Structural and functional thalamocortical connectivity study in female fibromyalgia.

Dysfunctional thalamocortical interactions have been suggested as putative mechanisms of ineffective pain modulation and also suggested as possible pathophysiology of fibromyalgia (FM). However, it remains unclear which specific thalamocortical networks are altered and whether it is related to abnormal pain perception in people with FM. Here, we conducted combined vertex-wise subcortical shape, cortical thickness, structural covariance, and resting-state functional connectivity analyses to address these questions. FM group exhibited a regional shape deflation of the left posterior thalamus encompassing the ventral posterior lateral and pulvinar nuclei. The structural covariance analysis showed that the extent of regional deflation of the left posterior thalamus was negatively covaried with the left inferior parietal cortical thickness in the FM group, whereas those two regions were positively covaried in the healthy controls. In functional connectivity analysis with the left posterior thalamus as a seed, FM group had less connectivity with the periaqueductal gray compared with healthy controls, but enhanced connectivity between the posterior thalamus and bilateral inferior parietal regions, associated with a lower electrical pain threshold at the hand dorsum (pain-free point). Overall, our findings showed the structural thalamic alteration interacts with the cortical regions in a functionally maladaptive direction, leading the FM brain more responsive to external stimuli and potentially contributing to pain amplification.

Characterization of kinesthetic motor imagery compared with visual motor imageries.

Motor imagery (MI) is the only way for disabled subjects to robustly use a robot arm with a brain-machine interface. There are two main types of MI. Kinesthetic motor imagery (KMI) is proprioceptive (OR somato-) sensory imagination and Visual motor imagery (VMI) represents a visualization of the corresponding movement incorporating the visual network. Because these imagery tactics may use different networks, we hypothesized that the connectivity measures could characterize the two imageries better than the local activity. Electroencephalography data were recorded. Subjects performed different conditions, including motor execution (ME), KMI, VMI, and visual observation (VO). We tried to classify the KMI and VMI by conventional power analysis and by the connectivity measures. The mean accuracies of the classification of the KMI and VMI were 98.5% and 99.29% by connectivity measures (alpha and beta, respectively), which were higher than those by the normalized power (p < 0.01, Wilcoxon paired rank test). Additionally, the connectivity patterns were correlated between the ME-KMI and between the VO-VMI. The degree centrality (DC) was significantly higher in the left-S1 at the alpha-band in the KMI than in the VMI. The MI could be well classified because the KMI recruits a similar network to the ME. These findings could contribute to MI training methods.

Change in left inferior frontal connectivity with less unexpected harmonic cadence by musical expertise.

In terms of harmonic expectancy, compared to an expected dominant-to-tonic and an unexpected dominant-to-supertonic, a dominant-to-submediant is a less unexpected cadence, the perception of which may depend on the subject's musical expertise. The present study investigated how aforementioned 3 different cadences are processed in the networks of bilateral inferior frontal gyri (IFGs) and superior temporal gyri (STGs) with magnetoencephalography. We compared the correct rate and brain connectivity in 9 music-majors (mean age, 23.5 ± 3.4 years; musical training period, 18.7 ± 4.0 years) and 10 non-music-majors (mean age, 25.2 ± 2.6 years; musical training period, 4.2 ± 1.5 years). For the brain connectivity, we computed the summation of partial directed coherence (PDC) values for inflows/outflows to/from each area (sPDCi/sPDCo) in bilateral IFGs and STGs. In the behavioral responses, music-majors were better than non-music-majors for all 3 cadences (p < 0.05). However, sPDCi/sPDCo was prominent only for the dominant-to-submediant in the left IFG. The sPDCi was more strongly enhanced in music-majors than in non-music-majors (p = 0.002, Bonferroni corrected), while the sPDCo was vice versa (p = 0.005, Bonferroni corrected). Our data show that music-majors, with higher musical expertise, are better in identifying a less unexpected cadence than non-music-majors, with connectivity changes centered on the left IFG.

Impaired pre-attentive auditory processing in fibromyalgia: A mismatch negativity (MMN) study.

OBJECTIVE: Fibromyalgia (FM) patients often show deficits in cognitive functions such as attention and working memory. We assumed that pre-attentive information processing, a crucial element in human perception and cognition, would be altered in FM patients. Thus, the objective of this study was to determine whether FM patients exhibit alterations in pre-attentive processing as assessed by auditory mismatch negativity (MMN). METHODS: Auditory evoked magnetic fields were recorded in FM patients (n=18) and healthy control subjects (n=21) during a duration-deviant auditory oddball paradigm. The magnetic mismatch negativity (MMNm) was obtained by subtracting responses to standard tones from responses to deviant tones. Pressure pain thresholds over the thenar and trapezius muscles were determined using an algometer. RESULTS: MMNm peak amplitudes in right hemispheres were attenuated, and the directional asymmetry coefficient of the MMNm amplitude was lower in FM patients, indicating a more leftward asymmetry than in healthy control subjects. Smaller right MMNm amplitude was associated with lower pressure pain thresholds of thenar muscles in FM patients. CONCLUSIONS: Our results suggested that pre-attentive processing of auditory information is impaired in FM patients. SIGNIFICANCE: This study provided neurophysiological evidence of impaired pre-attentive sensory change detection in FM.

Melody effects on ERANm elicited by harmonic irregularity in musical syntax.

Recent studies have reported that early right anterior negativity (ERAN) and its magnetic counterpart (ERANm) are evoked by harmonic irregularity in Western tonal music; however, those studies did not control for differences of melody. Because melody and harmony have an interdependent relationship and because melody (in this study melody is represented by the highest voice part) in a chord sequence may dominate, there is controversy over whether ERAN (or ERANm) changes arise from melody or harmony differences. To separate the effects of melody differences and harmonic irregularity on ERANm responses, we designed two magnetoencephalography experiments and behavioral test. Participants were presented with three types of chord progression sequences (Expected, Intermediate, and Unexpected) with different harmonic regularities in which melody differences were or were not controlled. In the uncontrolled melody difference experiment, the unexpected chord elicited a significantly largest ERANm, but in the controlled melody difference experiment, the amplitude of the ERANm peak did not differ among the three conditions. However, ERANm peak latency was delayed more than that in the uncontrolled melody difference experiment. The behavioral results show the difference between the two experiments even if harmonic irregularity was discriminated in the uncontrolled melody difference experiment. In conclusion, our analysis reveals that there is a relationship between the effects of harmony and melody on ERANm. Hence, we suggest that a melody difference in a chord progression is largely responsible for the observed changes in ERANm, reaffirming that melody plays an important role in the processing of musical syntax.

Aberrant auditory processing in schizophrenia and in subjects at ultra-high-risk for psychosis.

The N1 and the mismatch negativity (MMN) responses observed in electroencephalographic and magnetoencephalographic (MEG) recordings reflect sensory processing, sensory memory, and adaptation and are usually abnormal in patients with schizophrenia. However, their differential sensitivity to ultra-high-risk (UHR) status is controversial. The current study evaluated the sensitivity of MEG N1m, N1m adaptation, and magnetic counterpart of MMN (MMNm) in 16 UHR subjects, 15 schizophrenia patients, and 18 healthy controls (HCs) during a passive auditory oddball task. N1m adaptation was assessed using the difference in N1m dipole moment between the first and last standard tones in a standard stimulus sequence. N1m adaptation occurred in HCs, whereas neither the UHR nor the schizophrenia groups showed adaptation to the standard tone on repeated presentations. The UHR group had values between those for HCs and schizophrenia patients. Additionally, MMNm dipole moment was reduced in both the UHR and patient groups compared with HCs, whereas the UHR and schizophrenia groups did not differ from each other. These findings indicated that both N1m adaptation and MMNm were altered in UHR subjects and in schizophrenia patients, despite unaffected N1m dipole moment to the first standard tones. Moreover, both UHR and schizophrenia groups failed to show adaptation of the N1m to repeated standard tones. This failure in adaptation was more severe in patients than UHR subjects, suggesting that auditory adaptation may be sensitive to the progression of the illness and be an early biomarker of UHR for psychosis. Deficits in auditory sensory memory, on the other hand, may be similarly impaired in both groups.

Discrimination of timbre in early auditory responses of the human brain.

BACKGROUND: The issue of how differences in timbre are represented in the neural response still has not been well addressed, particularly with regard to the relevant brain mechanisms. Here we employ phasing and clipping of tones to produce auditory stimuli differing to describe the multidimensional nature of timbre. We investigated the auditory response and sensory gating as well, using by magnetoencephalography (MEG). METHODOLOGY/PRINCIPAL FINDINGS: Thirty-five healthy subjects without hearing deficit participated in the experiments. Two different or same tones in timbre were presented through conditioning (S1)-testing (S2) paradigm as a pair with an interval of 500 ms. As a result, the magnitudes of auditory M50 and M100 responses were different with timbre in both hemispheres. This result might support that timbre, at least by phasing and clipping, is discriminated in the auditory early processing. The second response in a pair affected by S1 in the consecutive stimuli occurred in M100 of the left hemisphere, whereas both M50 and M100 responses to S2 only in the right hemisphere reflected whether two stimuli in a pair were the same or not. Both M50 and M100 magnitudes were different with the presenting order (S1 vs. S2) for both same and different conditions in the both hemispheres. CONCLUSIONS/SIGNIFICANCES: Our results demonstrate that the auditory response depends on timbre characteristics. Moreover, it was revealed that the auditory sensory gating is determined not by the stimulus that directly evokes the response, but rather by whether or not the two stimuli are identical in timbre.

The effect of conditional probability of chord progression on brain response: an MEG study.

BACKGROUND: Recent electrophysiological and neuroimaging studies have explored how and where musical syntax in Western music is processed in the human brain. An inappropriate chord progression elicits an event-related potential (ERP) component called an early right anterior negativity (ERAN) or simply an early anterior negativity (EAN) in an early stage of processing the musical syntax. Though the possible underlying mechanism of the EAN is assumed to be probabilistic learning, the effect of the probability of chord progressions on the EAN response has not been previously explored explicitly. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, the empirical conditional probabilities in a Western music corpus were employed as an approximation of the frequencies in previous exposure of participants. Three types of chord progression were presented to musicians and non-musicians in order to examine the correlation between the probability of chord progression and the neuromagnetic response using magnetoencephalography (MEG). Chord progressions were found to elicit early responses in a negatively correlating fashion with the conditional probability. Observed EANm (as a magnetic counterpart of the EAN component) responses were consistent with the previously reported EAN responses in terms of latency and location. The effect of conditional probability interacted with the effect of musical training. In addition, the neural response also correlated with the behavioral measures in the non-musicians. CONCLUSIONS/SIGNIFICANCE: Our study is the first to reveal the correlation between the probability of chord progression and the corresponding neuromagnetic response. The current results suggest that the physiological response is a reflection of the probabilistic representations of the musical syntax. Moreover, the results indicate that the probabilistic representation is related to the musical training as well as the sensitivity of an individual.

An MEG study of alpha modulation in patients with schizophrenia and in subjects at high risk of developing psychosis.

BACKGROUND: Selective attention involves a dynamic interaction between attentional control systems and brain oscillations. In auditory processing, selective attention toward task-relevant stimuli and the inhibition of irrelevant information can be considered as aspects of top-down attentional control. Oscillatory rhythms in the alpha band have been found to play an important role during top-down processing. Because attention deficits have been noted in patients with schizophrenia, we examined alpha oscillations in schizophrenia and in the prodromal phase of psychosis. METHODS: The present study compared alpha oscillations using measures of both spectral power and inter-trial coherence in 17 subjects at ultra-high-risk, 10 patients with schizophrenia, and 18 matched normal control subjects. Whole-head magnetoencephalography (MEG) was conducted during an auditory oddball task to investigate alpha brain activity related to selective attention to target stimuli and selective inhibition of irrelevant stimuli. RESULTS: Patients with schizophrenia showed diminished alpha event-related desynchronization compared with the control subjects, while the ultra-high-risk subjects had values intermediate between the control subjects and schizophrenia patients. Similarly, alpha inter-trial phase coherence was lower in the schizophrenia patients than the ultra-high-risk subjects, and lower in the ultra-high-risk subjects than the normal control subjects. Furthermore, alpha band activity in the parieto-occipital region was more severely depressed in the schizophrenia patients than the ultra-high-risk subjects. CONCLUSIONS: The altered alpha band activity in the ultra-high-risk group indicates that a deficit in top-down attentional control exists before the onset of psychosis. The alpha event-related desynchronization and inter-trial coherence may reflect a functional decline in the prodromal phase of schizophrenia.

Assessment of language dominance by event-related oscillatory changes in an auditory language task: magnetoencephalography study.

The authors investigated the oscillatory changes induced by auditory language task to assess hemispheric dominance of language. Magnetoencephalography studies were conducted during word listening in 6 normal right-handed volunteers and 13 epilepsy patients who underwent Wada test. We carried out a time-frequency analysis of event-related desynchronization (ERD)/event-related synchronization (ERS) and intertrial coherence. We localized ERD/ERS on each subject's magnetic resonance images using beamformer. We compared ERD/ERS values between the left and right side of regions of interest in inferior frontal and superior temporal areas. We assessed the target frequency range that correlated best with the Wada test results. In all normal subjects, gamma ERD was lateralized to the left side in both the inferior frontal and superior temporal areas. In epilepsy patients, the concordance rate of gamma ERD and the Wada test results was 76.9% for the inferior frontal area and 69.2% for the superior temporal area. Gamma ERD can be considered as an indicator of language function, although it was not sufficient to replace the Wada test in the evaluation of epilepsy patients. The gamma ERD value of the inferior frontal area was more reliable for the assessment of language dominance compared with that obtained in the superior temporal area.

Thalamic changes in temporal lobe epilepsy with and without hippocampal sclerosis: a diffusion tensor imaging study.

OBJECTIVE: The seizure network may be different between temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) and without HS (TLE-HS). Chronic seizure activity may alter the diffusion properties of a seizure network. The thalamus is known to have an anatomical connection to the medial temporal area and to play a role in seizure modulation. This study aimed to evaluate differences in thalamic changes between TLE+HS and TLE-HS with diffusion tensor imaging (DTI). METHODS: Nine patients with TLE+HS and nine patients with TLE-HS were included in the study. All patients underwent surgery with good seizure outcomes. Hippocampal sclerosis was verified pathologically. Sixteen right-handed, normal subjects were enrolled as controls. DTI was acquired using 3.0 T MRI. The mean diffusivity (MD) and fractional anisotropy (FA) were calculated in the center of the bilateral thalamus with the DTIstudio program. RESULTS: The MD of bilateral thalami increased in both TLE groups compared to controls (p<0.05), while FA values did not differ from controls. The MD of the thalamus ipsilateral to the epileptogenic side was higher in the TLE+HS group than in the TLE-HS group (p=0.007). Onset age, seizure duration, seizure frequency and total seizure number were not correlated with FA and MD changes (p>0.05). CONCLUSION: Bilateral thalamic diffusion properties are altered in temporal lobe epilepsy. The presence of hippocampal sclerosis enhances the change ipsilaterally.

Pre-attentive auditory processing in ultra-high-risk for schizophrenia with magnetoencephalography.

BACKGROUND: It is uncertain whether the neurobiological abnormalities in schizophrenia emerge at the first episode of the disorder or are present during the prodromal phase. Recent neuroimaging studies indicate that some brain abnormalities are present in subjects at ultra-high-risk (UHR) for schizophrenia. Pre-attentive auditory deficits, which represent a core feature of schizophrenia, were investigated in individuals at UHR for schizophrenia. METHODS: We assessed early auditory processing indexed by the magnetoencephalographic mismatch negativity magnetic counterpart (MMNm) component elicited during a passive oddball paradigm in UHR individuals. Sixteen individuals at UHR for schizophrenia on the basis of clinical criteria and 18 healthy control subjects matched for age, gender, and education participated. A duration-deviant oddball paradigm was used to obtain MMNm dipole moment, which was measured with cortical source modeling. RESULTS: The UHR group showed a smaller right MMNm dipole moment than those of the control group. Group difference was observed in MMNm dipole latency, suggestive of slowed processing. The left MMNm dipole moment was negatively correlated with clinical symptoms measured by the Comprehensive Assessment of At-Risk Mental States positive symptom score. CONCLUSIONS: Our findings suggest that deficits in the early stage of auditory processing in individuals at UHR for schizophrenia exist before the onset of psychosis. The MMNm dipole moment might reflect the functional decline at the prodromal stage of schizophrenia.