Exploring the middle ear function in patients with a cluster of symptoms including tinnitus, hyperacusis, ear fullness and/or pain.

Middle ear muscle (MEM) abnormalities have been proposed to be involved in the development of ear-related symptoms such as tinnitus, hyperacusis, ear fullness, dizziness and/or otalgia. This cluster of symptoms have been called the Tonic Tensor Tympani Syndrome (TTTS) because of the supposed involvement of the tensor tympani muscle (TTM). However, the putative link between MEM dysfunction and the symptoms has not been proven yet and the detailed mechanisms (the causal chain) of TTTS are still elusive. It has been speculated that sudden loud sound (acoustic shock) may impair the functioning of the MEM, specifically the TTM, after an excessive contraction. This would result in inflammatory processes, activation of the trigeminal nerve and a change of the MEMs state into a hypersensitive one, that may be associated to the cluster of symptoms listed above. The goal of this study is to provide further insights into the mechanisms of TTTS. The middle ear function of 11 patients who reported TTTS symptoms has been investigated using either admittancemetry and/or measurement of air pressure in the sealed external auditory canal. While the former method measured the middle ear stiffness the latter provides an estimate of the tympanic membrane displacement. Most patients displayed results consistent with phasic contractions of the TTM (n = 9) and/or Eustachian Tube (ET) dysfunction (n = 6). The MEM contraction or ET dysfunction could be evoked by acoustic stimulation (n = 3), somatic maneuvers (n = 3), or pressure changes in the ear canal (n = 3). Spontaneous TTM contraction (n = 1) or ET opening (n = 1) could also be observed. Finally, voluntary contraction of MEM was also reported (n = 5). On the other hand, tonic contraction of the TTM could not be observed in any patient. The implications of these results for the mechanisms of TTTS are discussed.

Contraction of the stapedius and tensor tympani muscles explored by tympanometry and pressure measurement in the external auditory canal.

It has been suggested that tensor tympani muscle (TTM) contraction may be involved in the development of ear-related pathologies such as tinnitus, hyperacusis and otalgia, called the tonic tensor tympani syndrome (TTTS). However, as there is no precise measure of TTM function under normal and pathological states, its involvement remains speculative. When the TTM or the stapedius muscle (SM) contracts, they both generate an increase of middle ear stiffness that can be measured through middle ear admittance. However, this technique cannot differentiate the contraction between the two muscles. On the other hand, the air pressure measured in a sealed external auditory canal can provide a measure of the eardrum displacement that may be able to differentiate SM from TTM contraction. TTM is attached to the malleus, and its contraction causes a retraction of the eardrum inside the middle ear cavity, while SM can have a small but reversed effect on TTM displacement. To investigate this issue, we compared the middle ear admittance and air pressure in a sealed external ear canal upon auditory stimulation (sMEMC) and voluntary middle ear muscle contraction (vMEMC). In addition, we assessed the perceptual effect of vMEMC, including pitch and loudness matching of the fluttering noise produced by vMEMC and the threshold shifts, were measured. Out of the 14 ears tested, sMEMC was associated with a decrease of admittance in 93% (mean peak average: -0.06 ml, SD:0.04) and an increase of air pressure in 29% of ears (mean peak average: 8.1 Pa, SD:5.1). No decrease in air pressure was found upon sMEMC. For vMEMC (n = 8 ears), decreases were found for both admittance and air pressure in 100% and 88%, with a mean peak average of -0.38 ml, SD: 0.54 and -149 Pa, SD:156, for admittance and pressure respectively. These results suggest that SM and TTM are involved in sMEMC and vMEMC, respectively. In addition, vMEMC was associated with perceptual effects including a low-frequency sound, pitch-matched at ∼30 Hz (>15 dB SL), and a low-frequency hearing loss of at least 10 dB between 20 and 200 Hz. In conclusion, admittance and air pressure recordings provide useful and complementary information on middle ear muscle contraction and can be used to explore the middle ear function.

The experimental emergence of convention in a non-human primate.

Conventions form an essential part of human social and cultural behaviour and may also be important to other animal societies. Yet, despite the wealth of evidence that has accumulated for culture in non-human animals, we know surprisingly little about non-human conventions beyond a few rare examples. We follow the literature in behavioural ecology and evolution and define conventions as systematic behaviours that solve a coordination problem in which two or more individuals need to display complementary behaviour to obtain a mutually beneficial outcome. We start by discussing the literature on conventions in non-human primates from this perspective and conclude that all the ingredients for conventions to emerge are present and therefore that they ought to be more frequently observed. We then probe the emergence of conventions by using a unique novel experimental system in which pairs of Guinea baboons (Papio papio) can voluntarily participate together in touchscreen-based cognitive testing and we show that conventions readily emerge in our experimental set-up and that they share three fundamental properties of human conventions (arbitrariness, stability and efficiency). These results question the idea that observational learning, and imitation in particular, is necessary to establish conventions; they suggest that positive reinforcement is enough. This article is part of a discussion meeting issue 'The emergence of collective knowledge and cumulative culture in animals, humans and machines'.

Learned Overweight Internal Model Can Be Activated to Maintain Equilibrium When Tactile Cues Are Uncertain: Evidence From Cortical and Behavioral Approaches.

Human adaptive behavior in sensorimotor control is aimed to increase the confidence in feedforward mechanisms when sensory afferents are uncertain. It is thought that these feedforward mechanisms rely on predictions from internal models. We investigate whether the brain uses an internal model of physical laws (gravitational and inertial forces) to help estimate body equilibrium when tactile inputs from the foot sole are depressed by carrying extra weight. As direct experimental evidence for such a model is limited, we used Judoka athletes thought to have built up internal models of external loads (i.e., opponent weight management) as compared with Non-Athlete participants and Dancers (highly skilled in balance control). Using electroencephalography, we first (experiment 1) tested the hypothesis that the influence of tactile inputs was amplified by descending cortical efferent signals. We compared the amplitude of P1N1 somatosensory cortical potential evoked by electrical stimulation of the foot sole in participants standing still with their eyes closed. We showed smaller P1N1 amplitudes in the Load compared to No Load conditions in both Non-Athletes and Dancers. This decrease neural response to tactile stimulation was associated with greater postural oscillations. By contrast in the Judoka's group, the neural early response to tactile stimulation was unregulated in the Load condition. This suggests that the brain can selectively increase the functional gain of sensory inputs, during challenging equilibrium tasks when tactile inputs were mechanically depressed by wearing a weighted vest. In Judokas, the activation of regions such as the right posterior inferior parietal cortex (PPC) as early as the P1N1 is likely the source of the neural responses being maintained similar in both Load and No Load conditions. An overweight internal model stored in the right PPC known to be involved in maintaining a coherent representation of one's body in space can optimize predictive mechanisms in situations with high balance constraints (Experiment 2). This hypothesis has been confirmed by showing that postural reaction evoked by a translation of the support surface on which participants were standing wearing extra-weight was improved in Judokas.

Measuring social networks in primates: wearable sensors versus direct observations.

Network analysis represents a valuable and flexible framework to understand the structure of individual interactions at the population level in animal societies. The versatility of network representations is moreover suited to different types of datasets describing these interactions. However, depending on the data collection method, different pictures of the social bonds between individuals could a priori emerge. Understanding how the data collection method influences the description of the social structure of a group is thus essential to assess the reliability of social studies based on different types of data. This is however rarely feasible, especially for animal groups, where data collection is often challenging. Here, we address this issue by comparing datasets of interactions between primates collected through two different methods: behavioural observations and wearable proximity sensors. We show that, although many directly observed interactions are not detected by the sensors, the global pictures obtained when aggregating the data to build interaction networks turn out to be remarkably similar. Moreover, sensor data yield a reliable social network over short time scales and can be used for long-term studies, showing their important potential for detailed studies of the evolution of animal social groups.

Orexin in the Posterior Paraventricular Thalamus Mediates Hunger-Related Signals in the Nucleus Accumbens Core.

Animals use exteroceptive stimuli that have acquired, through learning, the ability to predict available resources allowing them to engage in adaptive behaviors. Meanwhile, peripheral signals related to internal state (e.g., hunger) provide information about current needs, modulating the ability of exteroceptive stimuli to drive food-seeking behavior [1, 2]. The nucleus accumbens core (NAcC) is essential for encoding the value of reward-predictive cues and controlling the level of behavioral responding [3-7]. However, the way in which interoceptive information related to physiological needs is integrated in the NAcC remains to be clarified. Located in the lateral and perifornical hypothalamic regions, orexin neurons [8, 9] are implicated in a wide range of functions, including arousal, feeding, and reward seeking [10-16]. Paraventricular thalamus (PVT) neurons receive a strong orexinergic projection [17] and are excited by orexins [18-20]. Hence, Kelley et al. [21] proposed that the PVT serves as an integrative relay, conveying hypothalamic energy-balance information to the NAc through its glutamatergic projection. Here, we test whether NAcC encoding of reward-predictive cues is modulated by the integration of posterior PVT (pPVT) orexin-mediated hunger-related signals. Using a cue-driven reward-seeking task, we show that satiety decreases cue responses in NAcC and pPVT neurons. Blockade of pPVT orexin-2 receptors reduces responding in hungry rats. Activation of pPVT neurons, either with local infusion of orexin-A or via optogenetics, positively controls NAcC cue responses and restores behavioral responding in sated rats, highlighting a circuit that integrates reward-predictive cues perceived in the environment with the current metabolic state of the animal.

Do gravity-related sensory information enable the enhancement of cortical proprioceptive inputs when planning a step in microgravity?

We recently found that the cortical response to proprioceptive stimulation was greater when participants were planning a step than when they stood still, and that this sensory facilitation was suppressed in microgravity. The aim of the present study was to test whether the absence of gravity-related sensory afferents during movement planning in microgravity prevented the proprioceptive cortical processing to be enhanced. We reestablished a reference frame in microgravity by providing and translating a horizontal support on which the participants were standing and verified whether this procedure restored the proprioceptive facilitation. The slight translation of the base of support (lateral direction), which occurred prior to step initiation, stimulated at least cutaneous and vestibular receptors. The sensitivity to proprioceptive stimulation was assessed by measuring the amplitude of the cortical somatosensory-evoked potential (SEP, over the Cz electrode) following the vibration of the leg muscle. The vibration lasted 1 s and the participants were asked to either initiate a step at the vibration offset or to remain still. We found that the early SEP (90-160 ms) was smaller when the platform was translated than when it remained stationary, revealing the existence of an interference phenomenon (i.e., when proprioceptive stimulation is preceded by the stimulation of different sensory modalities evoked by the platform translation). By contrast, the late SEP (550 ms post proprioceptive stimulation onset) was greater when the translation preceded the vibration compared to a condition without pre-stimulation (i.e., no translation). This suggests that restoring a body reference system which is impaired in microgravity allowed a greater proprioceptive cortical processing. Importantly, however, the late SEP was similarly increased when participants either produced a step or remained still. We propose that the absence of step-induced facilitation of proprioceptive cortical processing results from a decreased weight of proprioception in the absence of balance constraints in microgravity.

Different populations of subthalamic neurons encode cocaine vs. sucrose reward and predict future error.

The search for treatment of cocaine addiction raises the challenge to find a way to diminish motivation for the drug without decreasing it for natural rewards. Subthalamic nucleus (STN) inactivation decreases motivation for cocaine while increasing motivation for food, suggesting that STN can dissociate different rewards. Here, we investigated how rat STN neurons respond to cues predicting cocaine or sucrose and to reward delivery while rats are performing a discriminative stimuli task. We show that different neuronal populations of STN neurons encode cocaine and sucrose. In addition, we show that STN activity at the cue onset predicts future error. When changing the reward predicted unexpectedly, STN neurons show capacities of adaptation, suggesting a role in reward-prediction error. Furthermore, some STN neurons show a response to executive error (i.e., "oops neurons") that is specific to the missed reward. These results position the STN as a nexus where natural rewards and drugs of abuse are coded differentially and can influence the performance. Therefore, STN can be viewed as a structure where action could be taken for the treatment of cocaine addiction.

Biases in the perception of self-motion during whole-body acceleration and deceleration.

Several studies have investigated whether vestibular signals can be processed to determine the magnitude of passive body motions. Many of them required subjects to report their perceived displacements offline, i.e., after being submitted to passive displacements. Here, we used a protocol that allowed us to complement these results by asking subjects to report their introspective estimation of their displacement continuously, i.e., during the ongoing body rotation. To this end, participants rotated the handle of a manipulandum around a vertical axis to indicate their perceived change of angular position in space at the same time as they were passively rotated in the dark. The rotation acceleration (Acc) and deceleration (Dec) lasted either 1.5 s (peak of 60°/s(2), referred to as being "High") or 3 s (peak of 33°/s(2), referred to as being "Low"). The participants were rotated either counter-clockwise or clockwise, and all combinations of acceleration and deceleration were tested (i.e., AccLow-DecLow; AccLow-DecHigh; AccHigh-DecLow; AccHigh-DecHigh). The participants' perception of body rotation was assessed by computing the gain, i.e., ratio between the amplitude of the perceived rotations (as measured by the rotating manipulandum's handle) and the amplitude of the actual chair rotations. The gain was measured at the end of the rotations, and was also computed separately for the acceleration and deceleration phases. Three salient findings resulted from this experiment: (i) the gain was much greater during body acceleration than during body deceleration, (ii) the gain was greater during High compared to Low accelerations and (iii) the gain measured during the deceleration was influenced by the preceding acceleration (i.e., Low or High). These different effects of the angular stimuli on the perception of body motion can be interpreted in relation to the consequences of body acceleration and deceleration on the vestibular system and on higher-order cognitive processes.

Reducing the desire for cocaine with subthalamic nucleus deep brain stimulation.

Deep brain stimulation (DBS) is a reversible technique that is currently used for the treatment of Parkinson disease and may be suitable for the treatment of psychiatric disorders. Whether DBS inactivates the target structure is still a matter of debate. Here, from findings obtained in rats, we propose DBS of the subthalamic nucleus (STN) as a possible treatment for cocaine addiction to be further tested in human studies. We show that STN DBS reversibly reduces the motivation to work for an i.v. injection of cocaine, and it increases motivation to work for sucrose pellets. These opposite effects may result from STN DBS effect on the positive affective properties of these rewards. Indeed, we further show that STN DBS reduces the preference for a place previously associated with the rewarding properties of cocaine, and it increases the preference for a place associated with food. Because these findings are consistent with those observed after STN lesions [Baunez C, Dias C, Cador M, Amalric M (2005) Nat Neurosci 8:484-489], they suggest that STN DBS mimics an inactivation of the STN on motivational processes. Furthermore, given that one of the major challenges for cocaine addiction is to find a treatment that reduces the craving for the drug without diminishing the motivation for naturally rewarding activities, our findings validate STN as a good target and DBS as the appropriate technique for a promising therapeutic strategy in the treatment of cocaine addiction.

Beyond the reward pathway: coding reward magnitude and error in the rat subthalamic nucleus.

It was recently shown that subthalamic nucleus (STN) lesions affect motivation for food, cocaine, and alcohol, differentially, according to either the nature of the reward or the preference for it. The STN may thus code a reward according to its value. Here, we investigated how the firing of subthalamic neurons is modulated during expectation of a predicted reward between two possibilities (4 or 32% sucrose solution). The firing pattern of neurons responding to predictive cues and to reward delivery indicates that STN neurons can be divided into subpopulations responding specifically to one reward and less or giving no response to the other. In addition, some neurons ("oops" neurons) specifically encode errors as they respond only during error trials. These results reveal that the STN plays a critical role in ascertaining the value of the reward and seems to encode that value differently depending on the magnitude of the reward. These data highlight the importance of the STN in the reward circuitry of the brain.

Automatic testing of cognitive performance in baboons maintained in social groups.

Laboratory procedures used to study the cognitive functions of primates traditionally have involved removal of the subjects from their living quarters to be tested singly in a remote experimental room. This article presents an alternative research strategy favoring testing primates while they are maintained in their social group. The automatic learning device for monkeys (ALDM) is a computerized test system controlled by an automatic radio frequency identification of subjects. It is provided ad lib inside the social group of monkeys, for voluntary self-testing on a 24-h schedule. Nine baboons were tested with ALDM during a 7-month period. Experiments were performed to assess learning in motor control and abstract reasoning tasks. The results revealed high trial frequencies and excellent learning performance, even in tasks involving the highest cognitive complexities. A different study using ALDM with a group of 3 rhesus monkeys revealed social influences on learning. Beyond its interest for cognitive psychologists, ALDM is of interest for pharmacologists and cognitive neuroscientists working with nonhuman primates. ALDM also can serve as an enrichment tool for captive animals and may be used to study a variety of species other than primates.