Vagus nerve stimulation improves working memory performance

ABSTRACT Vagus nerve stimulation (VNS) is used for treating refractory epilepsy and major depression. While the impact of this treatment on seizures has been established, its impact on human cognition remains equivocal. The goal of this study is to elucidate the immediate effects of vagus nerve stimulation on attention, cognition, and emotional reactivity in patients with epilepsy. Twenty patients (12 male and 8 female; 45 ± 13 years old) treated with VNS due to refractory epilepsy participated in the study. Subjects performed a computer-based test of executive functions embedded with emotional distractors while their brain activity was recorded with electroencephalography. Subjects’ cognitive performance, early visual event-related potential N1, and frontal alpha asymmetry were studied when cyclic vagus nerve stimulation was on and when it was off. We found that vagus nerve stimulation improved working memory performance as seen in reduced errors on a subtask that relied on working memory, odds ratio (OR) = 0.63 (95% confidence interval, CI [0.47, 0.85]) and increased N1 amplitude, F(1, 15) = 10.17, p = .006. In addition, vagus nerve stimulation resulted in longer reaction time, F(1, 16) = 8.23, p = .019, and greater frontal alpha asymmetry, F(1, 16) = 11.79, p = .003, in response to threat-related distractors. This is the first study to show immediate improvement in working memory performance in humans with clinically relevant vagus nerve stimulation. Furthermore, vagus nerve stimulation had immediate effects on emotional reactivity evidenced in behavior and brain physiology.

[1]  R. Davidson.  Cerebral asymmetry, emotion, and affective style. , 1995 .

[2]  Arvi Yli-Hankala,et al.  Improved cognitive flexibility after aortic valve replacement surgery. , 2016, Interactive cardiovascular and thoracic surgery.

[3]  H. Sackeim,et al.  The effects of vagus nerve stimulation on cognitive performance in patients with treatment-resistant depression. , 2001, Neuropsychiatry, neuropsychology, and behavioral neurology.

[4]  S. Krahl,et al.  Post-training Unilateral Vagal Stimulation Enhances Retention Performance in the Rat , 1995, Neurobiology of Learning and Memory.

[5]  J. Mcglone,et al.  Quality of Life and Memory after Vagus Nerve Stimulator Implantation for Epilepsy , 2008, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[6]  E. Vogel,et al.  Interactions between attention and working memory , 2006, Neuroscience.

[7]  A. Kujawa,et al.  The relation between electroencephalogram asymmetry and attention biases to threat at baseline and under stress , 2013, Brain and Cognition.

[8]  Jari Peräkylä,et al.  Greater Attention to Task-Relevant Threat Due to Orbitofrontal Lesion. , 2017, Journal of neurotrauma.

[9]  Jari Peräkylä,et al.  Enhanced attention capture by emotional stimuli in mild traumatic brain injury. , 2015, Journal of neurotrauma.

[10]  C. MacLeod,et al.  Anxiety and the Allocation of Attention to Threat , 1988, The Quarterly journal of experimental psychology. A, Human experimental psychology.

[11]  Charles R. Yang,et al.  Current perspectives of the roles of the central norepinephrine system in anxiety and depression , 2010, Depression and anxiety.

[12]  E. V. Van Bockstaele,et al.  Efferent projections of the nucleus of the solitary tract to peri‐locus coeruleus dendrites in rat brain: Evidence for a monosynaptic pathway , 1999, The Journal of comparative neurology.

[13]  Anda H. van Stegeren.  The role of the noradrenergic system in emotional memory. , 2008, Acta psychologica.

[14]  R. Knight,et al.  Low attentional engagement makes attention network activity susceptible to emotional interference , 2014, Neuroreport.

[15]  L. Hirsch,et al.  Rates and predictors of patient-reported cognitive side effects of antiepileptic drugs: An extended follow-up , 2015, Seizure.

[16]  G Chouvet,et al.  Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology. , 1991, Progress in brain research.

[17]  Jukka Peltola,et al.  Human anterior thalamic nuclei are involved in emotion–attention interaction , 2015, Neuropsychologia.

[18]  R. Knight,et al.  Trees over forest: unpleasant stimuli compete for attention with global features , 2010, Neuroreport.

[19]  Christian E Elger,et al.  Vagus nerve stimulation is associated with mood improvements in epilepsy patients , 2000, Epilepsy Research.

[20]  M. Kindt,et al.  Selective Attention and Anxiety: A Perspective on Developmental Issues and the Causal Status , 2001 .

[21]  H. Sackeim,et al.  Vagus nerve stimulation (VNS) for major depressive episodes: one year outcomes , 2002, Biological Psychiatry.

[22]  R. Knight,et al.  Emotionally arousing stimuli compete for attention with left hemispace , 2007, Neuroreport.

[23]  K. Hartikainen,et al.  Threat interferes with response inhibition , 2012, Neuroreport.

[24]  Evelien Carrette,et al.  The antidepressant-like effect of vagus nerve stimulation is mediated through the locus coeruleus. , 2015, Journal of psychiatric research.

[25]  Steven A. Connor,et al.  β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus , 2015, Learning & memory.

[26]  Juha Öhman,et al.  Persistent symptoms in mild to moderate traumatic brain injury associated with executive dysfunction , 2010, Journal of clinical and experimental neuropsychology.

[27]  Cedric L. Williams,et al.  The effects of peripheral vagal nerve stimulation at a memory-modulating intensity on norepinephrine output in the basolateral amygdala. , 2004, Behavioral neuroscience.

[28]  S. Bishop,et al.  Neural Mechanisms Underlying Selective Attention to Threat , 2008, Annals of the New York Academy of Sciences.

[29]  E. Ben-Menachem,et al.  Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. , 1994, Epilepsia.

[30]  Patrik Vuilleumier,et al.  Beware and be aware: Capture of spatial attention by fear-related stimuli in neglect , 2001, Neuroreport.

[31]  J. Dean,et al.  Prevention of Intractable Partial Seizures by Intermittent Vagal Stimulation in Humans: Preliminary Results , 1990, Epilepsia.

[32]  E. Ben-Menachem,et al.  Vagus Nerve Stimulation for Treatment of Partial Seizures: 1. A Controlled Study of Effect on Seizures , 1994, Epilepsia.

[33]  M. Kalia,et al.  Brainstem projections of sensory and motor components of the vagus nerve in the rat , 1982, The Journal of comparative neurology.

[34]  Dean K. Naritoku,et al.  Enhanced recognition memory following vagus nerve stimulation in human subjects , 1999, Nature Neuroscience.

[35]  Kristl Vonck,et al.  The antidepressant mechanism of action of vagus nerve stimulation: Evidence from preclinical studies , 2015, Neuroscience & Biobehavioral Reviews.

[36]  Douglas C. Smith,et al.  Increased extracellular concentrations of norepinephrine in cortex and hippocampus following vagus nerve stimulation in the rat , 2006, Brain Research.

[37]  K. Rijkers,et al.  Vagus nerve stimulation has a positive effect on mood in patients with refractory epilepsy , 2012, Clinical Neurology and Neurosurgery.

[38]  Kaj Blennow,et al.  Vagus nerve stimulation in patients with Alzheimer's disease: Additional follow-up results of a pilot study through 1 year. , 2006, The Journal of clinical psychiatry.

[39]  R. Knight,et al.  Transient interference of right hemispheric function due to automatic emotional processing , 2000, Neuropsychologia.

[40]  Cole A. Giller,et al.  Vagus Nerve Stimulation (VNS™) for Treatment-Resistant Depression: Efficacy, Side Effects, and Predictors of Outcome , 2001, Neuropsychopharmacology.

[41]  Robert Goodman,et al.  Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study∗ ∗ See accompanying Editorial, in this issue. , 2000, Biological Psychiatry.

[42]  Jonathan D. Cohen,et al.  An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. , 2005, Annual review of neuroscience.

[43]  G. Morris,et al.  Effects of Vagal Nerve Stimulation on Cognition and Quality of Life in Epilepsy , 2001, Epilepsy & Behavior.

[44]  S. Luck,et al.  On the role of selective attention in visual perception. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[45]  R. Raedt,et al.  Increased hippocampal noradrenaline is a biomarker for efficacy of vagus nerve stimulation in a limbic seizure model , 2011, Journal of neurochemistry.

[46]  E. Ben-Menachem,et al.  Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer's disease: a pilot study. , 2002, The Journal of clinical psychiatry.

[47]  Jukka Peltola,et al.  Immediate effects of deep brain stimulation of anterior thalamic nuclei on executive functions and emotion-attention interaction in humans , 2014, Journal of clinical and experimental neuropsychology.

[48]  R. Raedt,et al.  Vagus nerve stimulation…25 years later! What do we know about the effects on cognition? , 2014, Neuroscience & Biobehavioral Reviews.

[49]  T. Dalgleish,et al.  Biases of attention and memory in disorders of anxiety and depression , 1990 .

[50]  S. Hillyard,et al.  Modulations of sensory-evoked brain potentials indicate changes in perceptual processing during visual-spatial priming. , 1991, Journal of experimental psychology. Human perception and performance.

[51]  Ulrich Müller,et al.  Noradrenergic modulation of working memory and emotional memory in humans , 2006, Psychopharmacology.

[52]  K. Hartikainen,et al.  Human Brain Reacts to Transcranial Extraocular Light , 2016, PloS one.