Binding by Asynchrony: The Neuronal Phase Code

Neurons display continuous subthreshold oscillations and discrete action potentials (APs). When APs are phase-locked to the subthreshold oscillation, we hypothesize they represent two types of information: the presence/absence of a sensory feature and the phase of subthreshold oscillation. If subthreshold oscillation phases are neuron-specific, then the sources of APs can be recovered based on the AP times. If the spatial information about the stimulus is converted to AP phases, then APs from multiple neurons can be combined into a single axon and the spatial configuration reconstructed elsewhere. For the reconstruction to be successful, we introduce two assumptions: that a subthreshold oscillation field has a constant phase gradient and that coincidences between APs and intracellular subthreshold oscillations are neuron-specific as defined by the “interference principle.” Under these assumptions, a phase-coding model enables information transfer between structures and reproduces experimental phenomenons such as phase precession, grid cell architecture, and phase modulation of cortical spikes. This article reviews a recently proposed neuronal algorithm for information encoding and decoding from the phase of APs (Nadasdy, 2009). The focus is given to the principles common across different systems instead of emphasizing system specific differences

Micro-, Meso- and Macro-Dynamics of the Brain

Neurosciences, Neurology, Psychiatr

Information Encoding and Reconstruction from the Phase of Action Potentials

Fundamental questions in neural coding are how neurons encode, transfer, and reconstruct information from the pattern of action potentials (APs) exchanged between different brain structures. We propose a general model of neural coding where neurons encode information by the phase of their APs relative to their subthreshold membrane oscillations. We demonstrate by means of simulations that AP phase retains the spatial and temporal content of the input under the assumption that the membrane potential oscillations are coherent across neurons and between structures and have a constant spatial phase gradient. The model explains many unresolved physiological observations and makes a number of concrete, testable predictions about the relationship between APs, local field potentials, and subthreshold membrane oscillations, and provides an estimate of the spatio-temporal precision of neuronal information processing

Using large-scale neural models to interpret connectivity measures of cortico-cortical dynamics at millisecond temporal resolution

Over the last two decades numerous functional imaging studies have shown that higher order cognitive functions are crucially dependent on the formation of distributed, large-scale neuronal assemblies (neurocognitive networks), often for very short durations. This has fueled the development of a vast number of functional connectivity measures that attempt to capture the spatiotemporal evolution of neurocognitive networks. Unfortunately, interpreting the neural basis of goal directed behavior using connectivity measures on neuroimaging data are highly dependent on the assumptions underlying the development of the measure, the nature of the task, and the modality of the neuroimaging technique that was used. This paper has two main purposes. The first is to provide an overview of some of the different measures of functional/effective connectivity that deal with high temporal resolution neuroimaging data. We will include some results that come from a recent approach that we have developed to identify the formation and extinction of task-specific, large-scale neuronal assemblies from electrophysiological recordings at a ms-by-ms temporal resolution. The second purpose of this paper is to indicate how to partially validate the interpretations drawn from this (or any other) connectivity technique by using simulated data from large-scale, neurobiologically realistic models. Specifically, we applied our recently developed method to realistic simulations of MEG data during a delayed match-to-sample (DMS) task condition and a passive viewing of stimuli condition using a large-scale neural model of the ventral visual processing pathway. Simulated MEG data using simple head models were generated from sources placed in V1, V4, IT, and prefrontal cortex (PFC) for the passive viewing condition. The results show how closely the conclusions obtained from the functional connectivity method match with what actually occurred at the neuronal network level

Six Principles of Visual Cortical Dynamics

A fundamental goal in vision science is to determine how many neurons in how many areas are required to compute a coherent interpretation of the visual scene. Here I propose six principles of cortical dynamics of visual processing in the first 150 ms following the appearance of a visual stimulus. Fast synaptic communication between neurons depends on the driving neurons and the biophysical history and driving forces of the target neurons. Under these constraints, the retina communicates changes in the field of view driving large populations of neurons in visual areas into a dynamic sequence of feed-forward communication and integration of the inward current of the change signal into the dendrites of higher order area neurons (30–70 ms). Simultaneously an even larger number of neurons within each area receiving feed-forward input are pre-excited to sub-threshold levels. The higher order area neurons communicate the results of their computations as feedback adding inward current to the excited and pre-excited neurons in lower areas. This feedback reconciles computational differences between higher and lower areas (75–120 ms). This brings the lower area neurons into a new dynamic regime characterized by reduced driving forces and sparse firing reflecting the visual areas interpretation of the current scene (140 ms). The population membrane potentials and net-inward/outward currents and firing are well behaved at the mesoscopic scale, such that the decoding in retinotopic cortical space shows the visual areas’ interpretation of the current scene. These dynamics have plausible biophysical explanations. The principles are theoretical, predictive, supported by recent experiments and easily lend themselves to experimental tests or computational modeling

Neural Processing in the Three Layer Turtle Visual Cortex

In this thesis we investigate neural processing in turtle visual cortex. To this end, we characterize the nature of both spontaneous, ongoing neural activity as well as activity evoked by visual stimulation. Data are collected from whole brain eye-attached preparations, recording with extracellular and intracellular electrodes. We investigate the activity of action potentials as well as the slower local field potential activity. To investigate response properties, we explore spatial properties of receptive fields, temporal properties of spontaneous and evoked activity, response adaptation, and correlations between different types of activity as well as between activity recorded in different regions. To study the roles of rhythmic oscillations in the local field potential, we examine temporal and spectral properties of oscillations. We look at the distributions of durations of oscillatory bursts as well as the distributions of the dominant frequencies within those oscillations. We also investigate the variability of these features and produce similar results in a model simulation. Lastly, we investigate criticality and the statistics of neural activity over a range of scales in the turtle visual cortex. We use neuronal avalanches to reveal scale-free cortical dynamics and power-law statistics, which have been hypothesized to optimize information processing

Capture of fixation by rotational flow; a deterministic hypothesis regarding scaling and stochasticity in fixational eye movements.

Visual scan paths exhibit complex, stochastic dynamics. Even during visual fixation, the eye is in constant motion. Fixational drift and tremor are thought to reflect fluctuations in the persistent neural activity of neural integrators in the oculomotor brainstem, which integrate sequences of transient saccadic velocity signals into a short term memory of eye position. Despite intensive research and much progress, the precise mechanisms by which oculomotor posture is maintained remain elusive. Drift exhibits a stochastic statistical profile which has been modeled using random walk formalisms. Tremor is widely dismissed as noise. Here we focus on the dynamical profile of fixational tremor, and argue that tremor may be a signal which usefully reflects the workings of oculomotor postural control. We identify signatures reminiscent of a certain flavor of transient neurodynamics; toric traveling waves which rotate around a central phase singularity. Spiral waves play an organizational role in dynamical systems at many scales throughout nature, though their potential functional role in brain activity remains a matter of educated speculation. Spiral waves have a repertoire of functionally interesting dynamical properties, including persistence, which suggest that they could in theory contribute to persistent neural activity in the oculomotor postural control system. Whilst speculative, the singularity hypothesis of oculomotor postural control implies testable predictions, and could provide the beginnings of an integrated dynamical framework for eye movements across scales

Shifts of Gamma Phase across Primary Visual Cortical Sites Reflect Dynamic Stimulus-Modulated Information Transfer

Distributed neural processing likely entails the capability of networks to reconfigure dynamically the directionality and strength of their functional connections. Yet, the neural mechanisms that may allow such dynamic routing of the information flow are not yet fully understood. We investigated the role of gamma band (50–80 Hz) oscillations in transient modulations of communication among neural populations by using measures of direction-specific causal information transfer. We found that the local phase of gamma-band rhythmic activity exerted a stimulus-modulated and spatially-asymmetric directed effect on the firing rate of spatially separated populations within the primary visual cortex. The relationships between gamma phases at different sites (phase shifts) could be described as a stimulus-modulated gamma-band wave propagating along the spatial directions with the largest information transfer. We observed transient stimulus-related changes in the spatial configuration of phases (compatible with changes in direction of gamma wave propagation) accompanied by a relative increase of the amount of information flowing along the instantaneous direction of the gamma wave. These effects were specific to the gamma-band and suggest that the time-varying relationships between gamma phases at different locations mark, and possibly causally mediate, the dynamic reconfiguration of functional connections

Behavioral and fMRI-based Characterization of Cognitive Processes Supporting Learning and Retrieval of Memory for Words in Young Adults

A novel word is rarely defined explicitly during the first encounter. With repeated exposure, a decontextualized meaning of the word is integrated into semantic memory. With the overarching goal of characterizing the functional neuroanatomy of semantic processing in young adults, we employed a contextual word learning paradigm, creating novel synonyms for common animal/artifact nouns that, along with additional real words, served as stimuli for the lexical-decision based functional MRI (fMRI) experiment. Young adults (n=28) were given two types of word learning training administered in multiple sessions spread out over three days. The first type of training provided perceptual form-only training to pseudoword (PW) stimuli using a PW-detection task. The second type of training assigned the meaning of common artifacts and animals to PWs using multiple sentences to allow contextual meaning acquisition, essentially creating novel synonyms. The underlying goals were twofold: 1) to test, using a behavioral semantic priming paradigm, the hypothesis that novel words acquired in adulthood get integrated into existing semantic networks (discussed in Chapter 2); and 2) to investigate the functional neuroanatomy of semantic processing in young adults, at the single word level, using the newly learned as well as previously known word stimuli as a conduit (discussed in Chapter 3). As outlined in Chapter 2, in addition to the semantic priming test mentioned above, two additional behavioral tests were administered to assess word learning success. The first was a semantic memory test using a two-alternative sentence completion task. Participants demonstrated robust accuracy (~87%) in choosing the appropriate meaning-trained item to complete a novel sentence. Second, an old/new item recognition test was administered using both meaning and form trained stimuli (old) as well as novel foil PWs (new). Participants demonstrated: a) high discriminability between trained and novel PW stimuli. (d-prime=2.72); and b)faster reaction times and higher accuracy for meaning-trained items relative to perceptually-trained items, consistent with prior level-of-processing research. The results from the recognition and semantic memory tests confirmed that subjects could explicitly recognize trained items as well as demonstrate knowledge of the newly acquired synonymous meanings. Finally, using a lexical decision task, a semantic priming test assessed semantic integration using the novel trained items as primes for word targets that had no prior episodic association to the primes. Relative to perceptually trained primes, meaning-trained primes significantly facilitated lexical decision latencies for synonymous word targets. Taken together, the behavioral findings outlined above demonstrate that a contextual approach is effective in facilitating word learning in young adults. Words learned over a few experimental sessions were successfully retained in declarative memory, as demonstrated by behavioral performance in the semantic memory and recognition memory experiments. In addition, relative to perceptually-trained PWs, the newly meaning-trained PWs, when used as primes in a semantic priming test, facilitated lexical decisions for synonymous real words, with which the primes had no prior episodic association. The latter finding confirms our primary behavioral hypothesis that novel words acquired in adulthood are represented similarly, i.e. integrated in the same semantic memory representational network, as common words likely acquired early in the lifetime. Chapter 3 outlines the findings from the fMRI experiment used to investigate the functional neuroanatomy of semantic processing using the newly learned as well as previously known words as stimuli in a lexical decision task. fMRI data were collected using a widely-spaced event-related design, allowing isolation of item-level hemodynamic responses. Two fMRI sessions were administered separated by 2-3 days, the 1st session conducted prior to, and the 2nd session following word-learning training. Using the same items as stimuli in the fMRI sessions conducted before and after behavioral training, facilitated a within-item analysis where each item effectively served as its own control. A set of stringent criteria, outlined below, were established a-priori describing characteristics expected from regions with a role in retrieving/processing meanings at the single word level. We expected a putative semantic processing region to exhibit: a) higher BOLD activity during the 1st fMRI session for real words relative to novel PWs; b) reduced BOLD activity for repeated real words presented in the 2nd fMRI session relative to levels seen in the 1st fMRI session; c) higher BOLD activity for meaning-trained PWs relative to novel PWs; d) higher BOLD activity for meaning-trained PWs relative to perceptually-trained PWs, e) higher BOLD activity for correctly identified meaning-trained PWs (hits) relative to their incorrect counterparts (misses). Given their previously documented associations with semantic processing, we expected to identify regions in left middle temporal gyrus (MTG) and left ventral inferior frontal gyrus (vIFG) to exhibit timecourses consistent with most of the semantic criteria outlined above. Individual ANOVA contrasts, essentially targeting each of the criteria outlined above, were conducted at the voxelwise level. A fixed effects analysis based on 4 correct trial ANOVA contrasts (corresponding to criteria a-d, above) generated 81 regions of interest; and two individual error vs. correct trial ANOVA contrasts generated an additional 16 regions, for a total of 97 study-driven regions. Using region-level ANOVAs and qualitative timecourse examinations, the regions were probed for the presence of the effects outlined in the above criteria. To ensure a comprehensive analysis, additional regions were garnered from prior studies that have used a variety of tasks to target semantic processing. The literature-derived regions were subjected to similar ANOVAs and qualitative timecourse analysis as was conducted on the study-driven regions to examine if the regions exhibited effects outlined in the above criteria. The above analysis resulted in three principal observations. First, we identified regions in the left parahippocamal gyrus (PHG) and left medial superior frontal cortex (mSFC) that, by satisfying essentially all the above criteria, demonstrated a role in semantic memory retrieval for recently acquired and previously known words. Second, despite strong expectations, regions in the left MTG and left vIFG failed to show activity in support of a role in semantic retrieval for the novel words. On the contrary, the profiles seen in the two said regions, namely a ‘word \u3e novel PW’ and a word repetition suppression effect, were consistent with a role in semantic retrieval exclusively for the previously known words. The latter observation suggests that the novel words have yet to undergo adequate consolidation to engage, in addition to PHG and mSFC, canonical semantic regions such as left MTG. Third, despite the potentially crucial distinctions noted in Chapter 3, left lateral/medial parietal regions implicated in episodic memory retrieval exhibited many similar properties as those outlined for PHG and mSFC above during retrieval of newly learned words. Crucially, instead of exhibiting repetition suppression for real words, as observed in PHG/mSFC, the parietal regions showed the opposite effect resembling the episodic ‘old\u3enew’ retrieval success effect. The latter observation argues against a sematic role and in support of an episodic role consistent with previous literature. Taken together, these observations suggest that in addition to the role played by PHG/mSFC supporting semantic memory retrieval for the novel words, the parietal regions are also making significant contributions for memory retrieval of the novel words via complementary episodic processes. Finally, using item-level timecourses derived from the 97 study-driven ROI, clustering algorithms were used to group regions with similar characteristics, with the goal of identifying a cluster corresponding to a putative semantic brain system. A number of clusters were identified containing regions with anatomical and functional correspondence to previously well-characterized systems. For instance, a cluster containing regions in left lateral parietal cortex, precuneus, and superior frontal cortex corresponding to a previously described episodic memory retrieval system (Nelson et al., 2010) was identified. Two additional clusters, corresponding to frontoparietal and cinguloopercular task control systems (Dosenbach et al., 2006, 2007) were also among the identified clusters. However, the clustering analysis did not identify a cluster of regions with semantic properties, such as PHG and mSFC noted above, that could potentially correspond with a semantic brain system. The above outlined findings from the current study, juxtaposed with prior findings from the literature, were interpreted in the following manner. The two regions identified in the current study, i.e. left parahippocampal gyrus and medial superior frontal gyrus, constitute regions that are used for learning new words, and are also recruited during semantic retrieval of previously well-established meanings. In addition, the current results also suggest complementary episodic contributions to the word learning process from regions in left parietal/superior frontal cortex. The latter observation may imply strong episodic contributions to the observed behavioral semantic priming effects. A potential counter argument, i.e. in support of a semantic basis for the priming effects, is the shared recruitment, in a manner consistent with semantics, of PHG/mSFC by both novel and real word stimuli. The left middle temporal gyrus, a region that the task-evoked and neuropsychological literature consistently associates with word-level semantic processing, was not recruited during memory retrieval of novel words, despite robust engagement by previously known word stimuli. Given their association with category-selective semantic deficits, as well as their role in conceptual/perceptual processing in healthy brains, the memory consolidation literature proposes regions in the lateral temporal lobes as potential neocortical loci for consolidated long-term memory. In the current setting, it is likely the case that the novel words have yet to be adequately consolidated to engage left MTG as did the previously known words. Finally, the left vIFG exhibited similar characteristics as the left middle temporal gyrus, in that it was not recruited by the newly meaning trained stimuli, despite showing engagement by previously known words. Given that the region failed to appear in our primary contrasts, even those targeting real word stimuli, and its absence in other prior studies that have used similar lexical decision tasks as the current study, we have a slightly different interpretation for that region. The left vIFG is typically recruited in task settings that require controlled/strategic meaning retrieval, a process that may not be critical for adequate performance of the lexical decision task as employed in the current study. Taken together, these findings suggest that a relatively small amount of word learning training is sufficient to create novel words that, in young adults, behaviorally resemble the semantic characteristics of well-known words. On the other hand, the fMRI findings, particularly the failure of the newly meaning-trained items to engage regions that are canonically responsive to single word meanings (e.g. middle temporal gyrus), may suggest a more protracted timecourse for the functional signature of novel words to resemble that of well-known words. That said, the fMRI findings identified brain regions (left PHG/mSFC) that, consistent with the memory consolidation literature, serve as the functional neuroanatomical “bridge” that connects the novel words to the eventual functional representational destination