The origin of pleasant sensations: Insight from direct electrical brain stimulation.

Research into the neuroanatomical basis of emotions has resulted in a plethora of studies over the last twenty years. However, studies about positive emotions and pleasant sensations remain rare and their anatomical-functional bases are less understood than that of negative emotions. Pleasant sensations can be evoked by electrical brain stimulations (EBS) during stereotactic electroencephalography (SEEG) performed for pre-surgical exploration in patients with drug-resistant epilepsy. We conducted a retrospective analysis of 10 106 EBS performed in 329 patients implanted with SEEG in our epileptology department. We found that 13 EBS in 9 different patients evoked pleasant sensations (.60% of all responses). By contrast we collected 111 emotional responses of negative valence (i.e., 5.13% of all responses). EBS evoking pleasant sensations were applied at 50 Hz with an average intensity of 1.4 ± .55 mA (range .5-2 mA). Pleasant sensations were reported by nine patients of which three patients presented responses to several EBS. We found a male predominance among the patients reporting pleasant sensations and a prominent role of the right cerebral hemisphere. Results show the preponderant role of the dorsal anterior insula and amygdala in the occurrence of pleasant sensations.

Navigation strategies in patients with vestibular loss tested in a virtual reality T-maze.

During navigation, humans mainly rely on egocentric and allocentric spatial strategies, two different frames of reference working together to build a coherent representation of the environment. Spatial memory deficits during navigation have been repeatedly reported in patients with vestibular disorders. However, little is known about how vestibular disorders can change the use of spatial navigation strategies. Here, we used a new reverse T-maze paradigm in virtual reality to explore whether vestibular loss specifically modifies the use of egocentric or allocentric spatial strategies in patients with unilateral (n = 23) and bilateral (n = 23) vestibular loss compared to healthy volunteers (n = 23) matched for age, sex and education level. Results showed that the odds of selecting and using a specific strategy in the T-maze were significantly reduced in both unilateral and bilateral vestibular loss. An exploratory analysis suggests that only right vestibular loss decreased the odds of adopting a spatial strategy, indicating an asymmetry of vestibular functions. When considering patients who used strategies to navigate, we observed that a bilateral vestibular loss reduced the odds to use an allocentric strategy, whereas a unilateral vestibular loss decreased the odds to use an egocentric strategy. Age was significantly associated with an overall lower chance to adopt a navigation strategy and, more specifically, with a decrease in the odds of using an allocentric strategy. We did not observe any sex difference in the ability to select and use a specific navigation strategy. Findings are discussed in light of previous studies on visuo-spatial abilities and studies of vestibulo-hippocampal interactions in peripheral vestibular disorders. We discuss the potential impact of the history of the disease (chronic stage in patients with a bilateral vestibulopathy vs. subacute stage in patients with a unilateral vestibular loss), of hearing impairment and non-specific attentional deficits in patients with vestibular disorders.

Apamin treatment accelerates equilibrium recovery and gaze stabilization in unilateral vestibular neurectomized cats: Cellular and behavioral aspects.

Sudden and complete unilateral loss of peripheral vestibular inputs evokes characteristic vestibular syndrome comprised of posturo-locomotor, oculomotor, vegetative and cognitive symptoms. Subsequently to the vestibular insult, a neurophysiological process called central vestibular compensation promotes the progressive restoration of the posture and balance. The modulation of the excitability of vestibular secondary neurons has been demonstrated to be a key process of this mechanism. However, the molecular mechanisms that support this modulatory process have thus far not been fully identified. The present study used a combination of a radio-labeled apamin binding experiment and a functional assessment of the vestibular function to demonstrate that unilateral vestibular neurectomy (UVN) induces both ipsi- and contralateral up-regulation of the apamin-sensitive calcium-activated small conductance K+ (SK) channels, within the first days following the insult. We also demonstrate that apamin administration during the acute phase of the vestibular syndrome significantly reduces both the posturo-locomotor and vestibulo-ocular deficits induced by the UVN. This is illustrated by the reduction of both the spontaneous nystagmus and the static and dynamic balance unsteadiness. These data suggest that the regulation of SK channel expression may be part of the vestibular compensation process. It is also indicated that the pharmacological modulation of SK channels may be a potential way to alleviate the vestibular syndrome.

Betahistine Treatment in a Cat Model of Vestibular Pathology: Pharmacokinetic and Pharmacodynamic Approaches.

This study is a pharmacokinetic (PK) and pharmacodynamics (PD) approach using betahistine doses levels in unilateral vestibular neurectomized cats (UVN) comparable to those used in humans for treating patients with Menière's disease. The aim is to investigate for the first time oral betahistine administration (0.2 and 2 mg/kg/day) with plasma concentrations of betahistine and its major metabolite 2-pyridylacetic acid (2-PAA) (N = 9 cats), the time course of posture recovery (N = 13 cats), and the regulation of the enzyme synthesizing histamine (histidine decarboxylase: HDC) in the tuberomammillary nuclei (TMN) of UVN treated animals (N = the same 13 cats plus 4 negative control cats). In addition the effect of co-administration of the lower betahistine dose (0.2 mg/kg/day) and selegiline (1 mg/kg/day), an inhibitor of the monamine oxidase B (MAOBi) implicated in betahistine catabolism was investigated. The PK parameters were the peak concentration (Cmax), the time when the maximum concentration is reached (Tmax) for both betahistine and 2-PAA and the area under the curve (AUC). The PD approach consisted at quantifying the surface support area, which is a good estimation of posture recovery. The plasma concentration-time-profiles of betahistine and 2-PAA in cats were characterized by early Cmax-values followed by a phase of rapid decrease of plasma concentrations and a final long lasting low level of plasma concentrations. Co administration of selegiline and betahistine increased values of Cmax and AUC up to 146- and 180-fold, respectively. The lowest dose of betahistine (0.2 mg/kg) has no effects on postural function recovery but induced an acute symptomatic effect characterized by a fast balance improvement (4-6 days). The higher dose (2 mg/kg) and the co-administration treatment induced both this acute effect plus a significant acceleration of the recovery process. The histaminergic activity of the neurons in the TMN was significantly increased under treatment with the 2 mg/kg betahistine daily dose, but not with the lower dose alone or in combination with selegiline. The results show for the first time that faster balance recovery in UVN treated cats is accompanied with high plasma concentrations of betahistine and 2-PAA, and upregulation of HDC immunopositive neurons in the TMN. The higher betahistine dose gives results similar to those obtained with the lower dose when co-administrated with an inhibitor of betahistine metabolism, selegiline. From a clinical point of view, the study provides new perspectives for Menière's disease treatment, regarding the daily betahistine dose that should be necessary for fast and slow metabolizers.

Comparative analysis of pharmacological treatments with N-acetyl-DL-leucine (Tanganil) and its two isomers (N-acetyl-L-leucine and N-acetyl-D-leucine) on vestibular compensation: Behavioral investigation in the cat.

Head roll tilt, postural imbalance and spontaneous nystagmus are the main static vestibular deficits observed after an acute unilateral vestibular loss (UVL). In the UVL cat model, these deficits are fully compensated over 6 weeks as the result of central vestibular compensation. N-Acetyl-dl-leucine is a drug prescribed in clinical practice for the symptomatic treatment of acute UVL patients. The present study investigated the effects of N-acetyl-dl-leucine on the behavioral recovery after unilateral vestibular neurectomy (UVN) in the cat, and compared the effects of each of its two isomers N-acetyl-L-leucine and N-acetyl-D-leucine. Efficacy of these three drug treatments has been evaluated with respect to a placebo group (UVN+saline water) on the global sensorimotor activity (observation grids), the posture control (support surface measurement), the locomotor balance (maximum performance at the rotating beam test), and the spontaneous vestibular nystagmus (recorded in the light). Whatever the parameters tested, the behavioral recovery was strongly and significantly accelerated under pharmacological treatments with N-acetyl-dl-leucine and N-acetyl-L-leucine. In contrast, the N-acetyl-D-leucine isomer had no effect at all on the behavioral recovery, and animals of this group showed the same recovery profile as those receiving a placebo. It is concluded that the N-acetyl-L-leucine isomer is the active part of the racemate component since it induces a significant acceleration of the vestibular compensation process similar (and even better) to that observed under treatment with the racemate component only.

Static and dynamic posture control in postlingual cochlear implanted patients: effects of dual-tasking, visual and auditory inputs suppression.

Posture control is based on central integration of multisensory inputs, and on internal representation of body orientation in space. This multisensory feedback regulates posture control and continuously updates the internal model of body's position which in turn forwards motor commands adapted to the environmental context and constraints. The peripheral localization of the vestibular system, close to the cochlea, makes vestibular damage possible following cochlear implant (CI) surgery. Impaired vestibular function in CI patients, if any, may have a strong impact on posture stability. The simple postural task of quiet standing is generally paired with cognitive activity in most day life conditions, leading therefore to competition for attentional resources in dual-tasking, and increased risk of fall particularly in patients with impaired vestibular function. This study was aimed at evaluating the effects of postlingual cochlear implantation on posture control in adult deaf patients. Possible impairment of vestibular function was assessed by comparing the postural performance of patients to that of age-matched healthy subjects during a simple postural task performed in static (stable platform) and dynamic (platform in translation) conditions, and during dual-tasking with a visual or auditory memory task. Postural tests were done in eyes open (EO) and eyes closed (EC) conditions, with the CI activated (ON) or not (OFF). Results showed that the postural performance of the CI patients strongly differed from the controls, mainly in the EC condition. The CI patients showed significantly reduced limits of stability and increased postural instability in static conditions. In dynamic conditions, they spent considerably more energy to maintain equilibrium, and their head was stabilized neither in space nor on trunk: they behaved dynamically without vision like an inverted pendulum while the controls showed a whole body rigidification strategy. Hearing (prosthesis on) as well as dual-tasking did not really improve the dynamic postural performance of the CI patients. We conclude that CI patients become strongly visual dependent mainly in challenging postural conditions, a result they have to be awarded of particularly when getting older.

How body position changes visual vertical perception after unilateral vestibular loss.

Visual vertical perception, posture and equilibrium are impaired in patients with a unilateral vestibular loss. The present study was designed to investigate whether body position (standing upright, sitting on a chair and lying supine) influences the visual vertical perception in Menière's patients tested before and after a unilateral vestibular neurotomy. Data were compared with sex- and age-matched healthy participants. During the first postoperative month the body position strongly influences the visual vertical perception. The ipsilesional deviation of the visual vertical judgment gradually increased from standing upright to sitting and to lying supine. The present data indicate that visual vertical perception improves when postural control is more demanding. This suggests that postural balance is a key reference for vertical perception, at least up to one month after vestibular loss.