Precisely Timed Signal Transmission in Neocortical Networks with Reliable Intermediate-Range Projections

The mammalian neocortex has a remarkable ability to precisely reproduce behavioral sequences or to reliably retrieve stored information. In contrast, spiking activity in behaving animals shows a considerable trial-to-trial variability and temporal irregularity. The signal propagation and processing underlying these conflicting observations is based on fundamental neurophysiological processes like synaptic transmission, signal integration within single cells, and spike formation. Each of these steps in the neuronal signaling chain has been studied separately to a great extend, but it has been difficult to judge how they interact and sum up in active sub-networks of neocortical cells. In the present study, we experimentally assessed the precision and reliability of small neocortical networks consisting of trans-columnar, intermediate-range projections (200–1000 μm) on a millisecond time-scale. Employing photo-uncaging of glutamate in acute slices, we activated a number of distant presynaptic cells in a spatio-temporally precisely controlled manner, while monitoring the resulting membrane potential fluctuations of a postsynaptic cell. We found that signal integration in this part of the network is highly reliable and temporally precise. As numerical simulations showed, the residual membrane potential variability can be attributed to amplitude variability in synaptic transmission and may significantly contribute to trial-to-trial output variability of a rate signal. However, it does not impair the temporal accuracy of signal integration. We conclude that signals from intermediate-range projections onto neocortical neurons are propagated and integrated in a highly reliable and precise manner, and may serve as a substrate for temporally precise signal transmission in neocortical networks

Irregular speech rate dissociates auditory cortical entrainment, evoked responses, and frontal alpha

The entrainment of slow rhythmic auditory cortical activity to the temporal regularities in speech is considered to be a central mechanism underlying auditory perception. Previous work has shown that entrainment is reduced when the quality of the acoustic input is degraded, but has also linked rhythmic activity at similar time scales to the encoding of temporal expectations. To understand these bottom-up and top-down contributions to rhythmic entrainment, we manipulated the temporal predictive structure of speech by parametrically altering the distribution of pauses between syllables or words, thereby rendering the local speech rate irregular while preserving intelligibility and the envelope fluctuations of the acoustic signal. Recording EEG activity in human participants, we found that this manipulation did not alter neural processes reflecting the encoding of individual sound transients, such as evoked potentials. However, the manipulation significantly reduced the fidelity of auditory delta (but not theta) band entrainment to the speech envelope. It also reduced left frontal alpha power and this alpha reduction was predictive of the reduced delta entrainment across participants. Our results show that rhythmic auditory entrainment in delta and theta bands reflect functionally distinct processes. Furthermore, they reveal that delta entrainment is under top-down control and likely reflects prefrontal processes that are sensitive to acoustical regularities rather than the bottom-up encoding of acoustic features

Embedding of Cortical Representations by the Superficial Patch System

Pyramidal cells in layers 2 and 3 of the neocortex of many species collectively form a clustered system of lateral axonal projections (the superficial patch system—Lund JS, Angelucci A, Bressloff PC. 2003. Anatomical substrates for functional columns in macaque monkey primary visual cortex. Cereb Cortex. 13:15-24. or daisy architecture—Douglas RJ, Martin KAC. 2004. Neuronal circuits of the neocortex. Annu Rev Neurosci. 27:419-451.), but the function performed by this general feature of the cortical architecture remains obscure. By comparing the spatial configuration of labeled patches with the configuration of responses to drifting grating stimuli, we found the spatial organizations both of the patch system and of the cortical response to be highly conserved between cat and monkey primary visual cortex. More importantly, the configuration of the superficial patch system is directly reflected in the arrangement of function across monkey primary visual cortex. Our results indicate a close relationship between the structure of the superficial patch system and cortical responses encoding a single value across the surface of visual cortex (self-consistent states). This relationship is consistent with the spontaneous emergence of orientation response-like activity patterns during ongoing cortical activity (Kenet T, Bibitchkov D, Tsodyks M, Grinvald A, Arieli A. 2003. Spontaneously emerging cortical representations of visual attributes. Nature. 425:954-956.). We conclude that the superficial patch system is the physical encoding of self-consistent cortical states, and that a set of concurrently labeled patches participate in a network of mutually consistent representations of cortical inpu

First activity and interactions in thalamus and cortex using raw single-trial EEG and MEG elicited by somatosensory stimulation

Introduction: One of the primary motivations for studying the human brain is to comprehend how external sensory input is processed and ultimately perceived by the brain. A good understanding of these processes can promote the identification of biomarkers for the diagnosis of various neurological disorders; it can also provide ways of evaluating therapeutic techniques. In this work, we seek the minimal requirements for identifying key stages of activity in the brain elicited by median nerve stimulation.Methods: We have used a priori knowledge and applied a simple, linear, spatial filter on the electroencephalography and magnetoencephalography signals to identify the early responses in the thalamus and cortex evoked by short electrical stimulation of the median nerve at the wrist. The spatial filter is defined first from the average EEG and MEG signals and then refined using consistency selection rules across ST. The refined spatial filter is then applied to extract the timecourses of each ST in each targeted generator. These ST timecourses are studied through clustering to quantify the ST variability. The nature of ST connectivity between thalamic and cortical generators is then studied within each identified cluster using linear and non-linear algorithms with time delays to extract linked and directional activities. A novel combination of linear and non-linear methods provides in addition discrimination of influences as excitatory or inhibitory.Results: Our method identifies two key aspects of the evoked response. Firstly, the early onset of activity in the thalamus and the somatosensory cortex, known as the P14 and P20 in EEG and the second M20 for MEG. Secondly, good estimates are obtained for the early timecourse of activity from these two areas. The results confirm the existence of variability in ST brain activations and reveal distinct and novel patterns of connectivity in different clusters.Discussion: It has been demonstrated that we can extract new insights into stimulus processing without the use of computationally costly source reconstruction techniques which require assumptions and detailed modeling of the brain. Our methodology, thanks to its simplicity and minimal computational requirements, has the potential for real-time applications such as in neurofeedback systems and brain-computer interfaces

Assessing Neuronal Synchrony and Brain Function Through Local Field Potential and Spike Analysis

Studies of neuronal network oscillations and rhythmic neuronal synchronization have led to a number of important insights in recent years, giving us a better understanding of the temporal organization of neuronal activity related to essential brain functions like sensory processing and cognition. Important principles and theories have emerged from these findings, including the communication through coherence hypothesis, which proposes that synchronous oscillations render neuronal communication effective, selective, and precise. The implications of such a theory may be universal for brain function, as the determinants of neuronal communication inextricably shape the neuronal representation of information in the brain. However, the study of communication through coherence is still relatively young. Since its articulation in 2005, the theory has predominantly been applied to assess cortical function and its communication with downstream targets in different sensory and behavioral conditions. The results herein are intended to bolster this hypothesis and explore new ways in which oscillations coordinate neuronal communication in distributed regions. This includes the development of new analytic tools for interpreting electrophysiological patterns, inspired by phase synchronization and spike train analysis. These tools aim to offer fast results with clear statistical and physiological interpretation

Analysis of the structure of time-frequency information in electromagnetic brain signals

This thesis encompasses methodological developments and experimental work aimed at revealing information contained in time, frequency, and time–frequency representations of electromagnetic, specifically magnetoencephalographic, brain signals. The work can be divided into six endeavors. First, it was shown that sound slopes increasing in intensity from undetectable to audible elicit event-related responses (ERRs) that predict behavioral sound detection. This provides an opportunity to use non-invasive brain measures in hearing assessment. Second, the actively debated generation mechanism of ERRs was examined using novel analysis techniques, which showed that auditory stimulation did not result in phase reorganization of ongoing neural oscillations, and that processes additive to the oscillations accounted for the generation of ERRs. Third, the prerequisites for the use of continuous wavelet transform in the interrogation of event-related brain processes were established. Subsequently, it was found that auditory stimulation resulted in an intermittent dampening of ongoing oscillations. Fourth, information on the time–frequency structure of ERRs was used to reveal that, depending on measurement condition, amplitude differences in averaged ERRs were due to changes in temporal alignment or in amplitudes of the single-trial ERRs. Fifth, a method that exploits mutual information of spectral estimates obtained with several window lengths was introduced. It allows the removal of frequency-dependent noise slopes and the accentuation of spectral peaks. Finally, a two-dimensional statistical data representation was developed, wherein all frequency components of a signal are made directly comparable according to spectral distribution of their envelope modulations by using the fractal property of the wavelet transform. This representation reveals noise buried processes and describes their envelope behavior. These examinations provide for two general conjectures. The stability of structures, or the level of stationarity, in a signal determines the appropriate analysis method and can be used as a measure to reveal processes that may not be observable with other available analysis approaches. The results also indicate that transient neural activity, reflected in ERRs, is a viable means of representing information in the human brain.reviewe

Information integration and neural plasticity in sensory processing investigated at the levels of single neurons, networks, and perception

In this doctoral thesis, several aspects of information integration and learning in neural systems are investigated at the levels of single neurons, networks, and perception. In the first study presented here, we asked the question of how contextual, multiplicative interactions can be mediated in single neurons by the physiological mechanisms available in the brain. Multiplicative interactions are omnipresent in the nervous system and although a wealth of possible mechanisms were proposed over the last decades, the physiological origin of multiplicative interactions in the brain remains an open question. We investigated permissive gating as a possible multiplication mechanism. We proposed an integrate-and-fire model neuron that incorporates a permissive gating mechanism and investigated the model analytically and numerically due to its abilities to realize multiplication between two input streams. The applied gating mechanism realizes multiplicative interactions of firing rates on a wide range of parameters and thus provides a feasible model for the realization of multiplicative interactions on the single neuron level. In the second study we asked the question of how gaze-invariant representations of visual space can develop in a self-organizing network that incorporates the gating model neuron presented in the first study. To achieve a stable representation of our visual environment our brain needs to transform the representation of visual stimuli from a retina-centered coordinate system to a frame of reference that is independent of changes in gaze direction. In the network presented here, receptive fields and gain fields organized in overlayed topographic maps that reflected the spatio-temporal statistics of the training input stream. Topographic maps supported a gaze-invariant representation in an output layer when the network was trained with natural input statistics. Our results show that gaze-invariant representations of visual space can be learned in an unsupervised way by a biologically plausible network based on the spatio-temporal statistics of visual stimulation and eye position signals under natural viewing conditions. In the third study we investigated psychophysically the effect of a three day meditative Zen retreat on tactile abilities of the finger tips. Here, meditators strongly altered the statistics of their attentional focus by focussing sustained attention on their right index finger for hours. Our data shows that sustained sensory focussing on a particular body part, here the right index finger, significantly affects tactile acuity indicating that merely changing the statistics of the attentional focus without external stimulation or training can improve tactile acuity. In the view of activity-dependent plasticity that is outlined in this thesis, the main driving force for development and alterations of neural representations is nothing more than neural activity itself. Patterns of neural activity shape our brains during development and significant changes in the patterns of neural activity inevitably change mature neural representations. At the same time, the patterns of neural activity are formed by environmental sensory inputs as well as by contextual, multiplicative inputs like gaze-direction or by internally generated signals like the attentional focus. In this way, our environments as well as our inner mental states shape our neural representations and our perception at any time

Examining motor unit stability of first dorsal interosseous (FDI) and biceps brachii (BB) muscles in healthy and older adults using decomposition-based quantitative electromyography (DQEMG)

Aging of the human neuromuscular system is associated with gradual decline in motor unit (MU) number leading to denervation of muscle fibers and subsequent compensatory reinnervation from surviving MUs. Lower limb muscles exhibit age-related increased MU instability (measured electrophysiologically), however not much is known regarding MU stability of aging upper limb muscles. The purpose of this study was to examine agerelated MU loss in upper limb muscles (first dorsal interosseous [FDI] and biceps brachii [BB]) and the impact on MU stability in younger and older healthy subjects using electrophysiological near fiber analysis from decomposition-based quantitative electromyography (DQEMG). FDI and BB muscles from older (74 ± 5 years) and younger (31 ± 13 years) healthy subjects were examined through surface and intramuscular collection of EMG signals during volitional contractions, which were analyzed with DQEMG. Older subjects showed significantly larger MUs associated with greater instability in the form of near fiber (NF) jiggle and NF jitter in the FDI and BB muscles when compared to younger controls. These results suggest that age-dependent MU remodeling and progressive reduction in FDI and BB MU pools are associated with greater transmission instability at the neuromuscular junction