Application of evoked response audiometry for specifying aberrant gamma oscillations in schizophrenia.

Gamma oscillations probed using auditory steady-state response (ASSR) are promising clinical biomarkers that may give rise to novel therapeutic interventions for schizophrenia. Optimizing clinical settings for these biomarker-driven interventions will require a quick and easy assessment system for gamma oscillations in psychiatry. ASSR has been used in clinical otolaryngology for evoked response audiometry (ERA) in order to judge hearing loss by focusing on the phase-locked response detectability via an automated analysis system. Herein, a standard ERA system with 40- and 46-Hz ASSRs was applied to evaluate the brain pathophysiology of patients with schizophrenia. Both ASSRs in the ERA system showed excellent detectability regarding the phase-locked response in healthy subjects and sharply captured the deficits of the phase-locked response caused by aberrant gamma oscillations in individuals with schizophrenia. These findings demonstrate the capability of the ERA system to specify patients who have aberrant gamma oscillations. The ERA system may have a potential to serve as a real-world clinical medium for upcoming biomarker-driven therapeutics in psychiatry.

Suppression of Low-Frequency Gamma Oscillations by Activation of 40-Hz Oscillation.

Gamma oscillations have received considerable attention owing to their association with cognitive function and various neuropsychiatric disorders. However, interactions of gamma oscillations at different frequency bands in humans remain unclear. In the present magnetoencephalographic study, brain oscillations in a wide frequency range were examined using a time-frequency analysis during the 20-, 30-, 40-, and 50-Hz auditory stimuli in 21 healthy subjects. First, dipoles for auditory steady-state response (ASSR) were estimated and interaction among oscillations at 10-60 Hz was examined using the source strength waveforms. Results showed the suppression of ongoing low-gamma oscillations at approximately 30 Hz during stimulation at 40 Hz. Second, multi-dipole analyses suggested that the main dipole for ASSR and dipoles for suppressed low-frequency gamma oscillations were distinct. Third, an all-sensor analysis was performed to clarify the distribution of the 40-Hz ASSR and suppression of low-frequency gamma oscillations. Notably, the area of suppression surrounded the center of the 40-Hz ASSR and showed a trend of extending to the vertex, indicating that different groups of neurons were responsible for these two gamma oscillations and that the 40-Hz oscillation circuit have specific inhibitory innervation to the low-gamma circuit.

Visual gamma oscillations predict sensory sensitivity in females as they do in males.

Gamma oscillations are driven by local cortical excitatory (E)-inhibitory (I) loops and may help to characterize neural processing involving excitatory-inhibitory interactions. In the visual cortex reliable gamma oscillations can be recorded with magnetoencephalography (MEG) in the majority of individuals, which makes visual gamma an attractive candidate for biomarkers of brain disorders associated with E/I imbalance. Little is known, however, about if/how these oscillations reflect individual differences in neural excitability and associated sensory/perceptual phenomena. The power of visual gamma response (GR) changes nonlinearly with increasing stimulation intensity: it increases with transition from static to slowly drifting high-contrast grating and then attenuates with further increase in the drift rate. In a recent MEG study we found that the GR attenuation predicted sensitivity to sensory stimuli in everyday life in neurotypical adult men and in men with autism spectrum disorders. Here, we replicated these results in neurotypical female participants. The GR enhancement with transition from static to slowly drifting grating did not correlate significantly with the sensory sensitivity measures. These findings suggest that weak velocity-related attenuation of the GR is a reliable neural concomitant of visual hypersensitivity and that the degree of GR attenuation may provide useful information about E/I balance in the visual cortex.

Test-retest reliability of tone- and 40 Hz train-evoked gamma oscillations in female rats and their sensitivity to low-dose NMDA channel blockade.

RATIONALE: Schizophrenia patients consistently show deficits in sensory-evoked broadband gamma oscillations and click-evoked entrainment at 40 Hz, called the 40-Hz auditory steady-state response (ASSR). Since such evoked oscillations depend on cortical N-methyl D-aspartic acid (NMDA)-mediated network activity, they can serve as pharmacodynamic biomarkers in the preclinical and clinical development of drug candidates engaging these circuits. However, there are few test-retest reliability data in preclinical species, a prerequisite for within-subject testing paradigms. OBJECTIVE: We investigated the long-term psychometric stability of these measures in a rodent model. METHODS: Female rats with chronic epidural implants were used to record tone- and 40 Hz click-evoked responses at multiple time points and across six sessions, spread over 3 weeks. We assessed reliability using intraclass correlation coefficients (ICC). Separately, we used mixed-effects ANOVA to examine time and session effects. Individual subject variability was determined using the coefficient of variation (CV). Lastly, to illustrate the importance of long-term measure stability for within-subject testing design, we used low to moderate doses of an NMDA antagonist MK801 (0.025-0.15 mg/kg) to disrupt the evoked response. RESULTS: We found that 40-Hz ASSR showed good reliability (ICC=0.60-0.75), while the reliability of tone-evoked gamma ranged from poor to good (0.33-0.67). We noted time but no session effects. Subjects showed a lower variance for ASSR over tone-evoked gamma. Both measures were dose-dependently attenuated by NMDA antagonism. CONCLUSION: Overall, while both evoked gamma measures use NMDA transmission, 40-Hz ASSR showed superior psychometric properties of higher ICC and lower CV, relative to tone-evoked gamma.

Efficacy of preclinical pharmacological interventions against alterations of neuronal network oscillations in Alzheimer's disease: A systematic review.

Despite the development of multiple pharmacological approaches over the years aimed at treating Alzheimer's Disease (AD) only very few have been approved for clinical use in patients. To date there still exists no disease-modifying treatment that could prevent or rescue the cognitive impairment, particularly of memory aquisition, that is characteristic of AD. One of the possibilities for this state of affairs might be that the majority of drug discovery efforts focuses on outcome measures of decreased neuropathological biomarkers characteristic of AD, without taking into acount neuronal processes essential to the generation and maintenance of memory processes. Particularly, the capacity of the brain to generate theta (θ) and gamma (γ) oscillatory activity has been strongly correlated to memory performance. Using a systematic review approach, we synthesize the existing evidence in the literature on pharmacological interventions that enhance neuronal theta (θ) and/or gamma (γ) oscillations in non-pathological animal models and in AD animal models. Additionally, we synthesize the main outcomes and neurochemical systems targeted. We propose that functional biomarkers such as cognition-relevant neuronal network oscillations should be used as outcome measures during the process of research and development of novel drugs against cognitive impairment in AD.

Global and Parallel Cortical Processing Based on Auditory Gamma Oscillatory Responses in Humans.

Gamma oscillations are physiological phenomena that reflect perception and cognition, and involve parvalbumin-positive γ-aminobutyric acid-ergic interneuron function. The auditory steady-state response (ASSR) is the most robust index for gamma oscillations, and it is impaired in patients with neuropsychiatric disorders such as schizophrenia and autism. Although ASSR reduction is known to vary in terms of frequency and time, the neural mechanisms are poorly understood. We obtained high-density electrocorticography recordings from a wide area of the cortex in 8 patients with refractory epilepsy. In an ASSR paradigm, click sounds were presented at frequencies of 20, 30, 40, 60, 80, 120, and 160 Hz. We performed time-frequency analyses and analyzed intertrial coherence, event-related spectral perturbation, and high-gamma oscillations. We demonstrate that the ASSR is globally distributed among the temporal, parietal, and frontal cortices. The ASSR was composed of time-dependent neural subcircuits differing in frequency tuning. Importantly, the frequency tuning characteristics of the late-latency ASSR varied between the temporal/frontal and parietal cortex, suggestive of differentiation along parallel auditory pathways. This large-scale survey of the cortical ASSR could serve as a foundation for future studies of the ASSR in patients with neuropsychiatric disorders.

Neural network dynamics underlying gamma synchronization deficits in schizophrenia.

Gamma-band (40-Hz) activity is critical for cortico-cortical transmission and the integration of information across neural networks during sensory and cognitive processing. Patients with schizophrenia show selective reductions in the capacity to support synchronized gamma-band oscillations in response to auditory stimulation presented 40-Hz. Despite widespread application of this 40-Hz auditory steady-state response (ASSR) as a translational electroencephalographic biomarker for therapeutic development for neuropsychiatric disorders, the spatiotemporal dynamics underlying the ASSR have not been fully characterized. In this study, a novel Granger causality analysis was applied to assess the propagation of gamma oscillations in response to 40-Hz steady-state stimulation across cortical sources in schizophrenia patients (n = 426) and healthy comparison subjects (n = 293). Both groups showed multiple ASSR source interactions that were broadly distributed across brain regions. Schizophrenia patients showed distinct, hierarchically sequenced connectivity abnormalities. During the response onset interval, patients exhibited abnormal increased connectivity from the inferior frontal gyrus to the superior temporal gyrus, followed by decreased connectivity from the superior temporal to the middle cingulate gyrus. In the later portion of the ASSR response (300-500 ms), patients showed significantly increased connectivity from the superior temporal to the middle frontal gyrus followed by decreased connectivity from the left superior frontal gyrus to the right superior and middle frontal gyri. These findings highlight both the orchestration of distributed multiple sources in response to simple gamma-frequency stimulation in healthy subjects as well as the patterns of deficits in the generation and maintenance of gamma-band oscillations across the temporo-frontal sources in schizophrenia patients.

Reduced auditory steady state responses in autism spectrum disorder.

BACKGROUND: Auditory steady state responses (ASSRs) are elicited by clicktrains or amplitude-modulated tones, which entrain auditory cortex at their specific modulation rate. Previous research has reported reductions in ASSRs at 40 Hz for autism spectrum disorder (ASD) participants and first-degree relatives of people diagnosed with ASD (Mol Autism. 2011;2:11, Biol Psychiatry. 2007;62:192-197). METHODS: Using a 1.5 s-long auditory clicktrain stimulus, designed to elicit an ASSR at 40 Hz, this study attempted to replicate and extend these findings. Magnetencephalography (MEG) data were collected from 18 adolescent ASD participants and 18 typically developing controls. RESULTS: The ASSR localised to bilateral primary auditory regions. Regions of interest were thus defined in left and right primary auditory cortex (A1). While the transient gamma-band response (tGBR) from 0-0.1 s following presentation of the clicktrain stimulus was not different between groups, for either left or right A1, the ASD group had reduced oscillatory power at 40 Hz from 0.5 to 1.5 s post-stimulus onset, for both left and right A1. Additionally, the ASD group had reduced inter-trial coherence (phase consistency over trials) at 40 Hz from 0.64-0.82 s for right A1 and 1.04-1.22 s for left A1. LIMITATIONS: In this study, we did not conduct a clinical autism assessment (e.g. the ADOS), and therefore, it remains unclear whether ASSR power and/or ITC are associated with the clinical symptoms of ASD. CONCLUSION: Overall, our results support a specific reduction in ASSR oscillatory power and inter-trial coherence in ASD, rather than a generalised deficit in gamma-band responses. We argue that this could reflect a developmentally relevant reduction in non-linear neural processing.

Combining predictive coding and neural oscillations enables online syllable recognition in natural speech.

On-line comprehension of natural speech requires segmenting the acoustic stream into discrete linguistic elements. This process is argued to rely on theta-gamma oscillation coupling, which can parse syllables and encode them in decipherable neural activity. Speech comprehension also strongly depends on contextual cues that help predicting speech structure and content. To explore the effects of theta-gamma coupling on bottom-up/top-down dynamics during on-line syllable identification, we designed a computational model (Precoss-predictive coding and oscillations for speech) that can recognise syllable sequences in continuous speech. The model uses predictions from internal spectro-temporal representations of syllables and theta oscillations to signal syllable onsets and duration. Syllable recognition is best when theta-gamma coupling is used to temporally align spectro-temporal predictions with the acoustic input. This neurocomputational modelling work demonstrates that the notions of predictive coding and neural oscillations can be brought together to account for on-line dynamic sensory processing.

Gamma Entrainment in a Large Retrospective Cohort: Implications for Photic Stimulation Therapy for Alzheimer's Disease.

BACKGROUND: Studies on mice models of Alzheimer's disease (AD) have suggested potential therapeutic benefits of intermittent photic stimulation at 40 Hz. OBJECTIVE: We examined the physiological response of 40 Hz intermittent photic stimulation (IPS) on routine EEG in a large retrospective cohort to investigate the effects of age on induced gamma oscillations by intermittent photic stimulation. Since most AD patients are elderly, it is important for future research to know if age affects photic stimulation. METHODS: Retrospective data from 1,464 subjects aged 0- 91. We performed frequency analysis and automatic peak detection and used regression analysis to investigate the effects of age and sex on peak frequencies and amplitude changes. To investigate the spread of the induced gamma oscillations, we assessed averaged topographies of 40 Hz band power. RESULTS: There was a statistically significant but very minor effect of age on amplitude change (- 0.002 normalized power per year, p < 0.0001) but not for sex (p = 0.728). Detection probability of induced peaks was significantly predicted by both age (OR = 0.988, CI 95 % [0.984, 0.993], p < 0.00001) and sex (OR = 0.625, CI 95 % [0.496, 0.787>], p < 0.0001). The induced 40 Hz gamma entrainment is spatially confined to the occipital area. CONCLUSION: There is a significant effect of age on induced gamma activity, but advanced age does not fundamentally change the behavior of the response in either magnitude or spatial distribution. This fact is important regarding future research into the possible therapeutic effects of photic stimulation in patients with AD.

Non-pharmacological treatment changes brain activity in patients with dementia.

Non-pharmacological treatment (NPT) improves cognitive functions and behavioural disturbances in patients with dementia, but the underlying neural mechanisms are unclear. In this observational study, 21 patients with dementia received NPTs for several months. Patients were scanned using magnetoencephalography twice during the NPT period to evaluate NPT effects on resting-state brain activity. Additionally, cognitive functions and behavioural disturbances were measured using the Mini-Mental State Examination (MMSE-J) and a short version of the Dementia Behaviour Disturbance Scale (DBD-13) at the beginning and the end of the NPT period. In contrast to the average DBD-13 score, the average MMSE-J score improved after the NPT period. Magnetoencephalography data revealed a reduced alpha activity in the right temporal lobe and fusiform gyrus, as well as an increased low-gamma activity in the right angular gyrus. DBD-13 score changes were correlated with beta activity in the sensorimotor area. These findings corroborate previous studies confirming NPT effects on brain activity in healthy participants and people at risk of dementia. Our results provide additional evidence that brains of patients with dementia have the capacity for plasticity, which may be responsible for the observed NPT effects. In dementia, NPT might lead to improvements in the quality of life.

Brain-Heart Interactions Underlying Traditional Tibetan Buddhist Meditation.

Despite accumulating evidence suggesting improvement in one's well-being as a result of meditation, little is known about if or how the brain and the periphery interact to produce these behavioral and mental changes. We hypothesize that meditation reflects changes in the neural representations of visceral activity, such as cardiac behavior, and investigated the integration of neural and visceral systems and the spontaneous whole brain spatiotemporal dynamics underlying traditional Tibetan Buddhist meditation. In a large cohort of long-term Tibetan Buddhist monk meditation practitioners, we found distinct transient modulations of the neural response to heartbeats in the default mode network (DMN), along with large-scale network reconfigurations in the gamma and theta bands of electroencephalography (EEG) activity induced by meditation. Additionally, temporal-frontal network connectivity in the EEG theta band was negatively correlated with the duration of meditation experience, and gamma oscillations were uniquely, directionally coupled to theta oscillations during meditation. Overall, these data suggest that the neural representation of cardiac activity in the DMN and large-scale spatiotemporal network integrations underlie the fundamental neural mechanism of meditation and further imply that meditation may utilize cortical plasticity, inducing both immediate and long-lasting changes in the intrinsic organization and activity of brain networks.

What's in Your Gamma? Activation of the Ventral Fronto-Parietal Attentional Network in Response to Distracting Sounds.

Auditory attention operates through top-down (TD) and bottom-up (BU) mechanisms that are supported by dorsal and ventral brain networks, respectively, with the main overlap in the lateral prefrontal cortex (lPFC). A good TD/BU balance is essential to be both task-efficient and aware of our environment, yet it is rarely investigated. Oscillatory activity is a novel method to probe the attentional dynamics with evidence that gamma activity (>30 Hz) could signal BU processing and thus would be a good candidate to support the activation of the ventral BU attention network. Magnetoencephalography data were collected from 21 young adults performing the competitive attention task, which enables simultaneous investigation of BU and TD attentional mechanisms. Distracting sounds elicited an increase in gamma activity in regions of the BU ventral network. TD attention modulated these gamma responses in regions of the inhibitory cognitive control system: the medial prefrontal and anterior cingulate cortices. Finally, distracting-sound-induced gamma activity was synchronous between the auditory cortices and several distant brain regions, notably the lPFC. We provide novel insight into the role of gamma activity 1) in supporting the activation of the ventral BU attention network and 2) in subtending the TD/BU attention balance in the PFC.

Gamma-Band Auditory Steady-State Response as a Neurophysiological Marker for Excitation and Inhibition Balance: A Review for Understanding Schizophrenia and Other Neuropsychiatric Disorders.

Altered gamma oscillations have attracted considerable attention as an index of the excitation/inhibition (E/I) imbalance in schizophrenia and other neuropsychiatric disorders. The auditory steady-state response (ASSR) has been the most robust probe of abnormal gamma oscillatory dynamics in schizophrenia. Here, we review recent ASSR studies in patients with schizophrenia and other neuropsychiatric disorders. Preclinical ASSR research, which has contributed to the elucidation of the underlying pathophysiology of these diseases, is also discussed. The developmental trajectory of the ASSR has been explored and may show signs of the maturation and disruption of E/I balance in adolescence. Animal model studies have shown that synaptic interactions between parvalbumin-positive GABAergic interneurons and pyramidal neurons contribute to the regulation of E/I balance, which is related to the generation of gamma oscillation. Therefore, ASSR alteration may be a significant electrophysiological finding related to the E/I imbalance in neuropsychiatric disorders, which is a cross-disease feature and may reflect clinical staging. Future studies regarding ASSR generation, especially in nonhuman primate models, will advance our understanding of the brain circuit and the molecular mechanisms underlying neuropsychiatric disorders.

Emergence of ß and γ networks following multisensory training.

Our perceptual reality relies on inferences about the causal structure of the world given by multiple sensory inputs. In ecological settings, multisensory events that cohere in time and space benefit inferential processes: hearing and seeing a speaker enhances speech comprehension, and the acoustic changes of flapping wings naturally pace the motion of a flock of birds. Here, we asked how a few minutes of (multi)sensory training could shape cortical interactions in a subsequent unisensory perceptual task. For this, we investigated oscillatory activity and functional connectivity as a function of individuals' sensory history during training. Human participants performed a visual motion coherence discrimination task while being recorded with magnetoencephalography. Three groups of participants performed the same task with visual stimuli only, while listening to acoustic textures temporally comodulated with the strength of visual motion coherence, or with auditory noise uncorrelated with visual motion. The functional connectivity patterns before and after training were contrasted to resting-state networks to assess the variability of common task-relevant networks, and the emergence of new functional interactions as a function of sensory history. One major finding is the emergence of a large-scale synchronization in the high γ (gamma: 60-120Hz) and ß (beta: 15-30Hz) bands for individuals who underwent comodulated multisensory training. The post-training network involved prefrontal, parietal, and visual cortices. Our results suggest that the integration of evidence and decision-making strategies become more efficient following congruent multisensory training through plasticity in network routing and oscillatory regimes.

Deletion of Fmr1 from Forebrain Excitatory Neurons Triggers Abnormal Cellular, EEG, and Behavioral Phenotypes in the Auditory Cortex of a Mouse Model of Fragile X Syndrome.

Fragile X syndrome (FXS) is a leading genetic cause of autism with symptoms that include sensory processing deficits. In both humans with FXS and a mouse model [Fmr1 knockout (KO) mouse], electroencephalographic (EEG) recordings show enhanced resting state gamma power and reduced sound-evoked gamma synchrony. We previously showed that elevated levels of matrix metalloproteinase-9 (MMP-9) may contribute to these phenotypes by affecting perineuronal nets (PNNs) around parvalbumin (PV) interneurons in the auditory cortex of Fmr1 KO mice. However, how different cell types within local cortical circuits contribute to these deficits is not known. Here, we examined whether Fmr1 deletion in forebrain excitatory neurons affects neural oscillations, MMP-9 activity, and PV/PNN expression in the auditory cortex. We found that cortical MMP-9 gelatinase activity, mTOR/Akt phosphorylation, and resting EEG gamma power were enhanced in CreNex1/Fmr1Flox/y conditional KO (cKO) mice, whereas the density of PV/PNN cells was reduced. The CreNex1/Fmr1Flox/y cKO mice also show increased locomotor activity, but not the anxiety-like behaviors. These results indicate that fragile X mental retardation protein changes in excitatory neurons in the cortex are sufficient to elicit cellular, electrophysiological, and behavioral phenotypes in Fmr1 KO mice. More broadly, these results indicate that local cortical circuit abnormalities contribute to sensory processing deficits in autism spectrum disorders.

Theta and Gamma Bands Encode Acoustic Dynamics over Wide-Ranging Timescales.

Natural sounds contain acoustic dynamics ranging from tens to hundreds of milliseconds. How does the human auditory system encode acoustic information over wide-ranging timescales to achieve sound recognition? Previous work (Teng et al. 2017) demonstrated a temporal coding preference for the theta and gamma ranges, but it remains unclear how acoustic dynamics between these two ranges are coded. Here, we generated artificial sounds with temporal structures over timescales from ~200 to ~30 ms and investigated temporal coding on different timescales. Participants discriminated sounds with temporal structures at different timescales while undergoing magnetoencephalography recording. Although considerable intertrial phase coherence can be induced by acoustic dynamics of all the timescales, classification analyses reveal that the acoustic information of all timescales is preferentially differentiated through the theta and gamma bands, but not through the alpha and beta bands; stimulus reconstruction shows that the acoustic dynamics in the theta and gamma ranges are preferentially coded. We demonstrate that the theta and gamma bands show the generality of temporal coding with comparable capacity. Our findings provide a novel perspective-acoustic information of all timescales is discretised into two discrete temporal chunks for further perceptual analysis.

Abnormal brain gamma oscillations in response to auditory stimulation in Dravet syndrome.

OBJECTIVE: To evaluate the capability of children with Dravet syndrome to generate brain γ-oscillatory activity in response to auditory steady-state stimulation. METHODS: Fifty-one subjects were included: 13 with Dravet syndrome with SCN1A gene alterations, 26 with non-Dravet epilepsies and 12 healthy controls. Responses to auditory steady-state stimulation elicited with a chirp-modulated tone between 1 and 120 Hz were collected in subjects and compared across groups. RESULTS: Subjects with Dravet syndrome showed weak or no responses in the 1-120 Hz frequency range. Healthy controls showed oscillatory responses following the frequency of the modulation that were maximal in the low (30-70 Hz) and high (80-120) γ-ranges both, in the power and inter-trial coherence estimates. Non-Dravet epileptic children showed differences in the auditory responses when compared with the healthy controls but were able to generate oscillatory evoked activities following the frequency-varying stimulation. CONCLUSIONS: The ability to generate brain γ-oscillatory activity of children with Dravet in response to a chirp-modulated auditory stimulus is highly impaired, is not due to epilepsy and is consistent with the Nav1.1 channel dysfunction affecting interneuron activity seen in Dravet mouse models. SIGNIFICANCE: The reported deficits in the brain oscillatory activity evoked by chirp modulated tones in children with Dravet is compatible with Dravet syndrome disease mechanisms and constitutes a potential biomarker for future disease-modifying interventions.

Cortical gamma-synchrony measured with magnetoencephalography is a marker of clinical status and predicts clinical outcome in stroke survivors.

BACKGROUND: The outcome of stroke survivors is difficult to anticipate. While the extent of the anatomical brain lesion is only poorly correlated with the prognosis, functional measures of cortical synchrony, brain networks and cortical plasticity seem to be good predictors of clinical recovery. In this field, gamma (>30 Hz) cortical synchrony is an ideal marker of brain function, as it plays a crucial role for the integration of information, it is an indirect marker of Glutamate/GABA balance and it directly estimates the reserve of parvalbulin-positive neurons, key players in synaptic plasticity. In this study we measured gamma synchronization driven by external auditory stimulation with magnetoencephalography and tested whether it was predictive of the clinical outcome in stroke survivors undergoing intensive rehabilitation in a tertiary rehabilitation center. MATERIAL AND METHODS: Eleven stroke survivors undergoing intensive rehabilitation were prospectively recruited. Gamma synchrony was measured non-invasively within one month from stroke onset with magnetoencephalography, both at rest and during entrainment with external 40 Hz amplitude modulated binaural sounds. Lesion location and volume were quantitatively assessed through a high-resolution anatomical MRI. Barthel index (BI) and Functional Independence Measure (FIM) scales were measured at the beginning and at the end of the admission to the rehabilitation unit. RESULTS: The spatial distribution of cortical gamma synchrony was altered, and the physiological right hemispheric dominance observed in healthy controls was attenuated or lost. Entrained gamma synchronization (but not resting state gamma synchrony) showed a very high correlation with the clinical status at both admission and discharge (both BI and FIM). Neither clinical status nor gamma synchrony showed a correlation with lesion volume. CONCLUSIONS: Cortical gamma synchrony related to auditory entrainment can be reliably measured in stroke patients. Gamma synchrony is strongly associated with the clinical outcome of stroke survivors undergoing rehabilitation.

Network dynamics of Broca's area during word selection.

Current models of word-production in Broca's area (i.e. left ventro-lateral prefrontal cortex, VLPFC) posit that sequential and staggered semantic, lexical, phonological and articulatory processes precede articulation. Using millisecond-resolution intra-cranial recordings, we evaluated spatiotemporal dynamics and high frequency functional interconnectivity between left VLPFC regions during single-word production. Through the systematic variation of retrieval, selection, and phonological loads, we identified specific activation profiles and functional coupling patterns between these regions that fit within current psycholinguistic theories of word production. However, network interactions underpinning these processes activate in parallel (not sequentially), while the processes themselves are indexed by specific changes in network state. We found evidence that suggests that pars orbitalis is coupled with pars triangularis during lexical retrieval, while lexical selection is terminated via coupled activity with M1 at articulation onset. Taken together, this work reveals that speech production relies on very specific inter-regional couplings in rapid sequence in the language dominant hemisphere.