Phase-locking Factor Research Articles

Motor oscillations reveal new correlates of error processing in the human brain

It has been demonstrated that during motor responses, the activation of the motor cortical regions emerges in close association with the activation of the medial frontal cortex implicated with performance monitoring and cognitive control. The present study explored the oscillatory neurodynamics of response-related potentials during correct and error responses to test the hypothesis that such continuous communication would modify the characteristics of motor potentials during performance errors. Electroencephalogram (EEG) was recorded at 64 electrodes in a four-choice reaction task and response-related potentials (RRPs) of correct and error responses were analysed. Oscillatory RRP components at extended motor areas were analysed in the theta (3.5–7 Hz) and delta (1–3 Hz) frequency bands with respect to power, temporal synchronization (phase-locking factor, PLF), and spatial synchronization (phase-locking value, PLV). Major results demonstrated that motor oscillations differed between correct and error responses. Error-related changes (1) were frequency-specific, engaging delta and theta frequency bands, (2) emerged already before response production, and (3) had specific regional topographies at posterior sensorimotor and anterior (premotor and medial frontal) areas. Specifically, the connectedness of motor and sensorimotor areas contra-lateral to the response supported by delta networks was substantially reduced during errors. Also, there was an error-related suppression of the phase stability of delta and theta oscillations at these areas. This synchronization reduction was accompanied by increased temporal synchronization of motor theta oscillations at bi-lateral premotor regions and by two distinctive error-related effects at medial frontal regions: (1) a focused fronto-central enhancement of theta power and (2) a separable enhancement of the temporal synchronization of delta oscillations with a localized medial frontal focus. Together, these observations indicate that the electrophysiological signatures of performance errors are not limited to the medial frontal signals, but they also involve the dynamics of oscillatory motor networks at extended cortical regions generating the movement. Also, they provide a more detailed picture of the medial frontal processes activated in relation to error processing.

Abnormal phase entrainment of low- and high-gamma-band auditory steady-state responses in schizophrenia

IntroductionGamma-band oscillatory deficits have attracted considerable attention as promising biomarkers of schizophrenia (SZ). Notably, a reduced auditory steady-state response (ASSR) in the low gamma band (40 Hz) is widely recognized as a robust finding among SZ patients. However, a comprehensive investigation into the potential utility of the high-gamma-band ASSR in detecting altered neural oscillations in SZ has not yet been conducted.MethodsThe present study aimed to assess the ASSR using magnetoencephalography (MEG) data obtained during steady-state stimuli at frequencies of 20, 30, 40, and 80 Hz from 23 SZ patients and 21 healthy controls (HCs). To evaluate the ASSR, we examined the evoked power and phase-locking factor (PLF) in the time-frequency domain for both the primary and secondary auditory cortices. Furthermore, we calculated the phase-locking angle (PLA) to examine oscillatory phase lead or delay in SZ patients. Taking advantage of the high spatial resolution of MEG, we also focused on the hemispheric laterality of low- and high-gamma-band ASSR deficits in SZ.ResultsWe found abnormal phase delay in the 40 Hz ASSR within the bilateral auditory cortex of SZ patients. Regarding the 80 Hz ASSR, our investigation identified an aberrant phase lead in the left secondary auditory cortex in SZ, accompanied by reduced evoked power in both auditory cortices.DiscussionGiven that abnormal phase lead on 80 Hz ASSR exhibited the highest discriminative power between HC and SZ, we propose that the examination of PLA in the 80 Hz ASSR holds significant promise as a robust candidate for identifying neurophysiological endophenotypes associated with SZ. Furthermore, the left-hemisphere phase lead observed in the deficits of 80 Hz PLA aligns with numerous prior studies, which have consistently proposed that SZ is characterized by left-lateralized brain dysfunctions.

Hearing Aid Delay Effects on Neural Phase Locking.

This study was designed to examine the effects of hearing aid delay on the neural representation of the temporal envelope. It was hypothesized that the comb-filter effect would disrupt neural phase locking, and that shorter hearing aid delays would minimize this effect. Twenty-one participants, ages 50 years and older, with bilateral mild-to-moderate sensorineural hearing loss were recruited through print advertisements in local senior newspapers. They were fitted with three different sets of hearing aids with average processing delays that ranged from 0.5 to 7 msec. Envelope-following responses (EFRs) were recorded to a 50-msec /da/ syllable presented through a speaker placed 1 meter in front of the participants while they wore the three sets of hearing aids with open tips. Phase-locking factor (PLF) and stimulus-to-response (STR) correlations were calculated from these recordings. Recordings obtained while wearing hearing aids with a 0.5-msec processing delay showed higher PLF and STR correlations compared with those with either 5-msec or 7-msec delays. No differences were noted between recordings of hearing aids with 5-msec and 7-msec delays. The degree of difference between hearing aids was greater for individuals who had milder degrees of hearing loss. Hearing aid processing delays disrupt phase locking due to mixing of processed and unprocessed sounds in the ear canal when using open domes. Given previous work showing that better phase locking correlates with better speech-in-noise performance, consideration should be given to reducing hearing aid processing delay in the design of hearing aid algorithms.

Classification of Parkinson’s disease with dementia using phase locking factor of event-related oscillations to visual and auditory stimuli

Objective. In the last decades, machine learning approaches have been widely used to distinguish Parkinson’s disease (PD) and many other neuropsychiatric diseases. They also speed up the clinicians and facilitate decision-making for several conditions with similar clinical symptoms. The current study attempts to detect PD with dementia (PDD) by event-related oscillations (EROs) during cognitive processing in two modalities, i.e. auditory and visual. Approach. The study was conducted to discriminate PDD from healthy controls (HC) using event-related phase-locking factors in slow frequency ranges (delta and theta) during visual and auditory cognitive tasks. Seventeen PDD and nineteen HC were included in the study, and linear discriminant analysis was used as a classifier. During classification analysis, multiple settings were implemented by using different sets of channels (overall, fronto-central and temporo-parieto-occipital (TPO) region), frequency bands (delta-theta combined, delta, theta, and low theta), and time of interests (0.1–0.7 s, 0.1–0.5 s and 0.1–0.3 s for delta, delta-theta combined; 0.1–0.4 s for theta and low theta) for spatial-spectral-temporal searchlight procedure. Main results. The classification performance results of the current study revealed that if visual stimuli are applied to PDD, the delta and theta phase-locking factor over fronto-central region have a remarkable contribution to detecting the disease, whereas if auditory stimuli are applied, the phase-locking factor in low theta over TPO and in a wider range of frequency (1–7 Hz) over the fronto-central region classify HC and PDD with better performances. Significance. These findings show that the delta and theta phase-locking factor of EROs during visual and auditory stimuli has valuable contributions to detecting PDD.

Decrease in gamma-band auditory steady-state response in patients with treatment-resistant schizophrenia

BackgroundThirty percent of patients with schizophrenia do not respond to non-clozapine antipsychotics and are termed treatment-resistant schizophrenia (TRS). The 40-Hz auditory steady-state response (ASSR) is a well-known to be reduced in patients with schizophrenia compared to healthy controls (HCs), suggesting impaired gamma oscillation in schizophrenia. Given no ASSR study on TRS, we aimed to examine the neurophysiological basis of TRS employing 40-Hz ASSR paradigm. MethodWe compared ASSR measures among HCs, patients with non-TRS, and patients with TRS. TRS criteria were defined by a score of 4 or higher on two items of the Positive and Negative Syndrome Scale (PANSS) positive symptoms despite standard antipsychotic treatment. Participants were examined for ASSR with 40-Hz click-train stimulus, and then time-frequency analysis was performed to calculate evoked power and phase-locking factor (PLF) of 40-Hz ASSR. ResultsA total of 79 participants were included: 27 patients with TRS (PANSS = 92.6 ± 15.8); 27 patients with non-TRS (PANSS = 63.3 ± 14.7); and 25 HCs. Evoked power in 40-Hz ASSR was lower in the TRS group than in the HC group (F2,79 = 8.37, p = 0.015; TRS vs. HCs: p = 0.012, d = 1.1) while no differences in PLF were found between the groups. ConclusionThese results suggest that glutamatergic and GABAergic neurophysiological dysfunctions are involved in the pathophysiology of TRS. Our findings warrant more comprehensive and longitudinal studies for deep phenotyping of TRS.

The Association between Electroencephalography with Auditory Steady-State Response and Postoperative Delirium.

Delirium is a disorder of consciousness and a risk factor for cognitive dysfunction and poor prognosis. We hypothesized that preoperative gamma activities would be linked to postoperative delirium. We enrolled 71 subjects for elective surgery and recorded auditory steady-state response (ASSR) by electroencephalography (EEG) before the surgery and examined postoperative delirium with DSM-5. The EEG data were analyzed for baseline power, and ASSR evoked power (EP) and phase-locking factor (PLF) within the gamma range. Postoperative delirium was found in 18 patients (delirium group) but not in 53 patients (non-delirium group). There were no significant differences in the 40-Hz EP or PLF between the two groups. The baseline gamma activity negatively correlated with the 40-Hz PLF in the non-delirium group (ρ = -0.444, p < 0.01). The correlation between baseline gamma activity and 40-Hz EP was not significant in either the delirium or non-delirium group. In all patients, both preoperative PLF and EP had no significant correlations with the Delirium Rating Scale Revised-98 and the Memorial Delirium Assessment Measure at the post-operation, respectively. The disruption of the neurophysiological relationship between baseline gamma activity before sound stimuli and the PLF of the 40-Hz ASSR may be one of the potential neurophysiological indicators associated with postoperative delirium.

Effect of dopamine receptor-related compounds on naïve common marmosets for auditory steady-state response.

Abnormalities of auditory steady-state responses (ASSRs) and the effects of antipsychotic drugs on ASSRs have been investigated in patients with schizophrenia. It is presumed that drugs do not directly affect ASSRs because its abnormalities are associated with schizophrenia. Therefore, to investigate the direct effect of drugs on ASSRs, we established an ASSR evaluation system for common marmosets in a naïve state. Dopamine D1 receptor stimulation (SKF-81297, 2 mg/kg ip) significantly increased evoked power (EP) at 40 Hz. The phase locking factor (PLF) was increased significantly at 20, 30, 40, and 80 Hz. However, administration of a dopamine D1 receptor antagonist (SCH-39166, 0.3 mg/kg ip) resulted in a significant decrease in EP and PLF at 30 Hz. Dopamine D2 receptor stimulation (quinpirole, 1 mg/kg im) tended to increase EP and induced power (IP) at all frequencies, and a significant difference was observed at 30 Hz IP. There was no change in PLF at all frequencies. In addition, dopamine D2 receptor blockade (raclopride, 3 mg/kg ip) reduced EP and PLF at 30 Hz. Subcutaneous administration of the serotonin dopamine antagonist, risperidone (0.3 mg/kg), tended to increase IP and decrease PLF, but not significantly. Taken together, it is possible to compare the differences in the mode of action of drugs on ASSRs using naïve nonhuman primates.NEW & NOTEWORTHY We measured the effects of dopamine receptor-related compounds on ASSR in marmosets. D1 receptor stimulation increased the phase locking factor (PLF) and evoked power (EP), and reduced the induced power (IP). D2 receptor stimulation increased the IP. D1 and D2 receptor blockers reduced the PLF and EP at 30 Hz. Different modes of action of various drugs related to psychiatric disorders were evaluated by administering antipsychotic drugs to naïve marmosets.

FV 19 Tracking complexity and causality during cortical reorganization and motor recovery after stroke

I: Combined TMS and EEG represents a non-invasive approach that informs about the local neural state as well as signal propagation within the functional network. Particularly, it has proven powerful at an individual level. In the context of stroke, the individual understanding of the neural mechanisms of reorganization that underlie recovery of function would, in consequence, enable the optimization of rehabilitation strategies including non-invasive neuromodulation. Again, in the context of stroke, TMS-EEG has recently not only revealed the occurrence of the phenomenon of local sleep-like slow waves in conscious awake stroke patients, but has also put these in association to the level of motor deficits and, crucially, the potential of neurological recovery in the chronic phase after stroke. However, a profound mechanistic understanding of the causal underpinnings of stroke recovery and a systematic link from the presence of sleep-like waves after stroke to their behavioral consequences require longitudinal measurements paralleled by clinical assessments. We, therefore, applied the method of TMS-EEG in a cohort of stroke patients in the first two weeks post-stroke, and followed both the course of functional recovery and the development of alterations of TMS-EEG responses through motor reorganization to the chronic stage. M: TMS over ipsilesional M1 combined with EEG in 40 patients with unilateral mild to severe motor deficits due to first-ever ischemic stroke was acquired in the first two weeks after stroke. 35 patients could be re-assessed behaviorally and 28 patients also participated in the TMS-EEG experiments in the chronic phase. TMS-evoked EEG activity of ipsilesional M1 was quantified by spectral and phase domain analysis yielding (i) the occurrence of TMS-evoked slow waves, (ii) cortical off-periods, i.e. high frequency suppression of EEG power, and (iii) local causal interactions quantified by means of phase-locking factor (PLF). Moreover, (iv) alterations of complex global interactions were indexed by the Perturbational Complexity Index (PCI). R: We demonstrated that the slow wave response locally evoked by the perturbation of ipsilesional M1 is associated with a cortical off-period and underpinned by a loss of global signal complexity and a rapid disruption of causal effects in the first weeks post-stroke. However, tracking these signal alterations in combination to the course of motor recovery during the reorganization after stroke revealed that sleep-like waves, independent on the degree of recovery, disappeared in the chronic stage, though their occurrence in the acute stage post-stroke is an indicator for a subsequent poor functional recovery. C: By linking slow waves and the deterioration of global brain dynamics to recovery after stroke, our findings not only link stroke to cortical bistability, a neuronal mechanism precisely characterized in NREM sleep, but put it in a behaviorally and clinically meaningful perspective.

Frequency-dependent effects of EEG phase resetting on reaction time

There is trial-to-trial variability in the reaction time to stimulus presentation. Since this variability exists even in an identical stimulus condition, it reflects the internal neural dynamics of the brain. To understand the neural dynamics that influence the reaction time, we conducted an electroencephalogram (EEG) experiment in which participants were asked to press a response button as quickly as possible when a stimulus was visually presented. Phase-locking factor analysis revealed that phase resetting in two frequency bands, which appeared 0.2 s after the stimulus presentation, characterized the reaction time. The combination of the theta band phase resetting in the left parietal region and the delta band phase resetting mainly in the posterior region was associated with the fastest reaction time, whereas delta band phase resetting without theta band phase resetting was associated with the faster reaction time. The results indicated that there were frequency-dependent effects in the relationships between the EEG phase resetting and reaction time.

Frequency- and Area-Specific Phase Entrainment of Intrinsic Cortical Oscillations by Repetitive Transcranial Magnetic Stimulation.

Synchronous oscillations are ubiquitous throughout the cortex, but the frequency of oscillations differs from area to area. To elucidate the mechanistic architectures underlying various rhythmic activities, we tested whether spontaneous neural oscillations in different local cortical areas and large-scale networks can be phase-entrained by direct perturbation with distinct frequencies of repetitive transcranial magnetic stimulation (rTMS). While recording the electroencephalogram (EEG), we applied single-pulse TMS (sp-TMS) and rTMS at 5, 11, and 23 Hz over the motor or visual cortex. We assessed local and global modulation of phase dynamics using the phase-locking factor (PLF). sp-TMS to the motor and the visual cortex triggered a transient increase in PLF in distinct frequencies that peaked at 21 and 8 Hz, respectively. rTMS at 23 Hz over the motor cortex and 11 Hz over the visual cortex induced a prominent and progressive increase in PLF that lasted for a few cycles after the termination of rTMS. Moreover, the local increase in PLF propagated to other cortical areas. These results suggest that distinct cortical areas have area-specific oscillatory frequencies, and the manipulation of oscillations in local areas impacts other areas through the large-scale oscillatory network with the corresponding frequency specificity. We speculate that rTMS that is close to area-specific frequencies (natural frequencies) enables direct manipulation of brain dynamics and is thus useful for investigating the causal roles of synchronous neural oscillations. Moreover, this technique could be used to treat clinical symptoms associated with impaired oscillations and synchrony.

Decreased Gamma Auditory Steady-State Response Is Associated With Impaired Real-World Functioning in Unmedicated Patients at Clinical High Risk for Psychosis.

Deficits in synchronous, gamma-frequency neural oscillations may contribute to schizophrenia patients' real-world functional impairment and can be measured electroencephalographically using the auditory steady-state response (ASSR). Gamma ASSR deficits have been reported in schizophrenia patients and individuals at clinical high risk (CHR) for developing psychosis. We hypothesized that, in CHR patients, gamma ASSR would correlate with real-world functioning, consistent with a role for gamma synchrony deficits in functional impairment. A total of 35 CHR patients rated on Global Functioning: Social and Role scales had EEG recorded while listening to 1-ms, 93-dB clicks presented at 40 Hz in 500-ms trains, in response to which 40-Hz evoked power and intertrial phase-locking factor (PLF) were measured. In CHR patients, lower 40-Hz PLF correlated with lower social functioning. Gamma synchrony deficits may be a biomarker of real-world impairment at early stages of the schizophrenia disease trajectory.

Long-Term Test-Retest Reliability of Auditory Gamma Oscillations Between Different Clinical EEG Systems.

ObjectiveThere is increasing interest in the utility of gamma-band activity for assessing various brain functions, including perception, language, memory, and cognition. The auditory steady-state response (ASSR) involves neural activity in the brain elicited by trains of a click sound, and its maximum response is obtained at 40 Hz (40-Hz ASSR). Abnormalities of the 40-Hz ASSR are also widely reported in patients with schizophrenia. Thus, the test-retest reliability of the ASSR is important for its clinical and translational application. However, there are only limited studies reporting the short-term reliability between acquisitions at two time points made using the same electroencephalogram (EEG) system. Furthermore, the long-term reliability between multiple EEG systems and the reliability of spontaneous gamma activity are unknown but are crucial for multicenter collaborative research.MethodsWe examined the long-term test–retest reliability of 40-Hz ASSR oscillatory activities indexed by the phase locking factor (PLF), evoked power, and (non-phase-locked) induced power between two clinical 19-electrode EEG systems [recorded twice for EEG-1 (time1 and time2) and EEG-2 (time3 and time4)] at four time points from 14 healthy controls over a duration of 5 months. Test-retest reliability was examined using intraclass correlation coefficients (ICCs).ResultsBoth PLF and evoked power showed good to excellent ICCs (>0.60), mainly in the Fz-electrode, both within each EEG system—EEG-1 [(time1 vs. time2) PLF: ICC = 0.66, evoked power: ICC = 0.88] and EEG-2 [(time3 vs. time4) PLF: ICC = 0.82, evoked power: ICC = 0.77]—and between the two EEG systems [(EEG-1 vs. EEG-2) PLF: ICC = 0.73, evoked power: ICC = 0.84]. In contrast, induced power showed the highest (excellent) ICC between the two EEG systems (ICC = 0.95) mainly in the Cz-electrode. For PLF, the Fz-electrode showed better test-retest reliability across all EEG recordings than the Cz-electrode (Fz: ICC = 0.67, Cz: ICC = 0.63), whereas we found similar excellent reproducibility across all EEG recordings from both electrodes for evoked power (Fz: ICC = 0.79, Cz: ICC = 0.77) and induced power (Fz: ICC = 0.79, Cz: ICC = 0.80).ConclusionThe 40-Hz ASSR oscillatory activities, including induced power, showed excellent test-retest reliability, even when using different EEG systems over a duration of 5 months. These findings confirm the utility of the 40-Hz ASSR as a reliable clinical and translatable biomarker for multicenter collaborative research.

Aberrant Auditory Steady-State Response of Awake Mice After Single Application of the NMDA Receptor Antagonist MK-801 Into the Medial Geniculate Body

BackgroundSystemic administration of noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists such as MK-801 is widely used to model psychosis of schizophrenia (SZ). Acute systemic MK-801 in rodents caused an increase of the auditory steady-state responses (ASSRs), the oscillatory neural responses to periodic auditory stimulation, while most studies in patients with SZ reported a decrease of ASSRs. This inconsistency may be attributable to the comprehensive effects of systemic administration of MK-801. Here, we examined how the ASSR is affected by selectively blocking NMDAR in the thalamus.MethodsWe implanted multiple electrodes in the auditory cortex (AC) and prefrontal cortex to simultaneously record the local field potential and spike activity (SA) of multiple sites from awake mice. Click-trains at a 40-Hz repetition rate were used to evoke the ASSR. We compared the mean trial power and phase-locking factor and the firing rate of SA before and after microinjection of MK-801 (1.5 µg) into the medial geniculate body (MGB).ResultsWe found that both the AC and prefrontal cortex showed a transient local field potential response at the onset of click-train stimulus, which was less affected by the application of MK-801 in the MGB. Following the onset response, the AC also showed a response continuing throughout the stimulus period, corresponding to the ASSR, which was suppressed by the application of MK-801.ConclusionOur data suggest that the MGB is one of the generators of ASSR, and NMDAR hypofunction in the thalamocortical projection may account for the ASSR deficits in SZ.

Aging-related changes in motor response-related theta activity

It has been suggested that a distributed oscillatory system in the brain operating in the theta (3.5–7 Hz) frequency range plays a major role in coordinating motor actions. The major objective of the present study was to explore the effects of human aging on the neurodynamics of motor-related EEG theta activity during correct motor response generation. Response-related potentials of young and older adults elicited in auditory and visual four-choice sensorimotor tasks were analyzed in the time-frequency domain. The phase-locking factor and total power were computed at motor cortical regions contra- and ipsilateral to the movement and at the midline to reflect phase synchronization and power of motor theta oscillations. Major results demonstrated that in both young and older adults, a pronounced response-locked theta activity (3.5–7 Hz) was generated at premotor, motor and sensorimotor cortical regions contra-lateral to the responding hand. Aging was associated with a decreased lateral asymmetry in the phase synchronization of only the left-hand responses. Also, there was a strong aging-related suppression of theta power at the medial fronto-central region that was specifically enhanced and correlated with response speed only in young adults. These results confirm the involvement of theta oscillations in movement generation in relation to action coordination in humans. Also, they show that aging is associated with a dysfunction of the oscillatory theta system for motor action regulation due to a strong suppression of a medial frontal integrating mechanism and an impaired balance in the functional control of responses with the right and the left hand.

Auditory Cortex Volume and Gamma Oscillation Abnormalities in Schizophrenia.

We investigated whether the gray matter volume of primary auditory cortex (Heschl's gyrus [HG]) was associated with abnormal patterns of auditory γ activity in schizophrenia, namely impaired γ synchronization in the 40-Hz auditory steady-state response (ASSR) and increased spontaneous broadband γ power. (The γ data were previously reported in Hirano et al, JAMA Psychiatry, 2015;72:813-821). Participants were 24 healthy controls (HC) and 23 individuals with chronic schizophrenia (SZ). The ASSR was obtained from the electroencephalogram to click train stimulation at 20, 30, and 40 Hz rates. Dipole source localization of the ASSR was used to provide a spatial filter of auditory cortex activity, from which ASSR evoked power and phase locking factor (PLF), and induced γ power were computed. HG gray matter volume was derived from structural magnetic resonance imaging at 3 T with manually traced regions of interest. As expected, HG gray matter volume was reduced in SZ compared with HC. In SZ, left hemisphere ASSR PLF and induced γ power during the 40-Hz stimulation condition were positively and negatively correlated with left HG gray matter volume, respectively. These results provide evidence that cortical gray matter structure, possibly resulting from reduced synaptic connectivity at the microcircuit level, is related to impaired γ synchronization and increased spontaneous γ activity in schizophrenia.

On the relevance of EEG resting theta activity for the neurophysiological dynamics underlying motor inhibitory control.

The modulation of theta frequency activity plays a major role in inhibitory control processes. However, the relevance of resting theta band activity and of the ability to spontaneously modulate this resting theta activity for neural mechanisms underlying inhibitory control is elusive. Various theoretical conceptions suggest to take these aspects into consideration. In the current study, we examine whether the strength of resting theta band activity or the ability to modulate the resting state theta activity affects response inhibition. We combined EEG-time frequency decomposition and beamforming in a conflict-modulated Go/Nogo task. A sample of N = 66 healthy subjects was investigated. We show that the strength of resting state theta activity modulates the effects of conflicts during motor inhibitory control. Especially when resting theta activity was low, conflicts strongly affected response inhibition performance and total theta band activity during Nogo trials. These effects were associated with theta-related activity differences in the superior (BA7) and inferior parietal cortex (BA40). The results were very specific for total theta band activity since evoked theta activity and measures of intertrial phase coherency (phase-locking factor) were not affected. The data suggest that the strength of resting state theta activity modulates processing of a theta-related alarm or surprise signal during inhibitory control. The ability to voluntarily modulate theta band activity did not affect conflict-modulated inhibitory control. These findings have important implications for approaches aiming to optimize human cognitive control.

Auditory entrainment of motor responses in older adults with and without Parkinson’s disease: An MEG study

Medical therapies applied to Parkinson’s disease (PD) have advanced tremendously since the 1960’s based on advances in our understanding of the underlying neurophysiology. Behavioral therapies, such as rhythmic auditory stimulation (RAS), have been developed more recently and demonstrated efficacy. However, the neural mechanisms of RAS are only vaguely understood. In this study, we examined the neurophysiology of RAS using magnetoencephalography (MEG) in a sample of older adults with (21 people) and without PD (23 participants). All participants underwent high-density MEG during a beat-based cued tapping task with rhythmic and non-rhythmic patterns, and the resulting data were analyzed using a Bayesian image reconstruction method. Complex wavelet based time-frequency decomposition was used to compute inter-trial phase locking factor (PLF) to auditory stimuli for left and right signal space projection vectors. Tapping with a rhythm compared to a non-rhythmic sequence resulted in differential brain activity in each group: (i) a greater activation of temporal, motor and parietal areas was found in healthy adults; (ii) a greater reliance on parietal and frontal gyri was found in PD participants. During rhythmic tapping, older adults without PD had significantly stronger neural activity in bilateral frontal, supplementary and primary motor areas compared to those with PD. Conversely, older adults with PD exhibited significantly stronger activity in the bilateral parietal regions, as well as the rolandic operculum and bilateral supramarginal gyri, relative to their healthy peers. These data suggest that RAS mobilizes diverse oscillatory networks; Healthy controls may shift to frontal areas mobilization whereas PD patients rely on parietal areas to a greater extent, which may reflect frontal network dysfunction with compensation in PD, and could serve as specific regions of interest for further RAS studies.

Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine

Abnormal gamma-band oscillations (GBO) have been frequently associated with the pathophysiology of schizophrenia. GBO are modulated by glutamate, a neurotransmitter, which is continuously discussed to shape the complex symptom spectrum in schizophrenia. The current study examined the effects of ketamine, a glutamate N-methyl-d-aspartate receptor (NMDAR) antagonist, on the auditory-evoked gamma-band response (aeGBR) and psychopathological outcomes in healthy volunteers to investigate neuronal mechanisms of psychotic behavior. In a placebo-controlled, randomized crossover design, the aeGBR power, phase-locking factor (PLF) during a choice reaction task, the Positive and Negative Syndrome Scale (PANSS) and the Altered State of Consciousness (5D-ASC) Rating Scale were assessed in 25 healthy subjects. Ketamine was applied in a subanaesthetic dose. Low-resolution brain electromagnetic tomography was used for EEG source localization. Significant reductions of the aeGBR power and PLF were identified under ketamine administration compared to placebo (p < 0.01). Source-space analysis of aeGBR generators revealed significantly reduced current source density (CSD) within the anterior cingulate cortex during ketamine administration. Ketamine induced an increase in all PANSS (p < 0.001) as well as 5D-ASC scores (p < 0.01) and increased response times (p < 0.001) and error rates (p < 0.01). Only negative symptoms were significantly associated with an aeGBR power decrease (p = 0.033) as revealed by multiple linear regression. These findings argue for a substantial role of the glutamate system in the mediation of dysfunctional gamma band responses and negative symptomatology of schizophrenia and are compatible with the NMDAR hypofunction hypothesis of schizophrenia.

The influence of aerobic fitness on top-down and bottom-up mechanisms of interference control.

Extensive evidence has demonstrated the relationship between aerobic fitness and cognitive function in early adulthood. Little is known, however, about whether the cognitive benefits of aerobic fitness are related to the modulation of top-down or bottom-up mechanisms in the control of executive attention. The present study aimed to shed light on this question by evaluating the phase-locking factor (PLF) of electroencephalogram (EEG) signal during cognitive control. Higher fit and lower fit young adults performed a neuropsychological test of cognitive control (i.e., Stroop color-naming task) with concurrent EEG recording. In line with previous literature, behavioral results showed that higher fit individuals performed better on the Stroop task overall. Interestingly, beta phase synchronization was larger during the incongruent condition than the congruent condition for higher fit but not for lower fit individuals, suggesting a more effective use of top-down control in the former. However, no such effect was seen for gamma activity, indicating that bottom-up mechanisms are unlikely to account for the differences in performance explained by fitness levels. Altogether, these findings suggest that the greater cognitive control observed in higher fit individuals is associated with differences in the control of top-down rather than bottom-up processing, consistent with the hypothesis of selective improvement. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

A novel approach for assessing neuromodulation using phase-locked information measured with TMS-EEG

Neuromodulation therapies such as electroconvulsive therapy (ECT) are used to treat several neuropsychiatric disorders, including major depressive disorder (MDD). Recent work has highlighted the use of combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) to evaluate the therapeutic effects of neuromodulation; particularly, the phase locking factor (PLF) and phase locking value (PLV) can reportedly assess neuromodulation-induced functional changes in cortical networks. To examine changes in TMS-induced PLV and PLF before and after ECT, and their relationship with depression severity in patients with MDD, TMS-EEG and the Montgomery–Åsberg Depression Rating Scale (MADRS; depression severity) were implemented before and after ECT in 10 patients with MDD. Single-pulse TMS was applied to the visual and motor areas to induce phase propagation in the visuo-motor network at rest. Functional changes were assessed using PLF and PLV data. Pre-ECT TMS-induced alpha band (9–12 Hz) PLV was negatively correlated with depression severity, and increments of post-ECT from pre-ECT TMS-induced alpha band PLV were positively correlated with the reduction in depression severity. Moreover, we found a negative correlation between pre-ECT TMS-induced PLF at TMS-destination and depression severity. Finally, differences in post-ECT TMS-induced PLF peak latencies between visual and motor areas were positively correlated with depression severity. TMS-EEG-based PLV and PLF may be used to assess the therapeutic effects of neuromodulation and depressive states, respectively. Furthermore, our results provide new insights about the neural mechanisms of ECT and depression.