2014

Corticothalamic phase synchrony and cross-frequency coupling predict human memory formation

Authors:

  • Catherine M. Sweeney-Reed

  • Tino Zaehle

  • Jürgen Voges

  • Friedhelm Schmitt

  • Lars Buentjen

  • Klaus Kopitzki

  • Christine Esslinger

  • Hermann Hinrichs

  • Hans-Jochen Heinze

  • Robert T. Knight

  • Alan Richardson-Klavehn

Date: 2014

DOI: 10.7554/eLife.05352.001

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Abstract:

The anterior thalamic nucleus (ATN) is thought to play an important role in a brain network involving the hippocampus and neocortex, which enables human memories to be formed. However, its small size and location deep within the brain have impeded direct investigation in humans with non-invasive techniques. Here we provide direct evidence for a functional role for the ATN in memory formation from rare simultaneous human intrathalamic and scalp electroencephalogram (EEG) recordings from eight volunteering patients receiving intrathalamic electrodes implanted for the treatment of epilepsy, demonstrating real-time communication between neocortex and ATN during successful memory encoding. Neocortical-ATN theta oscillatory phase synchrony of local field potentials and neocortical-theta-to-ATN-gamma cross-frequency coupling during presentation of complex photographic scenes predicted later memory for the scenes, demonstrating a key role for the ATN in human memory encoding.

Before it is too late: Addressing professional responsibility in late-onset Alzheimer's dementia research and pre symptomatic prediction

Authors:

  • Silke Schichtanz

  • Mark Schweda

  • Jesse Ballenger

  • Patrick J. Fox

  • Jodi Halpern

  • J. Kramer

  • Guy Micco

  • Stephen G. Post

  • Charis Thompson

  • Robert T. Knight

  • William Jagust

Date: 2014

DOI: 10.3389/fnhum.2014.00921

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Abstract:

The development of a wide array of molecular and neuroscientific biomarkers can provide the possibility to visualize the course of Alzheimer’s disease (AD) at early stages. Many of these biomarkers are aimed at detecting not only a preclinical, but also a pre-symptomatic state. They are supposed to facilitate clinical trials aiming at treatments that attack the disease at its earliest stage or even prevent it. The increasing number of such biomarkers currently tested and now partly proposed for clinical implementation calls for critical reflection on their aims, social benefits, and risks. This position paper summarizes major challenges and responsibilities. Its focus is on the ethical and social problems involved in the organization and application of dementia research, as well as in healthcare provision from a cross-national point of view. The paper is based on a discussion of leading dementia experts from neuroscience, neurology, social sciences, and bioethics in the United States and Europe. It thus reflects a notable consensus across various disciplines and national backgrounds. We intend to initiate a debate on the need for actions within the researchers’ national and international communities.

Damage to dorsolateral prefrontal cortex diminishes the impact of honesty motives on altruistic giving


Authors:

  • Lusha Zhu

  • Adrianna C. Jenkins

  • Eric Set

  • Robert T. Knight

  • Pearl H. Chiu

  • B.R. King-Casas

  • Ming Hsu

Date: 2014

DOI: 10.1038/nn.3798

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Abstract:

Substantial correlational evidence suggests that prefrontal regions are critical to honest and dishonest behavior, but causal evidence specifying the nature of this involvement remains absent. We found that lesions of the human dorsolateral prefrontal cortex (DLPFC) decreased the effect of honesty concerns on behavior in economic games that pit honesty motives against self-interest, but did not affect decisions when honesty concerns were absent. These results point to a causal role for DLPFC in honest behavior.

Double Dissociation of the roles of the left and right prefrontal cortices in anticipatory regulation of action

Authors:

  • Stephanie Ries

  • Ian Greenhouse

  • Nina F. Dronkers

  • Kathleen Y. Haaland

  • Robert T. Knight

Date: 2014

DOI: 10.1016/j.neuropsychologia.2014.08.026

PubMed: 25201047

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Abstract:

Recent actions can benefit or disrupt our current actions and the prefrontal cortex (PFC) is thought to play a major role in the regulation of these actions before they occur. The left PFC has been associated with overcoming interference from past events in the context of language production and working memory. The right PFC, and especially the right IFG, has been associated with preparatory inhibition processes. But damage to the right PFC has also been associated with impairment in sustaining actions in motor intentional disorders. Moreover, bilateral dorsolateral PFC has been associated with the ability to maintain task-sets, and improve the performance of current actions based on previous experience. However, potential hemispheric asymmetries in anticipatory regulation of action have not yet been delineated. In the present study, patients with left (n=7) vs. right (n=6) PFC damage due to stroke and 14 aged- and education-matched controls performed a picture naming and a verbal Simon task (participants had to say "right" or "left" depending on the color of the picture while ignoring its position). In both tasks, performance depended on the nature of the preceding trial, but in different ways. In the naming task, performance decreased if previous pictures were from the same rather than from different semantic categories (i.e., semantic interference effect). In the Simon task, performance was better for both compatible (i.e., response matching the position of the stimulus) and incompatible trials when preceded by a trial of the same compatibility (i.e. Gratton effect) relative to sequential trials of different compatibility. Left PFC patients were selectively impaired in picture naming; they had an increased semantic interference effect compared to both right PFC patients and aged-matched controls. Conversely, right PFC patients were selectively impaired in the Simon task compared to controls or left PFC patients; they showed no benefit when sequential trials were compatible (cC vs. iC trials) or a decreased Gratton effect. These results provide evidence for a double dissociation between left and right PFC in the anticipatory regulation of action. Our results are in agreement with a preponderant role of the left PFC in overcoming proactive interference from competing memory representations and provide evidence that the right PFC, plays a role in sustaining goal-directed actions consistent with clinical data in right PFC patients with motor intentional disorders.

Dynamic changes in phase-amplitude coupling facilitate spatial attention control in fronto-parietal cortex

Authors:

  • Sara Szczepanski

  • Nathan E. Crone

  • Rachel A. Kuperman

  • Kurtis I. Auguste

  • Josef Parvizi

  • Robert T. Knight

Date: 2014

DOI: 10.1371/journal.pbio.1001936

PubMed: 4144794

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Abstract:

Attention is a core cognitive mechanism that allows the brain to allocate limited resources depending on current task demands. A number of frontal and posterior parietal cortical areas, referred to collectively as the fronto-parietal attentional control network, are engaged during attentional allocation in both humans and non-human primates. Numerous studies have examined this network in the human brain using various neuroimaging and scalp electrophysiological techniques. However, little is known about how these frontal and parietal areas interact dynamically to produce behavior on a fine temporal (sub-second) and spatial (sub-centimeter) scale. We addressed how human fronto-parietal regions control visuospatial attention on a fine spatiotemporal scale by recording electrocorticography (ECoG) signals measured directly from subdural electrode arrays that were implanted in patients undergoing intracranial monitoring for localization of epileptic foci. Subjects (n=8) performed a spatial-cuing task, in which they allocated visuospatial attention to either the right or left visual field and detected the appearance of a target. We found increases in high gamma (HG) power (70–250 Hz) time-locked to trial onset that remained elevated throughout the attentional allocation period over frontal, parietal, and visual areas. These HG power increases were modulated by the phase of the ongoing delta/theta (2–5 Hz) oscillation during attentional allocation. Critically, we found that the strength of this delta/theta phase-HG amplitude coupling predicted reaction times to detected targets on a trial-by-trial basis. These results highlight the role of delta/theta phase-HG amplitude coupling as a mechanism for sub-second facilitation and coordination within human fronto-parietal cortex that is guided by momentary attentional demands.

Impact of orbitofrontal lesions on electrophysiological signals in a stop signal task


Authors:

  • Anne-Kristin Solbakk

  • Ingrid Funderud

  • Tor Endestad

  • Torstein Meling

  • Magnus Lindgren

  • Robert T. Knight

  • Ulrike M. Krämer

Date: 2014

DOI: 10.1162/jocn_a_00561

PubMed: 24392904

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Abstract:

Behavioral inhibition and performance monitoring are critical cognitive functions supported by distributed neural networks including the pFC. We examined neurophysiological correlates of motor response inhibition and action monitoring in patients with focal orbitofrontal (OFC) lesions (n = 12) after resection of a primary intracranial tumor or contusion because of traumatic brain injury. Healthy participants served as controls (n = 14). Participants performed a visual stop signal task. We analyzed behavioral performance as well as event-related brain potentials and oscillations. Inhibition difficulty was adjusted individually to yield an equal amount of successful inhibitions across participants. RTs of patients and controls did not differ significantly in go trials or in failed stop trials, and no differences were observed in estimated stop signal RT. However, electrophysiological response patterns during task performance distinguished the groups. Patients with OFC lesions had enhanced P3 amplitudes to congruent condition go signals and to stop signals. In stop trials, patients had attenuated N2 and error-related negativity, but enhanced error positivity. Patients also showed enhanced and prolonged post-error beta band increases for stop errors. This effect was particularly evident in patients whose lesion extended to the subgenual cingulate cortex. In summary, although response inhibition was not impaired, the diminished stop N2 and ERN support a critical role of the OFC in action monitoring. Moreover, the increased stop P3, error positivity, and post-error beta response indicate that OFC injury affected action outcome evaluation and support the notion that the OFC is relevant for the processing of abstract reinforcers such as performing correctly in the task.

Impaired facilitatory mechanisms of auditory selective attention after damage of the lateral prefrontal cortex

Authors:

  • Aurélie Bidet-Caulet

  • K. Buchanan

  • H. Viswanath

  • Jessica Black

  • Frederique Bonnet-Brilhault

  • Robert T. Knight

Date: 2014

DOI: 10.1093/cercor/bhu131

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Abstract:

There is growing evidence that auditory selective attention operates via distinct facilitatory and inhibitory mechanisms enabling selective enhancement and suppression of sound processing, respectively. The lateral prefrontal cortex (LPFC) plays a crucial role in the top-down control of selective attention. However, whether the LPFC controls facilitatory, inhibitory, or both attentional mechanisms is unclear. Facilitatory and inhibitory mechanisms were assessed, in patients with LPFC damage, by comparing event-related potentials (ERPs) to attended and ignored sounds with ERPs to these same sounds when attention was equally distributed to all sounds. In control subjects, we observed 2 late frontally distributed ERP components: a transient facilitatory component occurring from 150 to 250 ms after sound onset; and an inhibitory component onsetting at 250 ms. Only the facilitatory component was affected in patients with LPFC damage: this component was absent when attending to sounds delivered in the ear contralateral to the lesion, with the most prominent decreases observed over the damaged brain regions. These findings have 2 important implications: (i) they provide evidence for functionally distinct facilitatory and inhibitory mechanisms supporting late auditory selective attention; (ii) they show that the LPFC is involved in the control of the facilitatory mechanisms of auditory attention.


Low attentional engagement makes attention network activity susceptible to emotional interference

Authors:

  • Robert T. Knight

  • Kaisa M. Hartikainen

  • Keith H. Ogawa

  • Natasha Pickard

  • Anne-Kristin Solbakk

  • Verónica Mäki-Marttu

Date: 2014

DOI: 10.1097/WNR.0000000000000223

PubMed: 4162342

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Abstract:

The aim of this study was to investigate whether emotion–attention interaction depends on attentional engagement. To investigate emotional modulation of attention network activation, we used a functional MRI paradigm consisting of a visuospatial attention task with either frequent (high-engagement) or infrequent (low-engagement) targets and intermittent emotional or neutral distractors. The attention task recruited a bilateral frontoparietal network with no emotional interference on network activation when the attentional engagement was high. In contrast, when the attentional engagement was low, the unpleasant stimuli interfered with the activation of the frontoparietal attention network, especially in the right hemisphere. This study provides novel evidence for low attentional engagement making attention control network activation susceptible to emotional interference.

Decoding spectrotemporal features of overt and covert speech from the human cortex

Authors:

  • Stéphanie Martin

  • Peter Brunner

  • Chris Holdgraf

  • Hans-Jochen Heinze

  • Nathan E. Crone

  • Jochem W. Rieger

  • Gerwin Schalk

  • Robert T. Knight

  • Brian Pasley

Date: 2014

DOI: 10.3389/fneng.2014.00014

PubMed: 4034498

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Abstract:

Auditory perception and auditory imagery have been shown to activate overlapping brain regions. We hypothesized that these phenomena also share a common underlying neural representation. To assess this, we used electrocorticography intracranial recordings from epileptic patients performing an out loud or a silent reading task. In these tasks, short stories scrolled across a video screen in two conditions: subjects read the same stories both aloud (overt) and silently (covert). In a control condition the subject remained in a resting state. We first built a high gamma (70–150 Hz) neural decoding model to reconstruct spectrotemporal auditory features of self-generated overt speech. We then evaluated whether this same model could reconstruct auditory speech features in the covert speech condition. Two speech models were tested: a spectrogram and a modulation-based feature space. For the overt condition, reconstruction accuracy was evaluated as the correlation between original and predicted speech features, and was significant in each subject (p < 10−5; paired two-sample t-test). For the covert speech condition, dynamic time warping was first used to realign the covert speech reconstruction with the corresponding original speech from the overt condition. Reconstruction accuracy was then evaluated as the correlation between original and reconstructed speech features. Covert reconstruction accuracy was compared to the accuracy obtained from reconstructions in the baseline control condition. Reconstruction accuracy for the covert condition was significantly better than for the control condition (p < 0.005; paired two-sample t-test). The superior temporal gyrus, pre- and post-central gyrus provided the highest reconstruction information. The relationship between overt and covert speech reconstruction depended on anatomy. These results provide evidence that auditory representations of covert speech can be reconstructed from models that are built from an overt speech data set, supporting a partially shared neural substrate.

Spatial and temporal relationships of electrocorticographic alpha and gamma activity during auditory processing

Authors:

  • Cristhian Potes

  • Peter Brunner

  • Ayesegul Gunduz

  • Robert T. Knight

  • Gerwin Schalk

Date: 2014

DOI: Neuroimaging approaches have implicated multiple b

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Abstract:

Neuroimaging approaches have implicated multiple brain sites in musical perception, including the posterior part of the superior temporal gyrus and adjacent perisylvian areas. However, the detailed spatial and temporal relationship of neural signals that support auditory processing is largely unknown. In this study, we applied a novel inter-subject analysis approach to electrophysiological signals recorded from the surface of the brain (electrocorticography (ECoG)) in ten human subjects. This approach allowed us to reliably identify those ECoG features that were related to the processing of a complex auditory stimulus (i.e., continuous piece of music) and to investigate their spatial, temporal, and causal relationships. Our results identified stimulus-related modulations in the alpha (8–12 Hz) and high gamma (70–110 Hz) bands at neuroanatomical locations implicated in auditory processing. Specifically, we identified stimulus-related ECoG modulations in the alpha band in areas adjacent to primary auditory cortex, which are known to receive afferent auditory projections from the thalamus (80 of a total of 15,107 tested sites). In contrast, we identified stimulus-related ECoG modulations in the high gamma band not only in areas close to primary auditory cortex but also in other perisylvian areas known to be involved in higher-order auditory processing, and in superior premotor cortex (412/15,107 sites). Across all implicated areas, modulations in the high gamma band preceded those in the alpha band by 280 ms, and activity in the high gamma band causally predicted alpha activity, but not vice versa (Granger causality, p < 1e− 8). Additionally, detailed analyses using Granger causality identified causal relationships of high gamma activity between distinct locations in early auditory pathways within superior temporal gyrus (STG) and posterior STG, between posterior STG and inferior frontal cortex, and between STG and premotor cortex. Evidence suggests that these relationships reflect direct cortico-cortical connections rather than common driving input from subcortical structures such as the thalamus. In summary, our inter-subject analyses defined the spatial and temporal relationships between music-related brain activity in the alpha and high gamma bands. They provide experimental evidence supporting current theories about the putative mechanisms of alpha and gamma activity, i.e., reflections of thalamo-cortical interactions and local cortical neural activity, respectively, and the results are also in agreement with existing functional models of auditory processing.

Oscillatory dynamics track motor learning in human cortex

Authors:

  • S. Durschmid

  • Fanny Quandt

  • Ulrike M. Krämer

  • Hermann Hinrichs

  • R. T. Schultz

  • H. Pannek

  • Edward F. Chang

  • Robert T. Knight

Date: 2014

DOI: 10.1371/journal.pone.0089576

PubMed: 24586885

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Abstract:

Improving performance in motor skill acquisition is proposed to be supported by tuning of neural networks. To address this issue we investigated changes of phase-amplitude cross-frequency coupling (paCFC) in neuronal networks during motor performance improvement. We recorded intracranially from subdural electrodes (electrocorticogram; ECoG) from 6 patients who learned 3 distinct motor tasks requiring coordination of finger movements with an external cue (serial response task, auditory motor coordination task, go/no-go). Performance improved in all subjects and all tasks during the first block and plateaued in subsequent blocks. Performance improvement was paralleled by increasing neural changes in the trial-to-trial paCFC between theta ([Formula: see text]; 4-8 Hz) phase and high gamma (HG; 80-180 Hz) amplitude. Electrodes showing this covariation pattern (Pearson's r ranging up to .45) were located contralateral to the limb performing the task and were observed predominantly in motor brain regions. We observed stable paCFC when task performance asymptoted. Our results indicate that motor performance improvement is accompanied by adjustments in the dynamics and topology of neuronal network interactions in the [Formula: see text] and HG range. The location of the involved electrodes suggests that oscillatory dynamics in motor cortices support performance improvement with practice.

Hypertension drives parenchymal b -amyloid accumulationin the brain parenchyma

Authors:

  • Robert T. Knight

  • Hans-Jochen Heinze

  • Celine Bueche

  • Cheryl Hawkes

  • Cornelia Garz

  • Stefan Vielhaber

  • Johannes Attems

  • Klaus Reymann

  • Roxana Carare

  • Stefanie Schreiber

Date: 2014

DOI: 10.1002/acn3.27

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Abstract:

There is substantial controversy regarding the causative role of amyloid b (Ab)deposition in Alzheimer’s disease (AD). The cerebrovasculature plays an impor-tant role in the elimination of Ab from the brain and hypertension is a well-known risk factor for AD. In spontaneously hypertensive stroke-prone rats(SHRSP), an animal model of chronic arterial hypertension, cerebral small ves-sel disease (CSVD) leads to age-dependent parenchymal Ab accumulation simi-lar to that observed in AD. These data approve the neuropathological linkbetween CSVD and AD, confirm the challenge that parenchymal Ab depositionis a specific marker for AD and disclose the meaning of SHRSP as valid experi-mental model to investigate the association between hypertension, CSVD, and Ab plaques.