Transcutaneous Auricular Vagus Nerve Stimulation Attenuates Early Increases in Heart Rate Associated With the Cold Pressor Test.

INTRODUCTION: Transcutaneous auricular vagus nerve stimulation (taVNS) may be useful in treating disorders characterized by chronic parasympathetic disinhibition. Acute taVNS decreases resting heart rate in healthy individuals, but little is known regarding the effects of taVNS on the cardiac response to an acute stressor. To investigate effects on the acute stress response, we investigated how taVNS affected heart rate changes during a cold pressor test (CPT), a validated stress induction technique that reliably elicits a sympathetic stress response with marked increases in heart rate, anxiety, stress, and pain. MATERIALS AND METHODS: We recruited 24 healthy adults (ten women, mean age = 29 years) to participate in this randomized, crossover, exploratory trial. Each subject completed two taVNS treatments (one active, one sham) paired with CPTs in the same session. Order of active versus sham stimulation was randomized. Heart rate, along with ratings of anxiety, stress, and pain, was collected before, during, and after each round of taVNS/sham + CPT. RESULTS: In both stimulation conditions, heart rate was elevated from baseline in response to the CPT. Analyses also revealed a difference between active and sham taVNS during the first 40 seconds of the CPT (Δ heart rate [HR] = 12.75 ± 7.85 in the active condition; Δ HR = 16.09 ± 11.43 in the sham condition, p = 0.044). There were no significant differences in subjective ratings between active and sham taVNS. CONCLUSIONS: In this randomized, sham-controlled study, taVNS attenuated initial increases in HR in response to the CPT. Future studies are needed to investigate the effects of various taVNS doses and parameters on the CPT, in addition to other forms of stress induction. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT00113453.

DLPFC stimulation alters working memory related activations and performance: An interleaved TMS-fMRI study.

BACKGROUND: Findings from correlative neuroimaging studies link increased frontoparietal network (FPN) activation and default mode network (DMN) deactivation to enhanced high cognitive demand processing. To causally investigate FPN-DMN contributions to high cognitive demand processing, the current interleaved TMS-fMRI study simultaneously manipulated and indexed neural activity while tracking cognitive performance during high and low cognitive load conditions. METHODS: Twenty participants completed an n-back task consisting of four conditions (0-back, 0-backTMS, 2-back, 2-backTMS) while undergoing interleaved TMS-fMRI. During TMS concurrent with n-back blocks, TMS single pulses were delivered to the left DLPFC at 100% motor-threshold every 2.4s. RESULTS: TMS delivered during high cognitive load strengthened cognitive processing. FPN node activations and DMN node deactivations were increased in the high versus low cognitive load TMS condition. Contrary to our hypothesis, TMS did not increase high load related activation in FPN nodes. However, as hypothesized, increased DMN node deactivations emerged as a function of TMS during high load (right angular gyrus) and from interactions between cognitive load and TMS (right middle temporal gyrus). Load and TMS combined to dampen activation within the DMN at trend level (p = .058). Deactivation in a dorsomedial DMN node was associated with TMS driven improvements in high load cognitive processing. CONCLUSIONS: Exogenous perturbation of the DLPFC via single pulse TMS amplified DMN node deactivations and enhanced high cognitive demand processing. Neurobehavioral findings linking these effects hint at a promising, albeit preliminary, cognitive control substrate requiring replication in higher-powered studies that use control stimulation.

The Role of Amantadine Withdrawal in 3 Cases of Treatment-Refractory Altered Mental Status.

Amantadine, which was originally developed as an antiviral medication, functions as a dopamine agonist in the central nervous system and consequently is utilized in the treatment of Parkinson disease, drug-induced extrapyramidal reactions, and neuroleptic malignant syndrome. For reasons that are not entirely understood, abrupt changes in amantadine dosage can produce a severe withdrawal syndrome. Existing medical literature describes case reports of amantadine withdrawal leading to delirium, which at times has progressed to neuroleptic malignant syndrome. Amantadine withdrawal may be under-recognized by mental health clinicians, which has the potential to lead to protracted hospital courses and suboptimal outcomes. The goal of this case series is to highlight the role of amantadine withdrawal in the cases of 3 medically complex patients with altered mental status. In the first case, the cognitive side effects of electroconvulsive therapy masked acute amantadine withdrawal in a 64-year-old man with Parkinson disease. In the second case, a 75-year-old depressed patient developed a catatonic delirium when amantadine was discontinued. Finally, a refractory case of neuroleptic malignant syndrome in a 57-year-old patient with schizoaffective disorder rapidly resolved with the reintroduction of outpatient amantadine. These cases highlight several learning objectives regarding amantadine withdrawal syndrome: First, it may be concealed by co-occurring causes of delirium in medically complex patients. Second, its symptoms are likely to be related to a cortical and limbic dopamine shortage, which may be reversed with electroconvulsive therapy or reintroduction of amantadine. Third, its clinical presentation may occur on a spectrum and may include features suggestive of delirium, catatonia, or neuroleptic malignant syndrome.