Direct evidence for prediction signals in frontal cortex independent of prediction error

ABSTRACT

Predictive coding (PC) has been suggested as one of the main mechanisms used by brains to interact with complex environments. PC theories posit top-down prediction signals, which are compared with actual outcomes, yielding in turn prediction error (PE) signals, which are used, bottom-up, to modify the ensuing predictions. However, disentangling prediction from PE signals has been challenging. Critically, while many studies found indirect evidence for PC in the form of PE signals, direct evidence for the prediction signal is mostly lacking. Here, we provide clear evidence, obtained from intracranial cortical recordings in human surgical patients, that the human lateral prefrontal cortex evinces prediction signals while anticipating an event. Patients listened to task-irrelevant sequences of repetitive tones including infrequent predictable or unpredictable pitch deviants. The broadband high-frequency amplitude (HFA) was decreased prior to the onset of expected relative to unexpected deviants in the frontal cortex only, and its amplitude was sensitive to the increasing likelihood of deviants following longer trains of standards in the unpredictable condition. Single-trial HFA predicted deviations and correlated with poststimulus response to deviations. These results provide direct evidence for frontal cortex prediction signals independent of PE signals.

AUTHORS

• Stefan Dürschmid

• Christoph Reichert

• Hermann Hinrichs

• Hans-Jochen Heinze

• Heidi E Kirsch

• Robert T Knight

• Leon Y Deouell

Date: 2018

DOI: 10.1093/cercor/bhy331

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Lesions to the fronto-parietal network impact alpha-band phase synchrony and cognitive control

Abstract:

Long-range phase synchrony in the α-oscillation band (near 10 Hz) has been proposed to facilitate information integration across anatomically segregated regions. Which areas may top-down regulate such cross-regional integration is largely unknown. We previously found that the moment-to-moment strength of high-α band (10–12 Hz) phase synchrony co-varies with activity in a fronto-parietal (FP) network. This network is critical for adaptive cognitive control functions such as cognitive flexibility required during set-shifting. Using electroencephalography (EEG) in 23 patients with focal frontal lobe lesions (resected tumors), we tested the hypothesis that the FP network is necessary for modulation of high-α band phase synchrony. Global phase-synchrony was measured using an adaptation of the phase-locking value (PLV) in a sliding window procedure, which allowed for measurement of changes in EEG-based resting-state functional connectivity across time. As hypothesized, the temporal modulation (range and standard deviation) of high-α phase synchrony was reduced as a function of FP network lesion extent, mostly due to dorsolateral prefrontal cortex (dlPFC) lesions. Furthermore, patients with dlPFC lesions exhibited reduced cognitive flexibility as measured by the Trail-Making Test (set-shifting). Our findings provide evidence that the FP network is necessary for modulatory control of high-α band long-range phase synchrony, and linked to cognitive flexibility.

Authors:

• Sepideh Sadaghiani

• Pascasie L Dombert

• Marianne Løvstad

• Ingrid Funderud

• Torstein R Meling

• Tor Endestad

• Robert T Knight

• Anne-Kristin Solbakk

• Mark D’Esposito

Date: 2018

DOI: 10.1093/cercor/bhy296

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Hippocampal CA1 gamma power predicts the precision of spatial memory judgments

Abstract:

The hippocampus plays a critical role in spatial memory. However, the exact neural mechanisms underlying high-fidelity spatial memory representations are unknown. We report findings from presurgical epilepsy patients with bilateral hippocampal depth electrodes performing an object-location memory task that provided a broad range of spatial memory precision. During encoding, patients were shown a series of objects along the circumference of an invisible circle. At test, the same objects were shown at the top of the circle (0°), and patients used a dial to move the object to its location shown during encoding. Angular error between the correct location and the indicated location was recorded as a continuous measure of performance. By registering pre- and postimplantation MRI scans, we were able to localize the electrodes to specific hippocampal subfields. We found a correlation between increased gamma power, thought to reflect local excitatory activity, and the precision of spatial memory retrieval in hippocampal CA1 electrodes. Additionally, we found a similar relationship between gamma power and memory precision in the dorsolateral prefrontal cortex and a directional relationship between activity in this region and in the CA1, suggesting that the dorsolateral prefrontal cortex is involved in postretrieval processing. These results indicate that local processing in hippocampal CA1 and dorsolateral prefrontal cortex supports high-fidelity spatial memory representations.

Authors:

• Rebecca F. Stevenson

• Jie Zheng

• Lilit Mnatsakanyan

• Sumeet Vadera

• Robert T. Knight

• Jack J. Lin

• Michael A. Yassa

Date: 2018

DOI: 10.1073/pnas.1805724115

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Encoding of multiple reward-related computations in transient and sustained high-frequency activity in human OFC

Abstract:

Human orbitofrontal cortex (OFC) has long been implicated in value-based decision making. In recent years, convergent evidence from human and model organisms has further elucidated its role in representing reward-related computations underlying decision making. However, a detailed description of these processes remains elusive due in part to (1) limitations in our ability to observe human OFC neural dynamics at the timescale of decision processes and (2) methodological and interspecies differences that make it challenging to connect human and animal findings or to resolve discrepancies when they arise. Here, we sought to address these challenges by conducting multi-electrode electrocorticography(ECoG) recordings in neurosurgical patients during economic decision making to elucidate the electrophysiological signature, sub-second temporal profile, and anatomical distribution of reward-related computations within human OFC. We found that high-frequency activity (HFA) (70–200 Hz) reflected multiple valuation components grouped in two classes of valuation signals that were dissociable in temporal profile and information content: (1) fast, transient responses reflecting signals associated with choice and outcome processing, including anticipated risk and outcome regret, and (2) sustained responses explicitly encoding what happened in the immediately preceding trial. Anatomically, these responses were widely distributed in partially overlapping networks, including regions in the central OFC (Brodmann areas 11 and 13), which have been consistently implicated in reward processing in animal single-unit studies. Together, these results integrate insights drawn from human and animal studies and provide evidence for a role of human OFC in representing multiple reward computations.

Authors:

• Ignacio Saez

• Jack Lin

• Arjen Stolk

• Edward Chang

• Josef Parvizi

• Gerwin Schalk

• Robert T. Knight

• Ming Hsu

Date: 2018

DOI: 10.1016/j.cub.2018.07.045

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Human posterior parietal cortex responds to visual stimuli as early as peristriate occipital cortex

ABSTRACT

Much of what is known about the timing of visual processing in the brain is inferred from intracranial studies in monkeys, with human data limited to mainly noninvasive methods with lower spatial resolution. Here, we estimated visual onset latencies from electrocorticographic (ECoG) recordings in a patient who was implanted with 112 subdural electrodes, distributed across the posterior cortex of the right hemisphere, for presurgical evaluation of intractable epilepsy. Functional MRI prior to surgery was used to determine boundaries of visual areas. The patient was presented with images of objects from several categories. Event‐related potentials (ERPs) were calculated across all categories excluding targets, and statistically reliable onset latencies were determined, using a bootstrapping procedure over the single trial baseline activity in individual electrodes. The distribution of onset latencies broadly reflected the known hierarchy of visual areas, with the earliest cortical responses in primary visual cortex, and higher areas showing later responses. A clear exception to this pattern was a robust, statistically reliable and spatially localized, very early response, on the bank of the posterior intraparietal sulcus (IPS). The response in the IPS started nearly simultaneously with responses detected in peristriate visual areas, around 60 ms poststimulus onset. Our results support the notion of early visual processing in the posterior parietal lobe, not respecting traditional hierarchies, and give direct evidence for onset times of visual responses across the human cortex.

AUTHORS

• Tamar I. Regev 

• Jonathan Winawer 

• Edden M. Gerber 

• Robert T. Knight 

• Leon Y. Deouell

Date: 2018

DOI: 10.1111/ejn.14164

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Neural mechanisms of sustained attention are rhythmic

ABSTRACT

Classic models of attention suggest that sustained neural firing constitutes a neural correlate of sustained attention. However, recent evidence indicates that behavioral performance fluctuates over time, exhibiting temporal dynamics that closely resemble the spectral features of ongoing, oscillatory brain activity. Therefore, it has been proposed that periodic neuronal excitability fluctuations might shape attentional allocation and overt behavior. However, empirical evidence to support this notion is sparse. Here, we address this issue by examining data from large-scale subdural recordings, using two different attention tasks that track perceptual ability at high temporal resolution. Our results reveal that perceptual outcome varies as a function of the theta phase even in states of sustained spatial attention. These effects were robust at the single-subject level, suggesting that rhythmic perceptual sampling is an inherent property of the frontoparietal attention network. Collectively, these findings support the notion that the functional architecture of top-down attention is intrinsically rhythmic.

AUTHORS

• Randolph F. Helfrich

• Ian C. Fiebelkorn

• Sara M. Szczepanski

• Jack J. Lin

• Josef Parvizi

• Robert T. Knight

• Sabine Kastner

Date: 2018

DOI: 10.1016/j.neuron.2018.07.032

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Lateral prefrontal cortex lesion impairs regulation of internally and externally directed attention

ABSTRACT

According to the competition account of lexical selection in word production, conceptually driven word retrieval involves the activation of a set of candidate words in left temporal cortex and competitive selection of the intended word from this set, regulated by frontal cortical mechanisms. However, the relative contribution of these brain regions to competitive lexical selection is uncertain. In the present study, five patients with left prefrontal cortex lesions (overlapping in ventral and dorsal lateral cortex), eight patients with left lateral temporal cortex lesions (overlapping in middle temporal gyrus), and 13 matched controls performed a picture-word interference task. Distractor words were semantically related or unrelated to the picture, or the name of the picture (congruent condition). Semantic interference (related vs. unrelated), tapping into competitive lexical selection, was examined. An overall semantic interference effect was observed for the control and left-temporal groups separately. The left-frontal patients did not show a reliable semantic interference effect as a group. The left-temporal patients had increased semantic interference in the error rates relative to controls. Error distribution analyses indicated that these patients had more hesitant responses for the related than for the unrelated condition. We propose that left middle temporal lesions affect the lexical activation component, making lexical selection more susceptible to errors.

AUTHORS

• Julia W.Y. Kam

• Anne-Kristin Solbakk

• Tor Endestad

• Torstein R. Meling

• Robert T. Knight

Date: 2018

DOI: 10.1016/j.neuroimage.2018.03.063

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Integrated analysis of anatomical and electrophysiological human intracranial data

ABSTRACT

Human intracranial electroencephalography (iEEG) recordings provide data with much greater spatiotemporal precision than is possible from data obtained using scalp EEG, magnetoencephalography (MEG), or functional MRI. Until recently, the fusion of anatomical data (MRI and computed tomography (CT) images) with electrophysiological data and their subsequent analysis have required the use of technologically and conceptually challenging combinations of software. Here, we describe a comprehensive protocol that enables complex raw human iEEG data to be converted into more readily comprehensible illustrative representations. The protocol uses an open-source toolbox for electrophysiological data analysis (FieldTrip). This allows iEEG researchers to build on a continuously growing body of scriptable and reproducible analysis methods that, over the past decade, have been developed and used by a large research community. In this protocol, we describe how to analyze complex iEEG datasets by providing an intuitive and rapid approach that can handle both neuroanatomical information and large electrophysiological datasets. We provide a worked example using an example dataset. We also explain how to automate the protocol and adjust the settings to enable analysis of iEEG datasets with other characteristics. The protocol can be implemented by a graduate student or postdoctoral fellow with minimal MATLAB experience and takes approximately an hour to execute, excluding the automated cortical surface extraction.

AUTHORS

• Arjen Stolk

• Sandon Griffin

• Roemer van der Meij

• Callum Dewar

• Ignacio Saez

• Jack J. Lin

• Giovanni Piantoni

• Jan-Mathijs Schoffelen

• Robert T. Knight 

• Robert Oostenveld 

Date: 2018

DOI: 10.1038/s41596-018-0009-6

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Human in vivo tau pathology, impaired NREM sleep oscillations and memory decline in aging

Abstract:

Aging disrupts sleep. Moreover, these sleep impairments are exaggerated in Alzheimer’s disease, and are proposed to contribute to cognitive decline. Recent human studies have linked β-amyloid with non-rapid eye-movement (NREM) sleep disruption. However, the impact of tau pathology on human sleep oscillations and cognition remains uninvestigated. Here, we tested the hypothesis that tau burden within medial temporal lobe (MTL) impairs the coupled relationship between the two key NREM sleep oscillations—sleep spindles and slow waves, and their known support of hippocampal memory.

Authors:

• Joseph R. Winer

• Bryce A. Mander

• Randolph F. Helfrich

• Anne Maass

• Theresa M. Harrison

• Suzanne L. Baker

• Robert T. Knight

• William J. Jagust

• Matthew P. Walker

Date: 2018

DOI: 10.1016/j.jalz.2018.06.2344

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Multiplexing of Theta and Alpha Rhythms in the Amygdala-Hippocampal Circuit Supports Pattern Separation of Emotional Information

ABSTRACT

How do we remember emotional events? While emotion often leads to vivid recollection, the precision of emotional memories can be degraded, especially when discriminating among overlapping experiences in memory (i.e. pattern separation). Communication between the amygdala and the hippocampus has been proposed to support emotional memory but the exact neural mechanisms are not well understood. Here, we used intracranial depth electrode recordings in pre-surgical epilepsy patients to show that successful pattern separation of emotional stimuli is associated with theta band (3-7 Hz)-coordinated bidirectional interactions between the amygdala and the hippocampus. In contrast, we show that overgeneralization is associated with alpha band (7-13 Hz)-coordinated unidirectional influence from the amygdala to the hippocampus. These findings imply that alpha band synchrony may trigger overgeneralization of similar emotional events via amygdala-hippocampal directional coupling, which suggests a target for the treatment of psychiatric conditions such as post-traumatic stress disorder, where aversive memories are often overgeneralized.

AUTHORS

• Jie Zheng

• Rebecca F. Stevenson

• Bryce A. Mander

• Lilit Mnatsakanyan

• Frank P. K. Hsu

• Sumeet Vadera

• Robert T. Knight

• Michael A. Yassa

• Jack J. Lin

Date: 2018

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A lexical semantic hub for heteromodal naming in middle fusiform gyrus

ABSTRACT

Semantic memory underpins our understanding of objects, people, places, and ideas. Anomia, a disruption of semantic memory access, is the most common residual language disturbance and is seen in dementia and following injury to temporal cortex. While such anomia has been well characterized by lesion symptom mapping studies, its pathophysiology is not well understood. We hypothesize that inputs to the semantic memory system engage a specific heteromodal network hub that integrates lexical retrieval with the appropriate semantic content. Such a network hub has been proposed by others, but has thus far eluded precise spatiotemporal delineation. This limitation in our understanding of semantic memory has impeded progress in the treatment of anomia. We evaluated the cortical structure and dynamics of the lexical semantic network in driving speech production in a large cohort of patients with epilepsy using electrocorticography (n = 64), functional MRI (n = 36), and direct cortical stimulation (n = 30) during two generative language processes that rely on semantic knowledge: visual picture naming and auditory naming to definition. Each task also featured a non-semantic control condition: scrambled pictures and reversed speech, respectively. These large-scale data of the left, language-dominant hemisphere uniquely enable convergent, high-resolution analyses of neural mechanisms characterized by rapid, transient dynamics with strong interactions between distributed cortical substrates. We observed three stages of activity during both visual picture naming and auditory naming to definition that were serially organized: sensory processing, lexical semantic processing, and articulation. Critically, the second stage was absent in both the visual and auditory control conditions. Group activity maps from both electrocorticography and functional MRI identified heteromodal responses in middle fusiform gyrus, intraparietal sulcus, and inferior frontal gyrus; furthermore, the spectrotemporal profiles of these three regions revealed coincident activity preceding articulation. Only in the middle fusiform gyrus did direct cortical stimulation disrupt both naming tasks while still preserving the ability to repeat sentences. These convergent data strongly support a model in which a distinct neuroanatomical substrate in middle fusiform gyrus provides access to object semantic information. This under-appreciated locus of semantic processing is at risk in resections for temporal lobe epilepsy as well as in trauma and strokes that affect the inferior temporal cortex—it may explain the range of anomic states seen in these conditions. Further characterization of brain network behaviour engaging this region in both healthy and diseased states will expand our understanding of semantic memory and further development of therapies directed at anomia.

AUTHORS

• Kiefer J. Forseth 

• Cihan M. Kadipasaoglu

• Christopher R. Conner

• Gregory Hickok 

• Robert T. Knight 

• Nitin Tandon

Date: 2018

DOI: 10.1093/brain/awy120

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Decoding Inner Speech Using Electrocorticography: Progress and Challenges Toward a Speech Prosthesis

ABSTRACT

Certain brain disorders resulting from brainstem infarcts, traumatic brain injury, cerebral palsy, stroke, and amyotrophic lateral sclerosis, limit verbal communication despite the patient being fully aware. People that cannot communicate due to neurological disorders would benefit from a system that can infer internal speech directly from brain signals. In this review article, we describe the state of the art in decoding inner speech, ranging from early acoustic sound features, to higher order speech units. We focused on intracranial recordings, as this technique allows monitoring brain activity with high spatial, temporal, and spectral resolution, and therefore is a good candidate to investigate inner speech. Despite intense efforts, investigating how the human cortex encodes inner speech remains an elusive challenge, due to the lack of behavioral and observable measures. We emphasize various challenges commonly encountered when investigating inner speech decoding, and propose potential solutions in order to get closer to a natural speech assistive device.

AUTHORS

• Stephanie Martin

• Iñaki Iturrate

• José del R. Millán

• Robert T. Knight

• Brian N. Pasley

Date: 2018

DOI: 10.3389/fnins.2018.00422

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Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke

ABSTRACT

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation.

AUTHORS

• Dhakshin S. Ramanathan

• Ling Guo

• Tanuj Gulati

• April K. Hishinuma

• Seok-Joon Won

• Robert T. Knight

• Edward F. Chang

• Raymond A. Swanson

• Karunesh Ganguly

Date: 2018

DOI: 10.1038/s41591-018-0058-y

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Orbitofrontal damage reduces auditory sensory response in humans

AUTHORS

• Julia W.Y. Kam

• Anne-Kristin Solbakk

• Ingrid Funderud

• Tor Endestad

• Torstein R. Meling

• Robert T. Knight

Date: 2017

DOI: 10.1016/j.cortex.2017.12.023.

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Dynamic frontotemporal systems process space and time in working memory

ABSTRACT

How do we rapidly process incoming streams of information in working memory, a cognitive mechanism central to human behavior? Dominant views of working memory focus on the prefrontal cortex (PFC), but human hippocampal recordings provide a neurophysiological signature distinct from the PFC. Are these regions independent, or do they interact in the service of working memory? We addressed this core issue in behavior by recording directly from frontotemporal sites in humans performing a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. Theta band oscillations drove bidirectional interactions between the PFC and medial temporal lobe (MTL; including the hippocampus). MTL theta oscillations directed the PFC preferentially during the processing of spatiotemporal information, while PFC theta oscillations directed the MTL for all types of information being processed in working memory. These findings reveal an MTL theta mechanism for processing space and time and a domain-general PFC theta mechanism, providing evidence that rapid, dynamic MTL–PFC interactions underlie working memory for everyday experiences.

AUTHORS

• Elizabeth L. Johnson

• Jenna N. Adams

• Anne-Kristin Solbakk

• Tor Endestad

• Pål G. Larsson

• Jugoslav Ivanovic

• Torstein R. Meling

• Jack J. Lin

• Robert T. Knight

Date: 2018

DOI: 10.1371/journal.pbio.2004274

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Old brains come uncoupled in sleep: slow wave-spindle synchrony, brain atrophy, and forgetting

ABSTRACT

The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults. Directional cross-frequency coupling analyses demonstrated that the slow wave governs a precise temporal coordination of sleep spindles, the quality of which predicts overnight memory retention. Moreover, selective atrophy within the medial frontal cortex in older adults predicted a temporal dispersion of this slow wave-spindle coupling, impairing overnight memory consolidation and leading to forgetting. Prefrontal-dependent deficits in the spatiotemporal coordination of NREM sleep oscillations therefore represent one pathway explaining age-related memory decline.

AUTHORS

• Randolph F. Helfrich

• Bryce A. Mander

• William J. Jagust

• Robert T. Knight

• Matthew P. Walker

Date: 2018

DOI: 10.1016/j.neuron.2017.11.020

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