Persistent neuronal activity in human prefrontal cortex links perception and action

ABSTRACT

How do humans flexibly respond to changing environmental demands on a subsecond temporal scale? Extensive research has highlighted the key role of the prefrontal cortex in flexible decision-making and adaptive behaviour, yet the core mechanisms that translate sensory information into behaviour remain undefined. Using direct human cortical recordings, we investigated the temporal and spatial evolution of neuronal activity (indexed by the broadband gamma signal) in 16 participants while they performed a broad range of self-paced cognitive tasks. Here we describe a robust domain- and modality-independent pattern of persistent stimulus-to-response neural activation that encodes stimulus features and predicts motor output on a trial-by-trial basis with near-perfect accuracy. Observed across a distributed network of brain areas, this persistent neural activation is centred in the prefrontal cortex and is required for successful response implementation, providing a functional substrate for domain-general transformation of perception into action, critical for flexible behaviour.

AUTHORS

• Matar Haller

• John Case

• Nathan E. Crone

• Edward F. Chang

• David King-Stephens

• Kenneth D. Laxer

• Peter B. Weber

• Josef Parvizi

• Robert T. Knight

• Avgusta Y. Shestyuk

Date: 2017

DOI: 10.1038/s41562-017-0267-2

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Lesion evidence for a critical role of left posterior but not frontal areas in alpha–beta power decreases during context-driven word production

ABSTRACT

Different frequency bands in the electroencephalogram are postulated to support distinct language functions. Studies have suggested that alpha-beta power decreases may index word-retrieval processes. In context-driven word retrieval, participants hear lead-in sentences that either constrain the final word ('He locked the door with the') or not ('She walked in here with the'). The last word is shown as a picture to be named. Previous studies have consistently found alpha-beta power decreases prior to picture onset for constrained relative to unconstrained sentences, localised to the left lateral-temporal and lateral-frontal lobes. However, the relative contribution of temporal versus frontal areas to alpha-beta power decreases is unknown. We recorded the electroencephalogram from patients with stroke lesions encompassing the left lateral-temporal and inferior-parietal regions or left-lateral frontal lobe and from matched controls. Individual participant analyses revealed a behavioural sentence context facilitation effect in all participants, except for in the two patients with extensive lesions to temporal and inferior parietal lobes. We replicated the alpha-beta power decreases prior to picture onset in all participants, except for in the two same patients with extensive posterior lesions. Thus, whereas posterior lesions eliminated the behavioural and oscillatory context effect, frontal lesions did not. Hierarchical clustering analyses of all patients' lesion profiles, and behavioural and electrophysiological effects identified those two patients as having a unique combination of lesion distribution and context effects. These results indicate a critical role for the left lateral-temporal and inferior parietal lobes, but not frontal cortex, in generating the alpha-beta power decreases underlying context-driven word production.

AUTHORS

• Vitoria Piai

• Joost Rommers

• Robert T. Knight

Date: 2017

DOI: 10.1111/ejn.13695

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Should a Few Null Findings Falsify Prefrontal Theories of Conscious Perception?

ABSTRACT

Is activity in prefrontal cortex (PFC) critical for conscious perception? Major theories of consciousness make distinct predictions about the role of PFC, providing an opportunity to arbitrate between these views empirically. Here we address three common misconceptions: (1) PFC lesions do not affect subjective perception; (2) PFC activity does not reflect specific perceptual content; and (3) PFC involvement in studies of perceptual awareness is solely driven by the need to make reports required by the experimental tasks rather than subjective experience per se. These claims are incompatible with empirical findings, unless one focuses only on studies using methods with limited sensitivity. The literature highlights PFC's essential role in enabling the subjective experience in perception, contra the objective capacity to perform visual tasks; conflating the two can also be a source of confusion.

AUTHORS

• Brian Odegaard

• Robert T. Knight 

• Hakwan Lau

Date: 2017

DOI: 10.1523/JNEUROSCI.3217-16.2017

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Prefrontal cortex modulates posterior alpha oscillations during top-down guided visual perception

ABSTRACT

Conscious visual perception is proposed to arise from the selective synchronization of functionally specialized but widely distributed cortical areas. It has been suggested that different frequency bands index distinct canonical computations. Here, we probed visual perception on a fine-grained temporal scale to study the oscillatory dynam- ics supporting prefrontal-dependent sensory processing. We tested whether a predictive context that was embedded in a rapid visual stream modulated the perception of a subsequent near-threshold target. The rapid stream was presented either rhythmically at 10 Hz, to entrain parietooccipital alpha oscillations, or arrhythmically. We identified a 2- to 4-Hz delta signature that modulated posterior alpha activity and behavior during predictive trials. Importantly, delta-mediated top-down control diminished the behavioral effects of bottom-up alpha entrainment. Simultaneous source-reconstructed EEG and cross-frequency directionality analyses revealed that this delta activity originated from prefrontal areas and modulated posterior alpha power. Taken together, this study presents converging behavioral and electrophysiological evidence for frontal delta-mediated top-down control of posterior alpha activity, selectively facilitating visual perception.

AUTHORS

• Randolph F. Helfrich

• Melody Huang

• Guy Wilson

• Robert T. Knight

Date: 2017

DOI: 10.1073/pnas.1705965114

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Working memory replay prioritizes weakly attended events

ABSTRACT

One view of working memory posits that maintaining a series of events requires their sequential and equal mnemonic replay. Another view is that the content of working memory maintenance is prioritized by attention. We decoded the dynamics for retaining a sequence of items using magnetoencephalography, wherein participants encoded sequences of three stimuli depicting a face, a manufactured object, or a natural item and maintained them in working memory for 5000 ms. Memory for sequence position and stimulus details were probed at the end of the maintenance period. Decoding of brain activity revealed that one of the three stimuli dominated maintenance independent of its sequence position or category; and memory was enhanced for the selectively replayed stimulus. Analysis of event-related responses during the encoding of the sequence showed that the selectively replayed stimuli were determined by the degree of attention at encoding. The selectively replayed stimuli had the weakest initial encoding indexed by weaker visual attention signals at encoding. These findings do not rule out sequential mnemonic replay but reveal that attention influences the content of working memory maintenance by prioritizing replay of weakly encoded events. We propose that the prioritization of weakly encoded stimuli protects them from interference during the maintenance period, whereas the more strongly encoded stimuli can be retrieved from long-term memory at the end of the delay period.

AUTHORS

• Anna Jafarpour

• Will D. Penny

• Gareth Barnes

• Robert T. Knight

• Emrah Duzel

Date: 2017

DOI: http://dx.doi.org/10.1523/ENEURO.0171-17.2017

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Cortical Representation of Persistent Visual Stimuli

Abstract:

Research into visual neural activity has focused almost exclusively on onset- or change-driven responses and little is known about how information is encoded in the brain during sustained periods of visual perception. We used intracranial recordings in humans to determine the degree to which the presence of a visual stimulus is persistently encoded by neural activity. The correspondence between stimulus duration and neural response duration was strongest in early visual cortex and gradually diminished along the visual hierarchy, such that is was weakest in inferior-temporal category-selective regions. A similar posterior-anterior gradient was found within inferior temporal face-selective regions, with posterior but not anterior sites showing persistent face-selective activity. The results suggest that regions that appear uniform in terms of their category selectivity are dissociated by how they temporally represent a stimulus in support of ongoing visual perception, and delineate a large-scale organizing principle of the ventral visual stream.

Authors:

• Edden M. Gerber

• Tal Golan

• Robert T. Knight

• Leon Y. Deouell

Date: 2017

DOI: http://dx.doi.org/10.1016/j.neuroimage.2017.08.028

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Human hippocampal pre-activation predicts behavior

ABSTRACT

The response to an upcoming salient event is accelerated when the event is expected given the preceding events – i.e. a temporal context effect. For example, naming a picture following a strongly constraining temporal context is faster than naming a picture after a weakly constraining temporal context. We used sentences as naturalistic stimuli to manipulate expectations on upcoming pictures without prior training. Here, using intracranial recordings from the human hippocampus we found more power in the high-frequency band prior to high-expected pictures than weakly expected ones. We applied pattern similarity analysis on the temporal pattern of hippocampal high-frequency band activity in single hippocampal contacts. We found that greater similarity in the pattern of hippocampal field potentials between pre-picture interval and expected picture interval in the high-frequency band predicted picture-naming latencies. Additional pattern similarity analysis indicated that the hippocampal representations follow a semantic map. The results suggest that hippocampal pre- activation of expected stimuli is a facilitating mechanism underlying the powerful contextual behavioral effect.

AUTHORS

• Robert T. Knight

• Anna Jafarpour

• Vitoria Piai

• Jack J. Lin

Date: 2017

DOI: 10.1038/s41598-017-06477-5

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Anterior thalamic high frequency band activity is coupled with theta oscillations at rest

ABSTRACT

Cross-frequency coupling (CFC) between slow and fast brain rhythms, in the form of phase–amplitude coupling (PAC), is proposed to enable the coordination of neural oscillatory activity required for cognitive processing. PAC has been identified in the neocortex and mesial temporal regions, varying according to the cognitive task being performed and also at rest. PAC has also been observed in the anterior thalamic nucleus (ATN) during memory processing. The thalamus is active during the resting state and has been proposed to be involved in switching between task-free cognitive states such as rest, in which attention is internally-focused, and externally-focused cognitive states, in which an individual engages with environmental stimuli. It is unknown whether PAC is an ongoing phenomenon during the resting state in the ATN, which is modulated during different cognitive states, or whether it only arises during the performance of specific tasks. We analyzed electrophysiological recordings of ATN activity during rest from seven patients who received thalamic electrodes implanted for treatment of pharmacoresistant focal epilepsy. PAC was identified between theta (4–6 Hz) phase and high frequency band (80–150 Hz) amplitude during rest in all seven patients, which diminished during engagement in tasks involving an external focus of attention. The findings are consistent with the proposal that theta–gamma coupling in the ATN is an ongoing phenomenon, which is modulated by task performance.

AUTHORS

• Catherine M. Sweeney-Reed

• Tino Zauhle

• Jürgen Voges

• Friedhelm Schmitt

• Lars Buentjen

• Viola Borchardt

• Hermann Hinrichs

• Hans-Jochen Heinze

• Michael D. Rugg

• Robert T. Knight

Date: 2017

DOI: 10.3389/fnhum.2017.00358

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Bidirectional frontoparietal oscillatory systems support working memory

ABSTRACT

The ability to represent and select information in working memory provides the neurobiological infrastructure for human cognition. For 80 years, dominant views of working memory have focused on the key role of prefrontal cortex (PFC). However, more recent work has implicated posterior cortical regions, suggesting that PFC engagement during working memory is dependent on the degree of executive demand. We provide evidence from neurological patients with discrete PFC damage that challenges the dominant models attributing working memory to PFC-dependent systems. We show that neural oscillations, which provide a mechanism for PFC to communicate with posterior cortical regions, independently subserve communications both to and from PFC—uncovering parallel oscillatory mechanisms for working memory. Fourteen PFC patients and 20 healthy, age-matched controls performed a working memory task where they encoded, maintained, and actively processed information about pairs of common shapes. In controls, the electroencephalogram (EEG) exhibited oscillatory activity in the low-theta range over PFC and directional connectivity from PFC to parieto-occipital regions commensurate with executive processing demands. Concurrent alpha-beta oscillations were observed over parieto-occipital regions, with directional connectivity from parieto-occipital regions to PFC, regardless of processing demands. Accuracy, PFC low-theta activity, and PFC / parieto-occipital connectivity were attenuated in patients, revealing a PFC-independent, alpha-beta system. The PFC patients still demonstrated task proficiency, which indicates that the posterior alpha-beta system provides sufficient resources for working memory. Taken together, our findings reveal neurologically dissociable PFC and parieto-occipital systems and suggest that parallel, bidirectional oscillatory systems form the basis of working memory.

AUTHORS

• Elizabeth L. Johnson

• Callum Dewar

• Anne-Kristin Solbakk

• Tor Endestad

• Torstein Meling

• Robert T. Knight

Date: 2017

DOI: 10.1016/j.cub.2017.05.046

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Neuroplasticity of language in left-hemisphere stroke: evidence linking subsecond electrophysiology and structural connections

ABSTRACT

The understanding of neuroplasticity following stroke is predominantly based on neuroimaging measures that cannot address the subsecond neurodynamics of impaired language processing. We combined behavioral and electrophysiological measures and structural-connectivity estimates to characterize neuroplasticity underlying successful compensation of language abilities after left-hemispheric stroke. We recorded the electroencephalogram from patients with stroke lesions to the left temporal lobe and from matched controls during context-driven word retrieval. Participants heard lead-in sentences that either constrained the final word (“He locked the door with the”) or not (“She walked in here with the”). The last word was shown as a picture to be named. Individual-participant analyses were conducted, focusing on oscillatory power as a subsecond indicator of a brain region’s functional neurophysiological computations. All participants named pictures faster following constrained than unconstrained sentences, except for two patients, who had extensive damage to the left temporal lobe. Left-lateralized alpha–beta oscillatory power decreased in controls pre-picture presentation for constrained relative to unconstrained contexts. In patients, the alpha–beta power decreases were observed with the same time course as in controls but were lateralized to the intact right hemisphere. The right lateralization depended on the probability of white-matter connections between the bilateral temporal lobes. The two patients who performed poorly behaviorally showed no alpha–beta power decreases. Our findings suggest that incorporating direct measures of neural activity into investigations of neuroplasticity can provide important neural markers to help predict language recovery, assess the progress of neurorehabilitation, and delineate targets for therapeutic neuromodulation.

AUTHORS

• Vitoria Piai

• Lars Meyer

• Nina F. Dronkers

• Robert T. Knight

Date: 2017

DOI: 10.1002/hbm.23581

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Instantaneous voltage as an alternative to power- and phase-based interpretation of oscillatory brain activity

Abstract

For decades, oscillatory brain activity has been characterized primarily by measurements of power and phase. While many studies have linked those measurements to cortical excitability, their relationship to each other and to the physiological underpinnings of excitability is unclear. The recently proposed Function-through-Biased- Oscillations (FBO) hypothesis (Schalk, 2015) addressed these issues by suggesting that the voltage potential at the cortical surface directly reflects the excitability of cortical populations, that this voltage is rhythmically driven away from a low resting potential (associated with depolarized cortical populations) towards positivity (associated with hyperpolarized cortical populations). This view explains how oscillatory power and phase together influence the instantaneous voltage potential that directly regulates cortical excitability. This implies that the alternative measurement of instantaneous voltage of oscillatory activity should better predict cortical excitability compared to either of the more traditional measurements of power or phase. Using electrocorticographic (ECoG) data from 28 human subjects, the results of our study confirm this prediction: compared to oscillatory power and phase, the instantaneous voltage explained 20% and 31% more of the variance in broadband gamma, respectively, and power and phase together did not produce better predictions than the instantaneous voltage. These results synthesize the previously separate power- and phase-based interpretations and associate oscillatory activity directly with a physiological interpretation of cortical excitability. This alternative view has implications for the interpretation of studies of oscillatory activity and for current theories of cortical information transmission.

Authors

• Gerwin Schalk

• Joshua Marple

• Robert T. Knight

• William G. Coon

Date: 2017

DOI: 10.1016/j.neuroimage.2017.06.01

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Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity

ABSTRACT

Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70–150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain.

AUTHORS

• Stephanie Ries

• Rhummit K. Dhillon

• Alex Clarke

• David King-Stephens

• Kenneth Laxer

• Peter Weber

• Rachel A. Kuperman

• Kurtis I. Auguste

• Peter Brunner

• Gerwin Schalk

• Jack J. Lin

• Josef Parvizi

• Nathan E. Crone

• Nina F. Dronkers

• Robert T. Knight

Date: 2017

DOI: 10.1073/pnas.1620669114

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Effects of prefrontal cortex damage on emotion understanding: EEG and behavioural evidence

ABSTRACT

Humans are highly social beings that interact with each other on a daily basis. In these complex interactions, we get along by being able to identify others’ actions and infer their intentions, thoughts and feelings. One of the major theories accounting for this critical ability assumes that the understanding of social signals is based on a primordial tendency to simulate observed actions by activating a mirror neuron system. If mirror neuron regions are important for action and emotion recognition, damage to regions in this network should lead to deficits in these domains. In the current behavioural and EEG study, we focused on the lateral prefrontal cortex including dorsal and ventral prefrontal cortex and utilized a series of task paradigms, each measuring a different aspect of recognizing others’ actions or emotions from body cues. We examined 17 patients with lesions including (n = 8) or not including (n = 9) the inferior frontal gyrus, a core mirror neuron system region, and compared their performance to matched healthy control subjects (n = 18), in behavioural tasks and in an EEG observation—execution task measuring mu suppression. Our results provide support for the role of the lateral prefrontal cortex in understanding others’ emotions, by showing that even unilateral lesions result in deficits in both accuracy and reaction time in tasks involving the recognition of others’ emotions. In tasks involving the recognition of actions, patients showed a general increase in reaction time, but not a reduction in accuracy. Deficits in emotion recognition can be seen by either direct damage to the inferior frontal gyrus, or via damage to dorsal lateral prefrontal cortex regions, resulting in deteriorated performance and less EEG mu suppression over sensorimotor cortex.

AUTHORS

• Anat Perry

• Samantha N. Saunders

• Jennifer Stiso

• Callum Dewar

• James Lubell

• Torstein Meling

• Anne-Kristin Solbakk

• Tor Endestad

• Robert T. Knight

Date: 2017

DOI: 10.1093/brain/awx031

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Amygdala-hippocampal dynamics during salient information processing

ABSTRACT

Recognizing motivationally salient information is critical to guiding behaviour. The amygdala and hippocampus are thought to support this operation, but the circuit-level mechanism of this interaction is unclear. We used direct recordings in the amygdala and hippocampus from human epilepsy patients to examine oscillatory activity during processing of fearful faces compared with neutral landscapes. We report high gamma (70–180 Hz) activation for fearful faces with earlier stimulus evoked onset in the amygdala compared with the hippocampus. Attending to fearful faces compared with neutral landscape stimuli enhances low-frequency coupling between the amygdala and the hippocampus. The interaction between the amygdala and hippocampus is largely unidirectional, with theta/alpha oscillations in the amygdala modulating hippocampal gamma activity. Granger prediction, phase slope index and phase lag analysis corroborate this directional coupling. These results demonstrate that processing emotionally salient events in humans engages an amygdala-hippocampal network, with the amygdala influencing hippocampal dynamics during fear processing.

AUTHORS

• Robert T. Knight

• Avgusta Shestyuk

• Kristopher L. Anderson

• Jie Zheng

• Stephanie L. Leal

• Gultekin Gulsen

• Lilit Mnatsakanyan

• Sumeet Vadera

• Frank P.K. Hsu

• Michael A. Yassa

• Jack J. Lin

Date: 2017

DOI: 10.1038/ncomms14413

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Mirroring in the Human Brain: Deciphering the Spatial-Temporal Patterns of the Human Mirror Neuron System

ABSTRACT

Embodied theories of cognition emphasize the central role of sensorimotor transformations in the representation of others’ actions. Support for these theories is derived from the discovery of the mirror neuron system (MNS) in primates, from noninvasive techniques in humans, and from a limited number of intracranial studies. To understand the neural dynamics of the human MNS, more studies with precise spatial and temporal resolutions are essential. We used electrocorticography to define activation patterns in sensorimotor, parietal and/or frontal neuronal populations, during a viewing and grasping task. Our results show robust high gamma activation for both conditions in classic MNS sites. Furthermore, we provide novel evidence for 2 different populations of neurons: sites that were only active for viewing and grasping (“pure mirroring”) and sites that were also active between viewing and grasping, and perhaps serve a more general attentional role. Lastly, a subgroup of parietal electrodes showed earlier peaks than all other regions. These results highlight the complexity of spatial-temporal patterns within the MNS and provide a critical link between single-unit research in monkeys and noninvasive techniques in human.

AUTHORS

• Anat Perry

• Jennifer Stiso

• Edward F Chang

• Jack J Lin

• Josef Parvizi

• Robert T Knight

Date: 2017

DOI: 10.1093/cercor/bhx013

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Bringing Kids into the Scientific Review Process

ABSTRACT

Frontiers for Young Minds puts kids in charge of scientific publications by having them control the review process. This provides kids the ability to shape the way science is taught and to better understand the scientific method.

AUTHORS

• Robert T. Knight

• Sabine Kastner

Date: 2017

DOI: http://dx.doi.org/10.1016/j.neuron.2016.12.002

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