People with autism perceive drastic illusory changes for repeated verbal stimuli.

A core symptom of autism spectrum disorder (ASD) is restricted and repetitive behavior, characterized partly by insistence on sameness and excessively focused interest. This behavior has often been interpreted as a manifestation of anxiety and fear triggered by resistance to change. The implicit assumption underlying this interpretation is that perception per se (such as the judgment of sameness and changes in sensory stimuli) is not different between ASD and typically developed (TD) individuals, but that only the emotional response to the same amount of perceived change is. However, few studies have examined how individuals with ASD actually perceive a repeated presentation of the same sensory stimulus. To explore this issue, we conducted a listening test to compare perception of a repeated sound pattern, namely a spoken word, between ASD and TD groups. Prolonged listening to a repeated word without a pause may induce perceptual changes, which is known as the verbal transformation effect. We discovered that individuals with ASD tend to perceive more drastic changes or differences for the same repeated auditory pattern. This suggests that such variable perception incites individuals with ASD to persist for sameness.

Resting-State Functional Connectivity-Based Biomarkers and Functional MRI-Based Neurofeedback for Psychiatric Disorders: A Challenge for Developing Theranostic Biomarkers.

Psychiatric research has been hampered by an explanatory gap between psychiatric symptoms and their neural underpinnings, which has resulted in poor treatment outcomes. This situation has prompted us to shift from symptom-based diagnosis to data-driven diagnosis, aiming to redefine psychiatric disorders as disorders of neural circuitry. Promising candidates for data-driven diagnosis include resting-state functional connectivity MRI (rs-fcMRI)-based biomarkers. Although biomarkers have been developed with the aim of diagnosing patients and predicting the efficacy of therapy, the focus has shifted to the identification of biomarkers that represent therapeutic targets, which would allow for more personalized treatment approaches. This type of biomarker (i.e., "theranostic biomarker") is expected to elucidate the disease mechanism of psychiatric conditions and to offer an individualized neural circuit-based therapeutic target based on the neural cause of a condition. To this end, researchers have developed rs-fcMRI-based biomarkers and investigated a causal relationship between potential biomarkers and disease-specific behavior using functional MRI (fMRI)-based neurofeedback on functional connectivity. In this review, we introduce a recent approach for creating a theranostic biomarker, which consists mainly of 2 parts: (1) developing an rs-fcMRI-based biomarker that can predict diagnosis and/or symptoms with high accuracy, and (2) the introduction of a proof-of-concept study investigating the relationship between normalizing the biomarker and symptom changes using fMRI-based neurofeedback. In parallel with the introduction of recent studies, we review rs-fcMRI-based biomarker and fMRI-based neurofeedback, focusing on the technological improvements and limitations associated with clinical use.

P300 component of event-related potentials in persons with asperger disorder.

In the present study, we investigated auditory event-related potentials in adults with Asperger disorder and normal controls using an auditory oddball task and a novelty oddball task. Task performance and the latencies of P300 evoked by both target and novel stimuli in the two tasks did not differ between the two groups. Analysis of variance revealed that there was a significant interaction effect between group and electrode site on the mean amplitude of the P300 evoked by novel stimuli, which indicated that there was an altered distribution of the P300 in persons with Asperger disorder. In contrast, there was no significant interaction effect on the mean P300 amplitude elicited by target stimuli. Considering that P300 comprises two main subcomponents, frontal-central-dominant P3a and parietal-dominant P3b, our results suggested that persons with Asperger disorder have enhanced amplitude of P3a, which indicated activated prefrontal function in this task.

Hemodynamic responses of eye movement desensitization and reprocessing in posttraumatic stress disorder.

Eye movement desensitization and reprocessing (EMDR) is an effective psychological intervention for posttraumatic stress disorder (PTSD). Trauma-related recall (Recall) with eye movements (EMs) is thought to reduce distress. However, the neural mechanisms underlying this process remain unknown. Thirteen patients with PTSD received EMDR treatment over the course of 2-10 weeks. We assessed the change in hemoglobin concentration in the lateral prefrontal cortex (PFC) during Recall with and without EM using multi-channel near-infrared spectroscopy (NIRS). Clinical diagnosis and improvement were evaluated using the Clinician-Administered PTSD Scale. Recall with EM was associated with a significant decrease in oxygenated hemoglobin concentration ([oxy-Hb]) in the lateral PFC as compared with Recall without EM. Longitudinally, [oxy-Hb] during Recall significantly decreased and the amount of decrease was significantly correlated with clinical improvement when the post-treatment data was compared with that of the pre-treatment. Our results suggest that performing EM during Recall reduces the over-activity of the lateral PFC, which may be part of the biological basis for the efficacy of EMDR in PTSD. NIRS may be a useful tool for objective assessment of psychological intervention in PTSD.

Cadmium, lead, and selenium in cord blood and thyroid hormone status of newborns.

Cadmium (Cd), lead (Pb), and selenium (Se) concentrations in cord whole blood, sampled from 24 women at the time of delivery in a hospital in Tokyo in 2005, were determined by inductively coupled plasma mass spectrometry with a reaction cell. Signal enhancement caused by nonspectroscopic interference for Se was evident and the standard addition technique was essential for correcting the interference. Median concentration in cord bloods was 0.20 ng/g, 6.7 ng/g (0.67 microg/dL), and 191 ng/g for Cd, Pb and Se, respectively. Lead concentration was lower, whereas Se concentration was higher, than those reported in other countries. The trace element concentration was related to the levels of thyroid stimulating hormone (TSH) and free thyroxin (fT4) in the neonatal blood sampled at 4-6 days postpartum. A significantly negative correlation was observed between Cd concentrations in cord blood and TSH concentration in neonatal blood. The result indicated the possible effect of in utero Cd exposure on thyroid hormone status of newborns and that Cd exposure level should be assessed as a covariate in the survey on the relationship between in utero chemicals (e.g., PCBs) exposure and thyroid hormone status.

Multiple-time replicability of near-infrared spectroscopy recording during prefrontal activation task in healthy men.

Near-infrared spectroscopy (NIRS) has the potential for clinical application in neuropsychiatry because it enables non-invasive and convenient measurement of hemodynamic response to cognitive activation. Using 24-channel NIRS in 12 healthy men, we examined the replicability of oxy- and deoxy-hemoglobin concentration ([oxyHb], [deoxyHb]) changes in the prefrontal cortex during the category fluency task over four repeated sessions (each 1-week apart). Multiple methods were employed to evaluate the replicability of magnitude, location, and time course of the NIRS signals ([oxyHb], [deoxyHb]). Task performances did not differ significantly across sessions, nor were they significantly correlated with NIRS signals. Repeated measures ANOVA and variance component analysis indicated high replicability of magnitude for both NIRS measures, whereas the effect sizes of between-session differences in [oxyHb] were not negligible. The number and spatial location of significantly activated channels were sufficiently replicable for both measures, except that the across-session overlap of significantly activated channels was weak in [deoxyHb]. The time course of the activation was acceptably replicable in both measures. Taken together, these findings suggest there is considerable replicability of multiple-time measurements of prefrontal hemodynamics during cognitive activation in men. Further studies using different conditions or assessing sensitivity to longitudinal changes following interventions are necessary.

Abnormal glucose metabolism in the anterior cingulate cortex in patients with schizophrenia.

Changes in glucose metabolism were studied in the brains of schizophrenic patients treated with neuroleptics, using [(18)F]fluoro-deoxy-glucose positron emission tomography (FDG-PET). Fourteen male and eight female patients in their thirties and forties were studied in a resting state. Data from FDG-PET were processed with an anatomic standardization method, three-dimensional stereotactic surface projections (3D-SSP), which provided relative glucose metabolic values that mitigated the contamination of brain atrophy. Z-score maps indicating metabolic differences between the patient and control groups were also acquired. Metabolic values in 19 regions were evaluated in the right and left hemispheres. Patients showed decreased values in the frontal cortex, primary sensory regions and anterior cingulate cortex, more in the rostral affective subdivision than the dorsal cognitive subdivision in both hemispheres, and increased metabolic values in left and right basal ganglia, left temporal and right medial parietal regions. Values were more decreased in both anterior cingulate regions, and more increased in the right thalamus in male than female patients, suggesting gender-related dysfunction in the anterior cingulate and thalamus in schizophrenia. FDG-PET demonstrated that schizophrenia may be a disorder with a dysfunction of fronto-striatal-thalamic circuitry including the cingulate cortex.

Delayed automatic detection of change in speech sounds in adults with autism: a magnetoencephalographic study.

OBJECTIVE: Autism is a form of pervasive developmental disorder in which dysfunction in interpersonal relationships and communication is fundamental. This study evaluated neurophysiological abnormalities at the basic level of language processing, i.e. automatic change detection of speech and non-speech sounds, using magnetoencephalographic recording of mismatch response elicited by change in vowels and tones. METHODS: The auditory magnetic mismatch field (MMF) was evaluated in 9 adults with autism and 19 control subjects using whole-head magnetoencephalography. The MMF in response to the duration change of a pure tone or vowel /a/ and that in response to across-phoneme change between vowels /a/ and /o/, were recorded. RESULTS: The groups were not significantly different in MMF power under any conditions. However, the autism group showed a left-biased latency prolongation of the MMF particularly under the across-phoneme change condition, and this latency delay was significantly associated with greater symptom severity. CONCLUSIONS: These results suggest that adults with autism are associated with delayed processing for automatic change detection of speech sounds. These electrophysiological abnormalities at the earliest level of information processing may contribute to the basis for language deficits observed in autism. SIGNIFICANCE: These results provide the first evidence for delayed latency of phonetic MMF in adults with autism.

Reduced intracellular pH in the basal ganglia and whole brain measured by 31P-MRS in bipolar disorder.

The authors have previously reported that intracellular pH measured by phosphorus-31 magnetic resonance spectroscopy (31P-MRS) was decreased in the frontal lobes of patients with bipolar disorder. In the present study, phosphorus metabolism in the basal ganglia was examined in 13 patients with bipolar disorder and 10 matched controls by localized 31P-MRS. While no significant alteration of peak area ratios was found for all phosphorus metabolites, intracellular pH was significantly reduced in the basal ganglia in patients with bipolar disorder (7.014 +/- 0.045) compared with control subjects (7.066 +/- 0.047, P < 0.05). Unexpectedly, non-localized 31P-MR spectra also showed significantly lower levels of intracellular pH (6.970 +/- 0.025) than controls (6.986 +/- 0.024, P < 0.05). These results suggest that decreased intracellular pH in the brain of patients with bipolar disorder is not caused by dysfunction of the frontal lobes but reflect altered metabolism at the cellular level.

Effects of corollary discharge on event-related potentials during selective attention task in healthy men and women.

Corollary discharge is a brain electrical activity associated with self-monitoring, which distinguishes self from others in thoughts or behaviors. Corollary discharge can be non-invasively assessed using event-related potential (ERP) recordings in humans. Previous studies have revealed that the amplitude of the N100 component elicited during an "odd-ball" task is reduced while a healthy subject is vocalizing, which may index the effect of corollary discharge on auditory ERPs. In this study, we attempted to assess the effect of vocalization on ERP components including N100, mismatch negativity (MMN), negative difference wave (Nd), and P300 during a selective attention task in 22 healthy adults. We also evaluated the possible contribution of gender to these effects. N100 amplitudes elicited by unattended standard stimuli were reduced under the vocalization condition compared with those under the baseline condition. However, there were no significant effects of vocalization on MMN, Nd or P300. Moreover, there was no significant effect of gender to the corollary discharge. These results suggest that the effect of corollary discharge on auditory ERPs is limited to the perceptual stage of information processing in healthy men and women.

No effect of gender on tonal and phonetic mismatch negativity in normal adults assessed by a high-resolution EEG recording.

The auditory mismatch negativity (MMN) of event-related potential components has been widely used to assess the ability of auditory automatic change discrimination of verbal and nonverbal stimuli in healthy individuals and patients with various illnesses. To clarify the role of gender differences in the MMN, we compared the amplitude, latency, and topography of tonal and phonetic MMN between healthy males and females, using a high-density (128 channel) electroencephalography montage. The MMN was evaluated in 18 right-handed male and ten age-matched female adults. The MMN in response to a duration change of pure tone and that in response to a phonetic change (Japanese vowel /a/ versus /o/ with 150-ms duration) were recorded. There were no significant differences in amplitude, latency, or laterality for either tonal or phonetic MMN between male and female subjects. This lack of evidence for effects of gender on MMN in response to duration change of tones or that in response to changes of phonemes with a short duration in normal adults may be of relevance to a growing number of researchers who are studying the MMN in healthy individuals and various clinical groups.

Do high or low doses of anxiolytics and hypnotics affect mismatch negativity in schizophrenic subjects? An EEG and MEG study.

OBJECTIVE: Many studies have demonstrated mismatch negativity (MMN) attenuation in schizophrenia. Recently, investigators have shown that GABAergic inhibitory neurons may regulate MMN generation. Considering that a substantial proportion of schizophrenic patients receive anxiolytics and hypnotics that have affinity to GABA(A) receptors to reduce their comorbid symptoms of anxiety and sleep disturbances, we need to assess whether anxiolytics/hypnotics might affect their MMN generation. The aim of this study is to assess the possibility that high or low doses of anxiolytics/hypnotics received by schizophrenic subjects affect their mismatch negativity (MMN), using event-related potentials (ERPs) and magnetoencephalography (MEG). METHODS: Twenty-three and 16 patients with schizophrenia participated in the ERP and MEG studies, respectively. Three types of MMN (MMN in response to a duration change of pure-tone stimuli, within-category vowel change (Japanese vowel /a/ with short versus long duration), and across-category vowel change (vowel /a/ versus /o/)) were recorded. RESULTS: High or low doses of benzodiazepine had no significant effects on MMN amplitude/magnetic MMN power, topography/laterality, or latency under any conditions of the ERP or MEG study. CONCLUSIONS: These results suggest that chronic administration of anxiolytics/hypnotics does not significantly affect MMN in schizophrenia.