Vagus nerve stimulation: a new form of therapeutic brain stimulation

Although the vagus nerve has traditionally been considered to perform efferent functions, in reality it performs significant afferent functions as well, carrying information from the body, head, and neck to the brain. Preliminary studies examining this afferent activity led to the theory that vagus nerve stimulation (VNS) could successfully control seizure activity in persons who are refractory to antiepileptic medications. Unlike other forms of brain stimulation, VNS is unable to directly stimulate multiple discrete areas of the brain; however, through several pathways, it is able to relay sensory information to higher brain regions. An implantable VNS device known as the VNSTM NeuroCybernetic Prosthesis (NCP) System has been used in approximately 9,000 epilepsy patients in Europe and the United States since 1994. The implant has reduced seizure frequency by an average of 25% to 30%, with minimal side effects. Studies underway are also showing some degree of success in the management of treatment-refractory depression. The future efficacy of the implantable system in other disorders may depend on whether the implant can be more precisely focused to affect different brain regions. Research in this area is underway.     

Iatrogenic peripheral nerve damage and its forensic evaluation

Iatrogenic peripheral nervous lesions represent a regrettable complication of medical therapy. Legal regulations of the GDR make it possible for the practicing physician to remain an advocate of the patient's interests. The results of an analysis of 11 years of activities in the Magdeburg County Commission of Medical Experts are presented.     

Evoked potentials in cat auditory nerve: Suppression by prior tonal stimulation

Action potentials (AP) recorded from the eighth nerve of a cat to a tone pip, S₁, were suppressed when preceded by a monotic or dichotic conditioning tone, Tc. The suppression increased when (1) the interval between Tc and S1 was decreased, (2) either the intensity or the duration of Tc was increased, or (3) the difference in frequency between the two stimuli was reduced. Thus the nerve action potential amplitude correlates strongly, but inversely, with the loudness enhancement effects seen in man (Galambos, Bauer, Picton, Squires & Squires,Journal of the Acoustical Society of America, 1972, 52). Since Coats and Dickey (Journal of the Acoustical Society of America, 1972, 52) found that the human AP can be diminished by a preceding noise without reducing the loudness of a click, the available results suggest that a central mechanism functions to compensate for the reduction in AP amplitude. The dichotic effects could be accounted for by cross-hearing, thereby providing no evidence for a role of the olivocochlear bundle in the effects observed.

     

Intelligence, reaction times, and peripheral nerve conduction velocity

Two studies (with sample sizes of 85 and 88) are reported that investigated relationships among measures of intelligence, speed of information processing, and peripheral nerve conduction velocity (NCV). In both studies, NCV was significantly correlated with IQ scores (rs = .42 and .48) and with reaction times (RTs; rs = −.28 and −.18): Thus, faster NCV was associated with higher IQ scores and faster speed of processing. In both studies, NCV and RTs contributed significantly, in combination, to the prediction of fullscale IQ (shrunken multiple Rs = .53 and .57), but the expected pattern of causal relationships between the variables was not borne out. The results are interpreted in terms of a “neural efficiency” model of intelligence, which has recieved support from other studies of physiological correlates of human intelligence.     

Emotion and motor preparation: A transcranial magnetic stimulation study of corticospinal motor tract excitability

In the present study, we examined whether preparing motor responses under different emotional conditions alters motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation delivered to the motor cortex. Analyses revealed three findings: (1) Reaction times were expedited during exposure to unpleasant images, as compared with pleasant and neutral images; (2) force amplitude was greater during exposure to unpleasant images, as compared with pleasant and neutral images; and (3) MEPs were larger while participants viewed unpleasant images, as compared with neutral images. Hence, coupling the preparation of motor responses with the viewing of emotional images led to arousal-driven changes in corticospinal motor tract excitability, whereas movement speed and force production varied as a function of emotional valence. These findings demonstrate that the effects of emotion on the motor system manifest at varying sensitivity levels across behavioral and neurophysiological measures. Moreover, they validate the action readiness component of emotional experience by demonstrating that emotional states influence the execution of future movements but, alone, do not lead to overt movement.     

Cortico-spinal inhibition reflects time but not event preparation: neural mechanisms of preparation dissociated by transcranial magnetic stimulation.

Changes in cortico-spinal excitability related to time and event preparation were investigated by transcranial magnetic stimulation (TMS) of the motor cortex during the foreperiod of a movement-precuing task. Subjects performed a four alternative choice reaction time (RT) task involving a button-press with the index or middle finger (FI) of the left or right hand. Advance information about the to-be-signaled response was provided by a precue, which preceded the response signal by a 1 s foreperiod. The precue either indicated the hand (right or left) or FI (index or middle) with which the response would be executed or was uninformative. TMS was delivered to the left or right cortical hand area at one of five possible times during the foreperiod: -1000, -500, -333, -166 or 0 ms prior to the response signal. Surface EMG activity from a prime mover involved in flexion of the response FIs (Flexor digitorum superficialis) was used to measure the magnitude of the motor evoked potential (MEP) elicited by TMS. Cortico-spinal excitability--as assessed by the magnitude of the MEP evoked in the target muscle contralateral to the stimulated hemisphere--progressively decreased during the foreperiod. The identity of the precued responses, however, had no effect on MEP magnitude. These results suggest that preparation to respond at a particular time inhibited excitability of the cortico-spinal tract, while advance preparation to perform specific responses affected more central structures only.     

Effects of stimulation by three-dimensional natural images on prefrontal cortex and autonomic nerve activity: a comparison with stimulation using two-dimensional images

Empirical evidence suggests that three-dimensional (3D) images of nature promote physiological relaxation in humans by providing more realistic effects compared with two-dimensional (2D) images. However, no studies have evaluated the physiological relaxation effects of nature-derived 3D images on prefrontal cortex and autonomic nerve activity. The present study aimed to clarify the physiological relaxation effects of visual stimulation by 3D flower images on prefrontal cortex and autonomic nerve activity. Nineteen male university students (22.2 ± 0.6 years) were presented with 3D and 2D images of the water lily for 90 s. Prefrontal cortex activity was measured using near-infrared spectroscopy, while autonomic nerve activity was measured using heart rate variability (HRV). Psychological effects were determined using a modified semantic differential method (SD). Compared with visual stimulation by 2D images, that by 3D images resulted in a significant decrease in oxyhemoglobin concentration in the right prefrontal cortex, lower sympathetic activity as calculated by the ratio of the low-frequency to high-frequency HRV component, and a significantly greater realistic feeling as evidenced by higher SD ratings. In conclusion, visual stimulation by realistic 3D floral images promotes physiological relaxation more effectively than the corresponding 2D image.     

Beyond the treatment of epilepsy: new applications of vagus nerve stimulation in psychiatry

Vagus nerve stimulation (VNS) in humans generally refers to stimulation of the left vagus nerve at the cervical level VNS is an established treatment largely devoid of severe side effect for medically refractory partial onset seizures and has been used in more than 16,000 patients. Over the past 5 years, applications in other neuropsychiatric disorders have been investigated with a special emphasis on depression. Recent data from an open-label, multi-center pilot study involving 60 patients suggest a potential clinical usefulness in the acute and maintenance treatment of drug-resistant depressive disorder. The perspective of VNS as along-term treatment with the advantage of assured compliance makes it an interesting technique to potentially treat drug-resistant depression. However, definite therapeutic effects of clinical significance remain to be confirmed in large placebo-controlled trial. Results of clinical pilot studies involving patients suffering from obesity and Alzheimer's disease indicate that VNS might induce weight loss and improve cognition. Besides its clinical usefulness, VNS can be used as a research tool, allowing neurophysiologic investigations of the parasympathetic system and its interactions with other parts of the central nervous system.     

Expertise and peripheral autonomic activity during the preparation phase in shooting events

This study compared effectiveness of the concentration period in two groups of shooters to evaluate the influence of their expertise while concentrating on the target. Marksmen (pistol shooters, 10 men and 5 women) and pentathletes (6 men and 7 women) took part in a shooting competition in keeping with the rules of each event. Participants were then asked to imagine themselves shooting, at the laboratory. Five variables representing the activity of the autonomic nervous system were continuously recorded (skin resistance and potential, skin blood flow, skin temperature, instantaneous heart rate). Autonomic responses recorded during concentration, actual shooting, and mental imagery were compared by calculating the ratios concentration/ shooting and imagery/shooting. The resultant mean ratio was used to characterize each participant. The same autonomic nervous system pattern was observed during concentrating on the target, mental imagery, and actual shooting. However, marksmen showed ratios closer to 1.0 than pentathletes, absolute mean differences being .06 and .3, respectively. Shorter duration and weakest amplitude responses were recorded during the concentration phase in the Pentathlete group, suggesting that they have more difficulty in using mental imagery during competition than marksmen. When subjects performed well, a specific response pattern was observed in the Marksman group, but not in the Pentathlete group, except in skin potential. In both Marksman and Pentathlete groups, a majority of negative skin potential responses were found in the concentration and shooting phases for the best shots.     

Vagus nerve stimulation and Lennox-Gastaut syndrome: a review of the literature and data from the VNS patient registry

Lennox-Gastaut syndrome (LGS) is a severe form of childhood epilepsy that is usually refractory to medical management. When medication fails, alternative therapies are considered. Among these are two surgical options: corpus callosotomy and vagus nerve stimulation (VNS). Safety and efficacy are two important factor to consider when selecting an appropriate treatment. VNS is safer than callosotomy, but its efficacy is more difficult to assess. Available studies evaluate its effectiveness using a mixed population of patients (some with prior epilepsy surgery), a multitude of VNS settings, and variable endpoints. To estimate the efficacy of VNS in patients with LGS, a review of the medical literature and the VNS Patient Registry was performed. Within the limits of this type of study, the results showed that VNS appears to be equally as effective as callosotomy. Because VNS has a lower potential for adverse effects, these results suggest that VNS should be considered first in appropriately selected patients.     

Acute and chronic effects of cocaine on extinction-induced aggression.

Pigeons worked individually in a chamber containing a response key and a mirror. Pecking on the key was controlled by a multiple schedule in which a brief period of continuous food reinforcement alternated with a 5-minute period of extinction. Under baseline conditions, aggressive behavior (responding on the mirror) occurred at the onset of each extinction period. In Experiment I (acute drug administration), the aggressive behavior was decreased by doses of cocaine that had little or no effect on key pecking. Such food-reinforced responding was disrupted, however, by higher doses of cocaine. An attempt to mimic the disruptive drugs effects by a prefeeding manipulation was unsuccessful. In Experiment II (chronic drug administration), some tolerance developed to the disruptive effects of cocaine on the food-reinforced responding, except at the highest dose tested. There was no clear-cut indication of tolerance to the initial effect of cocaine on the aggressive behavior at any dose.     

Acute and chronic stress effects on performance in a forced-swim task

The effects of uncontrollable stressors on performance in a subsequent forced-swim paradigm were assessed in mice. Uncontrollable shock initially induced behavioral invigoration; however, within 24 h of stressor application, swimming behavior was depressed relative to nonstressed mice. The controllability of the stressor did not influence the initial invigoration, being present among escapably shocked mice as well as among mice that received (yoked) inescapable shock. In contrast, the depression of responding evident 24 h after stressor application was related to the availability of behavioral coping methods. Finally, following repeated exposure to footshock there was no indication of adaptation to the behavioral changes ordinarily induced by acute shock stress. The data were related to the effects of uncontrollable stressors on escape performance, and with respect to the use of this preparation as an animal model of human depression.     

Signal evaluation environment: a new method for the design of peripheral in-vehicle warning signals

An evaluation method called the Signal Evaluation Environment (SEE) was developed for use in the early stages of the design process of peripheral warning signals while driving. Accident analyses have shown that with complex driving situations such as intersections, the visual scan strategies of the driver contribute to overlooking other road users who have the right of way. Salient peripheral warning signals could disrupt these strategies and direct drivers’ attention towards these road users. To select effective warning signals, the SEE was developed as a laboratory task requiring visual–cognitive processes similar to those used at intersections. For validation of the SEE, four experiments were conducted using different stimulus characteristics (size, colour contrast, shape, flashing) that influence peripheral vision. The results confirm that the SEE is able to differentiate between the selected stimulus characteristics. The SEE is a useful initial tool for designing peripheral signals, allowing quick and efficient preselection of beneficial signals.     

Vagus nerve stimulation therapy in a patient with treatment-resistant depression: a case report of long-term follow-up and battery end-of-service

This is the first case report of a patient who received long-term (69-month) adjunctive vagus nerve stimulation (VNS) therapy for treatment-resistant depression (TRD) and reached VNS battery end-of-service (EOS). The patient is a 41-year-old female with depression who entered a study of adjunctive VNS therapy for TRD. Her Hamilton Rating Scale for Depression (HAM-D) scores dropped from a mean of 33.5 (pre-implantation baseline period) to 16 at the end of the 12-week acute-phase treatment period, and then fluctuated from <7 (normal range) to scores in the moderately depressed range (approximately 20) during long-term follow-up. Three and one-half years after VNS implantation, the patient's HAM-D scores began to increase from a score of 18 to a peak score of 27 approximately 16 months later (5-years post-implantation). The patient subsequently reported that she could no longer feel stimulation from the device and device interrogation 2 weeks later indicated battery EOS. The patient was hospitalized due to worsened depression, the pulse generator was replaced, and medication adjusted. HAM-D scores through the subsequent 9 months of follow-up returned to a pattern of fluctuations within the range noted during the long-term follow-up period prior to VNS battery EOS.     

Perception of different frequencies of cranial transcutaneous electrical nerve stimulation in normal and HIV-positive individuals.

Sine-wave transcutaneous electrical nerve stimulation (TENS) of varying frequencies applied across the cranium (ear to ear) has been demonstrated to evoke three different noncutaneous sensations in three discrete, nonoverlapping frequency bands in normal, healthy subjects. This report describes two studies which evaluate perception of these cranial TENS-evoked, frequency-dependent sensations in normal and HIV-positive individuals. In Exp. I, all of 50 normal, healthy subjects reported perceiving the same three noncutaneous sensations in the same three nonoverlapping frequency bands as long as stimulated and over repeated trials. In Exp. II, 34 HIV-positive individuals (14 asymptomatic, 9 ARC, 11 AIDS) who were free of neurological symptoms differed significantly from 10 normal, healthy controls, and from the norms observed in Exp. I, on perception of the three different TENS-evoked sensations. Also, inability to maintain perception of the stimulus over repeated trials, observed only in the HIV-positive individuals, increased significantly with severity of HIV infection.     

Hippocampal low-frequency stimulation and chronic mild stress similarly disrupt fear extinction memory in rats

Disruptions of fear extinction-related potentiation of synaptic efficacy in the connection between the hippocampus (HPC) and the medial prefrontal cortex (mPFC) have been shown to impair the recall of extinction memory. This study was undertaken to examine if chronic mild stress (CMS), which is known to alter induction of HPC–mPFC long-term potentiation, would also interfere with both extinction-related HPC–mPFC potentiation and extinction memory. Following fear conditioning (5 tone-shock pairings), rats were submitted to fear extinction (20 tone-alone presentations), which produced an increase in the amplitude of HPC–mPFC field potentials. HPC low-frequency stimulation (LFS), applied immediately after training, suppressed these changes and induced fear return during the retention test (5 tone-alone presentations). CMS, delivered before fear conditioning, did not interfere with fear extinction but blocked the development of extinction-related potentiation in the HPC–mPFC pathway and impaired the recall of extinction. These findings suggest that HPC LFS may provoke metaplastic changes in HPC outputs that may mimic alterations associated with a history of chronic stress.