24 over multiple experimental sessions, including a session after full-night sleep deprivation. We find that, just before cognitive lapses, the selective spiking responses of individual neurons in the medial temporal lobe (MTL) are attenuated, delayed, and lengthened. These 'neuronal lapses' are evident on a trial-by-trial basis when comparing the slowest behavioral PVT reaction times to the fastest. Furthermore, during cognitive lapses, LFPs exhibit a relative local increase in slow/theta activity that is correlated with degraded single-neuron responses and with baseline theta activity. Our results show that cognitive lapses involve local state-dependent changes in neuronal activity already present in the MTL.

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Figure 1: Sleep deprivation leads to cognitive lapses in a face/nonface categorization PVT.
Figure 2: Human single-neuron responses during the face/nonface categorization PVT experiment.
Figure 3: Reduced, delayed, and lengthened single-unit responses during cognitive lapses.
Figure 4: Cognitive lapses are associated with weaker gamma power increase and weaker slow/theta power decrease in MTL LFPs.

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Acknowledgements

We thank the subjects for their cooperation; M. Tran, E. Behnke, T. Fields, H. Gelbard-Sagiv, and M. Sagiv for assistance with data acquisition; and B. Salaz and N. Regev for administrative help. This work was supported by a Human Frontier Science Program (HFSP) Organization long-term fellowship (Y.N.), the Planning and Budgeting Committee of the Israeli Centers of Research Excellence (I-CORE) program and the Israel Science Foundation (grant no. 51/11, Y.N.), the FP7 Marie Curie Career Integration Grant (Y.N.), the Adelis Foundation (Y.N.), Société Française de Recherche et Médecine du Sommeil (SFRMS, T.A.), the Institute of Cognitive Studies of École Normale Superieure (IEC–ENS) (ANR-10-LABX-0087 and ANR-10-IDEX-0001-02 PSL*, T.A.), National Institute of Mental Health (NIMH) grant no. R01MH099231 (C.C. and G.T.), National Institute of Neurological Disorders and Stroke (NINDS) grant no. P01NS083514 (C.C. and G.T.), National Institute of General Medical Sciences grant no. R01GM116916 (G.T.), and NINDS grant nos. R01NS033221 and R01NS084017 (I.F.).

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Y.N., C.C., G.T., and I.F. conceived and designed the research, I.F. performed surgeries, Y.N. and N.S. collected data, Y.N., T.A., and A.M. analyzed data, and Y.N., T.A., C.C., G.T., and I.F. wrote the manuscript. All authors provided ongoing critical review of results and commented on the manuscript.

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Correspondence to Yuval Nir or Giulio Tononi or Itzhak Fried.

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Nir, Y., Andrillon, T., Marmelshtein, A. et al. Selective neuronal lapses precede human cognitive lapses following sleep deprivation. Nat Med 23, 1474–1480 (2017). https://doi.org/10.1038/nm.4433

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