Error-monitoring and post-error compensations: dissociation between perceptual failures and motor errors with and without awareness

Authors:

• Robert T. Knight

• Ana Navarro-Cebrian

• Andrew S. Kayser

Date: 2013

DOI: 10.1523/JNEUROSCI.0447-13.2013

PubMed: 23884943

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Abstract:

Whether humans adjust their behavior in response to unaware errors remains a controversial issue relevant to insight in neuropsychiatric conditions. Initial error awareness studies found that the error-related negativity (ERN), an event-related potential (ERP) originating in the medial prefrontal cortex after errors, activated equally for aware and unaware errors, suggesting a candidate preconscious mechanism. However, recent studies demonstrate that the ERN decreases after unaware errors. We hypothesized that the ERN is dependent upon awareness, and predicted that previous discrepancies might be due to unaware errors not being differentiated from perceptually uncertain, low-confidence responses that might increase the ERN amplitude. Here we addressed this hypothesis by distinguishing between aware errors, unaware errors, and uncertain responses, and using stimuli (faces) associated with well established sensory ERPs to evaluate the degree of stimulus processing for each trial type. We found that while aware and unaware errors were related to failures at the time of response, uncertain responses were due to failures at the time of stimulus processing indexed by lower amplitude sensory ERPs. Moreover, uncertain responses showed similar ERN activity as aware errors, in comparison with decreased activity for unaware errors. Finally, compared with aware errors, uncertain responses and unaware errors showed reduced neural compensations, such as alpha suppression. Together these findings suggest that the ERN is activated by aware motor errors as well as sensory failures, and that both awareness and certainty are necessary for neural adaptations after errors.

Preparatory attention after lesions to the lateral or orbital prefrontal cortex: an event-related potential study

Authors:

• Ingrid Funderud

• Marianne Lovstad

• Magnus Lindgren

• Tor Endestad

• Paulina Due-Tønnesse

• Torstein Meling

• Robert T. Knight

• Anne-Kristin Solbakk

Date: 2013

PubMed: 23831520

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Abstract:

The prefrontal cortex (PFC) plays a central role in preparatory and anticipatory attentional processes. To investigate whether subregions of the PFC play differential roles in these processes we investigated the effect of focal lesions to either lateral prefrontal (lateral PFC; n=11) or orbitofrontal cortex (OFC; n=13) on the contingent negative variation (CNV), an electrophysiological index of preparatory brain processes. The CNV was studied using a Go/NoGo delayed response task where an auditory S1 signaled whether or not an upcoming visual S2 was a Go or a NoGo stimulus. Neither early (500–1000 ms) nor late (3200–3700 ms) phase Go trial CNV amplitude was reduced for any of the patient groups in comparison to controls. However, the lateral PFC group showed enhanced Go trial early CNV and reduced late CNV Go/NoGo differentiation. These data suggests that normal orienting and evaluation as reflected by the CNV is intact after OFC lesions. The enhanced early CNV after lateral PFC damage may be due to failure in inhibition and the reduced late CNV difference wave confirms a deficit in preparatory attention after damage to this frontal subregion.

Independence of valence and reward in emotional word processing: Electrophysiological evidence

Authors:

• Laura Kaltwasser

• Stephanie Ries

• Werner Sommer

• Robert T. Knight

• Roel M. Willems

Date: 2013

DOI: 10.3389/fpsyg.2013.00168

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Abstract:

Both emotion and reward are primary modulators of cognition: Emotional word content enhances word processing, and reward expectancy similarly amplifies cognitive processing from the perceptual up to the executive control level. Here, we investigate how these primary regulators of cognition interact. We studied how the anticipation of gain or loss modulates the neural time course (event-related potentials, ERPs) related to processing of emotional words. Participants performed a semantic categorization task on emotional and neutral words, which were preceded by a cue indicating that performance could lead to monetary gain or loss. Emotion-related and reward-related effects occurred in different time windows, did not interact statistically, and showed different topographies. This speaks for an independence of reward expectancy and the processing of emotional word content. Therefore, privileged processing given to emotionally valenced words seems immune to short-term modulation of reward. Models of language comprehension should be able to incorporate effects of reward and emotion on language processing, and the current study argues for an architecture in which reward and emotion do not share a common neurobiological mechanism.

Multiplexed memories: a view from human cortex

Authors:

• Robert T. Knight

• Howard Eichenbaum

Date: 2013

DOI: 10.1038/nn.3341

PubMed: 23434977

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Abstract:

A study recording directly from the human brain shows that connectivity between the prefrontal cortex, parietal cortex and the medial temporal lobe across different frequency bands underlies successful memory retrieval.

Age-related frontal-parietal changes during the control of bottom-up and top-down attention: an ERP study

Authors:

• Ling Li

• Caterina Gratton

• Monica Fabiani

• Robert T. Knight

Date: 2013

DOI: 10.1016

PubMed: 22459599

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Abstract:

We investigated age-related changes in frontal and parietal scalp event-related potential (ERP) activity during bottom-up and top-down attention. Younger and older participants were presented with arrays constructed to induce either automatic "pop-out" (bottom-up) or effortful "search" (top-down) behavior. Reaction times (RTs) increased and accuracy decreased with age, with a greater age-related decline in accuracy for the search than for the pop-out condition. The latency of the P300 elicited by the visual search array was shorter in both conditions in the younger than in the older adults. Pop-out target detection was associated with greater activity at parietal than at prefrontal locations in younger participants and with a more equipotential prefrontal-parietal distribution in older adults. Search target detection was associated with greater activity at prefrontal than at parietal locations in older relative to younger participants. Thus, aging was associated with a more prefrontal P300 scalp distribution during the control of bottom-up and top-down attention. Early latency extrastriate potentials were enhanced and N2-posterior-contralateral (N2pc) was reduced in the older group, supporting the idea that the frontal enhancements may be due to a compensation for disinhibition and distraction in the older adults. Taken together these findings provide evidence that younger and older adults recruit different frontal-parietal networks during top-down and bottom-up attention, with older adults increasing their recruitment of a more frontally distributed network in both of these types of attention. This work is in accord with previous neuroimaging findings suggesting that older adults recruit more frontal activity in the service of a variety of tasks than younger adults.

Oscillations and behavior: the role of phase-amplitude coupling in cognition

Authors:

• Boaz Sadeh

• Sara Szczepanski

• Robert T. Knight

Date: 2013

Proceedings of the Third International Workshop on Advances in Electrocorticography

Authors:

• Anthony Ritaccio

• Michael Beauchamp

• Conrado Bosman

• Peter Brunner

• Edward F. Chang

• Nathan E. Crone

• Ayesegul Gunduz

• Disha Gupta

• Robert T. Knight

• Eric Leuthardt

• Brian Litt

• Daniel Moran

• Jeffrey G. Ojemann

• Josef Parvizi

• Nick F. Ramsey

• Jochem W. Rieger

• Jonathan Viventi

• Bradley Voytek

• Justin Williams

• Gerwin Schalk

Date: 2012

DOI: 10.1016/j.yebeh.2012.09.016

PubMed: 23160096

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Abstract:

The Third International Workshop on Advances in Electrocorticography (ECoG) was convened in Washington, DC, on November 10–11, 2011. As in prior meetings, a true multidisciplinary fusion of clinicians, scientists, and engineers from many disciplines gathered to summarize contemporary experiences in brain surface recordings. The proceedings of this meeting serve as evidence of a very robust and transformative field but will yet again require revision to incorporate the advances that the following year will surely bring.

Differential Go/NoGo activity in both contingent negative variation and spectral power

Authors:

• Ingrid Funderud

• Magnus Lindgren

• Marianne Lovstad

• Tor Endestad

• Bradley Voytek

• Robert T. Knight

• Anne-Kristin Solbakk

Date: 2012

DOI: 10.1371/journal.pone.0048504

PubMed: 23119040

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Abstract:

We investigated whether both the contingent negative variation (CNV), an event-related potential index of preparatory brain activity, and event-related oscillatory EEG activity differentiated Go and NoGo trials in a delayed response task. CNV and spectral power (4-100 Hz) were calculated from EEG activity in the preparatory interval in 16 healthy adult participants. As previously reported, CNV amplitudes were higher in Go compared to NoGo trials. In addition, event-related spectral power of the Go condition was reduced in the theta to low gamma range compared to the NoGo condition, confirming that preparing to respond is associated with modulation of event-related spectral activity as well as the CNV. Altogether, the impact of the experimental manipulation on both slow event-related potentials and oscillatory EEG activity may reflect coordinated dynamic changes in the excitability of distributed neural networks involved in preparation.

A method for event-related phase/amplitude coupling

Authors:

• Bradley Voytek

• Mark D'Esposito

• Nathan E. Crone

• Robert T. Knight

Date: 2012

DOI: 10.1016/j.neuroimage.2012.09.023

PubMed: 22986076

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Abstract:

Phase/amplitude coupling (PAC) is emerging as an important electrophysiological measure of local and long-distance neuronal communication. Current techniques for calculating PAC provide a numerical index that represents an average value across an arbitrarily long time period. This requires researchers to rely on block design experiments and temporal concatenation at the cost of the sub-second temporal resolution afforded by electrophysiological recordings. Here we present a method for calculating event-related phase/amplitude coupling (ERPAC) designed to capture the temporal evolution of task-related changes in PAC across events or between distant brain regions that is applicable to human or animal electromagnetic recording.

Human motor cortical activity is selectively phase-entrained on underlying rhythms

Authors:

• Kai J. Miller

• Dora Hermes

• Christopher J. Honey

• Adam O. Hebb

• Nick F. Ramsey

• Robert T. Knight

• Jeffrey G. Ojemann

• Eberhard E. Fetz

Date: 2012

DOI: 10.1371/journal.pcbi.1002655

PubMed: 22969416

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Abstract:

The functional significance of electrical rhythms in the mammalian brain remains uncertain. In the motor cortex, the 12-20 Hz beta rhythm is known to transiently decrease in amplitude during movement, and to be altered in many motor diseases. Here we show that the activity of neuronal populations is phase-coupled with the beta rhythm on rapid timescales, and describe how the strength of this relation changes with movement. To investigate the relationship of the beta rhythm to neuronal dynamics, we measured local cortical activity using arrays of subdural electrocorticographic (ECoG) electrodes in human patients performing simple movement tasks. In addition to rhythmic brain processes, ECoG potentials also reveal a spectrally broadband motif that reflects the aggregate neural population activity beneath each electrode. During movement, the amplitude of this broadband motif follows the dynamics of individual fingers, with somatotopically specific responses for different fingers at different sites on the pre-central gyrus. The 12-20 Hz beta rhythm, in contrast, is widespread as well as spatially coherent within sulcal boundaries and decreases in amplitude across the pre- and post-central gyri in a diffuse manner that is not finger-specific. We find that the amplitude of this broadband motif is entrained on the phase of the beta rhythm, as well as rhythms at other frequencies, in peri-central cortex during fixation. During finger movement, the beta phase-entrainment is diminished or eliminated. We suggest that the beta rhythm may be more than a resting rhythm, and that this entrainment may reflect a suppressive mechanism for actively gating motor function.

Anterior Cingulate Cortex and Cognitive Control: Neuropsychological and Electrophysiological Findings in Two Patients with Lesions to Dorsomedial Prefrontal Cortex

Authors:

• Marianne Lovstad

• Ingrid Funderud

• Torstein Meling

• Ulrike M. Krämer

• Bradley Voytek

• Paulina Due-Tønnesse

• Tor Endestad

• Magnus Lindgren

• Robert T. Knight

• Anne-Kristin Solbakk

Date: 2012

DOI: 10.1016/j.bandc.2012.07.008

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Abstract:

Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial prefrontal lesions, a hypothesis has been advanced claiming that the ACC is not involved in cognitive operations. In the current study, two comparably rare patients with unilateral lesions to dorsal medial prefrontal cortex (MPFC) encompassing the ACC were assessed with neuropsychological tests as well as Event-Related Potentials in two experimental paradigms known to engage prefrontal cortex (PFC). These included an auditory Novelty Oddball task and a visual Stop-signal task. Both patients performed normally on the Stroop test but showed reduced performance on tests of learning and memory. Moreover, altered attentional control was reflected in a diminished Novelty P3, whereas the posterior P3b to target stimuli was present in both patients. The error-related negativity, which has been hypothesized to be generated in the ACC, was present in both patients, but alterations of inhibitory behavior were observed. Although interpretative caution is generally called for in single case studies, and the fact that the lesions extended outside the ACC, the findings nevertheless suggest a role for MPFC in cognitive control that is not restricted to error monitoring.

Dynamics of anticipatory mechanisms during predictive context processing

Authors:

• Aurélie Bidet-Caulet

• P. G. Barbe

• S. Roux

• H. Viswanath

• C. Barthelemy

• N. Bruneau

• Robert T. Knight

• Frederique Bonnet-Brilhault

Date: 2012

DOI: 10.1111/j.1460-9568.2012.08223.x

PubMed: 22780698

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Abstract:

We employed an electroencephalography paradigm manipulating predictive context to dissociate the neural dynamics of anticipatory mechanisms. Subjects either detected random targets or targets preceded by a predictive sequence of three distinct stimuli. The last stimulus in the three-stimulus sequence (decisive stimulus) did not require any motor response but 100% predicted a subsequent target event. We showed that predictive context optimises target processing via the deployment of distinct anticipatory mechanisms at different times of the predictive sequence. Prior to the occurrence of the decisive stimulus, enhanced attentional preparation was manifested by reductions in the alpha oscillatory activities over the visual cortices, resulting in facilitation of processing of the decisive stimulus. Conversely, the subsequent 100% predictable target event did not reveal the deployment of attentional preparation in the visual cortices, but elicited enhanced motor preparation mechanisms, indexed by an increased contingent negative variation and reduced mu oscillatory activities over the motor cortices before movement onset. The present results provide evidence that anticipation operates via different attentional and motor preparation mechanisms by selectively pre-activating task-dependent brain areas as the predictability gradually increases.

Anterior insular cortex is necessary for empathetic pain perception

Authors:

• Xiaosi Gu

• Zhixian Gao

• Xingchao Wang

• Xun Liu

• Robert T. Knight

• Patrick R. Hof

• Jin Fan

Date: 2012

DOI: 10.1093/brain/aws199

PubMed: 22961548

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Abstract:

Empathy refers to the ability to perceive and share another person's affective state. Much neuroimaging evidence suggests that observing others' suffering and pain elicits activations of the anterior insular and the anterior cingulate cortices associated with subjective empathetic responses in the observer. However, these observations do not provide causal evidence for the respective roles of anterior insular and anterior cingulate cortices in empathetic pain. Therefore, whether these regions are 'necessary' for empathetic pain remains unknown. Herein, we examined the perception of others' pain in patients with anterior insular cortex or anterior cingulate cortex lesions whose locations matched with the anterior insular cortex or anterior cingulate cortex clusters identified by a meta-analysis on neuroimaging studies of empathetic pain perception. Patients with focal anterior insular cortex lesions displayed decreased discrimination accuracy and prolonged reaction time when processing others' pain explicitly and lacked a typical interference effect of empathetic pain on the performance of a pain-irrelevant task. In contrast, these deficits were not observed in patients with anterior cingulate cortex lesions. These findings reveal that only discrete anterior insular cortex lesions, but not anterior cingulate cortex lesions, result in deficits in explicit and implicit pain perception, supporting a critical role of anterior insular cortex in empathetic pain processing. Our findings have implications for a wide range of neuropsychiatric illnesses characterized by prominent deficits in higher-level social functioning.

Contribution of Subregions of Human Frontal Cortex to Novelty Processing

Authors:

• Marianne Lovstad

• Ingrid Funderud

• Magnus Lindgren

• Tor Endestad

• Paulina Due-Tønnesse

• Torstein Meling

• Bradley Voytek

• Robert T. Knight

• Anne-Kristin Solbakk

Date: 2012

DOI: 10.1162/jocn_a_00099

PubMed: 21812562

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Abstract:

Novelty processing was studied in patients with lesions centered in either OFC or lateral pFC (LPFC). An auditory novelty oddball ERP paradigm was applied with environmental sounds serving as task irrelevant novel stimuli. Lesions to the LPFC as well as the OFC resulted in a reduction of the frontal Novelty P3 response, supporting a key role of both frontal subdivisions in novelty processing. The posterior P3b to target sounds was unaffected in patients with frontal lobe lesions in either location, indicating intact posterior cortical target detection mechanisms. LPFC patients displayed an enhanced sustained negative slow wave (NSW) to novel sounds not observed in OFC patients, indicating prolonged resource allocation to task-irrelevant stimuli after LPFC damage. Both patient groups displayed an enhanced NSW to targets relative to controls. However, there was no difference in behavior between patients and controls suggesting that the enhanced NSW to targets may index an increased resource allocation to response requirements enabling comparable performance in the frontal lesioned patients. The current findings indicate that the LPFC and OFC have partly shared and partly differential contributions to the cognitive subcomponents of novelty processing.

Orbitofrontal cortex biases attention to emotional events

Authors:

• Kaisa M. Hartikainen

• Keith H. Ogawa

• Robert T. Knight

Date: 2012

PubMed: 22413757

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Abstract:

We examined the role of orbitofrontal (OF) cortex in regulating emotion-attention interaction and the balance between involuntary and voluntary attention allocation. We studied patients with OF lesion applying reaction time (RT) and event-related potential (ERP) measures in a lateralized visual discrimination task with novel task-irrelevant affective pictures (unpleasant, pleasant, or neutral) preceding a neutral target. This allowed for comparing the effects of automatic attention allocation to emotional versus neutral stimuli on subsequent voluntary attention allocation to target stimuli. N2-P3a and N2-P3b ERP components served as measures of involuntary and voluntary attention allocation correspondingly. Enhanced N2-P3a amplitudes to emotional distractors and reduced N2-P3b amplitudes to targets preceded by emotional distractors were observed in healthy subjects, suggesting automatic emotional orienting interfered with subsequent voluntary orienting. OF patients showed an opposite pattern with tendency towards reduced N2-P3a responses to emotional distractors, suggesting impaired automatic orienting to emotional stimuli due to orbitofrontal damage. Enhanced N2-P3b responses to targets preceded by any affective distractor were observed in OF patients, suggesting bias towards voluntary target-related attention allocation due to orbitofrontal lesion. Behavioral evidence indicated that left visual field (LVF) attention performance was modulated by emotional stimuli. Specifically, OF patients responded faster to LVF targets subsequent to pleasant emotional distractors. We suggest that damage to the orbitofrontal circuitry leads to dysbalance between voluntary and involuntary attention allocation in the context of affective distractors with predisposition to posterior target-related processing over frontal novelty and affect-related processing. Furthermore, we suggest that orbitofrontal influence on emotion-attention interaction is valence and hemisphere dependent.

The role of the lateral prefrontal cortex in inhibitory motor control

Authors:

• Ulrike M. Krämer

• Anne-Kristin Solbakk

• Ingrid Funderud

• Marianne Lovstad

• Tor Endestad

• Robert T. Knight

Date: 2012

DOI: 10.1016/j.cortex.2012.05.003

PubMed: 22699024

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Abstract:

Research on inhibitory motor control has implicated several prefrontal as well as subcortical and parietal regions in response inhibition. Whether prefrontal regions are critical for inhibition, attention or task-set representation is still under debate. We investigated the influence of the lateral prefrontal cortex (PFC) in a response inhibition task by using cognitive electrophysiology in prefrontal lesion patients. Patients and age- and education-matched controls performed in a visual Stop-signal task featuring lateralized stimuli, designed to challenge either the intact or lesioned hemisphere. Participants also underwent a purely behavioral Go/Nogo task, which included a manipulation of inhibition difficulty (blocks with 50 vs. 80% go-trials) and a Change-signal task that required switching to an alternative response. Patients and controls did not differ in their inhibitory speed (stop-signal and change-signal reaction time, SSRT and CSRT), but patients made more errors in the Go/Nogo task and showed more variable performance. The behavioral data stress the role of the PFC in maintaining inhibitory control but not in actual inhibition. These results support a dissociation between action cancellation and PFC-dependent action restraint. Laplacian transformed event-related potentials (ERPs) revealed reduced parietal activity in PFC patients in response to the stop-signals, and increased frontal activity over the intact hemisphere. This electrophysiological finding supports altered PFC-dependent visual processing of the stop-signal in parietal areas and compensatory activity in the intact frontal cortex. No group differences were found in the mu and beta decrease as measures of response preparation and inhibition at electrodes over sensorimotor cortex. Taken together, the data provide evidence for a central role of the lateral PFC in attentional control in the context of response inhibition.

Prefrontal lesions impair object-spatial integration.

Authors:

• Bradley Voytek

• Maryam Soltani

• Natasha Pickard

• Mark M. Kishiyama

• Robert T. Knight

Date: 2012

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Abstract:

How and where object and spatial information are perceptually integrated in the brain is a central question in visual cognition. Single-unit physiology, scalp EEG, and fMRI research suggests that the prefrontal cortex (PFC) is a critical locus for object-spatial integration. To test the causal participation of the PFC in an object-spatial integration network, we studied ten patients with unilateral PFC damage performing a lateralized object-spatial integration task. Consistent with single-unit and neuroimaging studies, we found that PFC lesions result in a significant behavioral impairment in object-spatial integration. Furthermore, by manipulating inter-hemispheric transfer of object-spatial information, we found that masking of visual transfer impairs performance in the contralesional visual field in the PFC patients. Our results provide the first evidence that the PFC plays a key, causal role in an object-spatial integration network. Patient performance is also discussed within the context of compensation by the non-lesioned PFC.

Human cortical sensorimotor network underlying feedback control of vocal pitch

Authors:

• Edward F. Chang

• Caroline A. Niziolek

• Robert T. Knight

• Srikantan S. Nagarajan

• John F. Houde

Date: 2013

DOI: 10.1073/pnas.1216827110

PubMed: 23345447

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Abstract:

The control of vocalization is critically dependent on auditory feedback. Here, we determined the human peri-Sylvian speech network that mediates feedback control of pitch using direct cortical recordings. Subjects phonated while a real-time signal processor briefly perturbed their output pitch (speak condition). Subjects later heard the same recordings of their auditory feedback (listen condition). In posterior superior temporal gyrus, a proportion of sites had suppressed responses to normal feedback, whereas other spatially independent sites had enhanced responses to altered feedback. Behaviorally, speakers compensated for perturbations by changing their pitch. Single-trial analyses revealed that compensatory vocal changes were predicted by the magnitude of both auditory and subsequent ventral premotor responses to perturbations. Furthermore, sites whose responses to perturbation were enhanced in the speaking condition exhibited stronger correlations with behavior. This sensorimotor cortical network appears to underlie auditory feedback-based control of vocal pitch in humans.

Reconstructing Speech from Human Auditory Cortex

Authors:

• Brian Pasley

• Stephen V. David

• Nima Mesgarani

• Adeen Flinker

• Shihab A. Shamma

• Nathan E. Crone

• Robert T. Knight

• Edward F. Chang

Date: 2012

DOI: 10.1371/journal.pbio.1001251

PubMed: 22303281

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Abstract:

How the human auditory system extracts perceptually relevant acoustic features of speech is unknown. To address this question, we used intracranial recordings from nonprimary auditory cortex in the human superior temporal gyrus to determine what acoustic information in speech sounds can be reconstructed from population neural activity. We found that slow and intermediate temporal fluctuations, such as those corresponding to syllable rate, were accurately reconstructed using a linear model based on the auditory spectrogram. However, reconstruction of fast temporal fluctuations, such as syllable onsets and offsets, required a nonlinear sound representation based on temporal modulation energy. Reconstruction accuracy was highest within the range of spectro-temporal fluctuations that have been found to be critical for speech intelligibility. The decoded speech representations allowed readout and identification of individual words directly from brain activity during single trial sound presentations. These findings reveal neural encoding mechanisms of speech acoustic parameters in higher order human auditory cortex.

Detecting event-related changes of multivariate phase coupling in dynamic brain networks

Authors:

• Ryan T. Canolty

• Charles F. Cadieu

• Kilian Koepsell

• Karunesh Ganguly

• Robert T. Knight

• Jose M. Carmena

Date: 2012

PubMed: 22236706

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Abstract:

Oscillatory phase coupling within large-scale brain networks is a topic of increasing interest within systems, cognitive, and theoretical neuroscience. Evidence shows that brain rhythms play a role in controlling neuronal excitability and response modulation, and regulate the efficacy of communication between cortical regions and distinct spatiotemporal scales. In this view, anatomically-connected brain areas form the scaffolding upon which neuronal oscillations rapidly create and dissolve transient functional networks. Importantly, testing these hypotheses requires methods designed to accurately reflect dynamic changes in multivariate phase coupling within brain networks. Unfortunately, phase coupling between neurophysiological signals is commonly investigated using suboptimal techniques. Here we describe how a recently-developed probabilistic model - Phase Coupling Estimation (PCE; Cadieu and Koepsell, 2010) - can be used to investigate changes in multivariate phase coupling, and we detail the advantages of this model over the commonly-employed phase-locking value (PLV). We show that the N-dimensional PCE is a natural generalization of the inherently bivariate PLV. Using simulations we show that PCE accurately captures both direct and indirect (network mediated) coupling between network elements in situations where PLV produces erroneous results. We present empirical results on recordings from humans and non-human primates and show that the PCE-estimated coupling values are different from those using the bivariate PLV. Critically on these empirical recordings, PCE output tends to be sparser than the PLVs, indicating fewer significant interactions and perhaps a more parsimonious description of the data. Finally, the physical interpretation of PCE parameters is straightforward: the PCE parameters correspond to interaction terms in a network of coupled oscillators. Forward modeling of a network of coupled oscillators with parameters estimated by PCE generates synthetic data with statistical characteristics identical to empirical signals. Given these advantages over the PLV, PCE is a useful tool for investigating multivariate phase coupling in distributed brain networks.