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Nicole Swann

University of Oregon, Human Physiology, Faculty Member

University of California, San Francisco, Neurological Surgery, Post-Doc

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I am an assistant professor at University of Oregon.

My research interests include studying cortical-basal ganglia interactions associated with movement and cognition in both health and disease. I use a combination of invasive (Electrocorticography, ECoG, and local field potentials, LFPs) and non-invasive (electroencephalography, EEG) electrophysiological techniques in humans.
Supervisors: Philip Starr, Adam Aron, and Robert Knight
Address: https://greenswann.wordpress.com

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University of South Alabama

Mohsin Mohammed

Yale University

Aristide Merola

The Hebrew University of Jerusalem

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Papers by Nicole Swann

Gamma Oscillations in the Hyperkinetic State Detected with Chronic Human Brain Recordings in Parkinson's Disease

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jun 15, 2016

Hyperkinetic states are common in human movement disorders, but their neural basis remains uncert... more Hyperkinetic states are common in human movement disorders, but their neural basis remains uncertain. One such condition is dyskinesia, a serious adverse effect of medical and surgical treatment for Parkinson's disease (PD). To study this, we used a novel, totally implanted, bidirectional neural interface to obtain multisite long-term recordings. We focus our analysis on two patients with PD who experienced frequent dyskinesia and studied them both at rest and during voluntary movement. We show that dyskinesia is associated with a narrowband gamma oscillation in motor cortex between 60 and 90 Hz, a similar, though weaker, oscillation in subthalamic nucleus, and strong phase coherence between the two. Dyskinesia-related oscillations are minimally affected by voluntary movement. When dyskinesia persists during therapeutic deep brain stimulation (DBS), the peak frequency of this signal shifts to half the stimulation frequency. These findings suggest a circuit-level mechanism for th...

Characteristics of Waveform Shape in Parkinson’s Disease Detected with Scalp Electroencephalography

eneuro

Neural activity in the ␤ frequency range (13-30 Hz) is excessively synchronized in Parkinson's di... more Neural activity in the ␤ frequency range (13-30 Hz) is excessively synchronized in Parkinson's disease (PD). Previous work using invasive intracranial recordings and non-invasive scalp electroencephalography (EEG) has shown that correlations between ␤ phase and broad-band ␥ (Ͼ50 Hz) amplitude [i.e., phase amplitude coupling (PAC)] are elevated in PD, perhaps a reflection of this synchrony. Recently, it has also been shown, in invasive human recordings, that non-sinusoidal features of ␤ oscillation shape also characterize PD. Here, we show that these features of ␤ waveform shape also distinguish PD patients on and off medication using non-invasive recordings in a dataset of 15 PD patients with resting scalp EEG. Specifically, ␤ oscillations over sensorimotor electrodes in PD patients off medication had greater sharpness asymmetry and steepness asymmetry than on medication (sign rank, p Ͻ 0.02, corrected). We also showed that ␤ oscillations over sensorimotor cortex most often had a canonical shape, and that using this prototypical shape as an inclusion criteria increased the effect size of our findings. Together, our findings suggest that novel ways of measuring ␤ synchrony that incorporate waveform shape could improve detection of PD pathophysiology in non-invasive recordings. Moreover, they motivate the consideration of waveform shape in future EEG studies.

Methods and Systems for Treating Neurological Movement Disorders

Electrocorticography reveals beta desynchronization in the basal ganglia-cortical loop during rest tremor in Parkinson's disease

Neurobiology of Disease, 2016

The pathophysiology of rest tremor in Parkinson&#39;s disease (PD) is not well understood, an... more The pathophysiology of rest tremor in Parkinson&#39;s disease (PD) is not well understood, and its severity does not correlate with the severity of other cardinal signs of PD. We hypothesized that tremor-related oscillatory activity in the basal-ganglia-thalamocortical loop might serve as a compensatory mechanism for the excessive beta band synchronization associated with the parkinsonian state. We recorded electrocorticography (ECoG) from the sensorimotor cortex and local field potentials (LFP) from the subthalamic nucleus (STN) in patients undergoing lead implantation for deep brain stimulation (DBS). We analyzed differences in measures of network synchronization during epochs of spontaneous rest tremor, versus epochs without rest tremor, occurring in the same subjects. The presence of tremor was associated with reduced beta power in the cortex and STN. Cortico-cortical coherence and phase-amplitude coupling (PAC) decreased during rest tremor, as did basal ganglia-cortical coherence in the same frequency band. Cortical broadband gamma power was not increased by tremor onset, in contrast to the movement-related gamma increase typically observed at the onset of voluntary movement. These findings suggest that the cortical representation of rest tremor is distinct from that of voluntary movement, and support a model in which tremor acts to decrease beta band synchronization within the basal ganglia-cortical loop.

Enabling closed-loop neurostimulation research with downloadable firmware upgrades

2015 IEEE Biomedical Circuits and Systems Conference (BioCAS), 2015

Demonstration: Enabling closed-loop neurostimulation with downloadable firmware upgrades

2015 IEEE Biomedical Circuits and Systems Conference (BioCAS), 2015

Task-related activity in sensorimotor cortex in Parkinson's disease and essential tremor: changes in beta and gamma bands

Frontiers in human neuroscience, 2015

In Parkinson's disease patients in the OFF medication state, basal ganglia local field potent... more In Parkinson's disease patients in the OFF medication state, basal ganglia local field potentials exhibit changes in beta and gamma oscillations that correlate with reduced voluntary movement, manifested as rigidity and akinesia. However, magnetoencephalography and low-resolution electrocorticography (ECoG) studies in Parkinson's patients suggest that changes in sensorimotor cortical oscillations differ from those of the basal ganglia. To more clearly define the role of sensorimotor cortex oscillatory activity in Parkinson's, we performed intraoperative, high-resolution (4 mm spacing) ECoG recordings in 10 Parkinson's patients (2 females, ages 47-72) undergoing deep brain stimulation (DBS) lead placement in the awake, OFF medication state. We analyzed ECoG potentials during a computer-controlled reaching task designed to separate movement preparation from movement execution and compared findings to similar invasive recordings in eight patients with essential tremor (...

Intracranial EEG shows primary motor and prefrontal signatures of stop signal response inhibition

by Nicole Swann, Nitin Tandon, and Ryan Canolty

NeuroImage, 2009

Motor System Interactions in the Beta Band Decrease during Loss of Consciousness.

Communication between brain areas and how they are influenced by changes in consciousness are not... more Communication between brain areas and how they are influenced by changes in consciousness are not fully understood. One hypothesis is that brain areas communicate via oscillatory processes, utilizing network-specific frequency bands, that can be measured with metrics that reflect between-region interactions, such as coherence and phase amplitude coupling (PAC). To evaluate this hypothesis, and understand how these interactions are modulated by state changes, we analyzed electrophysiological recordings in humans at different nodes of one well-studied brain network: the basal ganglia-thalamo-cortical (BGTC) loops of the motor system, during loss of consciousness induced by anesthesia. We recorded simultaneous electrocorticography (ECoG) over primary motor cortex (M1) with local field potentials (LFPs) from subcortical motor regions (either basal ganglia or thalamus) in 15 movement disorder patients during anesthesia (propofol) induction as a part of their surgery for deep brain stimulation. We observed reduced coherence and PAC between M1 and the subcortical nuclei, which was specific to the beta band (~18-24 Hz). The fact that this pattern occurs selectively in beta underscores the importance of this frequency band in the motor system, and supports the idea that oscillatory interactions at specific frequencies are related to the capacity for normal brain function and behavior.

Elevated Synchrony in Parkinson’s Disease Detected with Electroencephalography.

OBJECTIVE: Parkinson's disease (PD) can be difficult to diagnose and treat. Development of a biom... more OBJECTIVE: Parkinson's disease (PD) can be difficult to diagnose and treat. Development of a biomarker for PD would reduce these challenges by providing an objective measure of disease. Emerging theories suggest PD is characterized by excessive synchronization in the beta frequency band (∼20 Hz) throughout basal ganglia-thalamo-cortical loops. Recently we showed with invasive electrocorticography (ECoG) that one robust measure of this synchronization is the coupling of beta phase to broadband gamma amplitude (i.e. phase amplitude coupling, PAC). Other recent work suggests that high frequency activity is detectable at the scalp using electroencephalography (EEG). Motivated by these findings, we tested whether beta-gamma PAC over sensorimotor cortex, recorded non-invasively with EEG, differs between PD patients Off and On medications, and healthy Control subjects.METHODS: Resting EEG was compared from 15 PD patients and 16 healthy control subjects. PD patients were tested On and Off medications on different days, in a counterbalanced order. For each dataset we calculated PAC and compared results across groups.RESULTS: PAC was elevated in the patients Off medications compared to On medications (p=0.008) and for patients Off medications compared to Controls (p=0.009).INTERPRETATION: Elevated PAC is detectable using scalp EEG in PD patients Off medications compared to On, and compared to healthy Controls. This suggests that EEG PAC may provide a non-invasive biomarker of the Parkinsonian state. This biomarker could be used as a control signal for closed-loop control of deep brain stimulation devices, for adjustment of dopaminergic treatment, and also has the potential to aid in diagnosis. This article is protected by copyright. All rights reserved.© 2015 American Neurological Association.

Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease

by Nicole Swann and Coralie de Hemptinne

Deep brain stimulation (DBS) is increasingly applied for the treatment of brain disorders, but it... more Deep brain stimulation (DBS) is increasingly applied for the treatment of brain disorders, but its mechanism of action remains unknown. Here we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients, neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the beta rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as that of the reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive beta phase locking of motor cortex neurons.

Human and Nonhuman Primate Neurophysiology to Understand the Pathophysiology of Movement Disorders

Movement Disorders, 2015

Fronto-Basal-Ganglia Circuits for Stopping Action

Neural Basis of Motivational and Cognitive Control, 2011

Imagine you are sitting on your bicycle at an intersection waiting for the traffic light to turn ... more

Dissociation of Frontal and Medial Temporal Lobe Activity in Maintenance and Binding of Sequentially Presented Paired Associates

Journal of Cognitive Neuroscience, 2009

Substructures of the prefrontal cortex (PFC) and the medial-temporal lobe are critical for associ... more Substructures of the prefrontal cortex (PFC) and the medial-temporal lobe are critical for associating objects presented over time. Previous studies showing frontal and medial-temporal involvement in associative encoding have not addressed the response specificity of these regions to different aspects of the task, which include instructions to associate and binding of stimuli. This study used a novel paradigm to temporally separate these two components of the task by sequential presentation of individual images with or without associative instruction; fMRI was used to investigate the temporal involvement of the PFC and the parahippocampal cortex in encoding each component. Although both regions showed an enhanced response to the second stimulus of a pair, only the PFC had increased activation during the delay preceding a stimulus when associative instruction was given. These findings present new evidence that prefrontal and medial-temporal regions provide distinct temporal contributions during associative memory formation.

Intracranial Electroencephalography Reveals Different Temporal Profiles for Dorsal-and Ventro-lateral Prefrontal Cortex in Preparing to Stop Action

Preparing to stop an inappropriate action requires keeping in mind the task goal and using this t... more Preparing to stop an inappropriate action requires keeping in mind the task goal and using this to influence the action control system. We tested the hypothesis that different subregions of prefrontal cortex show different temporal profiles consistent with dissociable contributions to preparing-to-stop, with dorsolateral prefrontal cortex (DLPFC) representing the task goal and ventrolateral prefrontal cortex (VLPFC) implementing action control. Five human subjects were studied using electrocorticography recorded from subdural grids over right lateral frontal cortex. On each trial, a task cue instructed the subject whether stopping might be needed or not (Maybe Stop [MS] or No Stop [NS]), followed by a go cue, and on some MS trials, a subsequent stop signal. We focused on go trials, comparing MS with NS. In the DLPFC, most subjects had an increase in high gamma activity following the task cue and the go cue. In contrast, in the VLPFC, all subjects had activity after the go cue near the time of the motor response on MS trials, related to behavioral slowing, and significantly later than the DLPFC activity. These different temporal profiles suggest that DLPFC and VLPFC could have dissociable roles, with DLPFC representing task goals and VLPFC implementing action control.

Behavioral/Systems/Cognitive Deep Brain Stimulation of the Subthalamic Nucleus Altersthe Cortical Profile of Response Inhibition in the BetaFrequency Band: A Scalp EEG Study in Parkinson’s Disease

Stopping an initiated response could be implemented by a fronto-basal-ganglia circuit, including ... more Stopping an initiated response could be implemented by a fronto-basal-ganglia circuit, including the right inferior frontal cortex (rIFC) and the subthalamic nucleus (STN). Intracranial recording studies in humans reveal an increase in beta-band power (ϳ16 -20 Hz) within the rIFC and STN when a response is stopped. This suggests that the beta-band could be important for communication in this network. If this is the case, then altering one region should affect the electrophysiological response at the other. We addressed this hypothesis by recording scalp EEG during a stop task while modulating STN activity with deep brain stimulation. We studied 15 human patients with Parkinson's disease and 15 matched healthy control subjects. Behaviorally, patients OFF stimulation were slower than controls to stop their response. Moreover, stopping speed was improved for ON compared to OFF stimulation. For scalp EEG, there was greater beta power, around the time of stopping, for patients ON compared to OFF stimulation. This effect was stronger over the right compared to left frontal cortex, consistent with the putative right lateralization of the stopping network. Thus, deep brain stimulation of the STN improved behavioral stopping performance and increased the beta-band response over the right frontal cortex. These results complement other evidence for a structurally connected functional circuit between right frontal cortex and the basal ganglia. The results also suggest that deep brain stimulation of the STN may improve task performance by increasing the fidelity of information transfer within a fronto-basalganglia circuit.

STOP! How we inhibit acts

by Ian Greenhouse and Nicole Swann

Roles for the pre-supplementary motor area and the right inferior frontal gyrus in stopping action: Electrophysiological responses and functional and structural connectivity

by Nitin Tandon and Nicole Swann

Both the pre-supplementary motor area (preSMA) and the right inferior frontal gyrus (rIFG) are im... more Both the pre-supplementary motor area (preSMA) and the right inferior frontal gyrus (rIFG) are important for stopping action outright. These regions are also engaged when preparing to stop. We aimed to elucidate the roles of these regions by harnessing the high spatio-temporal resolution of electrocorticography (ECoG), and by using a task that engages both preparing to stop and stopping outright. First, we validated the task using fMRI in 16 healthy control participants to confirm that both the preSMA and the rIFG were active. Next, we studied a rare patient with intracranial grid coverage of both these regions, using macrostimulation, diffusion tractography, cortico-cortical evoked potentials (CCEPs) and task-based ECoG. Macrostimulation of the preSMA induced behavioral motor arrest. Diffusion tractography revealed a structural connection between the preSMA and rIFG. CCEP analysis showed that stimulation of the preSMA evoked strong local field potentials within 30 ms in rIFG. During the task, when preparing to stop, there was increased high gamma amplitude (~70-250 Hz) in both regions, with preSMA preceding rIFG by~750 ms. For outright stopping there was also a high gamma amplitude increase in both regions, again with preSMA preceding rIFG. Further, at the time of stopping, there was an increase in beta band activity (~16 Hz) in both regions, with significantly stronger inter-regional coherence for successful vs. unsuccessful stop trials. The results complement earlier reports of a structural/functional action control network between the preSMA and rIFG. They go further by revealing between-region timing differences in the high gamma band when preparing to stop and stopping outright. They also reveal strong between-region coherence in the beta band when stopping is successful. Implications for theories of action control are discussed.

Intracranial EEG Reveals a Time-and Frequency-Specific Role for the Right Inferior Frontal Gyrus and Primary Motor Cortex in Stopping Initiated Responses

by Nicole Swann, Nitin Tandon, and Ryan Canolty

Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary moto... more Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary motor cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from subdural electrodes in four patients while they performed a stop-signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band (ϳ16 Hz) for successful versus unsuccessful stop trials. This finding adds to evidence for a functional network for stopping because changes in beta frequency activity have also been observed in the basal ganglia in association with behavioral stopping.Inaddition,therightIFGresponseoccurred100 -250msafterthestopsignal,atimerangeconsistentwithaputativeinhibitorycontrol process rather than with stop-signal processing or feedback regarding success. A downstream target of inhibitory control is M1. In each patient, there was alpha/beta band desynchronization in M1 for stop trials. However, the degree of desynchronization in M1 was less for successfully than unsuccessfully stopped trials. This reduced desynchronization on successful stop trials could relate to increased GABA inhibition in M1. Together with other findings, the results suggest that behavioral stopping is implemented via synchronized activity in the beta frequency band in a right IFG/basal ganglia network, with downstream effects on M1.

Gamma Oscillations in the Hyperkinetic State Detected with Chronic Human Brain Recordings in Parkinson's Disease

The Journal of neuroscience : the official journal of the Society for Neuroscience, Jun 15, 2016

Hyperkinetic states are common in human movement disorders, but their neural basis remains uncert... more Hyperkinetic states are common in human movement disorders, but their neural basis remains uncertain. One such condition is dyskinesia, a serious adverse effect of medical and surgical treatment for Parkinson's disease (PD). To study this, we used a novel, totally implanted, bidirectional neural interface to obtain multisite long-term recordings. We focus our analysis on two patients with PD who experienced frequent dyskinesia and studied them both at rest and during voluntary movement. We show that dyskinesia is associated with a narrowband gamma oscillation in motor cortex between 60 and 90 Hz, a similar, though weaker, oscillation in subthalamic nucleus, and strong phase coherence between the two. Dyskinesia-related oscillations are minimally affected by voluntary movement. When dyskinesia persists during therapeutic deep brain stimulation (DBS), the peak frequency of this signal shifts to half the stimulation frequency. These findings suggest a circuit-level mechanism for th...

Characteristics of Waveform Shape in Parkinson’s Disease Detected with Scalp Electroencephalography

eneuro

Neural activity in the ␤ frequency range (13-30 Hz) is excessively synchronized in Parkinson's di... more Neural activity in the ␤ frequency range (13-30 Hz) is excessively synchronized in Parkinson's disease (PD). Previous work using invasive intracranial recordings and non-invasive scalp electroencephalography (EEG) has shown that correlations between ␤ phase and broad-band ␥ (Ͼ50 Hz) amplitude [i.e., phase amplitude coupling (PAC)] are elevated in PD, perhaps a reflection of this synchrony. Recently, it has also been shown, in invasive human recordings, that non-sinusoidal features of ␤ oscillation shape also characterize PD. Here, we show that these features of ␤ waveform shape also distinguish PD patients on and off medication using non-invasive recordings in a dataset of 15 PD patients with resting scalp EEG. Specifically, ␤ oscillations over sensorimotor electrodes in PD patients off medication had greater sharpness asymmetry and steepness asymmetry than on medication (sign rank, p Ͻ 0.02, corrected). We also showed that ␤ oscillations over sensorimotor cortex most often had a canonical shape, and that using this prototypical shape as an inclusion criteria increased the effect size of our findings. Together, our findings suggest that novel ways of measuring ␤ synchrony that incorporate waveform shape could improve detection of PD pathophysiology in non-invasive recordings. Moreover, they motivate the consideration of waveform shape in future EEG studies.

Methods and Systems for Treating Neurological Movement Disorders

Electrocorticography reveals beta desynchronization in the basal ganglia-cortical loop during rest tremor in Parkinson's disease

Neurobiology of Disease, 2016

The pathophysiology of rest tremor in Parkinson&#39;s disease (PD) is not well understood, an... more The pathophysiology of rest tremor in Parkinson&#39;s disease (PD) is not well understood, and its severity does not correlate with the severity of other cardinal signs of PD. We hypothesized that tremor-related oscillatory activity in the basal-ganglia-thalamocortical loop might serve as a compensatory mechanism for the excessive beta band synchronization associated with the parkinsonian state. We recorded electrocorticography (ECoG) from the sensorimotor cortex and local field potentials (LFP) from the subthalamic nucleus (STN) in patients undergoing lead implantation for deep brain stimulation (DBS). We analyzed differences in measures of network synchronization during epochs of spontaneous rest tremor, versus epochs without rest tremor, occurring in the same subjects. The presence of tremor was associated with reduced beta power in the cortex and STN. Cortico-cortical coherence and phase-amplitude coupling (PAC) decreased during rest tremor, as did basal ganglia-cortical coherence in the same frequency band. Cortical broadband gamma power was not increased by tremor onset, in contrast to the movement-related gamma increase typically observed at the onset of voluntary movement. These findings suggest that the cortical representation of rest tremor is distinct from that of voluntary movement, and support a model in which tremor acts to decrease beta band synchronization within the basal ganglia-cortical loop.

Enabling closed-loop neurostimulation research with downloadable firmware upgrades

2015 IEEE Biomedical Circuits and Systems Conference (BioCAS), 2015

Demonstration: Enabling closed-loop neurostimulation with downloadable firmware upgrades

2015 IEEE Biomedical Circuits and Systems Conference (BioCAS), 2015

Task-related activity in sensorimotor cortex in Parkinson's disease and essential tremor: changes in beta and gamma bands

Frontiers in human neuroscience, 2015

In Parkinson's disease patients in the OFF medication state, basal ganglia local field potent... more In Parkinson's disease patients in the OFF medication state, basal ganglia local field potentials exhibit changes in beta and gamma oscillations that correlate with reduced voluntary movement, manifested as rigidity and akinesia. However, magnetoencephalography and low-resolution electrocorticography (ECoG) studies in Parkinson's patients suggest that changes in sensorimotor cortical oscillations differ from those of the basal ganglia. To more clearly define the role of sensorimotor cortex oscillatory activity in Parkinson's, we performed intraoperative, high-resolution (4 mm spacing) ECoG recordings in 10 Parkinson's patients (2 females, ages 47-72) undergoing deep brain stimulation (DBS) lead placement in the awake, OFF medication state. We analyzed ECoG potentials during a computer-controlled reaching task designed to separate movement preparation from movement execution and compared findings to similar invasive recordings in eight patients with essential tremor (...

Intracranial EEG shows primary motor and prefrontal signatures of stop signal response inhibition

by Nicole Swann, Nitin Tandon, and Ryan Canolty

NeuroImage, 2009

Motor System Interactions in the Beta Band Decrease during Loss of Consciousness.

Communication between brain areas and how they are influenced by changes in consciousness are not... more Communication between brain areas and how they are influenced by changes in consciousness are not fully understood. One hypothesis is that brain areas communicate via oscillatory processes, utilizing network-specific frequency bands, that can be measured with metrics that reflect between-region interactions, such as coherence and phase amplitude coupling (PAC). To evaluate this hypothesis, and understand how these interactions are modulated by state changes, we analyzed electrophysiological recordings in humans at different nodes of one well-studied brain network: the basal ganglia-thalamo-cortical (BGTC) loops of the motor system, during loss of consciousness induced by anesthesia. We recorded simultaneous electrocorticography (ECoG) over primary motor cortex (M1) with local field potentials (LFPs) from subcortical motor regions (either basal ganglia or thalamus) in 15 movement disorder patients during anesthesia (propofol) induction as a part of their surgery for deep brain stimulation. We observed reduced coherence and PAC between M1 and the subcortical nuclei, which was specific to the beta band (~18-24 Hz). The fact that this pattern occurs selectively in beta underscores the importance of this frequency band in the motor system, and supports the idea that oscillatory interactions at specific frequencies are related to the capacity for normal brain function and behavior.

Elevated Synchrony in Parkinson’s Disease Detected with Electroencephalography.

OBJECTIVE: Parkinson's disease (PD) can be difficult to diagnose and treat. Development of a biom... more OBJECTIVE: Parkinson's disease (PD) can be difficult to diagnose and treat. Development of a biomarker for PD would reduce these challenges by providing an objective measure of disease. Emerging theories suggest PD is characterized by excessive synchronization in the beta frequency band (∼20 Hz) throughout basal ganglia-thalamo-cortical loops. Recently we showed with invasive electrocorticography (ECoG) that one robust measure of this synchronization is the coupling of beta phase to broadband gamma amplitude (i.e. phase amplitude coupling, PAC). Other recent work suggests that high frequency activity is detectable at the scalp using electroencephalography (EEG). Motivated by these findings, we tested whether beta-gamma PAC over sensorimotor cortex, recorded non-invasively with EEG, differs between PD patients Off and On medications, and healthy Control subjects.METHODS: Resting EEG was compared from 15 PD patients and 16 healthy control subjects. PD patients were tested On and Off medications on different days, in a counterbalanced order. For each dataset we calculated PAC and compared results across groups.RESULTS: PAC was elevated in the patients Off medications compared to On medications (p=0.008) and for patients Off medications compared to Controls (p=0.009).INTERPRETATION: Elevated PAC is detectable using scalp EEG in PD patients Off medications compared to On, and compared to healthy Controls. This suggests that EEG PAC may provide a non-invasive biomarker of the Parkinsonian state. This biomarker could be used as a control signal for closed-loop control of deep brain stimulation devices, for adjustment of dopaminergic treatment, and also has the potential to aid in diagnosis. This article is protected by copyright. All rights reserved.© 2015 American Neurological Association.

Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease

by Nicole Swann and Coralie de Hemptinne

Deep brain stimulation (DBS) is increasingly applied for the treatment of brain disorders, but it... more Deep brain stimulation (DBS) is increasingly applied for the treatment of brain disorders, but its mechanism of action remains unknown. Here we evaluate the effect of basal ganglia DBS on cortical function using invasive cortical recordings in Parkinson's disease (PD) patients undergoing DBS implantation surgery. In the primary motor cortex of PD patients, neuronal population spiking is excessively synchronized to the phase of network oscillations. This manifests in brain surface recordings as exaggerated coupling between the phase of the beta rhythm and the amplitude of broadband activity. We show that acute therapeutic DBS reversibly reduces phase-amplitude interactions over a similar time course as that of the reduction in parkinsonian motor signs. We propose that DBS of the basal ganglia improves cortical function by alleviating excessive beta phase locking of motor cortex neurons.

Human and Nonhuman Primate Neurophysiology to Understand the Pathophysiology of Movement Disorders

Movement Disorders, 2015

Fronto-Basal-Ganglia Circuits for Stopping Action

Neural Basis of Motivational and Cognitive Control, 2011

Imagine you are sitting on your bicycle at an intersection waiting for the traffic light to turn ... more

Dissociation of Frontal and Medial Temporal Lobe Activity in Maintenance and Binding of Sequentially Presented Paired Associates

Journal of Cognitive Neuroscience, 2009

Substructures of the prefrontal cortex (PFC) and the medial-temporal lobe are critical for associ... more Substructures of the prefrontal cortex (PFC) and the medial-temporal lobe are critical for associating objects presented over time. Previous studies showing frontal and medial-temporal involvement in associative encoding have not addressed the response specificity of these regions to different aspects of the task, which include instructions to associate and binding of stimuli. This study used a novel paradigm to temporally separate these two components of the task by sequential presentation of individual images with or without associative instruction; fMRI was used to investigate the temporal involvement of the PFC and the parahippocampal cortex in encoding each component. Although both regions showed an enhanced response to the second stimulus of a pair, only the PFC had increased activation during the delay preceding a stimulus when associative instruction was given. These findings present new evidence that prefrontal and medial-temporal regions provide distinct temporal contributions during associative memory formation.

Intracranial Electroencephalography Reveals Different Temporal Profiles for Dorsal-and Ventro-lateral Prefrontal Cortex in Preparing to Stop Action

Preparing to stop an inappropriate action requires keeping in mind the task goal and using this t... more Preparing to stop an inappropriate action requires keeping in mind the task goal and using this to influence the action control system. We tested the hypothesis that different subregions of prefrontal cortex show different temporal profiles consistent with dissociable contributions to preparing-to-stop, with dorsolateral prefrontal cortex (DLPFC) representing the task goal and ventrolateral prefrontal cortex (VLPFC) implementing action control. Five human subjects were studied using electrocorticography recorded from subdural grids over right lateral frontal cortex. On each trial, a task cue instructed the subject whether stopping might be needed or not (Maybe Stop [MS] or No Stop [NS]), followed by a go cue, and on some MS trials, a subsequent stop signal. We focused on go trials, comparing MS with NS. In the DLPFC, most subjects had an increase in high gamma activity following the task cue and the go cue. In contrast, in the VLPFC, all subjects had activity after the go cue near the time of the motor response on MS trials, related to behavioral slowing, and significantly later than the DLPFC activity. These different temporal profiles suggest that DLPFC and VLPFC could have dissociable roles, with DLPFC representing task goals and VLPFC implementing action control.

Behavioral/Systems/Cognitive Deep Brain Stimulation of the Subthalamic Nucleus Altersthe Cortical Profile of Response Inhibition in the BetaFrequency Band: A Scalp EEG Study in Parkinson’s Disease

Stopping an initiated response could be implemented by a fronto-basal-ganglia circuit, including ... more Stopping an initiated response could be implemented by a fronto-basal-ganglia circuit, including the right inferior frontal cortex (rIFC) and the subthalamic nucleus (STN). Intracranial recording studies in humans reveal an increase in beta-band power (ϳ16 -20 Hz) within the rIFC and STN when a response is stopped. This suggests that the beta-band could be important for communication in this network. If this is the case, then altering one region should affect the electrophysiological response at the other. We addressed this hypothesis by recording scalp EEG during a stop task while modulating STN activity with deep brain stimulation. We studied 15 human patients with Parkinson's disease and 15 matched healthy control subjects. Behaviorally, patients OFF stimulation were slower than controls to stop their response. Moreover, stopping speed was improved for ON compared to OFF stimulation. For scalp EEG, there was greater beta power, around the time of stopping, for patients ON compared to OFF stimulation. This effect was stronger over the right compared to left frontal cortex, consistent with the putative right lateralization of the stopping network. Thus, deep brain stimulation of the STN improved behavioral stopping performance and increased the beta-band response over the right frontal cortex. These results complement other evidence for a structurally connected functional circuit between right frontal cortex and the basal ganglia. The results also suggest that deep brain stimulation of the STN may improve task performance by increasing the fidelity of information transfer within a fronto-basalganglia circuit.

STOP! How we inhibit acts

by Ian Greenhouse and Nicole Swann

Roles for the pre-supplementary motor area and the right inferior frontal gyrus in stopping action: Electrophysiological responses and functional and structural connectivity

by Nitin Tandon and Nicole Swann

Both the pre-supplementary motor area (preSMA) and the right inferior frontal gyrus (rIFG) are im... more Both the pre-supplementary motor area (preSMA) and the right inferior frontal gyrus (rIFG) are important for stopping action outright. These regions are also engaged when preparing to stop. We aimed to elucidate the roles of these regions by harnessing the high spatio-temporal resolution of electrocorticography (ECoG), and by using a task that engages both preparing to stop and stopping outright. First, we validated the task using fMRI in 16 healthy control participants to confirm that both the preSMA and the rIFG were active. Next, we studied a rare patient with intracranial grid coverage of both these regions, using macrostimulation, diffusion tractography, cortico-cortical evoked potentials (CCEPs) and task-based ECoG. Macrostimulation of the preSMA induced behavioral motor arrest. Diffusion tractography revealed a structural connection between the preSMA and rIFG. CCEP analysis showed that stimulation of the preSMA evoked strong local field potentials within 30 ms in rIFG. During the task, when preparing to stop, there was increased high gamma amplitude (~70-250 Hz) in both regions, with preSMA preceding rIFG by~750 ms. For outright stopping there was also a high gamma amplitude increase in both regions, again with preSMA preceding rIFG. Further, at the time of stopping, there was an increase in beta band activity (~16 Hz) in both regions, with significantly stronger inter-regional coherence for successful vs. unsuccessful stop trials. The results complement earlier reports of a structural/functional action control network between the preSMA and rIFG. They go further by revealing between-region timing differences in the high gamma band when preparing to stop and stopping outright. They also reveal strong between-region coherence in the beta band when stopping is successful. Implications for theories of action control are discussed.

Intracranial EEG Reveals a Time-and Frequency-Specific Role for the Right Inferior Frontal Gyrus and Primary Motor Cortex in Stopping Initiated Responses

by Nicole Swann, Nitin Tandon, and Ryan Canolty

Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary moto... more Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary motor cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from subdural electrodes in four patients while they performed a stop-signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band (ϳ16 Hz) for successful versus unsuccessful stop trials. This finding adds to evidence for a functional network for stopping because changes in beta frequency activity have also been observed in the basal ganglia in association with behavioral stopping.Inaddition,therightIFGresponseoccurred100 -250msafterthestopsignal,atimerangeconsistentwithaputativeinhibitorycontrol process rather than with stop-signal processing or feedback regarding success. A downstream target of inhibitory control is M1. In each patient, there was alpha/beta band desynchronization in M1 for stop trials. However, the degree of desynchronization in M1 was less for successfully than unsuccessfully stopped trials. This reduced desynchronization on successful stop trials could relate to increased GABA inhibition in M1. Together with other findings, the results suggest that behavioral stopping is implemented via synchronized activity in the beta frequency band in a right IFG/basal ganglia network, with downstream effects on M1.