Sundeep Teki

Distinct Neural Substrates of Duration-Based and Beat-Based Auditory Timing

Research on interval timing strongly implicates the cerebellum and the basal ganglia as part of the timing network of the brain. Here we tested the hypothesis that the brain uses differential timing mechanisms and networks—specifically, that the cerebellum subserves the perception of the absolute duration of time intervals, whereas the basal ganglia mediate perception of time intervals relative to a regular beat. In a functional magnetic resonance imaging experiment, we asked human subjects to judge the difference in duration of two successive time intervals as a function of the preceding context of an irregular sequence of clicks (where the task relies on encoding the absolute duration of time intervals) or a regular sequence of clicks (where the regular beat provides an extra cue for relative timing). We found significant activations in an olivocerebellar network comprising the inferior olive, vermis, and deep cerebellar nuclei including the dentate nucleus during absolute, duration-based timing and a striato-thalamo-cortical network comprising the putamen, caudate nucleus, thalamus, supplementary motor area, premotor cortex, and dorsolateral prefrontal cortex during relative, beat-based timing. Our results support two distinct timing mechanisms and underlying subsystems: first, a network comprising the inferior olive and the cerebellum that acts as a precision clock to mediate absolute, duration-based timing, and second, a distinct network for relative, beat-based timing incorporating a striato-thalamo-cortical network.

Properties of the Internal Clock: First- and Second-Order Principles of Subjective Time

Humans share with other animals an ability to measure the passage of physical time and subjectively experience a sense of time passing. Subjective time has hallmark qualities, akin to other senses, which can be accounted for by formal, psychological, and neurobiological models of the internal clock. These include first-order principles, such as changes in clock speed and how temporal memories are stored, and second-order principles, including timescale invariance, multisensory integration, rhythmical structure, and attentional time-sharing. Within these principles there are both typical individual differences--influences of emotionality, thought speed, and psychoactive drugs--and atypical differences in individuals affected with certain clinical disorders (e.g., autism, Parkinsons disease, and schizophrenia). This review summarizes recent behavioral and neurobiological findings and provides a theoretical framework for considering how changes in the properties of the internal clock impact time perception and other psychological domains.

A unified model of time perception accounts for duration-based and beat-based timing mechanisms.

Accurate timing is an integral aspect of sensory and motor processes such as the perception of speech and music and the execution of skilled movement. Neuropsychological studies of time perception in patient groups and functional neuroimaging studies of timing in normal participants suggest common neural substrates for perceptual and motor timing. A timing system is implicated in core regions of the motor network such as the cerebellum, inferior olive, basal ganglia, pre-supplementary, and supplementary motor area, pre-motor cortex as well as higher-level areas such as the prefrontal cortex. In this article, we assess how distinct parts of the timing system subserve different aspects of perceptual timing. We previously established brain bases for absolute, duration-based timing and relative, beat-based timing in the olivocerebellar and striato-thalamo-cortical circuits respectively (Teki et al., 2011). However, neurophysiological and neuroanatomical studies provide a basis to suggest that timing functions of these circuits may not be independent. Here, we propose a unified model of time perception based on coordinated activity in the core striatal and olivocerebellar networks that are interconnected with each other and the cerebral cortex through multiple synaptic pathways. Timing in this unified model is proposed to involve serial beat-based striatal activation followed by absolute olivocerebellar timing mechanisms.

Slow GABA Transient and Receptor Desensitization Shape Synaptic Responses Evoked by Hippocampal Neurogliaform Cells

The kinetics of GABAergic synaptic currents can vary by an order of magnitude depending on the cell type. The neurogliaform cell (NGFC) has recently been identified as a key generator of slow GABAA receptor-mediated volume transmission in the isocortex. However, the mechanisms underlying slow GABAA receptor-mediated IPSCs and their use-dependent plasticity remain unknown. Here, we provide experimental and modeling data showing that hippocampal NGFCs generate an unusually prolonged (tens of milliseconds) but low-concentration (micromolar range) GABA transient, which is responsible for the slow response kinetics and which leads to a robust desensitization of postsynaptic GABAA receptors. This strongly contributes to the use-dependent synaptic depression elicited by various patterns of NGFC activity including the one detected during theta network oscillations in vivo. Synaptic depression mediated by NGFCs is likely to play an important modulatory role in the feedforward inhibition of CA1 pyramidal cells provided by the entorhinal cortex.

Reading Front to Back: MEG Evidence for Early Feedback Effects During Word Recognition

Magnetoencephalography studies in humans have shown word-selective activity in the left inferior frontal gyrus (IFG) approximately 130 ms after word presentation ( Pammer et al. 2004; Cornelissen et al. 2009; Wheat et al. 2010). The role of this early frontal response is currently not known. We tested the hypothesis that the IFG provides top-down constraints on word recognition using dynamic causal modeling of magnetoencephalography data collected, while subjects viewed written words and false font stimuli. Subject-specific dipoles in left and right occipital, ventral occipitotemporal and frontal cortices were identified using Variational Bayesian Equivalent Current Dipole source reconstruction. A connectivity analysis tested how words and false font stimuli differentially modulated activity between these regions within the first 300 ms after stimulus presentation. We found that left inferior frontal activity showed stronger sensitivity to words than false font and a stronger feedback connection onto the left ventral occipitotemporal cortex (vOT) in the first 200 ms. Subsequently, the effect of words relative to false font was observed on feedforward connections from left occipital to ventral occipitotemporal and frontal regions. These findings demonstrate that left inferior frontal activity modulates vOT in the early stages of word processing and provides a mechanistic account of top-down effects during word recognition.

A brain basis for musical hallucinations

The physiological basis for musical hallucinations (MH) is not understood. One obstacle to understanding has been the lack of a method to manipulate the intensity of hallucination during the course of experiment. Residual inhibition, transient suppression of a phantom percept after the offset of a masking stimulus, has been used in the study of tinnitus. We report here a human subject whose MH were residually inhibited by short periods of music. Magnetoencephalography (MEG) allowed us to examine variation in the underlying oscillatory brain activity in different states. Source-space analysis capable of single-subject inference defined left-lateralised power increases, associated with stronger hallucinations, in the gamma band in left anterior superior temporal gyrus, and in the beta band in motor cortex and posteromedial cortex. The data indicate that these areas form a crucial network in the generation of MH, and are consistent with a model in which MH are generated by persistent reciprocal communication in a predictive coding hierarchy.

Single-subject oscillatory gamma responses in tinnitus

This study used magnetoencephalography to record oscillatory activity in a group of 17 patients with chronic tinnitus. Two methods, residual inhibition and residual excitation, were used to bring about transient changes in spontaneous tinnitus intensity in order to measure dynamic tinnitus correlates in individual patients. In residual inhibition, a positive correlation was seen between tinnitus intensity and both delta/theta (6/14 patients) and gamma band (8/14 patients) oscillations in auditory cortex, suggesting an increased thalamocortical input and cortical gamma response, respectively, associated with higher tinnitus states. Conversely, 4/4 patients exhibiting residual excitation demonstrated an inverse correlation between perceived tinnitus intensity and auditory cortex gamma oscillations (with no delta/theta changes) that cannot be explained by existing models. Significant oscillatory power changes were also identified in a variety of cortical regions, most commonly midline lobar regions in the default mode network, cerebellum, insula and anterior temporal lobe. These were highly variable across patients in terms of areas and frequency bands involved, and in direction of power change. We suggest a model based on a local circuit function of cortical gamma-band oscillations as a process of mutual inhibition that might suppress abnormal cortical activity in tinnitus. The work implicates auditory cortex gamma-band oscillations as a fundamental intrinsic mechanism for attenuating phantom auditory perception.

Segregation of complex acoustic scenes based on temporal coherence.

In contrast to the complex acoustic environments we encounter everyday, most studies of auditory segregation have used relatively simple signals. Here, we synthesized a new stimulus to examine the detection of coherent patterns (‘figures’) from overlapping ‘background’ signals. In a series of experiments, we demonstrate that human listeners are remarkably sensitive to the emergence of such figures and can tolerate a variety of spectral and temporal perturbations. This robust behavior is consistent with the existence of automatic auditory segregation mechanisms that are highly sensitive to correlations across frequency and time. The observed behavior cannot be explained purely on the basis of adaptation-based models used to explain the segregation of deterministic narrowband signals. We show that the present results are consistent with the predictions of a model of auditory perceptual organization based on temporal coherence. Our data thus support a role for temporal coherence as an organizational principle underlying auditory segregation. DOI: http://dx.doi.org/10.7554/eLife.00699.001

Navigating the auditory scene: An expert role for the hippocampus

Over a typical career piano tuners spend tens of thousands of hours exploring a specialized acoustic environment. Tuning requires accurate perception and adjustment of beats in two-note chords that serve as a navigational device to move between points in previously learned acoustic scenes. It is a two-stage process that depends on the following: first, selective listening to beats within frequency windows, and, second, the subsequent use of those beats to navigate through a complex soundscape. The neuroanatomical substrates underlying brain specialization for such fundamental organization of sound scenes are unknown. Here, we demonstrate that professional piano tuners are significantly better than controls matched for age and musical ability on a psychophysical task simulating active listening to beats within frequency windows that is based on amplitude modulation rate discrimination. Tuners show a categorical increase in gray matter volume in the right frontal operculum and right superior temporal lobe. Tuners also show a striking enhancement of gray matter volume in the anterior hippocampus, parahippocampal gyrus, and superior temporal gyrus, and an increase in white matter volume in the posterior hippocampus as a function of years of tuning experience. The relationship with gray matter volume is sensitive to years of tuning experience and starting age but not actual age or level of musicality. Our findings support a role for a core set of regions in the hippocampus and superior temporal cortex in skilled exploration of complex sound scenes in which precise sound “templates” are encoded and consolidated into memory over time in an experience-dependent manner.

Gamma band pitch responses in human auditory cortex measured with magnetoencephalography

We have previously used direct electrode recordings in two human subjects to identify neural correlates of the perception of pitch (Griffiths, Kumar, Sedley et al., Direct recordings of pitch responses from human auditory cortex, Curr. Biol. 22 (2010), pp. 1128–1132). The present study was carried out to assess virtual-electrode measures of pitch perception based on non-invasive magnetoencephalography (MEG). We recorded pitch responses in 13 healthy volunteers using a passive listening paradigm and the same pitch-evoking stimuli (regular interval noise; RIN) as in the previous study. Source activity was reconstructed using a beamformer approach, which was used to place virtual electrodes in auditory cortex. Time-frequency decomposition of these data revealed oscillatory responses to pitch in the gamma frequency band to occur, in Heschls gyrus, from 60 Hz upwards. Direct comparison of these pitch responses to the previous depth electrode recordings shows a striking congruence in terms of spectrotemporal profile and anatomical distribution. These findings provide further support that auditory high gamma oscillations occur in association with RIN pitch stimuli, and validate the use of MEG to assess neural correlates of normal and abnormal pitch perception.