Neuromodulation in Beta-Band Power Between Movement Execution and Inhibition in the Human Hippocampus.

INTRODUCTION: The hippocampus is thought to be involved in movement, but its precise role in movement execution and inhibition has not been well studied. Previous work with direct neural recordings has found beta-band (13-30 Hz) modulation in both movement execution and inhibition throughout the motor system, but the role of beta-band modulation in the hippocampus during movement inhibition is not well understood. Here, we perform a Go/No-Go reaching task in ten patients with medically refractory epilepsy to study human hippocampal beta-power changes during movement. MATERIALS AND METHODS: Ten epilepsy patients (5 female; ages 21-46) were implanted with intracranial depth electrodes for seizure monitoring and localization. Local field potentials were sampled at 2000 Hz during a Go/No-Go movement task. Comparison of beta-band power between Go and No-Go conditions was conducted using Wilcoxon signed-rank hypothesis testing for each patient. Sub-analyses were conducted to assess differences in the anterior vs posterior contacts, ipsilateral vs contralateral contacts, and male vs female beta-power values. RESULTS: Eight out of ten patients showed significant beta-power decreases during the Go movement response (p < 0.05) compared to baseline. Eight out of ten patients also showed significant beta-power increases in the No-Go condition, occurring in the absence of movement. No significant differences were noted between ipsilateral vs contralateral contacts nor in anterior vs posterior hippocampal contacts. Female participants had a higher task success rate than males and had significantly greater beta-power increases in the No-Go condition (p < 0.001). CONCLUSION: These findings indicate that increases in hippocampal beta power are associated with movement inhibition. To the best of our knowledge, this study is the first to report this phenomenon in the human hippocampus. The beta band may represent a state-change signal involved in motor processing. Future focus on the beta band in understanding human motor and impulse control will be vital.

Gamma-band modulation in the human amygdala during reaching movements.

OBJECTIVE: Motor brain-computer interface (BCI) represents a new frontier in neurological surgery that could provide significant benefits for patients living with motor deficits. Both the primary motor cortex and posterior parietal cortex have successfully been used as a neural source for human motor BCI, leading to interest in exploring other brain areas involved in motor control. The amygdala is one area that has been shown to have functional connectivity to the motor system; however, its role in movement execution is not well studied. Gamma oscillations (30-200 Hz) are known to be prokinetic in the human cortex, but their role is poorly understood in subcortical structures. Here, the authors use direct electrophysiological recordings and the classic "center-out" direct-reach experiment to study amygdaloid gamma-band modulation in 8 patients with medically refractory epilepsy. METHODS: The study population consisted of 8 epilepsy patients (2 men; age range 21-62 years) who underwent implantation of micro-macro depth electrodes for seizure localization and EEG monitoring. Data from the macro contacts sampled at 2000 Hz were used for analysis. The classic center-out direct-reach experiment was used, which consists of an intertrial interval phase, a fixation phase, and a response phase. The authors assessed the statistical significance of neural modulation by inspecting for nonoverlapping areas in the 95% confidence intervals of spectral power for the response and fixation phases. RESULTS: In 5 of the 8 patients, power spectral analysis showed a statistically significant increase in power within regions of the gamma band during the response phase compared with the fixation phase. In these 5 patients, the 95% bootstrapped confidence intervals of trial-averaged power in contiguous frequencies of the gamma band during the response phase were above, and did not overlap with, the confidence intervals of trial-averaged power during the fixation phase. CONCLUSIONS: To the authors' knowledge, this is the first time that direct neural recordings have been used to show gamma-band modulation in the human amygdala during the execution of voluntary movement. This work indicates that gamma-band modulation in the amygdala could be a contributing source of neural signals for use in a motor BCI system.

Understanding the human conflict processing network: A review of the literature on direct neural recordings during performance of a modified stroop task.

The Stroop Task is a well-known neuropsychological task developed to investigate conflict processing in the human brain. Our group has utilized direct intracranial neural recordings in various brain regions during performance of a modified color-word Stroop Task to gain a mechanistic understanding of non-emotional human conflict processing. The purpose of this review article is to: 1) synthesize our own studies into a model of human conflict processing, 2) review the current literature on the Stroop Task and other conflict tasks to put our research in context, and 3) describe how these studies define a network in conflict processing. The figures presented are reprinted from our prior publications and key publications referenced in the manuscript. We summarize all studies to date that employ invasive intracranial recordings in humans during performance of conflict-inducing tasks. For our own studies, we analyzed local field potentials (LFPs) from patients with implanted stereotactic electroencephalography (SEEG) electrodes, and we observed intracortical oscillation patterns as well as intercortical temporal relationships in the hippocampus, amygdala, and orbitofrontal cortex (OFC) during the cue-processing phase of a modified Stroop Task. Our findings suggest that non-emotional human conflict processing involves modulation across multiple frequency bands within and between brain structures.

A review of neurophysiological effects and efficiency of waveform parameters in deep brain stimulation.

Neurostimulation has diverse clinical applications and potential as a treatment for medically refractory movement disorders, epilepsy, and other neurological disorders. However, the parameters used to program electrodes-polarity, pulse width, amplitude, and frequency-and how they are adjusted have remained largely untouched since the 1970 s. This review summarizes the state-of-the-art in Deep Brain Stimulation (DBS) and highlights the need for further research to uncover the physiological mechanisms of neurostimulation. We focus on studies that reveal the potential for clinicians to use waveform parameters to selectively stimulate neural tissue for therapeutic benefit, while avoiding activating tissue associated with adverse effects. DBS uses cathodic monophasic rectangular pulses with passive recharging in clinical practice to treat neurological conditions such as Parkinson's Disease. However, research has shown that stimulation efficiency can be improved, and side effects reduced, through modulating parameters and adding novel waveform properties. These developments can prolong implantable pulse generator lifespan, reducing costs and surgery-associated risks. Waveform parameters can stimulate neurons based on axon orientation and intrinsic structural properties, providing clinicians with more precise targeting of neural pathways. These findings could expand the spectrum of diseases treatable with neuromodulation and improve patient outcomes.

Theta low-gamma phase amplitude coupling in the human orbitofrontal cortex increases during a conflict-processing task.

Objective. The human orbitofrontal cortex (OFC) is involved in automatic response inhibition and conflict processing, but the mechanism of frequency-specific power changes that control these functions is unknown. Theta and gamma activity have been independently observed in the OFC during conflict processing, while theta-gamma interactions in other brain areas have been noted primarily in studies of memory. Within the OFC, it is possible that theta-gamma phase amplitude coupling (PAC) drives conflict processing. This study aims to characterize the coupled relationship between theta and gamma frequency bands in the OFC during conflict processing using a modified Stroop task.Approach. Eight epilepsy patients implanted with OFC stereotactic electroencephalography electrodes participated in a color-word modified Stroop task. PAC between theta phase and gamma amplitude was assessed to determine the timing and magnitude of neural oscillatory changes. Group analysis was conducted using a non-parametric cluster-permutationt-test on coherence values.Main results.Theta-low gamma (LG) PAC significantly increased in five out of eight patients during successful trials of the incongruent condition compared with the congruent condition. Significant increases in theta-LG PAC were most prominent during cue processing 200-800 ms after cue presentation. On group analysis, trial-averaged mean theta-LG PAC was statistically significantly greater in the incongruent condition compared to the congruent condition (p< 0.001, Cohen'sd= 0.51).Significance.For the first time, we report that OFC theta phase and LG amplitude coupling increases during conflict resolution. Given the delayed onset after cue presentation, OFC theta-LG PAC may contribute to conflict processing after conflict detection and before motor response. This explanation follows the hypothesis that global theta waves modulate local gamma signals. Understanding this relationship within the OFC will help further elucidate the neural mechanisms of human conflict resolution.

Baseline hippocampal beta band power is lower in the presence of movement uncertainty.

Objective.This study aimed to characterize hippocampal neural signatures of uncertainty by measuring beta band power in the period prior to movement cue.Approach. Participants with epilepsy were implanted with hippocampal depth electrodes for stereo electroencephalographic (SEEG) monitoring. Hippocampal beta (13-30 Hz) power changes have been observed during motor tasks such as the direct reach (DR) and Go/No-Go (GNG) tasks. The primary difference between the tasks is the presence of uncertainty about whether movement should be executed. Previous research on cortical responses to uncertainty has found that baseline beta power changes with uncertainty. SEEG data were sampled throughout phases of the DR and GNG tasks. Beta-band power during the fixation phase was compared between the DR and GNG task using a Wilcoxon rank sum test. This unpaired test was also used to analyze response times from cue to task completion between tasks.Main results.Eight patients who performed both reaching tasks were analyzed in this study. Movement response times in the GNG task were on average 210 milliseconds slower than in the DR task. All patients exhibited a significantly increased response latency in the GNG task compared to the DR task (Wilcoxon rank-sum p-value < 0.001). Six out of eight patients demonstrated statistically significant differences in beta power in single hippocampal contacts between the fixation phases of the GNG and DR tasks. At the group level, baseline beta power was significantly lower in the GNG task than in the DR task (Wilcoxon rank-sum p-value < 0.001).Significance. This novel study found that, in the presence of task uncertainty, baseline beta power in the hippocampus is lower than in its absence. This finding implicates movement uncertainty as an important factor in baseline hippocampal beta power during movement preparation.

Hippocampal and Orbitofrontal Theta Band Coherence Diminishes During Conflict Resolution.

OBJECTIVE: Coherence between the hippocampus and other brain structures has been shown with the theta frequency (3-8 Hz). Cortical decreases in theta coherence are believed to reflect response accuracy efficiency. However, the role of theta coherence during conflict resolution is poorly understood in noncortical areas. In this study, coherence between the hippocampus and orbitofrontal cortex (OFC) was measured during a conflict resolution task. Although both brain areas have been previously implicated in the Stroop task, their interactions are not well understood. METHODS: Nine patients were implanted with stereotactic electroencephalography contacts in the hippocampus and OFC. Local field potential data were sampled throughout discrete phases of a Stroop task. Coherence was calculated for hippocampal and OFC contact pairs, and coherence spectrograms were constructed for congruent and incongruent conditions. Coherence changes during cue processing were identified using a nonparametric cluster-permutation t test. Group analysis was conducted to compare overall theta coherence changes among conditions. RESULTS: In 6 of 9 patients, decreased theta coherence was observed only during the incongruent condition (P < 0.05). Congruent theta coherence did not change from baseline. Group analysis showed lower theta coherence for the incongruent condition compared with the congruent condition (P < 0.05). CONCLUSIONS: Theta coherence between the hippocampus and OFC decreased during conflict. This finding supports existing theories that theta coherence desynchronization contributes to improved response accuracy and processing efficiency during conflict resolution. The underlying theta coherence observed between the hippocampus and OFC during conflict may be distinct from its previously observed role in memory.

Amygdaloid theta-band power increases during conflict processing in humans.

The amygdala is a medial temporal lobe structure known to be involved in processing emotional conflict. However, its role in processing non-emotional conflict is not well understood. Previous studies have utilized the Stroop Task to examine brain modulation of humans under the color-word conflict scenario, which is non-emotional conflict processing, and found hippocampal theta-band (4-7 Hz) modulation. This study aims to survey amygdaloid theta power changes during non-emotional conflict processing using intracranial depth electrodes in nine epileptic patients (3 female; age 20-62). All patients were asked to perform a modified Stroop task. During task performance, local field potential (LFP) data was recorded from macro contacts sampled at 2 K Hz and used for analysis. Mean theta power change from baseline was compared between the incongruent and congruent task condition groups using a paired sample t-test. Seven patients were available for analysis after artifact exclusion. In five out of seven patients, statistically significant increases in theta-band power from baseline were noted during the incongruent task condition (paired sample t-test p < 0.001), including one patient exhibiting theta power increases in both task conditions. Average response time was 1.07 s (failure trials) and 1.04 s (success trials). No speed-accuracy tradeoff was noted in this analysis. These findings indicate that human amygdaloid theta-band modulation may play a role in processing non-emotional conflict. It builds directly upon work suggesting that the amygdala processes emotional conflict and provides a neurophysiological mechanism for non-emotional conflict processing as well.

Beta-band modulation in the human hippocampus during a conflict response task.

Objective. Identify the role of beta-band (13-30 Hz) power modulation in the human hippocampus during conflict processing.Approach. We investigated changes in the spectral power of the beta band (13-30 Hz) as measured by depth electrode leads in the hippocampus during a modified Stroop task in six patients with medically refractory epilepsy. Previous work done with direct electrophysiological recordings in humans has shown hippocampal theta-band (3-8 Hz) modulation during conflict processing. Local field potentials sampled at 2 k Hz were used for analysis and a non-parametric cluster-permutationt-test was used to identify the time period and frequency ranges of significant power change during cue processing (i.e. post-stimulus, pre-response).Main results. In five of the six patients, we observe a statistically significant increase in hippocampal beta-band power during successful conflict processing in the incongruent trial condition (cluster-based correction for multiple comparisons,p< 0.05). There was no significant beta-band power change observed during the cue-processing period of the congruent condition in the hippocampus of these patients.Significance. The beta-power changes during conflict processing represented here are consistent with previous studies suggesting that the hippocampus plays a role in conflict processing, but it is the first time that the beta band has been shown to be involved in humans with direct electrophysiological evidence. We propose that beta-band modulation plays a role in successful conflict detection and automatic response inhibition in the human hippocampus as studied during a conflict response task.

Beta-band power modulation in the human hippocampus during a reaching task.

OBJECTIVE: Characterize the role of the beta-band (13-30 Hz) in the human hippocampus during the execution of voluntary movement. APPROACH: We recorded electrophysiological activity in human hippocampus during a reach task using stereotactic electroencephalography (SEEG). SEEG has previously been utilized to study the theta band (3-8 Hz) in conflict processing and spatial navigation, but most studies of hippocampal activity during movement have used noninvasive measures such as fMRI. We analyzed modulation in the beta band (13-30 Hz), which is known to play a prominent role throughout the motor system including the cerebral cortex and basal ganglia. We conducted the classic 'center-out' direct-reach experiment with nine patients undergoing surgical treatment for medically refractory epilepsy. MAIN RESULTS: In seven of the nine patients, power spectral analysis showed a statistically significant decrease in power within the beta band (13-30 Hz) during the response phase, compared to the fixation phase, of the center-out direct-reach task using the Wilcoxon signed-rank hypothesis test (p < 0.05). SIGNIFICANCE: This finding is consistent with previous literature suggesting that the hippocampus may be involved in the execution of movement, and it is the first time that changes in beta-band power have been demonstrated in the hippocampus using human electrophysiology. Our findings suggest that beta-band modulation in the human hippocampus may play a role in the execution of voluntary movement.

A Phantom Study of the Spatial Precision and Accuracy of Stereotactic Localization Using Computed Tomography Imaging with the Leksell Stereotactic System.

BACKGROUND: Stereotactic localization of neurosurgical targets traditionally relies on computed tomography (CT), which is considered the optimal imaging modality for geometric accuracy. However, in-depth investigations that characterize the precision and accuracy of CT images are lacking. We used a CT phantom to examine interscanner precision and interprotocol accuracy in coordinate localization. METHODS: A polymethylacrylate phantom was scanned with Toshiba Aquilion 64 and GE Healthcare LightSpeed 16 CT scanners, using both helical and incremental single-slice (SS) image acquisition protocols. The X, Y, and Z coordinates of 94 points across 6 surfaces of the phantom were physically measured. The CT scan-derived coordinates were compared with the phantom coordinates and with each other to determine accuracy and precision, respectively. RESULTS: Using the SS imaging protocol, the mean (SD) interscanner disparity in localization was 0.93 (0.39) mm, given by the average Euclidean distance between the coordinates of the 2 scanners. This discrepancy significantly varied by axis and surface, with the greatest discrepancy in the Z-axis of 0.30 mm (95% confidence interval, 0.25-0.35; P = 0.05) and on the superior surface of 1.30 mm (95% confidence interval, 1.15-1.45; P = 0.05). SS acquisition was significantly more accurate than the helical protocol. CONCLUSIONS: We found evidence of clinically relevant inconsistency between 2 CT scanners used for stereotactic localization. SS image acquisition was superior to helical scanning with respect to localization accuracy. Interscanner consistency cannot be assumed. Institutions would benefit from identifying the errors inherent in their CT scanners.