Laminar specificity of the auditory perceptual awareness negativity: A biophysical modeling study.

How perception of sensory stimuli emerges from brain activity is a fundamental question of neuroscience. To date, two disparate lines of research have examined this question. On one hand, human neuroimaging studies have helped us understand the large-scale brain dynamics of perception. On the other hand, work in animal models (mice, typically) has led to fundamental insight into the micro-scale neural circuits underlying perception. However, translating such fundamental insight from animal models to humans has been challenging. Here, using biophysical modeling, we show that the auditory awareness negativity (AAN), an evoked response associated with perception of target sounds in noise, can be accounted for by synaptic input to the supragranular layers of auditory cortex (AC) that is present when target sounds are heard but absent when they are missed. This additional input likely arises from cortico-cortical feedback and/or non-lemniscal thalamic projections and targets the apical dendrites of layer-5 (L5) pyramidal neurons. In turn, this leads to increased local field potential activity, increased spiking activity in L5 pyramidal neurons, and the AAN. The results are consistent with current cellular models of conscious processing and help bridge the gap between the macro and micro levels of perception-related brain activity.

Laminar Specificity of the Auditory Perceptual Awareness Negativity: A Biophysical Modeling Study.

How perception of sensory stimuli emerges from brain activity is a fundamental question of neuroscience. To date, two disparate lines of research have examined this question. On one hand, human neuroimaging studies have helped us understand the large-scale brain dynamics of perception. On the other hand, work in animal models (mice, typically) has led to fundamental insight into the micro-scale neural circuits underlying perception. However, translating such fundamental insight from animal models to humans has been challenging. Here, using biophysical modeling, we show that the auditory awareness negativity (AAN), an evoked response associated with perception of target sounds in noise, can be accounted for by synaptic input to the supragranular layers of auditory cortex (AC) that is present when target sounds are heard but absent when they are missed. This additional input likely arises from cortico-cortical feedback and/or non-lemniscal thalamic projections and targets the apical dendrites of layer-V pyramidal neurons (PNs). In turn, this leads to increased local field potential activity, increased spiking activity in layer-V PNs, and the AAN. The results are consistent with current cellular models of conscious processing and help bridge the gap between the macro and micro levels of perception-related brain activity. Author Summary: To date, our understanding of the brain basis of conscious perception has mostly been restricted to large-scale, network-level activity that can be measured non-invasively in human subjects. However, we lack understanding of how such network-level activity is supported by individual neurons and neural circuits. This is at least partially because conscious perception is difficult to study in experimental animals, where such detailed characterization of neural activity is possible. To address this gap, we used biophysical modeling to gain circuit-level insight into an auditory brain response known as the auditory awareness negativity (AAN). This response can be recorded non-invasively in humans and is associated with perceptual awareness of sounds of interest. Our model shows that the AAN likely arises from specific cortical layers and cell types. These data help bridge the gap between circuit- and network-level theories of consciousness, and could lead to new, targeted treatments for perceptual dysfunction and disorders of consciousness.

Electrophysiological evidence of sustained attention to music among conscious participants and unresponsive hospice patients at the end of life.

OBJECTIVE: To characterize electrophysiological activity, and likely neural sources of that activity, associated with listening to music in both healthy participants and in a small group of hospice patients both when responsive and when unresponsive hours before death. METHODS: Young, healthy participants (N = 22) were asked to attend to (Active condition) and to ignore (Passive condition) brief (6 s) music excerpts. A smaller group (N = 13) of hospice patients was asked to attend to the same musical excerpts (Active condition only), both when they were responsive (N = 8) and again when they became unresponsive (N = 4) only hours before death. EEG-derived event-related spectral perturbations (ERSPs) to music stimuli, and their approximate neural sources, were computed for each individual in both groups. RESULTS: In the healthy participants, alpha-band ERSP during the music excerpts in a group-level analysis was significantly lower in posterio-parietal brain areas in the Active condition than in the Passive condition (event-related desynchronization, ERD). Moreover, in an analysis of individual ERSP data, most (18 of 22 or 84%) healthy participants showed meaningful sustained (4 or more seconds) alpha-band suppression in one or more posterio-parietal brain areas when they were asked to attend to the music, whereas far fewer healthy participants (only 7 of 19 or 37%) generated the same response when asked to ignore the music, indicating that posterio-parietal alpha-band ERD could be a useful marker of music listening. Similarly, 75% of eight responsive hospice patients, and 100% of four unresponsive hospice patients showed sustained posterio-parietal alpha-band suppression when asked to attend to the music, indicating that they could be listening to the music covertly even when overtly unresponsive. CONCLUSIONS: Some (but likely not all, as other patients will vary from those we studied) unresponsive patients at the end of life might be able to listen to music, despite being unable to overtly indicate their awareness. SIGNIFICANCE: Music stimulation may be a promising way to engage unresponsive patients.

Resting state network activation and functional connectivity in the dying brain.

OBJECTIVE: To characterize electrophysiological functional connectivity within both the default mode network (DMN) and the task-positive network (TPN) among a small group of unresponsive hospice patients at the end of life. METHODS: EEG recordings from resting state were analysed to identify brain regions in the DMN and TPN of 30 young, healthy controls, and of 9 hospice patients when they were responsive and of 5 patients when they became unresponsive during the last hours of life. RESULTS: The prevalence of activation and connectivity within the DMN was similar across all participant groups. Overall functional connectivity was higher between brain regions within the DMN than between brain regions within TPN for all participant groups. The number of functional connections within the DMN, however, was greater than those within the TPN among controls and responsive hospice patients but not among unresponsive hospice patients. CONCLUSIONS: Some unresponsive patients may have the functional architecture to support internally-oriented thought at the end of life. Resting state default mode - task positive network anticorrelations may be present among some unresponsive hospice patients. SIGNIFICANCE: Some unresponsive end of life patients may be able to mind-wander. Implications for internally-oriented awareness at the end of life are discussed.

Electrophysiological evidence of preserved hearing at the end of life.

This study attempts to answer the question: "Is hearing the last to go?" We present evidence of hearing among unresponsive actively dying hospice patients. Individual ERP (MMN, P3a, and P3b) responses to deviations in auditory patterns are reported for conscious young, healthy control participants, as well as for hospice patients, both when the latter were conscious, and again when they became unresponsive to their environment. Whereas the MMN (and perhaps too the P3a) is considered an automatic response to auditory irregularities, the P3b is associated with conscious detection of oddball targets. All control participants, and most responsive hospice patients, evidenced a "local" effect (either a MMN, a P3a, or both) and some a "global" effect (P3b) to deviations in tone, or deviations in auditory pattern. Importantly, most unresponsive patients showed evidence of MMN responses to tone changes, and some showed a P3a or P3b response to either tone or pattern changes. Thus, their auditory systems were responding similarly to those of young, healthy controls just hours from end of life. Hearing may indeed be one of the last senses to lose function as humans die.

Search asymmetry in a serial auditory task: Neural source analyses of EEG implicate attention strategies.

Here we report a detailed analysis of the fast network dynamics underlying P3a and P3b event-related potential (ERP) subcomponents generated during an unconventional serial auditory search paradigm. We dissect the electroencephalographic (EEG) data from an earlier study of ours, using a variety of advanced signal processing techniques, in order to discover how the brain is processing auditory targets differently when they possess a rare, salient, unpredictable feature not shared with distractors than when targets lack this feature but distractors have it. We find that brain regions associated with the Ventral Attention Network (VAN) are the primary neural generators of the P3a subcomponent in response to feature-present targets, whereas regions associated with the Dorsal Attention Network (DAN), as well as regions associated with detecting auditory oddball stimuli (ODD), may be the primary neural generators of the P3b, in the context of our study, and perhaps in search paradigms in general. Moreover, measurements of the time courses of oscillatory power changes and inter-regional synchronization in theta and low-gamma frequency bands were consistent with the early activation and synchronization within the VAN associated with the P3a subcomponent, and with the later activation and synchronization within the DAN and ODD networks associated with the P3b subcomponent. Implications of these finding for the mechanisms underlying search asymmetry phenomena are discussed.

Sequential search asymmetry: Behavioral and psychophysiological evidence from a dual oddball task.

We conducted five experiments in order to explore the generalizability of a new type of search asymmetry, which we have termed sequential search asymmetry, across sensory modalities, and to better understand its origin. In all five experiments rare oddballs occurred randomly within longer sequences of more frequent standards. Oddballs and standards all consisted of rapidly-presented runs of five pure tones (Experiments 1 and 5) or five colored annuli (Experiments 2 through 4) somewhat analogous to simultaneously-presented feature-present and feature-absent stimuli in typical visual search tasks. In easy tasks feature-present reaction times and P300 latencies were shorter than feature-absent ones, similar to findings in search tasks with simultaneously-presented stimuli. Moreover the P3a subcomponent of the P300 ERP was strongly apparent only in the feature-present condition. In more difficult tasks requiring focused attention, however, RT and P300 latency differences disappeared but the P300 amplitude difference was significant. Importantly in all five experiments d' for feature-present targets was larger than that for feature-absent targets. These results imply that sequential search asymmetry arises from discriminability differences between feature-present and feature-absent targets. Response time and P300 latency differences can be attributed to the use of different attention strategies in search for feature-present and feature-absent targets, indexed by the presence of a dominant P3a subcomponent in the feature-present target-evoked P300s that is lacking in the P300s to the feature-absent targets.

Brain regional networks active during the mismatch negativity vary with paradigm.

We used independent component analysis (ICA) of high-density EEG recordings coupled with single dipole fitting to identify the dominant brain regions active during the MMN in two different versions of a passive oddball paradigm: a simple, monotic, frequency-deviant paradigm and a more complex, dichotic, frequency-deviant paradigm with deviants occurring in either ear alone or in both ears at the same time. In both paradigms we found brain regional sources in the temporal and frontal cortices active during the MMN period, consistent with some previous studies. In the simpler paradigm, the scalp-potential variance during the earlier (70-120 ms) MMN was mostly accounted for by a wide array of temporal, frontal, and parietal sources. In the more complex paradigm, however, a generator in the prefrontal cortex accounted for a substantial amount of the variance of the scalp potential during the somewhat later MMN period (120-200 ms). These findings are consistent with a more nuanced view of the MMN and its generators than has been held in the past.