The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential.

BACKGROUND: Transcutaneous vagus nerve stimulation (tVNS) is a new, non-invasive technique being investigated as an intervention for a variety of clinical disorders, including epilepsy and depression. It is thought to exert its therapeutic effect by increasing central norepinephrine (NE) activity, but the evidence supporting this notion is limited. OBJECTIVE: In order to test for an impact of tVNS on psychophysiological and hormonal indices of noradrenergic function, we applied tVNS in concert with assessment of salivary alpha amylase (SAA) and cortisol, pupil size, and electroencephalograph (EEG) recordings. METHODS: Across three experiments, we applied real and sham tVNS to 61 healthy participants while they performed a set of simple stimulus-discrimination tasks. Before and after the task, as well as during one break, participants provided saliva samples and had their pupil size recorded. EEG was recorded throughout the task. The target for tVNS was the cymba conchae, which is heavily innervated by the auricular branch of the vagus nerve. Sham stimulation was applied to the ear lobe. RESULTS: P3 amplitude was not affected by tVNS (Experiment 1A: N = 24; Experiment 1B: N = 20; Bayes factor supporting null model = 4.53), nor was pupil size (Experiment 2: N = 16; interaction of treatment and time: p = .79). However, tVNS increased SAA (Experiments 1A and 2: N = 25) and attenuated the decline of salivary cortisol compared to sham (Experiment 2: N = 17), as indicated by significant interactions involving treatment and time (p = .023 and p = .040, respectively). CONCLUSION: These findings suggest that tVNS modulates hormonal indices but not psychophysiological indices of noradrenergic function.

Task-free spectral EEG dynamics track and predict patient recovery from severe acquired brain injury.

For some patients, coma is followed by a state of unresponsiveness, while other patients develop signs of awareness. In practice, detecting signs of awareness may be hindered by possible impairments in the patient's motoric, sensory, or cognitive abilities, resulting in a substantial proportion of misdiagnosed disorders of consciousness. Task-free paradigms that are independent of the patient's sensorimotor and neurocognitive abilities may offer a solution to this challenge. A limitation of previous research is that the large majority of studies on the pathophysiological processes underlying disorders of consciousness have been conducted using cross-sectional designs. Here, we present a study in which we acquired a total of 74 longitudinal task-free EEG measurements from 16 patients (aged 6-22 years, 12 male) suffering from severe acquired brain injury, and an additional 16 age- and education-matched control participants. We examined changes in amplitude and connectivity metrics of oscillatory brain activity within patients across their recovery. Moreover, we applied multi-class linear discriminant analysis to assess the potential diagnostic and prognostic utility of amplitude and connectivity metrics at the individual-patient level. We found that over the course of their recovery, patients exhibited nonlinear frequency band-specific changes in spectral amplitude and connectivity metrics, changes that aligned well with the metrics' frequency band-specific diagnostic value. Strikingly, connectivity during a single task-free EEG measurement predicted the level of patient recovery approximately 3 months later with 75% accuracy. Our findings show that spectral amplitude and connectivity track patient recovery in a longitudinal fashion, and these metrics are robust pathophysiological markers that can be used for the automated diagnosis and prognosis of disorders of consciousness. These metrics can be acquired inexpensively at bedside, and are fully independent of the patient's neurocognitive abilities. Lastly, our findings tentatively suggest that the relative preservation of thalamo-cortico-thalamic interactions may predict the later reemergence of awareness, and could thus shed new light on the pathophysiological processes that underlie disorders of consciousness.

Effect of epilepsy on psychomotor function in children with uncomplicated epilepsy.

This study assessed the impact of epilepsy on motor function in children. We aimed to analyze the effect in uncomplicated epilepsies (cryptogenic partial and idiopathic generalized epilepsy). A group of 87 children with epilepsy (47 males, 40 females; mean age 8y, standard deviation [SD] ly 9mo, range 4y 11mo to 12y 11mo), but without learning disability* or other neurological comorbid disorders, was compared with a control group of 107 children (76 males, 31 females; mean age 8y 4mo, SD 2y 2mo, range 4y 7mo to 12y 2mo). The differences in main motor skills and psychomotor speed were analyzed using the Movement ABC and computerized measures for simple reaction times and finger tapping. No significant difference in motor function was found. The overall psychomotor development of children with epilepsy is comparable to controls. However, a significant slowing of psychomotor speed in the group with epilepsy was reported. No relation with antiepileptic drug treatment was demonstrated and no difference in psychomotor speed between different types of epilepsy was found. The existence of a condition leading to excessive neuronal discharge leads to a general cortical inhibition. The slowing of psychomotor speed in children with uncomplicated epilepsy may be the behavioural presentation of this inhibition.

Error-related brain potentials are differentially related to awareness of response errors: evidence from an antisaccade task.

The error negativity (Ne/ERN) and error positivity (Pe) are two components of the event-related brain potential (ERP) that are associated with action monitoring and error detection. To investigate the relation between error processing and conscious self-monitoring of behavior, the present experiment examined whether an Ne and Pe are observed after response errors of which participants are unaware. Ne and Pe measures, behavioral accuracy, and trial-to-trial subjective accuracy judgments were obtained from participants performing an antisaccade task, which elicits many unperceived, incorrect reflex-like saccades. Consistent with previous research, subjectively unperceived saccade errors were almost always immediately corrected, and were associated with faster correction times and smaller saccade sizes than perceived errors. Importantly, irrespective of whether the participant was aware of the error or not, erroneous saccades were followed by a sizable Ne. In contrast, the Pe was much more pronounced for perceived than for unperceived errors. Unperceived errors were characterized by the absence of posterror slowing. These and other results are consistent with the view that the Ne and Pe reflect the activity of two separate error monitoring processes, of which only the later process, reflected by the Pe, is associated with conscious error recognition and remedial action.

Mental fatigue and task control: planning and preparation.

The effects of mental fatigue on planning and preparation for future actions were examined, using a task switching paradigm. Fatigue was induced by "time on task," with subjects performing a switch task continuously for 2 hr. Subjects had to alternate between tasks on every second trial, so that a new task set was required on every second trial. Manipulations of response-stimulus intervals (RSIs) were used to examine whether subjects prepared themselves for the task change. Behavioral measurements, event-related potentials (ERPs), and mood questionnaires were used to assess the effects of mental fatigue. Reaction times (RTs) were faster on trials in which no change in task set was required in comparison with switch trials, requiring a new task set. Long RSIs were used efficiently to prepare for the processing of subsequent stimuli. With increasing mental fatigue, preparation processes seemed to become less adequate and the number of errors increased. A clear poststimulus parietal negativity was observed on repetition trials, which reduced with time on task. This attention-related component was less pronounced in switch trials; instead, ERPs elicited in switch trials showed a clear frontal negativity. This negativity was also diminished by time on task. ERP differences between repetition and switch trials became smaller with increasing time on task.

Inhibitory inefficiency and failures of intention activation: age-related decline in the control of saccadic eye movements.

Young and older adults' control of saccadic eye movements was compared using an antisaccade task, which requires the inhibition of a reflexive saccade toward a peripheral onset cue followed by an intentional saccade in the opposite direction. In 2 experiments, an age-related decline was found in the suppression of reflexive eye movements, as indicated by an increased proportion of saccades toward the cue, and a longer time needed to initiate correct antisaccades. The results from Experiment 2 suggested that older adults' slower antisaccades may be explained partly in terms of increased failures to maintain the cue-action representation at a sufficient activation level. The results suggest that the notion of selective preservation with age of the ability to inhibit spatial responses does not apply to the active inhibition of prepotent spatial responses.

Preparation of site-specific isotopically labelled zervamicins, the antibiotic peptaibols produced by Emericellopsis salmosynnemata.

A simple procedure for the preparation of the specifically labelled peptide antibiotic zervamicins IC, IIA and IIB has been developed. The zervamicin molecules are labelled with stable isotopes by culturing the Emericellopsis salmosynnemata on a well-defined synthetic medium containing the highly isotopically enriched amino acid. To obtain the peptide with the specifically and highly enriched amino acid residue, precautions have been taken to prevent any de novo biosynthesis of the particular amino acid from unlabelled precursors. The enrichment of the labelled peptide is determined by mass spectrometric analysis. Following this method we have incorporated [2',4',5',6',7'-2H5]-L-Trp-1, [1'-15N]-L-Trp-1 and [2',3',4',5',6'-2H5]-L-Phl-16 into zervamicins IC, IIA and IIB on the preparative scale and without scrambling of the label. Thus, using the procedures described, isotopically labelled zervamicins can be prepared, allowing them to be studied by solid-state NMR.