Cortical source estimates of gamma band amplitude and phase are different in schizophrenia

Reductions in gamma band phase synchrony and evoked power have been reported in schizophrenic subjects in response to auditory stimuli. These results have been observed in the EEG at one or two electrode sites. We wished to extend these results using magnetic field data to estimate the responses at the neural generators themselves in each hemisphere. Whole head magnetoencephalographic (MEG) recordings were used to estimate the phase and amplitude behavior of sources in primary auditory cortex in both hemispheres of schizophrenic and comparison subjects. Both ipsi- and contralateral cases were evaluated using a driving (40 Hz modulated 1 kHz carrier) and a non-driving (1 kHz tone) stimulus. We used source space projection (SSP) to collapse the magnetic field data into estimates of the time course of source strengths in individual trials. Complex wavelet based time–frequency decomposition was used to compute inter-trial phase locking factor (PLF), and mean evoked and induced amplitude for each cortical generator. Schizophrenic subjects showed reduced SSP PLF and evoked source strength for contralateral generators responding to the driving stimulus in both hemispheres. For the pure tone stimulus, only the left hemisphere PLF's in the transient window were reduced. In contrast, subjects with schizophrenia exhibited higher induced 40 Hz power to both stimulus types, consistent with the reduced PLF findings. The method of SSP combined with wavelet based complex demodulation produces a significant improvement in signal-to-noise ratio, and directly estimates the activity of the cortical generators responsible for gamma band auditory MEG evoked fields. Schizophrenic subjects exhibit significant impairment of generation and phase locking of this activity in auditory cortex, suggesting an impairment of GABA-ergic inhibitory interneuronal modulation of pyramidal cell activity.     

Correlates of perceptual awareness in human primary auditory cortex revealed by an informational masking experiment

The presence of an auditory event may remain undetected in crowded environments, even when it is well above the sensory threshold. This effect, commonly known as informational masking, allows for isolating neural activity related to perceptual awareness, by comparing repetitions of the same physical stimulus where the target is either detected or not. Evidence from magnetoencephalography (MEG) suggests that auditory-cortex activity in the latency range 50-250 ms is closely coupled with perceptual awareness. Here, BOLD fMRI and MEG were combined to investigate at which stage in the auditory cortex neural correlates of conscious auditory perception can be observed. Participants were asked to indicate the perception of a regularly repeating target tone, embedded within a random multi-tone masking background. Results revealed widespread activation within the auditory cortex for detected target tones, which was delayed but otherwise similar to the activation of an unmasked control stimulus. The contrast of detected versus undetected targets revealed activity confined to medial Heschl's gyrus, where the primary auditory cortex is located. These results suggest that activity related to conscious perception involves the primary auditory cortex and is not restricted to activity in secondary areas.     

Evidence of vibrotactile input to human auditory cortex

Low frequency vibrations can be detected by both tactile and auditory systems. The aim of the present study is to find out, by means of whole-scalp magnetoencephalography (MEG), whether vibrotactile stimulation alone would activate human auditory cortical areas. We recorded MEG signals from eleven normal-hearing adults to 200-Hz vibrations (on average 19.5 dB above the individual tactile detection threshold), delivered to right-hand fingertips. All subjects reported a perception of a sound when they touched the vibrating tube, and they reported to perceive nothing when not touching the tube. The vibrotactile stimuli elicited clear and reproducible vibrotactile evoked fields (VTEFs) in ten subjects, whereas no MEG responses were observed when the tube was not touched. First responses to the vibrotactile stimuli, peaking around 60 ms, originated in the primary somatosensory cortex in all subjects. They were followed by activations in the auditory cortices, either bilaterally (N = 5) or unilaterally (N = 5), and by activations in the secondary somatosensory (SII) cortex, either contralaterally (N = 3) or ipsilaterally (N = 4). Both the SII and auditory activations consisted of transient responses at 100-200 ms. Additional auditory sustained activation was identified in nine subjects, either bilaterally (N = 2) or ipsilaterally (N = 7), at 200-700 ms. Our results suggest convergence of vibrotactile input to the auditory cortex in normal-hearing adults, in agreement with results previously obtained in a congenitally deaf adult.     

Stimuli of varying spatial scale induce gamma activity with distinct temporal characteristics in human visual cortex

Gamma activity to stationary grating stimuli was studied non-invasively using MEG recordings in humans. Using a spatial filtering technique, we localized gamma activity to primary visual cortex. We tested the hypothesis that spatial frequency properties of visual stimuli may be related to the temporal frequency characteristics of the associated cortical responses. We devised a method to assess temporal frequency differences between stimulus-related responses that typically exhibit complex spectral shapes. We applied this methodology to either single-trial (induced) or time-averaged (evoked) responses in four frequency ranges (0-40, 20-60, 40-80 and 60-100 Hz) and two time windows (either the entire duration of stimulus presentation or the first second following stimulus onset). Our results suggest that stimuli of varying spatial frequency induce responses that exhibit significantly different temporal frequency characteristics. These effects were particularly accentuated for induced responses in the classical gamma frequency band (20-60 Hz) analyzed over the entire duration of stimulus presentation. Strikingly, examining the first second of the responses following stimulus onset resulted in significant loss in stimulus specificity, suggesting that late signal components contain functionally relevant information. These findings advocate a functional role of gamma activity in sensory representation. We suggest that stimulus specific frequency characteristics of MEG signals can be mapped to processes of neuronal synchronization within the framework of coupled dynamical systems.     

Transient brain responses predict the temporal dynamics of sound detection in humans

The neural events leading up to the conscious experience of stimulus events have remained elusive. Here we describe stimulation conditions under which activation in human auditory cortex can be used to predict the temporal dynamics of behavioral sound detection. Subjects were presented with auditory stimuli whose energy smoothly increased from a silent to a clearly audible level over either 1, 1.5, or 2 s. Magnetoencephalographic (MEG) recordings were carried out in the passive and active recording conditions. In the active condition, the subjects were instructed to attend to the auditory stimuli and to press a response key when these became audible. In both conditions, the stimuli elicited a prominent transient response whose emergence is unexplainable by changes in stimulus intensity alone. This transient response was larger in amplitude over the right hemisphere and in the active condition. Importantly, behavioral sound detection followed this brain activation with a constant delay of 180 ms, and further the latency variations of the brain response were directly carried over to behavioral reaction times. Thus, noninvasively measured transient events in the human auditory cortex can be used to predict accurately the temporal course of sound detection and may therefore turn out to be useful in clinical settings.     

Spatiotemporal dynamics of electrocorticographic high gamma activity during overt and covert word repetition

Language is one of the defining abilities of humans. Many studies have characterized the neural correlates of different aspects of language processing. However, the imaging techniques typically used in these studies were limited in either their temporal or spatial resolution. Electrocorticographic (ECoG) recordings from the surface of the brain combine high spatial with high temporal resolution and thus could be a valuable tool for the study of neural correlates of language function. In this study, we defined the spatiotemporal dynamics of ECoG activity during a word repetition task in nine human subjects. ECoG was recorded while each subject overtly or covertly repeated words that were presented either visually or auditorily. ECoG amplitudes in the high gamma (HG) band confidently tracked neural changes associated with stimulus presentation and with the subject's verbal response. Overt word production was primarily associated with HG changes in the superior and middle parts of temporal lobe, Wernicke's area, the supramarginal gyrus, Broca's area, premotor cortex (PMC), primary motor cortex. Covert word production was primarily associated with HG changes in superior temporal lobe and the supramarginal gyrus. Acoustic processing from both auditory stimuli as well as the subject's own voice resulted in HG power changes in superior temporal lobe and Wernicke's area. In summary, this study represents a comprehensive characterization of overt and covert speech using electrophysiological imaging with high spatial and temporal resolution. It thereby complements the findings of previous neuroimaging studies of language and thus further adds to current understanding of word processing in humans.     

Spatiotemporal reconstruction of the auditory steady-state response to frequency modulation using magnetoencephalography

The aim of this study was to investigate the mechanisms involved in the perception of perceptually salient frequency modulation (FM) using auditory steady-state responses (ASSRs) measured with magnetoencephalography (MEG). Previous MEG studies using frequency-modulated amplitude modulation as stimuli (Luo et al., 2006, 2007) suggested that a phase modulation encoding mechanism exists for low (< 5 Hz) FM modulation frequencies but additional amplitude modulation encoding is required for faster FM modulation frequencies. In this study single-cycle sinusoidal FM stimuli were used to generate the ASSR. The stimulus was either an unmodulated 1-kHz sinusoid or a 1-kHz sinusoid that was frequency-modulated with a repetition rate of 4, 8, or 12 Hz. The fast Fourier transform (FFT) of each MEG channel was calculated to obtain the phase and magnitude of the ASSR in sensor-space and multivariate Hotelling's T² statistics were used to determine the statistical significance of ASSRs. MEG beamformer analyses were used to localise the ASSR sources. Virtual electrode analyses were used to reconstruct the time series at each source. FFTs of the virtual electrode time series were calculated to obtain the amplitude and phase characteristics of each source identified in the beamforming analyses. Multivariate Hotelling's T² statistics were used to determine the statistical significance of these reconstructed ASSRs. The results suggest that the ability of auditory cortex to phase-lock to FM is dependent on the FM pulse rate and that the ASSR to FM is lateralised to the right hemisphere.     

Differential brain activation patterns during perception of voice and tone onset time series: a MEG study

Evoked magnetic fields were recorded from 18 adult volunteers using magnetoencephalography (MEG) during perception of speech stimuli (the endpoints of a voice onset time (VOT) series ranging from /ga/ to /ka/), analogous nonspeech stimuli (the endpoints of a two-tone series varying in relative tone onset time (TOT), and a set of harmonically complex tones varying in pitch. During the early time window (approximately 60 to approximately 130 ms post-stimulus onset), activation of the primary auditory cortex was bilaterally equal in strength for all three tasks. During the middle (approximately 130 to 800 ms) and late (800 to 1400 ms) time windows of the VOT task, activation of the posterior portion of the superior temporal gyrus (STGp) was greater in the left hemisphere than in the right hemisphere, in both group and individual data. These asymmetries were not evident in response to the nonspeech stimuli. Hemispheric asymmetries in a measure of neurophysiological activity in STGp, which includes the supratemporal plane and cortex inside the superior temporal sulcus, may reflect a specialization of association auditory cortex in the left hemisphere for processing speech sounds. Differences in late activation patterns potentially reflect the operation of a postperceptual process (e.g., rehearsal in working memory) that is restricted to speech stimuli.     

Of cats and women: temporal dynamics in the right temporoparietal cortex reflect auditory categorical processing of vocalizations

Understanding the temporal dynamics underlying cortical processing of auditory categories is complicated by difficulties in equating temporal and spectral features across stimulus classes. In the present magnetoencephalography (MEG) study, female voices and cat sounds were filtered so as to match in most of their acoustic properties, and the respective auditory evoked responses were investigated with a paradigm that allowed us to examine auditory cortical processing of two natural sound categories beyond the physical make-up of the stimuli. Three cat or human voice sounds were first presented to establish a categorical context. Subsequently, a probe sound that was congruent, incongruent, or ambiguous to this context was presented. As an index of a categorical mismatch, MEG responses to incongruent sounds were stronger than the responses to congruent sounds at ~250 ms in the right temporoparietal cortex, regardless of the sound category. Furthermore, probe sounds that could not be unambiguously attributed to any of the two categories ("cat" or "voice") evoked stronger responses after the voice than cat context at 200-250 ms, suggesting a stronger contextual effect for human voices. Our results suggest that categorical templates for human and animal vocalizations are established at ~250 ms in the right temporoparietal cortex, likely reflecting continuous online analysis of spectral stimulus features during auditory categorizing task.     

Sustained responses for pitch and vowels map to similar sites in human auditory cortex

Several studies have shown enhancement of auditory evoked sustained responses for periodic over non-periodic sounds and for vowels over non-vowels. Here, we directly compared pitch and vowels using synthesized speech with a "damped" amplitude modulation. These stimuli were parametrically varied to yield four classes of matched stimuli: (1) periodic vowels (2) non-periodic vowels, (3) periodic non-vowels, and (4) non-periodic non-vowels. 12 listeners were studied with combined MEG and EEG. Sustained responses were reliably enhanced for vowels and periodicity. Dipole source analysis revealed that a vowel contrast (vowel-non-vowel) and the periodicity-pitch contrast (periodic-non-periodic) mapped to the same site in antero-lateral Heschl's gyrus. In contrast, the non-periodic, non-vowel condition mapped to a more medial and posterior site. The sustained enhancement for vowels was significantly more prominent when the vowel identity was varied, compared to a condition where only one vowel was repeated, indicating selective adaptation of the response. These results render it unlikely that there are spatially distinct fields for vowel and pitch processing in the auditory cortex. However, the common processing of vowels and pitch raises the possibility that there is an early speech-specific field in Heschl's gyrus.     

Induced and evoked neural correlates of orientation selectivity in human visual cortex

Orientation discrimination is much better for patterns oriented along the horizontal or vertical (cardinal) axes than for patterns oriented obliquely, but the neural basis for this is not known. Previous animal neurophysiology and human neuroimaging studies have demonstrated only a moderate bias for cardinal versus oblique orientations, with fMRI showing a larger response to cardinals in primary visual cortex (V1) and EEG demonstrating both increased magnitudes and reduced latencies of transient evoked responses. Here, using MEG, we localised and characterised induced gamma and transient evoked responses to stationary circular grating patches of three orientations (0, 45, and 90° from vertical). Surprisingly, we found that the sustained gamma response was larger for oblique, compared to cardinal, stimuli. This "inverse oblique effect" was also observed in the earliest (80 ms) evoked response, whereas later responses (120 ms) showed a trend towards the reverse, "classic", oblique response. Source localisation demonstrated that the sustained gamma and early evoked responses were localised to medial visual cortex, whilst the later evoked responses came from both this early visual area and a source in a more inferolateral extrastriate region. These results suggest that (1) the early evoked and sustained gamma responses manifest the initial tuning of V1 neurons, with the stronger response to oblique stimuli possibly reflecting increased tuning widths for these orientations, and (2) the classic behavioural oblique effect is mediated by an extrastriate cortical area and may also implicate feedback from extrastriate to primary visual cortex.     

Scanning silence: mental imagery of complex sounds

In this functional magnetic resonance imaging (fMRI) study, we investigated the neural basis of mental auditory imagery of familiar complex sounds that did not contain language or music. In the first condition (perception), the subjects watched familiar scenes and listened to the corresponding sounds that were presented simultaneously. In the second condition (imagery), the same scenes were presented silently and the subjects had to mentally imagine the appropriate sounds. During the third condition (control), the participants watched a scrambled version of the scenes without sound. To overcome the disadvantages of the stray acoustic scanner noise in auditory fMRI experiments, we applied sparse temporal sampling technique with five functional clusters that were acquired at the end of each movie presentation. Compared to the control condition, we found bilateral activations in the primary and secondary auditory cortices (including Heschl's gyrus and planum temporale) during perception of complex sounds. In contrast, the imagery condition elicited bilateral hemodynamic responses only in the secondary auditory cortex (including the planum temporale). No significant activity was observed in the primary auditory cortex. The results show that imagery and perception of complex sounds that do not contain language or music rely on overlapping neural correlates of the secondary but not primary auditory cortex.     

Cortical representation of dermatomes: MEG-derived maps after tactile stimulation

Mechanical stimulation of skin receptors is known to evoke cortical responses arising from the somatosensory cortex. Here we present a magnetoencephalographic (MEG) study where dermatomal somatosensory-evoked fields (DSSEFs) were recorded after mechanical stimulation of sacral (S1), lumbar (L3), thoracic (Th7), and cervical (C4) dermatomes in three healthy volunteers. All MEG measurements were repeated in order to test the replicability of the results. DSSEFs were successfully measured and modeled in all three participants. The topography and temporal dynamics of cortical responses derived after stimulation of each dermatome are described. We found that cortical-evoked responses can be reliably recorded using MEG after mechanical stimulation of dermatomes when a sufficiently large skin region within the dermatome is stimulated. Primary sensory cortex response (SI) to each of the four dermatomes was replicable and showed stability over time. The MEG-derived individual maps of activation confirm the somatotopic representation of dermatomes in primary sensory cortex and the utility of MEG recordings in disentangling the interactions between primary and secondary sensory cortex during somatic perception.     

Discrimination and categorization of speech and non-speech sounds in an MEG delayed-match-to-sample study

We investigated the perception and categorization of speech (vowels, syllables) and non-speech (tones, tonal contours) stimuli using MEG. In a delayed-match-to-sample paradigm, participants listened to two sounds and decided if they sounded exactly the same or different (auditory discrimination, AUD), or if they belonged to the same or different categories (category discrimination, CAT). Stimuli across the two conditions were identical; the category definitions for each kind of sound were learned in a training session before recording. MEG data were analyzed using an induced wavelet transform method to investigate task-related differences in time-frequency patterns. In auditory cortex, for both AUD and CAT conditions, an alpha (8-13 Hz) band activation enhancement during the delay period was found for all stimulus types. A clear difference between AUD and CAT conditions was observed for the non-speech stimuli in auditory areas and for both speech and non-speech stimuli in frontal areas. The results suggest that alpha band activation in auditory areas is related to both working memory and categorization for new non-speech stimuli. The fact that the dissociation between speech and non-speech occurred in auditory areas, but not frontal areas, points to different categorization mechanisms and networks for newly learned (non-speech) and natural (speech) categories.     

Simultaneous MEG and intracranial EEG recordings during attentive reading

The relationship between neural oscillations recorded at various spatial scales remains poorly understood partly due to an overall dearth of studies utilizing simultaneous measurements. In an effort to study quantitative markers of attention during reading, we performed simultaneous magnetoencephalography (MEG) and intracranial electroencephalography (iEEG) recordings in four epileptic patients. Patients were asked to attend to a specific color when presented with an intermixed series of red words and green words, with words of a given color forming a cohesive story. We analyzed alpha, beta, and gamma band oscillatory responses to the word presentation and compared the strength and spatial organization of those responses in both electrophysiological recordings. Time-frequency analysis of iEEG revealed a network of clear attention-modulated high gamma band (50–150 Hz) power increases and alpha/beta (9–25 Hz) suppressions in response to the words. In addition to analyses at the sensor level, MEG time-frequency analysis was performed at the source level using a sliding window beamformer technique. Strong alpha/beta suppressions were observed in MEG reconstructions, in tandem with iEEG effects. While the MEG counterpart of high gamma band enhancement was difficult to interpret at the sensor level in two patients, MEG time-frequency source reconstruction revealed additional activation patterns in accordance with iEEG results. Importantly, iEEG allowed us to confirm that several sources of gamma band modulation observed with MEG were indeed of cortical origin rather than EMG muscular or ocular artifact.     

Processing the acoustic effect of size in speech sounds

The length of a vocal tract is reflected in the sound it is producing. The length of the vocal tract is correlated with body size and humans are very good at making size judgments based on the acoustic effect of vocal tract length only. Here we investigate the underlying mechanism for processing this main auditory cue to size information in the human brain. Sensory encoding of the acoustic effect of vocal tract length (VTL) depends on a time-stabilized spectral scaling mechanism that is independent of glottal pulse rate (GPR, or voice pitch); we provide evidence that a potential neural correlate for such a mechanism exists in the medial geniculate body (MGB). The perception of the acoustic effect of speaker size is influenced by GPR suggesting an interaction between VTL and GPR processing; such an interaction occurs only at the level of non-primary auditory cortex in planum temporale and anterior superior temporal gyrus. Our findings support a two-stage model for the processing of size information in speech based on an initial stage of sensory analysis as early as MGB, and a neural correlate of the perception of source size in non-primary auditory cortex.     

Evidence for a frontal cortex role in both auditory and somatosensory habituation: a MEG study

Auditory and somatosensory responses to paired stimuli were investigated for commonality of frontal activation that may be associated with gating using magnetoencephalography (MEG). A paired stimulus paradigm for each sensory evoked study tested right and left hemispheres independently in ten normal controls. MR-FOCUSS, a current density technique, imaged simultaneously active cortical sources. Each subject showed source localization, in the primary auditory or somatosensory cortex, for the respective stimuli following both the first (S1) and second (S2) impulses. Gating ratios for the auditory M50 response, equivalent to the P50 in EEG, were 0.54+/-0.24 and 0.63+/-0.52 for the right and left hemispheres. Somatosensory gating ratios were evaluated for early and late latencies as the pulse duration elicits extended response. Early gating ratios for right and left hemispheres were 0.69+/-0.21 and 0.69+/-0.41 while late ratios were 0.81+/-0.41 and 0.80+/-0.48. Regions of activation in the frontal cortex, beyond the primary auditory or somatosensory cortex, were mapped within 25 ms of peak S1 latencies in 9/10 subjects during auditory stimulus and in 10/10 subjects for somatosensory stimulus. Similar frontal activations were mapped within 25 ms of peak S2 latencies for 75% of auditory responses and for 100% of somatosensory responses. Comparison between modalities showed similar frontal region activations for 17/20 S1 responses and for 13/20 S2 responses. MEG offers a technique for evaluating cross modality gating. The results suggest similar frontal sources are simultaneously active during auditory and somatosensory habituation.