LFP publications

In everyday settings, information processing depends on attentional focus, available cognitive resources, and stimulus characteristics such as its valence. Despite insights from laboratory studies, multisensory information processing in complex, realistic environments remains poorly understood. Using whole-head magnetoencephalography and eye tracking in a driving simulation, we addressed two research questions: (1) What are the distinct signatures of (socio-)emotional speech processing and visuo-spatial cognition in the dual task of driving and listening and (2) is information processing co-modulated by valence of speech and workload? We hypothesised two antagonistic processing modes: A top-down guided mode for (socio-)emotional speech processing and a bottom-up stimulus-driven mode for visuo-spatial cognition under high workload. A third mode was proposed to regulate emotional interference during driving under high visuo-spatial load and limited cognitive capacity. Its involvement is hypothesised to be co-modulated by valence and workload. Spatial clustering of oscillatory source activity supported the hypotheses: During emotional compared with neutral speech, parietal beta-band power increased, which likely supported processes related to predictive listening and socio-emotional cognition. In this top-down guided mode, driving-related activity decreased, as indicated by greater parietal alpha- and reduced gamma-band power. During high visuo-spatial workload, linked to the bottom-up stimulus-driven mode, gamma-band power increased in motor and orbitofrontal cortices, whereas beta-band power decreased in motor and temporo-parietal regions. Moreover, increased pupil dilation and decreased gaze dispersion were associated with this bottom-up stimulus-driven mode and visuo-spatial cognitive demands. Multivariate pattern analyses identified the third regulatory mode reflected in fronto-temporal gamma-band oscillations. It was co-modulated by valence and workload: Under low workload drives, gamma-band activity increased for negative compared with positive speech, pointing to the recruitment of inhibitory control processes. Under high workload drives with heightened visuo-spatial demands, gamma-band activity increased for positive speech, but decreased for negative speech, suggesting reduced cognitive resources and impaired control. To conclude, we found converging evidence of distinct signatures for (socio-)emotional speech, visuo-spatial cognition, and interference regulation in naturalistic multisensory environments. We propose that the top-down guided mode represents anticipatory listening and socio-emotional cognition, whereas the bottom-up stimulus-driven mode reflects the allocation of resources to driving-related spatial and sensorimotor processing but also cognitive strain under heightened task demands. Fronto-temporal gamma oscillations likely enable flexible up- and down-regulation of emotional speech processing in response to potential interference in complex, naturalistic environments.

Hearing depends on glutamatergic synaptic transmission mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). AMPARs are tetramers, where inclusion of the GluA2 subunit reduces overall channel conductance and Ca 2+ permeability. Cochlear afferent synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs) contain the AMPAR subunits GluA2, 3, and 4. However, the tetrameric complement of cochlear AMPAR subunits is not known. It was recently shown in mice that chronic intracochlear delivery of IEM-1460, an antagonist selective for GluA2-lacking AMPARs [also known as Ca 2+ -permeable AMPARs (CP-AMPARs)], before, during, and after acoustic overexposure prevented both the trauma to ANF synapses and the ensuing reduction of cochlear nerve activity in response to sound. Surprisingly, baseline measurements of cochlear function before exposure were unaffected by chronic intracochlear delivery of IEM-1460. This suggested that cochlear afferent synapses contain GluA2-lacking CP-AMPARs alongside GluA2-containing Ca 2+ -impermeable AMPA receptors (CI-AMPARs), and that the former can be antagonized for protection while the latter remain conductive. Here, we investigated hearing function in the guinea pig during acute local or systemic delivery of CP-AMPAR antagonists. Acute intracochlear delivery of IEM-1460 or systemic delivery of IEM-1460 or IEM-1925 reduced the amplitude of the ANF compound action potential (CAP) significantly, for all tone levels and frequencies, by > 50% without affecting CAP thresholds or distortion product otoacoustic emissions (DPOAE). Following systemic dosing, IEM-1460 levels in cochlear perilymph were ~ 30% of blood levels, on average, consistent with pharmacokinetic properties predicting permeation of the compounds into the brain and ear. Both compounds were metabolically stable with half-lives >5 h in vitro , and elimination half-lives in vivo of 118 min (IEM-1460) and 68 min (IEM-1925). Heart rate monitoring and off-target binding assays suggest an enhanced safety profile for IEM-1925 over IEM-1460. Compound potency on CAP reduction (IC 50 ~ 73 μM IEM-1460) was consistent with a mixture of GluA2-lacking and GluA2-containing AMPARs. These data strongly imply that cochlear afferent synapses of the guinea pig contain GluA2-lacking CP-AMPARs. We propose these CP-AMPARs may be acutely antagonized with systemic dosing, to protect from glutamate excitotoxicity, while transmission at GluA2-containing AMPARs persists to mediate hearing during the protection.

Interaural time differences (ITDs) are an important cue for the localization of sounds in azimuthal space. Both birds and mammals have specialized, tonotopically organized nuclei in the brain stem for the processing of ITD: medial superior olive in mammals and nucleus laminaris (NL) in birds. The specific way in which ITDs are derived was long assumed to conform to a delay-line model in which arrays of systematically arranged cells create a representation of auditory space with different cells responding maximally to specific ITDs. This model was supported by data from barn owl NL taken from regions above 3 kHz and from chicken above 1 kHz. However, data from mammals often do not show defining features of the Jeffress model such as a systematic topographic representation of best ITDs or the presence of axonal delay lines, and an alternative has been proposed in which neurons are not topographically arranged with respect to ITD and coding occurs through the assessment of the overall response of two large neuron populations, one in each hemisphere. Modeling studies have suggested that the presence of different coding systems could be related to the animal's head size and frequency range rather than their phylogenetic group. Testing this hypothesis requires data from across the tonotopic range of both birds and mammals. The aim of this study was to obtain in vivo recordings from neurons in the low-frequency range (<1000 Hz) of chicken NL. Our data argues for the presence of a modified Jeffress system that uses the slopes of ITD-selective response functions instead of their peaks to topographically represent ITD at mid- to high frequencies. At low frequencies, below several 100 Hz, the data did not support any current model of ITD coding. This is different to what was previously shown in the barn owl and suggests that constraints in optimal ITD processing may be associated with the particular demands on sound localization determined by the animal's ecological niche in the same way as other perceptual systems such as field of best vision.

Background and aims: The aim of this study was to evaluate the frontal intracortical connectivity during deep anaesthesia (burst-suppression). Methods: Experiments were carried out on 5 adult Sprague Dawley rats. The anaesthesia was induced and maintained with isoflurane. Following the induction of anaesthesia, rats were placed in a stereotactic instrument. A hole was drilled in the skull over the frontal cortex and electrodes were inserted in order to record the local field potentials. Rats were maintained in deep level anaesthesia (burst-suppression). The cortical connectivity was assessed by computing the coherence spectra. The frontal intracortical connectivity was calculated during burst, suppression (non-burst) and slow wave anaesthesia periods. Results: The global cortical connectivity (0.5-100 Hz) was 0.61 ± 0.078 during the burst periods compared to 0.55 ± 0.032 (p < 0.05) during the suppression periods and 0.55 ± 0.015 (p < 0.05) during slow wave anaesthesia. Conclusions: The global cortical connectivity increased during the burst periods compared to the suppression periods and slow wave anaesthesia. This increase in the cortical synchronization might be due to the subcortical origin of the bursts.