Varying Interstimulus Intervals Research Articles

Aperiodic EEG Predicts Variability of Visual Temporal Processing.

The human brain exhibits both oscillatory and aperiodic, or 1/f, activity. Although a large body of research has focused on the relationship between brain rhythms and sensory processes, aperiodic activity has often been overlooked as functionally irrelevant. Prompted by recent findings linking aperiodic activity to the balance between neural excitation and inhibition, we investigated its effects on the temporal resolution of perception. We recorded electroencephalography (EEG) from participants (both sexes) during the resting state and a task in which they detected the presence of two flashes separated by variable interstimulus intervals. Two-flash discrimination accuracy typically follows a sigmoid function whose steepness reflects perceptual variability or inconsistent integration/segregation of the stimuli. We found that individual differences in the steepness of the psychometric function correlated with EEG aperiodic exponents over posterior scalp sites. In other words, participants with flatter EEG spectra (i.e., greater neural excitation) exhibited increased sensory noise, resulting in shallower psychometric curves. Our finding suggests that aperiodic EEG is linked to sensory integration processes usually attributed to the rhythmic inhibition of neural oscillations. Overall, this correspondence between aperiodic neural excitation and behavioral measures of sensory noise provides a more comprehensive explanation of the relationship between brain activity and sensory integration and represents an important extension to theories of how the brain samples sensory input over time.

The recovery cycle of excitability assessed by a conventional electrodiagnostic machine: A study in healthy volunteers and in Charcot-Marie-Tooth 1A patients

ObjectiveTo validate the ‘paired pulses’ technique with a conventional electrodiagnostic machine (CEM) for studying the axonal excitability recovery cycle (ERC). MethodsPaired pulses, with a variable inter-stimulus interval, were delivered at the wrist along the median nerve. The CEM repeatability was verified in a group of 15 healthy volunteers (test/retest analysis). ERC was then applied in 40 healthy volunteers and 10 patients with Charcot-Marie-Tooth type 1A (CMT1A), using both the threshold tracking (TT) reference method and CEM (basal condition, during and after ischemia). ResultsCEM parameters evaluating absolute refractory and supernormal periods were reproducible (interclass correlation coefficient > 0.75). CEM results were consistent with TT method and literature data. In CMT1A, refractory and superexcitable periods were significantly reduced. According to receiving operator characteristic analysis, the CEM supernormal period area was the most relevant parameter for discriminating CMT1A from healthy volunteers (area under the curve = 0.98). ConclusionsCEM was a valid procedure for studying ERC. CMT1A patients exhibited ERC alterations due to modifications in passive membrane properties and of nodal ion channel distribution resulting from demyelination. SignificanceStudying ERC with CEM could be performed in routine practice in patients with peripheral neuropathies to provide information on motor axonal excitability.

Auditory brainstem response recovery from forward masking in insectivorous and frugivorous bats

Echolocating bats rely on precise temporal processing of sound, as echolocation calls may be emitted at rates as high as 150–200 sounds per second in the terminal “buzz” phase that precedes prey capture by insectivorous species. High call repetition rates could introduce forward masking effects that interfere with echo detection; however, echolocating bats may have evolved auditory specializations to prevent repetition suppression of auditory responses and facilitate detection of sounds separated by very brief time intervals. We assessed the time course of post-stimulus recovery of the auditory brainstem response (ABR) in two bat species that differ in the temporal characteristics of their sonar behaviors: the insectivorous Eptesicus fuscus, which uses high sonar call rates to capture prey and the frugivorous Carollia perspicillata, which uses lower call rates to forage. We recorded forward-masking ABRs to paired clicks at varied inter-stimulus intervals and measured recovery from prior stimulation as the ratio of response amplitudes and latencies evoked by the second stimulus relative to the first. We observed significant species-specific effects of forward masking on ABR responses in which E. fuscus maintained comparable responses to ISIs less than 4 ms compared to longer post-stimulus response recovery times (>6 ms) in C. perspicillata.

Temporal processing deficit in children and adolescents with autism spectrum disorder: An online assessment.

The sensory deficit has been considered as one of the core features in children and adolescents with autism spectrum disorder (ASD). The present study aimed to examine the temporal processing of simple and more complex auditory inputs in ASD children and adolescents with an online assessment that can be conducted remotely. One hundred fifty-eight children and adolescents aged 5-17 years participated in this study, including 79 ASD participants and 79 typically developing (TD) participants. The online assessment consisted of two temporal-order judgment tasks that required repeating the sequence of two pure tones or consonant-vowel (CV) syllabic pairs at varying interstimulus intervals (ISIs). Significantly lower accuracy rates were found in ASD than TD participants in the pure tone and the CV conditions with both short and long ISI. In addition, ASD participants (M = 245.97 ms) showed a significantly higher passing threshold than TD participants (M = 178.84 ms) in the CV task. Receiver operating characteristic analysis found that the age × ISI passing threshold composite yielded a sensitivity of 74.7% and a specificity of 50.6% at the cutoff point of -0.307 in differentiating ASD participants from TD participants. In sum, children and adolescents with ASD showed impaired temporal processing of both simple and more complex auditory stimuli, and the online assessment seems to be sensitive in differentiating individuals with ASD from those with TD.

Acupuncture-Induced Changes in Nociception, Measured by Pain-Related Evoked Potentials: A Pilot Mechanistic Study.

Objective: The nociceptive system has been implicated in acupuncture analgesia, although acupuncture's precise mechanism of action remains unknown. Electric pain-related evoked potentials (PREPs) have emerged as an effective and reliable electrophysiologic method for evaluation of the human nociceptive system by electric stimulation of nociceptive Aδ and C fibers. This pilot mechanistic study aims to assess the feasibility of using advanced PREP techniques together with electroacupuncture and to use PREPs to characterize acupuncture's effect on nociception. Methods: Seven healthy volunteers underwent a previously designed electroacupuncture protocol using acupoints in the legs bilaterally, which has been demonstrated to induce systemic analgesia. Advanced PREP techniques involving tripolar stimulating electrode, varying interstimulus interval, and incorporating a cognitive task during PREPs were used. PREPs were assessed before electroacupuncture, during electroacupuncture, and 30 min after electroacupuncture. Subjective pain perception in response to the PREP-related electric pain stimuli delivered to the nondominant hand was assessed on the visual analog scale (VAS) at baseline, during electroacupuncture, and 30 min postelectroacupuncture. Results: Reliable PREP N1, P1, and N2 waves were obtained from all subjects at the following average latencies: N1 = 131.5 msec, P1 = 189.4 msec, and N2 = 231.1 msec. Electroacupuncture caused a significant reduction in PREP N1P1 wave amplitudes from 25.6 to 15.4 μV (p = 0.006) and electric pain perception on the VAS-from 2.86 to 2.14 (p = 0.008), compared to baseline. These effects were sustained at 30 min postacupuncture with N1P1 wave amplitude 17.2 μV (p = 0.030) and VAS 2.28 (p = 0.030), compared to baseline. Conclusions: Electroacupuncture causes significant changes in objective nociception, measured by PREP N1P1 wave amplitudes, and in subjective nociception, measured by the VAS, and these effects are sustained for 30 min after electroacupuncture. Planned future studies will involve chronic pain populations and will aim to assess acupuncture's longer term analgesic effects.

Auditory perception dominates in motor rhythm reproduction.

It is commonly agreed that vision is more sensitive to spatial information, while audition is more sensitive to temporal information. When both visual and auditory information are available simultaneously, the modality appropriateness hypothesis predicts that, depending on the task, the most appropriate (i.e., reliable) modality dominates perception. While previous research mainly focused on discrepant information from different sensory inputs to scrutinize the modality appropriateness hypothesis, the current study aimed at investigating the modality appropriateness hypothesis when multimodal information was provided in a nondiscrepant and simultaneous manner. To this end, participants performed a temporal rhythm reproduction task for which the auditory modality is known to be the most appropriate. The experiment comprised an auditory (i.e., beeps), a visual (i.e., flashing dots), and an audiovisual condition (i.e., beeps and dots simultaneously). Moreover, constant as well as variable interstimulus intervals were implemented. Results revealed higher accuracy and lower variability in the auditory condition for both interstimulus interval types when compared to the visual condition. More importantly, there were no differences between the auditory and the audiovisual condition across both interstimulus interval types. This indicates that the auditory modality dominated multimodal perception in the task, whereas the visual modality was disregarded and hence did not add to reproduction performance.

The inclusion of interstimulus interval variability does not mitigate electrically-evoked fatigue of the knee extensors.

Transcutaneous electrical stimulation (TES) is used to activate muscles when volitional capacity is impaired but potential benefits are limited by rapid force loss (fatigue). Most TES fatigue protocols employ constant-frequency trains, with stimuli at a fixed interstimulus interval (ISI); however, a brief ISI between the first two pulses (variable-frequency train, VFT) to maximize the catchlike property of muscle can attenuate fatigue development. The purpose of this study was to investigate if a VFT that simulates intrinsic variability of voluntary motor unit discharge rates would also mitigate fatigue, owing to the sensitivity of muscle to acute activation history. On two visits, 24 healthy adults (25.3 ± 3.7years; 12 females) received 3min of intermittent TES to the quadriceps of the dominant leg. Trains of eight pulses at 10Hz were delivered with a constant (100ms) or variable ISI (80-120ms). Contractile impulse, rate of force development (RFD), and rate of relaxation (RFR) were determined for each tetanus RESULTS: During fatigue and recovery, contractile impulse did not differ between protocols (p ≥ 0.796) and sexes (p ≥ 0.493), with values of 77 ± 17% control at task end and 125 ± 19% control 2min later. RFD and RFR also showed no effect of the protocol (p ≥ 0.310) or participant sex (p ≥ 0.119). Both measures slowed (38 ± 23% and 33 ± 22%, respectively) but dissociated during recovery as RFD remained 16 ± 18% below control at 5min, whereas RFR recovered to control by 30s (101 ± 22%). Contrary to expectations, the VFT protocol did not attenuate fatigue development, which suggests no benefit to mimicking the inherent variability of motor unit discharge rates.

Mapping the Brain-Wide Network Effects by Optogenetic Activation of the Corpus Callosum.

Optogenetically driven manipulation of circuit-specific activity enables causality studies, but its global brain-wide effect is rarely reported. Here, we applied simultaneous functional magnetic resonance imaging (fMRI) and calcium recording with optogenetic activation of the corpus callosum (CC) connecting barrel cortices (BC). Robust positive BOLD was detected in the ipsilateral BC due to antidromic activity, spreading to the ipsilateral motor cortex (MC), and posterior thalamus (PO). In the orthodromic target, positive BOLD was reliably evoked by 2Hz light pulses, whereas 40 Hz light pulses led to reduced calcium, indicative of CC-mediated inhibition. This presumed optogenetic CC-mediated inhibition was further elucidated by pairing light pulses with whisker stimulation at varied interstimulus intervals. Whisker-induced positive BOLD and calcium signals were reduced at intervals of 50/100ms. The calcium-amplitude-modulation-based correlation with whole-brain fMRI signal revealed that the inhibitory effects spread to contralateral BC, ipsilateral MC, and PO. This work raises the need for fMRI to elucidate the brain-wide network activation in response to optogenetic stimulation.

Dissociated modulations of multivoxel activation patterns in the ventral and dorsal visual pathways by the temporal dynamics of stimuli.

IntroductionPrevious studies suggested temporal limitations of visual object identification in the ventral pathway. Moreover, multivoxel pattern analyses (MVPA) of fMRI activation have shown reliable encoding of various object categories including faces and tools in the ventral pathway. By contrast, the dorsal pathway is involved in reaching a target and grasping a tool, and quicker in processing the temporal dynamics of stimulus change. However, little is known about how activation patterns in both pathways may change according to the temporal dynamics of stimulus change.MethodsHere, we measured fMRI responses of two consecutive stimuli with varying interstimulus intervals (ISIs), and we compared how the two visual pathways respond to the dynamics of stimuli by using MVPA and information‐based searchlight mapping.ResultsWe found that the temporal dynamics of stimuli modulate responses of the two visual pathways in opposite directions. Specifically, slower temporal dynamics (longer ISIs) led to greater activity and better MVPA results in the ventral pathway. However, faster temporal dynamics (shorter ISIs) led to greater activity and better MVPA results in the dorsal pathway.ConclusionsThese results are the first to show how temporal dynamics of stimulus change modulated multivoxel fMRI activation pattern change. And such temporal dynamic response function in different ROIs along the two visual pathways may shed lights on understanding functional relationship and organization of these ROIs.

Investigating the role of temporal processing in developmental dyslexia: Evidence for a specific deficit in rapid visual segmentation.

The current study investigates the role of temporal processing in the visual domain in participants with developmental dyslexia (DD), the most common neurodevelopmental disorder, which is characterized by severe and specific difficulties in learning to read despite normal intelligence and adequate education. Specifically, our aim was to test whether DD is associated with a general impairment of temporal sensory processing or a specific deficit in temporal integration (which ensures stability of object identity and location) or segregation (which ensures sensitivity to changes in visual input). Participants with DD performed a task that measured both temporal integration and segregation using an identical sequence of two displays separated by a varying interstimulus interval (ISI) under two different task instructions. Results showed that participants with DD performed worse in the segregation task, with a shallower slope of the psychometric curve of percentage correct as a function of the ISI between the two target displays. Moreover, we found also a relationship between temporal segregation performance and text, words, and pseudowords reading speeds at the individual level. In contrast, no significant association between reading (dis)ability and temporal integration emerged. The current findings provide evidence for a difference in the fine temporal resolution of visual processing in DD and, considering the growing evidence about a link between visual temporal segregation and neural oscillations at specific frequencies, they support the idea that DD is characterized by an altered oscillatory sampling within the visual system.

The time course of priming in aphasia: An exploration of learning along a continuum of linguistic processing demands.

This study investigates learning in aphasia as manifested through automatic priming effects. There is growing evidence that people with aphasia have impairments beyond language processing that could affect their response to treatment. Therefore, better understanding these mechanisms would be beneficial for improving methods of rehabilitation. This study assesses semantic and repetition priming effects at varied interstimulus intervals, using stimuli that are both non-linguistic and linguistic in tasks that range from requiring nearly no linguistic processing to requiring both lexical and semantic processing. Results indicate that people with aphasia maintain typical patterns of learning across both linguistic and non-linguistic tasks as long as the implicit prime-target relationship does not depend on deep levels of linguistic processing. As linguistic processing demands increase, those with agrammatic aphasia may require more time to take advantage of learning through implicit prime-target relationships, and people with both agrammatic and non-agrammatic aphasia are more susceptible to breakdown of the semantic networks as processing demands on that system increase.

Implicit temporal predictability enhances pitch discrimination sensitivity and biases the phase of delta oscillations in auditory cortex

Can human listeners use implicit temporal contingencies in auditory input to form temporal predictions, and if so, how are these predictions represented endogenously? To assess this question, we implicitly manipulated temporal predictability in an auditory pitch discrimination task: unbeknownst to participants, the pitch of the standard tone could either be deterministically predictive of the temporal onset of the target tone, or convey no predictive information. Predictive and non-predictive conditions were presented interleaved in one stream, and separated by variable inter-stimulus intervals such that there was no dominant stimulus rhythm throughout. Even though participants were unaware of the implicit temporal contingencies, pitch discrimination sensitivity (the slope of the psychometric function) increased when the onset of the target tone was predictable in time (N = 49, 28 female, 21 male). Concurrently recorded EEG data (N = 24) revealed that standard tones that conveyed temporal predictions evoked a more negative N1 component than non-predictive standards. We observed no significant differences in oscillatory power or phase coherence between conditions during the foreperiod. Importantly, the phase angle of delta oscillations (1–3 Hz) in auditory areas in the post-standard and pre-target time windows predicted behavioral pitch discrimination sensitivity. This suggests that temporal predictions are encoded in delta oscillatory phase during the foreperiod interval. In sum, we show that auditory perception benefits from implicit temporal contingencies, and provide evidence for a role of slow neural oscillations in the endogenous representation of temporal predictions, in absence of exogenously driven entrainment to rhythmic input.

Large-Scale Networks for Auditory Sensory Gating in the Awake Mouse.

The amplitude of the brain response to a repeated auditory stimulus is diminished as compared to the response to the first tone (T1) for interstimulus intervals (ISI) lasting up to hundreds of milliseconds. This adaptation process, called auditory sensory gating (ASG), is altered in various psychiatric diseases including schizophrenia and is classically studied by focusing on early evoked cortical responses to the second tone (T2) using 500-ms ISI. However, mechanisms underlying ASG are still not well-understood. We investigated ASG in awake mice from the brainstem to cortex at variable ISIs (125–2000 ms) using high-density EEG and intracerebral recordings. While ASG decreases at longer ISIs, it is still present at durations (500–2000 ms) far beyond the time during which brain responses to T1 could still be detected. T1 induces a sequence of specific stable scalp EEG topographies that correspond to the successive activation of distinct neural networks lasting about 350 ms. These brain states remain unaltered if T2 is presented during this period, although T2 is processed by the brain, suggesting that ongoing networks of brain activity are active for longer than early evoked-potentials and are not overwritten by an upcoming new stimulus. Intracerebral recordings demonstrate that ASG is already present at the level of ventral cochlear nucleus (vCN) and inferior colliculus and is amplified across the hierarchy in bottom-up direction. This study uncovers the extended stability of sensory-evoked brain states and long duration of ASG, and sheds light on generators of ASG and possible interactions between bottom-up and top-down mechanisms.

0213 Acute Total Sleep Deprivation Impairs the Ability to Manage Response Conflict

The attention network test (ANT) measures the ability to use an alerting cue to detect a stimulus (alerting effect), use a spatial cue to shift the location of visual attention (orienting effect), and manage response conflict (conflict effect). Total sleep deprivation (TSD) has been shown to negatively affect cognitive functions, including distinct aspects of attention. As part of a laboratory study, we measured performance on the ANT to examine the impact of TSD on attentional functioning. 14 healthy adults (ages 21-39; 7 females/7 males) completed a 4-day (3-night) in-laboratory study. After a baseline night of sleep (9h sleep opportunity; 22:00-07:00), subjects underwent 38h TSD, followed by one night of recovery sleep (9h sleep opportunity; 22:00-07:00). A version of the ANT with variable inter-stimulus interval was administered at 09:00 during baseline, after 26h TSD, and after recovery sleep. Mixed-effects analysis of variance (ANOVA) showed marked impairment in the conflict effect during TSD (F2,26=4.74, P=0.018). The alerting (F2,26=0.02, P=0.98) and orienting (F226=0.25, P=0.78) effects were not significantly affected by TSD. Consistent with earlier findings, TSD did not significantly degrade the alerting effect on the ANT. In this study, TSD also did not significantly reduce the orienting effect. Thus, subjects maintained the ability to detect a stimulus and shift visual attention in response to cues, despite sleep deprivation. However, TSD had significant impact on the conflict effect, indicating that subjects experienced considerable difficulty managing response conflict while sleep-deprived. This finding is consistent with recent evidence that, independent of its effect on vigilant attention, sleep deprivation causes profound deficits in attentional flexibility. Jazz Pharmaceuticals

PB9. The ‘functional magnetic resonance imaging’ (fMRI) as a meaningful tool for the differentiation of sexual preferences

Context The research network ‘ Ne ural mechanisms u nderlying p edophilia and sexual offending against children: origins, assessment and therapy’ investigates mechanisms of sexual abuse of children and pedophilia by means of fMRI imaging, clinical interviews, and psychological testing. While pedophiles’ sexual fantasies refer to pre-pubertal children of the first Tanner Stage ( Tanner, 1978 ), hebephilic men prefer partners who are in puberty (Tanner Stage 2–3) ( Blanchard et al., 2009 ). But whether hebephilia can be seen as an independent entity is still controversial. Our previous research showed that the functional brain response patterns to sexual stimuli contain sufficient information to identify pedophiles (compared to teleiophiles) with a mean accuracy of 95% ( Ponseti, 2012 ). However, the treatment relies on a precise measurement of the sexual orientation. To this end, we tested whether standard second level analysis of brain responses to sexual stimuli and/ or whole brain calculations of BOLD-responses to sexual stimuli are useful to differentiate between pedophiles and hebephiles. Design During fMRI, participants (n = 328) were shown same- and opposite-sex images of nude children and adults in Tanner stages 1–5. The images were each shown for one second with a variable inter-stimulus interval of two seconds on average. The previous classification was based on clinical interviews, self-reported details (like sexual/masturbating fantasies) or according to criminal/medical records. We calculated differences in BOLD-signals for the sexual stimuli in the corresponding contrast images (i.e.one hebephiles’ contrast image was defined as ‘pubertal boy/girl’), as well as a whole brain functional BOLD response to each stimulus category. Results Preference specific brain activity was found in hebephilic as well in pedophilic participants in areas known to be involved in sexual stimulus processing. Conclusion Here we present evidence that whole brain response calculation provides a meaningful measure of sexual preferences in healthy and in paraphilic males. Particularly, response differences between pedophilic and hebephilic participants provide evidence that these clinical categories differ at the level of brain function.

EEG phase states at stimulus onset in a variable-ISI Go/NoGo task: Effects on ERP components

Previous EEG-ERP dynamics studies found non-random “preferred” EEG phases at stimulus onset in a fixed interstimulus interval (ISI) equiprobable auditory Go/NoGo paradigm, with substantial effects on ERP components. Here we changed to a variable ISI task to prevent/reduce preferential phase occurrence. Discrete Fourier transforms decomposed prestimulus EEG at Cz for each trial to calculate the phase of different frequencies at stimulus onset; we combined these into the delta, theta, alpha, and beta bands, and then sorted trials into phase quartiles for each. ERPs from the raw EEG, assessed using temporal Principal Components Analyses, were examined as a function of phase at stimulus onset. Preferential phase occurrence was reduced as predicted, but random phase substantially impacted component amplitudes. For example, negativity in delta enhanced Go and NoGo P3b; and in theta reduced NoGo but not Go P3b. Overall, EEG phases at stimulus onset support differential cognitive processing in this two-choice task.

Scenario Screen: A Dynamic and Context Dependent P300 Stimulator Screen Aimed at Wheelchair Navigation Control.

P300 spellers have been widely modified to implement nonspelling tasks. In this work, we propose a “scenario” stimulation screen that is a P300 speller variation to command a wheelchair. Our approach utilized a stimulation screen with an image background (scenario snapshot for a wheelchair) and stimulation markers arranged asymmetrically over relevant landmarks, such as suitable paths, doors, windows, and wall signs. Other scenario stimulation screen features were green/blue stimulation marker color scheme, variable Interstimulus Interval, single marker stimulus mode, and optimized stimulus sequence generator. Eighteen able-bodied subjects participated in the experiment; 78% had no experience in BCI usage. A waveform feature analysis and a Mann–Whitney U test performed over the pairs of target and nontarget coherent averages confirmed that 94% of the subjects elicit P300 (p < .005) on this modified stimulator. Least Absolute Shrinkage and Selection Operator optimization and Linear Discriminant Analysis were utilized for the automatic detection of P300. For evaluation with unseen data, target detection was computed (median sensitivity = 1.00 (0.78–1.00)), together with nontarget discrimination (median specificity = 1.00 (0.98–1.00)). The scenario screen adequately elicits P300 and seems suitable for commanding a wheelchair even when users have no previous experience on the BCI spelling task.

P 160 Temporal discrimination and temporal discrimination motor thresholds – association with age, proprioception, and polyneuropathy

Introduction Temporal discrimination threshold (TDT) and temporal motor discrimination threshold (TMDT) are measures of somatosensory processing indicating the shortest time interval at which two stimuli applied to skin or muscle, respectively, are detected to be asynchronous. TDT and/or TDMT have been shown to be increased in patients with movement disorders, like essential tremor, dystonia, or Parkinson”s disease. However, the meaning of these findings is still quite unclear. Here, we assessed the association of TDT and TDMT with age, proprioception, and polyneuropathy (PNP). Materials and methods 54 healthy subjects (age 29–75 years) and 15 patients with neurophysiologically confirmed PNP were included. TDT was tested with surface electrodes placed over thenar or dorsal foot region, respectively. TDMT was measured via an insulated tungsten needle microelectrode inserted at the motor point of flexor carpi radialis (FCR) or tibialis anterior (TA) muscle. Pairs of subsequent electric stimuli with varying interstimulus intervals (ISI) were provided, and discrimination thresholds were defined as the shortest ISI at which subjects were able to identify two separate stimuli. Proprioception of upper and lower limbs was assessed by custom-built devices, basically consisting of a goniometer without direct visual feedback of the respective extremity and its movements (flexion/extension). Subjects were instructed (i) to point to LED markers attached to the outside of the device, (ii) to move in proportion to arrows of different length shown on a computer screen, and (iii) to estimate their limb position after passive hand movements. Part of the assessment was conducted under dual task condition (tone-counting task). Pointing (or estimation) error (in degree) was taken as a measure of proprioceptive performance. Results In healthy subjects higher age was associated with higher TDT in every tested condition (right hand [ r = 0.358, p r = 0.359, p r = 0.591, p r = 0.505, p r = 0.317, p = 0.05]). In PNP patients, TDMT and TDT were significantly higher at all sites as compared to controls ( p Discussion Our results point to an association between higher age and poorer capacity of discriminating somatosensory stimuli. The correlation of performance in a particular pointing task of the hand with lower TDMT suggests this measure as a potential surrogate marker of proprioceptive function. Both TDT and TDMT were markedly increased in PNP patients, indicating their clinical meaning in diseases with affection of the proprioceptive system. This might also be the pathophysiological link to previous findings of elevated thresholds in movement disorders.

Temporal orienting precedes intersensory attention and has opposing effects on early evoked brain activity

Intersensory attention (IA) describes the process of directing attention to a specific modality. Temporal orienting (TO) characterizes directing attention to a specific moment in time. Previously, studies indicated that these two processes could have opposite effects on early evoked brain activity. The exact time-course and processing stages of both processes are still unknown. In this human electroencephalography study, we investigated the effects of IA and TO on visuo-tactile stimulus processing within one paradigm. IA was manipulated by presenting auditory cues to indicate whether participants should detect visual or tactile targets in visuo-tactile stimuli. TO was manipulated by presenting stimuli block-wise at fixed or variable inter-stimulus intervals. We observed that TO affects evoked activity to visuo-tactile stimuli prior to IA. Moreover, we found that TO reduces the amplitude of early evoked brain activity, whereas IA enhances it. Using beamformer source-localization, we observed that IA increases neural responses in sensory areas of the attended modality whereas TO reduces brain activity in widespread cortical areas. Based on these findings we derive an updated working model for the effects of temporal and intersensory attention on early evoked brain activity.

GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus.

Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the mechanisms of tinnitus.