Correction: Grasping Hand Verbs: Oscillatory Beta and Alpha Correlates of Action-Word Processing.

[This corrects the article DOI: 10.1371/journal.pone.0108059.].

Beta Peak Frequencies at Rest Correlate with Endogenous GABA+/Cr Concentrations in Sensorimotor Cortex Areas.

Neuronal oscillatory activity in the beta band (15-30 Hz) is a prominent signal within the human sensorimotor cortex. Computational modeling and pharmacological modulation studies suggest an influence of GABAergic interneurons on the generation of beta band oscillations. Accordingly, studies in humans have demonstrated a correlation between GABA concentrations and power of beta band oscillations. It remains unclear, however, if GABA concentrations also influence beta peak frequencies and whether this influence is present in the sensorimotor cortex at rest and without pharmacological modulation. In the present study, we investigated the relation between endogenous GABA concentration (measured by magnetic resonance spectroscopy) and beta oscillations (measured by magnetoencephalography) at rest in humans. GABA concentrations and beta band oscillations were measured for left and right sensorimotor and occipital cortex areas. A significant positive linear correlation between GABA concentration and beta peak frequency was found for the left sensorimotor cortex, whereas no significant correlations were found for the right sensorimotor and the occipital cortex. The results show a novel connection between endogenous GABA concentration and beta peak frequency at rest. This finding supports previous results that demonstrated a connection between oscillatory beta activity and pharmacologically modulated GABA concentration in the sensorimotor cortex. Furthermore, the results demonstrate that for a predominantly right-handed sample, the correlation between beta band oscillations and endogenous GABA concentrations is evident only in the left sensorimotor cortex.

Parkinsonian Rest Tremor Is Associated With Modulations of Subthalamic High-Frequency Oscillations.

BACKGROUND: High frequency oscillations (>200 Hz) have been observed in the basal ganglia of PD patients and were shown to be modulated by the administration of levodopa and voluntary movement. OBJECTIVE: The objective of this study was to test whether the power of high-frequency oscillations in the STN is associated with spontaneous manifestation of parkinsonian rest tremor. METHODS: The electromyogram of both forearms and local field potentials from the STN were recorded in 11 PD patients (10 men, age 58 [9.4] years, disease duration 9.2 [6.3] years). Patients were recorded at rest and while performing repetitive hand movements before and after levodopa intake. High-frequency oscillation power was compared across epochs containing rest tremor, tremor-free rest, or voluntary movement and related to the tremor cycle. RESULTS: We observed prominent slow (200-300 Hz) and fast (300-400 Hz) high-frequency oscillations. The ratio between slow and fast high-frequency oscillation power increased when tremor became manifest. This increase was consistent across nuclei (94%) and occurred in medication ON and OFF. The ratio outperformed other potential markers of tremor, such as power at individual tremor frequency, beta power, or low gamma power. For voluntary movement, we did not observe a significant difference when compared with rest or rest tremor. Finally, rhythmic modulations of high-frequency oscillation power occurred within the tremor cycle. CONCLUSIONS: Subthalamic high-frequency oscillation power is closely linked to the occurrence of parkinsonian rest tremor. The balance between slow and fast high-frequency oscillation power combines information on motor and medication state. © 2016 International Parkinson and Movement Disorder Society.

Low visual cortex GABA levels in hepatic encephalopathy: links to blood ammonia, critical flicker frequency, and brain osmolytes.

The pathogenesis of hepatic encephalopathy (HE) is not fully understood yet. Hyperammonemia due to liver failure and subsequent disturbance of cerebral osmolytic balance is thought to play a pivotal role in the emergence of HE. The aim of this in-vivo MR spectroscopy study was to investigate the levels of γ-aminobutyric acid (GABA) and its correlations with clinical symptoms of HE, blood ammonia, critical flicker frequency, and osmolytic levels. Thirty patients with minimal HE or HE1 and 16 age-matched healthy controls underwent graduation of HE according to the West-Haven criteria and including the critical flicker frequency (CFF), neuropsychometric testing and blood testing. Edited proton magnetic resonance spectroscopy ((1)H MRS) was used to non-invasively measure the concentrations of GABA, glutamate (Glu), glutamine (Gln), and myo-inositol (mI) - all normalized to creatine (Cr) - in visual and sensorimotor cortex. GABA/Cr in the visual area was significantly decreased in mHE and HE1 patients and correlated both to the CFF (r = 0.401, P = 0.013) and blood ammonia levels (r = -0.434, P = 0.006). Visual GABA/Cr was also strongly linked to mI/Cr (r = 0.720, P < 0.001) and Gln/Cr (r = -0.699, P < 0.001). No group differences or correlations were found for GABA/Cr in the sensorimotor area. Hepatic encephalopathy is associated with a regional specific decrease of GABA levels in the visual cortex, while no changes were revealed for the sensorimotor cortex. Correlations of visual GABA/Cr with CFF, blood ammonia, and osmolytic regulators mI and Gln indicate that decreased visual GABA levels might contribute to HE symptoms, most likely as a consequence of hyperammonemia.

Grasping hand verbs: oscillatory beta and alpha correlates of action-word processing.

The grounded cognition framework proposes that sensorimotor brain areas, which are typically involved in perception and action, also play a role in linguistic processing. We assessed oscillatory modulation during visual presentation of single verbs and localized cortical motor regions by means of isometric contraction of hand and foot muscles. Analogously to oscillatory activation patterns accompanying voluntary movements, we expected a somatotopically distributed suppression of beta and alpha frequencies in the motor cortex during processing of body-related action verbs. Magnetoencephalographic data were collected during presentation of verbs that express actions performed using the hands (H) or feet (F). Verbs denoting no bodily movement (N) were used as a control. Between 150 and 500 msec after visual word onset, beta rhythms were suppressed in H and F in comparison with N in the left hemisphere. Similarly, alpha oscillations showed left-lateralized power suppression in the H-N contrast, although at a later stage. The cortical oscillatory activity that typically occurs during voluntary movements is therefore found to somatotopically accompany the processing of body-related verbs. The combination of a localizer task with the oscillatory investigation applied to verb reading as in the present study provides further methodological possibilities of tracking language processing in the brain.

Hepatic encephalopathy is associated with slowed and delayed stimulus-associated somatosensory alpha activity.

OBJECTIVE: Hepatic encephalopathy (HE) is associated with motor symptoms and attentional deficits, which are related to pathologically slowed oscillatory brain activity. Here, potential alterations of oscillatory activity in the somatosensory system were investigated. METHODS: 21 patients with liver cirrhosis and varying HE severity and 7 control subjects received electrical stimulation of the right median nerve while brain activity was recorded using magnetoencephalography (MEG). Oscillatory activity within the contralateral primary somatosensory cortex (S1) and its stimulus-induced modulation were analyzed as a function of disease severity. RESULTS: Median nerve stimuli evoked an early broadband power increase followed by suppression and then rebound of S1 alpha and beta activity. Increasing HE severity as quantified by the critical flicker frequency (CFF) was associated with a slowing of the alpha peak frequency and a delay of the alpha rebound. CONCLUSION: The present results provide the first evidence for a slowing of oscillatory activity in the somatosensory system in HE in combination with a previously unknown deficit of S1 in adjusting activation levels back to baseline. SIGNIFICANCE: These findings advance the understanding of the manifold symptoms of HE by strengthening the theory that disease related slowing of oscillatory brain activity also affects the somatosensory system.

Beamformer source analysis and connectivity on concurrent EEG and MEG data during voluntary movements.

Electroencephalography (EEG) and magnetoencephalography (MEG) are the two modalities for measuring neuronal dynamics at a millisecond temporal resolution. Different source analysis methods, to locate the dipoles in the brain from which these dynamics originate, have been readily applied to both modalities alone. However, direct comparisons and possible advantages of combining both modalities have rarely been assessed during voluntary movements using coherent source analysis. In the present study, the cortical and sub-cortical network of coherent sources at the finger tapping task frequency (2-4 Hz) and the modes of interaction within this network were analysed in 15 healthy subjects using a beamformer approach called the dynamic imaging of coherent sources (DICS) with subsequent source signal reconstruction and renormalized partial directed coherence analysis (RPDC). MEG and EEG data were recorded simultaneously allowing the comparison of each of the modalities separately to that of the combined approach. We found the identified network of coherent sources for the finger tapping task as described in earlier studies when using only the MEG or combined MEG+EEG whereas the EEG data alone failed to detect single sub-cortical sources. The signal-to-noise ratio (SNR) level of the coherent rhythmic activity at the tapping frequency in MEG and combined MEG+EEG data was significantly higher than EEG alone. The functional connectivity analysis revealed that the combined approach had more active connections compared to either of the modalities during the finger tapping (FT) task. These results indicate that MEG is superior in the detection of deep coherent sources and that the SNR seems to be more vital than the sensitivity to theoretical dipole orientation and the volume conduction effect in the case of EEG.

Multi-modal causality analysis of eyes-open and eyes-closed data from simultaneously recorded EEG and MEG.

Owing to the recent advances in multi-modal data analysis, the aim of the present study was to analyze the functional network of the brain which remained the same during the eyes-open (EO) and eyes-closed (EC) resting task. The simultaneously recorded electroencephalogram (EEG) and magnetoencephalogram (MEG) were used for this study, recorded from five distinct cortical regions of the brain. We focused on the 'alpha' functional network, corresponding to the individual peak frequency in the alpha band. The total data set of 120 seconds was divided into three segments of 18 seconds each, taken from start, middle, and end of the recording. This segmentation allowed us to analyze the evolution of the underlying functional network. The method of time-resolved partial directed coherence (tPDC) was used to assess the causality. This method allowed us to focus on the individual peak frequency in the 'alpha' band (7-13 Hz). Because of the significantly higher power in the recorded EEG in comparison to MEG, at the individual peak frequency of the alpha band, results rely only on EEG. The MEG was used only for comparison. Our results show that different regions of the brain start to `disconnect' from one another over the course of time. The driving signals, along with the feedback signals between different cortical regions start to recede over time. This shows that, with the course of rest, brain regions reduce communication with each another.

A direct relationship between oscillatory subthalamic nucleus-cortex coupling and rest tremor in Parkinson's disease.

Electrophysiological studies suggest that rest tremor in Parkinson's disease is associated with an alteration of oscillatory activity. Although it is well known that tremor depends on cortico-muscular coupling, it is unclear whether synchronization within and between brain areas is specifically related to the presence and severity of tremor. To tackle this longstanding issue, we took advantage of naturally occurring spontaneous tremor fluctuations and investigated cerebral synchronization in the presence and absence of rest tremor. We simultaneously recorded local field potentials from the subthalamic nucleus, the magnetoencephalogram and the electromyogram of forearm muscles in 11 patients with Parkinson's disease (all male, age: 52-74 years). Recordings took place the day after surgery for deep brain stimulation, after withdrawal of anti-parkinsonian medication. We selected epochs containing spontaneous rest tremor and tremor-free epochs, respectively, and compared power and coherence between subthalamic nucleus, cortex and muscle across conditions. Tremor-associated changes in cerebro-muscular coherence were localized by Dynamic Imaging of Coherent Sources. Subsequently, cortico-cortical coupling was analysed by computation of the imaginary part of coherency, a coupling measure insensitive to volume conduction. After tremor onset, local field potential power increased at individual tremor frequency and cortical power decreased in the beta band (13-30 Hz). Sensor level subthalamic nucleus-cortex, cortico-muscular and subthalamic nucleus-muscle coherence increased during tremor specifically at tremor frequency. The increase in subthalamic nucleus-cortex coherence correlated with the increase in electromyogram power. On the source level, we observed tremor-associated increases in cortico-muscular coherence in primary motor cortex, premotor cortex and posterior parietal cortex contralateral to the tremulous limb. Analysis of the imaginary part of coherency revealed tremor-dependent coupling between these cortical areas at tremor frequency and double tremor frequency. Our findings demonstrate a direct relationship between the synchronization of cerebral oscillations and tremor manifestation. Furthermore, they suggest the feasibility of tremor detection based on local field potentials and might thus become relevant for the design of closed-loop stimulation systems.

Speech rhythms and multiplexed oscillatory sensory coding in the human brain.

Cortical oscillations are likely candidates for segmentation and coding of continuous speech. Here, we monitored continuous speech processing with magnetoencephalography (MEG) to unravel the principles of speech segmentation and coding. We demonstrate that speech entrains the phase of low-frequency (delta, theta) and the amplitude of high-frequency (gamma) oscillations in the auditory cortex. Phase entrainment is stronger in the right and amplitude entrainment is stronger in the left auditory cortex. Furthermore, edges in the speech envelope phase reset auditory cortex oscillations thereby enhancing their entrainment to speech. This mechanism adapts to the changing physical features of the speech envelope and enables efficient, stimulus-specific speech sampling. Finally, we show that within the auditory cortex, coupling between delta, theta, and gamma oscillations increases following speech edges. Importantly, all couplings (i.e., brain-speech and also within the cortex) attenuate for backward-presented speech, suggesting top-down control. We conclude that segmentation and coding of speech relies on a nested hierarchy of entrained cortical oscillations.

Pre- and post-stimulus alpha activity shows differential modulation with spatial attention during the processing of pain.

Extensive work using magneto- and electroencephalography (M/EEG) suggests that cortical alpha activity represents a top-down controlled gating mechanism employed by processes like attention across different modalities. However, it is not yet clear to what extent this presumed gating function of alpha activity also applies to the processing of pain. In the current study, a spatial attention paradigm was employed requiring subjects to attend to painful laser stimuli on one hand while ignoring stimuli on the other hand. Simultaneously, brain activity was recorded with MEG. In order to disentangle pre- and post-stimulus effects of attention, alpha activity was analyzed during time windows in anticipation of and in response to painful laser stimulation. Painful laser stimuli led to a suppression of alpha activity over both ipsi- and contralateral primary somatosensory areas irrespective if they were attended or ignored. Spatial attention was associated with a lateralization of anticipatory pre-stimulus alpha activity. Alpha activity was lower over primary somatosensory areas when the contralateral hand was attended compared to when the ipsilateral hand was attended, in line with the notion that oscillatory alpha activity regulates the flow of incoming information by engaging and/or disengaging early sensory areas. On the contrary, post-stimulus alpha activity, for stimuli on either hand, was consistently decreased with attention over contralateral areas. Most likely, this finding reflects an increased cortical activation and enhanced alerting if a painful stimulus is attended. The present results show that spatial attention results in a modulation of both pre- and post-stimulus alpha activity associated with pain. This flexible regulation of alpha activity matches findings from other modalities. We conclude that the assumed functional role of alpha activity as a top-down controlled gating mechanism includes pain processing and most likely represents a unified mechanism used throughout the brain.

Visually induced gamma-band activity predicts speed of change detection in humans.

Groups of activated neurons typically synchronize in the gamma-frequency band (30-100 Hz), and gamma-band synchronization has been implicated in numerous cognitive functions. Those functions are ultimately expressed as behavior and therefore, functional gamma-band synchronization should be directly related to behavior. We recorded the magnetoencephalogram in human subjects and used a visual stimulus to induce occipital gamma-band activity. We found that the strength of this gamma-band activity at a given moment predicted the speed with which the subject was able to report a change in the stimulus. This predictive effect was restricted in time, frequency and space: It started only around 200 ms before the behaviorally relevant stimulus change, was present only between 50 and 80 Hz, and was significant only in bilateral middle occipital gyrus, while the peak of overall visually induced gamma-band activity was found in the calcarine sulcus. These results suggest that visually induced gamma-band activity is functionally relevant for the efficient transmission of stimulus change information to brain regions issuing the corresponding motor response.

Localizing human visual gamma-band activity in frequency, time and space.

Neuronal gamma-band (30-100 Hz) synchronization subserves fundamental functions in neuronal processing. However, different experimental approaches differ widely in their success in finding gamma-band activity. We aimed at linking animal and human studies of gamma-band activity and at preparing optimized methods for an in-depth investigation of the mechanisms and functions of gamma-band activity and gamma-band coherence in humans. In the first step described here, we maximized the signal-to-noise ratio with which we can observe visually induced gamma-band activity in human magnetoencephalographic recordings. We used a stimulus and task design that evoked strong gamma-band activity in animals and combined it with multi-taper methods for spectral analysis and adaptive spatial filtering for source analysis. With this approach, we found human visual gamma-band activity very reliably across subjects and across multiple recording sessions of a given subject. While increases in gamma-band activity are typically accompanied by decreases in alpha- and beta-band activity, the gamma-band enhancement was often the spectral component with the highest signal-to-noise ratio. Furthermore, some subjects demonstrated two clearly separate visually induced gamma bands, one around 40 Hz and another between 70 and 80 Hz. Gamma-band activity was sustained for the entire stimulation period, which was up to 3 s. The sources of gamma-band activity were in the calcarine sulcus in all subjects. The results localize human visual gamma-band activity in frequency, time and space and the described methods allow its further investigation with great sensitivity.

Facilitation of soleus H-reflex amplitude evoked by cutaneous nerve stimulation at the wrist is not suppressed by rhythmic arm movement.

Neural connections between the cervical and lumbosacral spinal cord may assist in arm and leg coordination during locomotion. Currently the extent to which arm activity can modulate reflex excitability of leg muscles is not fully understood. We showed recently that rhythmic arm movement significantly suppresses soleus H-reflex amplitude probably via modification of presynaptic inhibition of the IA afferent pathway. Further, during walking reflexes evoked in leg muscles by stimulation of a cutaneous nerve at the wrist (superficial radial nerve; SR) are phase and task dependent. However, during walking both the arms and legs are rhythmically active thus it is difficult to identify the locus of such modulation. Here we examined the influence of SR nerve stimulation on transmission through the soleus H-reflex pathway in the leg during static contractions and during rhythmic arm movements. Nerve stimulation was delivered with the right shoulder in flexion or extension. H-reflexes were evoked alone (unconditioned) or with cutaneous conditioning via stimulation of the SR nerve (also delivered alone without H-reflex in separate trials). SR nerve stimulation significantly facilitated H-reflex amplitude during static contractions with the arm extended and countered the suppression of reflex amplitude induced by arm cycling. The results demonstrate that cutaneous feedback from the hand on to the soleus H-reflex pathway in the legs is not suppressed during rhythmic arm movement. This contrasts with the observation that rhythmic arm movement suppresses facilitation of soleus H-reflex when cutaneous nerves innervating the leg are stimulated. In conjunction with other data taken during walking, this suggests that the modulation of transmission through pathways from the SR nerve to the lumbosacral spinal cord is partly determined by rhythmic activity of both the arms and legs.

Neural control of rhythmic human arm movement: phase dependence and task modulation of hoffmann reflexes in forearm muscles.

Although we move our arms rhythmically during walking, running, and swimming, we know little about the neural control of such movements. Our working hypothesis is that neural mechanisms controlling rhythmic movements are similar in the human lumbar and cervical spinal cord. Thus reflex modulation during rhythmic arm movement should be similar to that seen during leg movement. Our main experimental hypotheses were that the amplitude of H-reflexes in the forearm muscles would be modulated during arm movement (i.e., phase-dependent) and would be inhibited during cycling compared with static contraction (i.e., task-dependent). Furthermore, to determine the locus of any modulation, we tested the effect that active and passive movement of the ipsilateral (relative to stimulated arm) and contralateral arm had on H-reflex amplitude. Subjects performed rhythmic arm cycling on a custom-made hydraulic ergometer in which the two arms could be constrained to move together (180 degrees out of phase) or could rotate independently. Position of the stimulated limb in the movement cycle is described with respect to the clock face. H-reflexes were evoked at 12, 3, 6, and 9 o'clock positions during static contraction as well as during rhythmic arm movements. Reflex amplitudes were compared between tasks at equal M wave amplitudes and similar levels of electromyographic (EMG) activity in the target muscle. Surface EMG recordings were obtained bilaterally from flexor carpi radialis as well as from other muscles controlling the wrist, elbow, and shoulder. Compared with reflexes evoked during static contractions, movement of the stimulated limb attenuated H-reflexes by 50.8% (P < 0.005), 65.3% (P < 0.001), and 52.6% (P < 0.001) for bilateral, active ipsilateral, and passive ipsilateral movements, respectively. In contrast, movement of the contralateral limb did not significantly alter H-reflex amplitude. H-reflexes were also modulated by limb position (P < 0.005). Thus task- and phase-dependent modulation were observed in the arm as previously demonstrated in the leg. The data support the hypothesis that neural mechanisms regulating reflex pathways in the moving limb are similar in the human upper and lower limbs. However, the inhibition of H-reflex amplitude induced by contralateral leg movement is absent in the arms. This may reflect the greater extent to which the arms can be used independently.