Relationship of the Acoustic Startle Response and Its Modulation to Adaptive and Maladaptive Behaviors in Typically Developing Children and Those With Autism Spectrum Disorders: A Pilot Study.

Background: Autism spectrum disorder (ASD) is associated with persistent impairments in adaptive functioning across multiple domains of daily life. Thus, investigation of the biological background of both adaptive and maladaptive behaviors may shed light on developing effective interventions for improving social adaptation in ASD. In this study, we examined the relationship between adaptive/maladaptive behaviors and the acoustic startle response (ASR) and its modulation, which are promising neurophysiological markers for ASD translational research. Method: We investigated the ASR and its modulation in 11 children with ASD and 18 with typical development (TD), analyzing the relationship between startle measures and adaptive/maladaptive behaviors assessed with the Vineland Adaptive Behavior Scales (VABS) Second Edition. Results: Peak-ASR latency was negatively correlated with the VABS total score and socialization domain score of adaptive behaviors, while the ASR magnitude for relatively weak stimuli of 75-85 dB was positively correlated with VABS maladaptive behavior scores. Prepulse inhibition (PPI) at the prepulse intensity of 70-75 dB was also correlated with VABS maladaptive behavior. However, these relationships did not remain significant after adjustment for multiple comparisons. Conclusions: Our results indicate that the prolonged peak-ASR latency of ASD children might be associated with impairment in the developmental level of adaptive behavior, and that the greater ASR magnitude to relatively weak acoustic stimuli and smaller PPI of ASD children might increase the risk of maladaptive behavior. Future studies that have larger sample sizes will be important for further elucidating the neurophysiological factors that underpin adaptive as well as maladaptive behaviors in ASD.

Acoustic Hyper-Reactivity and Negatively Skewed Locomotor Activity in Children With Autism Spectrum Disorders: An Exploratory Study.

Investigation of objective and quantitative behavioral phenotypes along with neurobiological endophenotypes might lead to increased knowledge of the mechanisms that underlie autism spectrum disorders (ASD). Here, we investigated the association between locomotor dynamics and characteristics of the acoustic startle response (ASR) and its modulation in ASD (n = 14) and typically developing (TD, n = 13) children. The ASR was recorded in response to acoustic stimuli in increments of 10 dB (65-105 dB SPL). We calculated the average ASR magnitude for each stimulus intensity and peak-ASR latency. Locomotor activity was continuously measured with a watch-type actigraph. We examined statistics of locomotor activity, such as mean activity levels and the skewness of activity. Children with ASD had a significantly greater ASR magnitude in response to a weak acoustic stimulus, which reflects acoustic hyper-reactivity. The skewness of all-day activity was significantly more negative in children with ASD than those with TD. Skewness of daytime activity was also more negative, although only of borderline statistical significance. For all children, the higher mean and more negatively skewed daytime activity, reflecting hyperactivity that was associated with sporadic large daytime "troughs," was significantly correlated with acoustic hyper-reactivity. The more negatively skewed locomotor activity occurring in the daytime was also associated with impaired sensorimotor gating, examined as prepulse inhibition at a prepulse intensity of 70 dB. This comprehensive investigation of locomotor dynamics and the ASR extends our understanding of the neurophysiology that underlies ASD.

Negatively Skewed Locomotor Activity Is Related to Autistic Traits and Behavioral Problems in Typically Developing Children and Those With Autism Spectrum Disorders.

An important objective for researchers and clinicians is to gain a better understanding of the factors that underlie autism spectrum disorders (ASDs). It is possible that investigating objective and quantitative behavioral phenotypes and their relationship to clinical characteristics, such as autistic traits and other emotional/behavioral problems, might facilitate this process. Given this, in the current study we examined the link between locomotor dynamics and clinical characteristics, including autistic traits and emotional/behavioral problems, in children with ASD (n = 14) and typically developing (TD) children (n = 13). A watch-type actigraph was used to continuously measure locomotor activity which was assessed in terms of mean activity levels and the skewness of activity. Parents assessed quantitative autistic traits using the Japanese version of the Social Responsiveness Scale (SRS) and emotional and behavioral problems using the Japanese version of the Strengths and Difficulties Questionnaire (SDQ). Results showed that among all children, all-day activity was more negatively skewed, suggesting sporadic large all-day "troughs" in activity and was significantly correlated with the SRS social awareness subscale score (ρ = -0.446, p = 0.038). In addition, the more negatively skewed daytime locomotor activity was associated with the SDQ Hyperactivity Inattention subscale score (ρ = -0.493, p = 0.020). The results of this study indicate that investigating locomotor dynamics may provide one way to increase understanding of the neurophysiological mechanisms underlying the clinical characteristics of ASD.

Relationship between physiological and parent-observed auditory over-responsiveness in children with typical development and those with autism spectrum disorders.

The objective of this study was to investigate relationships between caregiver-reported sensory processing abnormalities, and the physiological index of auditory over-responsiveness evaluated using acoustic startle response measures, in children with autism spectrum disorders and typical development. Mean acoustic startle response magnitudes in response to 65-105 dB stimuli, in increments of 10 dB, were analyzed in children with autism spectrum disorders and with typical development. Average peak startle latency was also examined. We examined the relationship of these acoustic startle response measures to parent-reported behavioral sensory processing patterns in everyday situations, assessed using the Sensory Profile for all participants. Low-threshold scores on the Sensory Profile auditory section were related to acoustic startle response magnitudes at 75 and 85 dB, but not to the lower intensities of 65 dB. The peak startle latency and acoustic startle response magnitudes at low-stimuli intensities of 65 and 75 dB were significantly related to the low-threshold quadrants (sensory sensitivity and sensation avoiding) scores and to the high-threshold quadrant of sensation seeking. Our results suggest that physiological assessment provides further information regarding auditory over-responsiveness to less-intense stimuli and its relationship to caregiver-observed sensory processing abnormalities in everyday situations.

Stability of the acoustic startle response and its modulation in children with typical development and those with autism spectrum disorders: A one-year follow-up.

Auditory hyper-reactivity is a common sensory-perceptual abnormality that interrupts behavioral adaptations in autism spectrum disorders (ASD). Recently, prolonged acoustic startle response (ASR) latency and hyper-reactivity to weak acoustic stimuli were reported in children with ASD. Indexes of ASR and its modulation are known to be stable biological markers for translational research in the adult population. However, little is known about the stability of these indexes in children. Thus, the objective of our study was to investigate the stability of neurophysiological ASR indexes in children with ASD and typical development (TD). Participants included 12 children with ASD and 24 with TD. Mean startle magnitudes to acoustic stimuli presented at 65-105 dB in increments of 10 dB were analyzed. Average peak startle latency (PSL), ASR modulation of habituation, and prepulse inhibition were also analyzed. These startle measures were examined after a follow-up period of 15.7 ± 5.1 months from baseline. At both baseline and in the follow-up period, children with ASD had significantly greater startle magnitudes to weak stimuli of 65-85 dB and more prolonged PSL compared with controls. Intraclass correlation coefficients for these ASR measures between both periods were 0.499-0.705. None of the ASR measures differed significantly between the two periods. Our results suggest that prolonged PSL and greater startle magnitudes to weak stimuli in children with ASD might serve as moderately stable neurophysiological indexes of ASD. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 673-679. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Relationship of the Acoustic Startle Response and Its Modulation to Emotional and Behavioral Problems in Typical Development Children and Those with Autism Spectrum Disorders.

Auditory hyper-reactivity is a common sensory-perceptual abnormality in autism spectrum disorders (ASD), which interrupts behavioral adaptation. We investigated acoustic startle response (ASR) modulations in 17 children with ASD and 27 with typical development (TD). Compared to TD, children with ASD had larger ASR magnitude to weak stimuli and more prolonged peak startle-latency. We could not find significant difference of prepulse inhibition (PPI) or habituation in ASD children compared to TD. However, habituation and PPI at 70-dB prepulses were negatively related to several subscales of Social Responsiveness Scale and the Strengths and Difficulties Questionnaire, when considering all children. Comprehensive investigation of ASR and its modulation might increase understanding of the neurophysiological impairments underlying ASD and other mental health problems in children.

Implied functional crossed cerebello-cerebral diaschisis and interhemispheric compensation during hand grasping more than 20 years after unilateral cerebellar injury in early childhood.

BACKGROUND: Crossed cerebello-cerebral diaschisis (CCCD) conventionally refers to decreased resting cerebral activity caused by injury to the contralateral cerebellum. We investigated whether functional activation of a contralesional cerebral cortical region controlling a specific task is reduced during task performance in a patient with a unilateral cerebellar lesion. We also examined functional compensation by the corresponding ipsilesional cerebral cortex. It was hypothesized that dysfunction of the primary sensorimotor cortex (SM1) contralateral to the cerebellar lesion would be detected together with a compensatory increase in neural activity of the ipsilesional SM1. To test these possibilities, we conducted non-invasive functional neuroimaging techniques for bilateral SM1 during hand grasping, a task known to activate predominantly the SM1 contralateral to the grasping hand. Activity in SM1 during hand grasping was measured electrophysiologically by magnetoencephalography and hemodynamically by near-infrared spectroscopy in an adult with mild right hemiataxia associated with a large injury of the right cerebellum due to resection of a tumor in early childhood. RESULTS: During left hand grasping, increased neural activity was detected predominantly in the right SM1, the typical developmental pattern. In contrast, neural activity increased in the bilateral SM1 with slight right-side dominance during right (ataxic) hand grasping. CONCLUSIONS: This study reported a case that implied functional CCCD and compensatory neural activity in the SM1 during performance of a simple hand motor task in an adult with unilateral cerebellar injury and mild hemiataxia 24 years prior to the study without rehabilitative interventions. This suggests that unilateral cerebellar injuries in early childhood may result in persistent functional abnormalities in the cerebrum into adulthood. Therapeutic treatments that target functional CCCD and interhemispheric compensation might be effective for treating ataxia due to unilateral cerebellar damage.

Frontal midline theta rhythm and gamma power changes during focused attention on mental calculation: an MEG beamformer analysis.

Frontal midline theta rhythm (Fmθ) appears widely distributed over medial prefrontal areas in EEG recordings, indicating focused attention. Although mental calculation is often used as an attention-demanding task, little has been reported on calculation-related activation in Fmθ experiments. In this study we used spatially filtered MEG and permutation analysis to precisely localize cortical generators of the magnetic counterpart of Fmθ, as well as other sources of oscillatory activity associated with mental calculation processing (i.e., arithmetic subtraction). Our results confirmed and extended earlier EEG/MEG studies indicating that Fmθ during mental calculation is generated in the dorsal anterior cingulate and adjacent medial prefrontal cortex. Mental subtraction was also associated with gamma event-related synchronization, as an index of activation, in right parietal regions subserving basic numerical processing and number-based spatial attention. Gamma event-related desynchronization appeared in the right lateral prefrontal cortex, likely representing a mechanism to interrupt neural activity that can interfere with the ongoing cognitive task.

Hyperreactivity to weak acoustic stimuli and prolonged acoustic startle latency in children with autism spectrum disorders.

BACKGROUND: People with autism spectrum disorders (ASD) are known to have enhanced auditory perception, however, acoustic startle response to weak stimuli has not been well documented in this population. The objectives of this study are to evaluate the basic profile of acoustic startle response, including peak startle latency and startle magnitude to weaker stimuli, in children with ASD and typical development (TD), and to evaluate their relationship to ASD characteristics. METHODS: We investigated acoustic startle response with weak and strong acoustic stimuli in 12 children with ASD and 28 children with TD, analyzing the relationship between startle measures and quantitative autistic traits assessed with the Social Responsiveness Scale (SRS). The electromyographic activity of the left orbicularis oculi muscle to acoustic stimuli of 65 to 115 dB sound pressure level (SPL), in increments of 5 dB, was measured to evaluate acoustic startle response. The average eyeblink magnitude for each acoustic stimuli intensity and the average peak startle latency of acoustic startle response were evaluated. RESULTS: The magnitude of the acoustic startle response to weak stimuli (85 dB or smaller) was greater in children with ASD. The peak startle latency was also prolonged in individuals with ASD. The average magnitude of the acoustic startle response for stimulus intensities greater than 85 dB was not significantly larger in the ASD group compared with the controls. Both greater startle magnitude in response to weak stimuli (particularly at 85 dB) and prolonged peak startle latency were significantly associated with total scores, as well as several subscales of the SRS in the whole sample. We also found a significant relationship between scores on the social cognition subscale of the SRS and the average magnitude of the acoustic startle response for stimulus intensities of 80 and 85 dB in the TD group. CONCLUSIONS: Children with ASD exhibited larger startle magnitude to weak stimuli and prolonged peak startle latency. These startle indices were related to several characteristics of ASD. A comprehensive investigation of acoustic startle response, including the magnitude of startle responses to weak stimuli and peak startle latency, might further our understanding of the neurophysiological impairments underlying ASD.

Frequency diversity of posterior oscillatory activity in human revealed by spatial filtered MEG.

The posterior EEG alpha rhythm is a distinctive feature of the normal brain in the waking state, consisting of oscillations within the 8-15 Hz frequency range over posterior cortical regions. This activity appears in resting, eyes-closed condition and is typically suppressed by eyes-opening. Other physiological rhythms in the alpha band, in particular the Rolandic mu rhythm, are proposed to include a fast component in the beta range. In this study we used spatial filtering techniques and permutation analysis to explore cortical source-power changes related to the magnetoencephalography (MEG) counterpart of the posterior alpha rhythm. We also aimed at determining a possible implication of components outside the alpha frequency range in the posterior rhythm reactivity to eye closure. We recorded resting brain activity using a whole-head MEG system in fifteen normal subjects. We applied an eyes-open/eyes-closed paradigm. A significant increase in alpha oscillations after eyes closing, representing the posterior alpha rhythm, was observed bilaterally in the occipital and parietal cortex, including the calcarine fissure and the parieto-occipital sulcus. We also found significant increase in beta (15-30 Hz) and low gamma (30-60 Hz) oscillations. This fast components and the classical alpha rhythm had similar topographic distribution in posterior brain regions, although with different strength and spatial extension. These features were highest for alpha synchronized oscillations, intermediate for beta, and lowest for gamma activity. These results suggest that, like the Rolandic mu rhythm, the MEG posterior dominant rhythm may be impure, with a mixture of predominant alpha oscillations and high-frequency components.

[Psychiatric issues of children and adults with autism spectrum disorders who remain undiagnosed].

Individuals of normal intelligence with autism spectrum disorders (ASD) tend to be diagnosed with ASD late in childhood or sometimes in adulthood, despite a persistent symptomatology. When such patients visit psychiatric clinics for co-occurring psychiatric symptoms, the diagnostic procedure can be challenging due to a lack of accurate developmental information and a mixed clinical presentation. The same is true for those with subthreshold autistic symptoms. Although individuals with subthreshold ASD also have social adjustment difficulties of a similar degree to those with ASD, the relative clinical significance of this population is unclear. Here, data from a large national population sample of schoolchildren were examined to determine the psychiatric needs of children with threshold and subthreshold autistic symptoms. First, autistic symptoms or traits assessed by the Social Responsiveness Scale (SRS), a quantitative behavioral measure, showed a continuous distribution in the general child population (n = 22,529), indicating no evidence of a natural gap that could differentiate children diagnosed with ASD from subthreshold or unaffected children. Second, data from 25,075 children demonstrated that having threshold autistic symptoms predicted a high psychiatric risk, as indicated by higher scores on the Strengths and Difficulties Questionnaire (SDQ; odds ratio [OR] 200.52, 95% confidence interval [CI]: 152.12-264.33), and that having subthreshold autistic symptoms indicated the same (OR 12.78, 95% CI: 11.52-14.18). Having threshold autistic symptoms predicted emotional problems (OR 20.19, 95% CI: 17.00-24.00), as did having subthreshold autistic symptoms (OR 5.90, 95% CI: 5.29-6.58). Third, among 2,250 children at a high psychiatric risk, most had threshold or subthreshold autistic symptoms (21 and 44%, respectively). These findings have important implications for the comprehensive psychiatric and developmental evaluation and treatment of this patient population, whose diagnosis and treatment are often delayed, and a further in-depth study is warranted.

[Endophenotypes in schizophrenia: a review of electrophysiological studies].

Schizophrenia patients consistently show some deficiency in electrophysiological measures, such as PPI (Prepulse Inhibition), ERP (Event-Related Potential) components (mismatch negativity, P50, P300), EEG (Electroencephalography), and MEG (Magnetoencephalography). These components have been intensively studied as quantitative biological markers (i.e., endophenotypes) for psychiatric disorders. Recently brain oscillations, especially gamma (30-80 Hz) band activity (GBA), are being increasingly investigated as new candidate endophenotypes. In this review, we summarize the current status, perspective, and limitations of representative paradigms for investigating abnormal electrophysiological components of schizophrenia, along with relevant genetic polymorphism.

Relationship of prepulse inhibition to temperament and character in healthy Japanese subjects.

Prepulse inhibition (PPI) of acoustic startle reflex (ASR) and personality, such as temperament and character, are considered candidate endophenotypes of schizophrenia. Gene polymorphism studies have provided evidence that both PPI and self-transcendence (ST) are polygenetic traits that involve several neurotransmitters, including the serotonin and dopamine signaling pathways. However, the relationship between PPI and temperament/character has not been properly addressed to date. Here, we investigated the link between PPI and temperament/character in 169 healthy Japanese subjects. A human startle response monitoring system was used to deliver acoustic startle stimuli and to record and score the electromyographic activity of the orbicularis oculi muscle. PPI was evaluated at signal-to-noise ratios (SnRs: intensity difference between background noise and prepulse) of +12, +16, and +20 dB. The lead interval (from prepulse onset to pulse onset) was 120 ms, and Temperament and Character Inventory was used in both groups. Significant correlations at SnR of +16 and +20 dB to ST were identified. Our results suggest that impaired sensorimotor gating, evaluated as lower PPI of ASR, of healthy subjects is correlated with self transcendence, the character which is closely related with schizophrenia and schizotypy.

Induced oscillatory responses during the Sternberg's visual memory task in patients with Alzheimer's disease and mild cognitive impairment.

In this study we used magnetoencephalography during a modified version of the Sternberg's memory recognition task performed by patients with early Alzheimer's disease (AD), mild cognitive impairment (MCI), and by age-matched healthy controls to identify differences in induced oscillatory responses. For analyses, we focused on the retention period of the working memory task. Multiple-source beamformer and Brain Voyager were used for localization of source-power changes across the cortex and for statistic group analyses, respectively. We found significant differences in oscillatory response during the task, specifically in beta and gamma frequency bands: patients with AD showed reduced beta event-related desynchronization (ERD) in the right central area compared to controls, and reduced gamma ERD in the left prefrontal and medial parietal cortex compared to patients with MCI. Our findings suggest that reduced oscillatory responses over certain brain regions in high frequency bands (i.e., beta, gamma), and especially in the beta band that was significantly different between AD patients and healthy subjects, may represent brain electromagnetic changes underlying visual-object working memory dysfunction in early AD, and a neurophysiological indicator of cognitive decline.

Resting-state EEG source localization and functional connectivity in schizophrenia-like psychosis of epilepsy.

BACKGROUND: It is unclear whether, like in schizophrenia, psychosis-related disruption in connectivity between certain regions, as an index of intrinsic functional disintegration, occurs in schizophrenia-like psychosis of epilepsy (SLPE). In this study, we sought to determine abnormal patterns of resting-state EEG oscillations and functional connectivity in patients with SLPE, compared with nonpsychotic epilepsy patients, and to assess correlations with psychopathological deficits. METHODOLOGY/PRINCIPAL FINDINGS: Resting EEG was recorded in 21 patients with focal epilepsy and SLPE and in 21 clinically-matched non-psychotic epilepsy controls. Source current density and functional connectivity were determined using eLORETA software. For connectivity analysis, a novel nonlinear connectivity measure called "lagged phase synchronization" was used. We found increased theta oscillations in regions involved in the default mode network (DMN), namely the medial and lateral parietal cortex bilaterally in the psychotic patients relative to their nonpsychotic counterparts. In addition, patients with psychosis had increased beta temporo-prefrontal connectivity in the hemisphere with predominant seizure focus. This functional connectivity in temporo-prefrontal circuits correlated with positive symptoms. Additionally, there was increased interhemispheric phase synchronization between the auditory cortex of the affected temporal lobe and the Broca's area correlating with auditory hallucination scores. CONCLUSIONS/SIGNIFICANCE: In addition to dysfunction of parietal regions that are part of the DMN, resting-state disrupted connectivity of the medial temporal cortex with prefrontal areas that are either involved in the DMN or implicated in psychopathological dysfunction may be critical to schizophrenia-like psychosis, especially in individuals with temporal lobe epilepsy. This suggests that DMN deficits might be a core neurobiological feature of the disorder, and that abnormalities in theta oscillations and beta phase synchronization represent the underlying neural activity.

Decreased α event-related synchronization in the left posterior temporal cortex in schizophrenia: a magnetoencephalography-beamformer study.

Alpha rhythm is one of the most prominent electromagnetic changes in the brain, and electroencephalography (EEG) alpha reactivity disturbance may sometimes represent an early sign of cerebral dysfunction. Although magnetoencephalography (MEG) has a better spatial resolution than EEG, it has not extensively been used to explore alpha-power change deficits in schizophrenia as a possible neurophysiological marker of the disease. The purpose of this study was to use MEG to identify abnormalities in alpha synchronization induced by eye-closing in schizophrenia patients compared to healthy controls, and to investigate whether alpha reactivity deficits correlate with clinical features of the disorder. MEG data were recorded in 22 schizophrenia patients and 20 age- and gender-matched controls during eyes-open/eyes-closed resting states. Cortical sources of event-related synchronization (ERS) were estimated using multiple source beamformer, and BrainVoyager was used for statistic group analysis. A significant decrease in ERS in the upper alpha band (10-13 Hz) was found in the left posterior temporal region in schizophrenia patients relative to controls, and this activity showed correlation with visual memory scores. This upper alpha ERS deficit may indicate left temporal dysfunction and visual-information processing impairment in schizophrenia, and upon further confirmation it might represent a neurophysiological state marker of the disorder.

Psychopathology and working memory-induced activation of the prefrontal cortex in schizophrenia-like psychosis of epilepsy: Evidence from magnetoencephalography.

AIM: The aim of this study was to investigate whether magnetoencephalographic oscillations underlying working memory dysfunction in the dorsolateral prefrontal cortex (DLPFC) are related to psychopathological disturbance in patients with schizophrenia-like psychosis of epilepsy (SLPE). METHODS: Twelve patients with SLPE and 14 non-psychotic epilepsy controls participated in this study. Magnetoencephalography was recorded while patients performed a visual working memory (WM) task. Psychopathology was assessed using a four-factor structure of the Brief Psychiatric Rating Scale, and regression analyses were carried out to examine the relative impact of severity of psychopathology on WM-induced activation of the DLPFC. RESULTS: We found that activation of the WM-compromising DLPFC, as indicated by increased alpha desynchronization in patients with SLPE compared with their non-psychotic counterparts, showed a positive linear correlation with disorganization symptom scores. This association remained significant after controlling for confounding factors, including age, task performance, IQ, and duration of psychosis. CONCLUSION: Our results indicate that abnormal activation in prefrontal areas engaged during working memory may be critical to domains of psychopathology, in particular disorganized thought-processing in patients with SLPE.

Frontal shift of posterior alpha activity is correlated with cognitive impairment in early Alzheimer's disease: a magnetoencephalography-beamformer study.

BACKGROUND: Induced-oscillatory activity is considered a key factor for understanding functional processes in the brain. Magnetoencephalography (MEG) can measure oscillatory activity non-invasively with higher spatial resolution than electroencephalography (EEG). However, MEG has rarely been used to explore functional abnormalities that may represent state markers in patients with Alzheimer's disease (AD). METHODS: Thirteen patients with early AD and 14 age-matched normal controls participated in the present study. Magnetoencephalography activity was acquired during eyes-open and eyes-closed states. Alpha event-related synchronization (ERS) after eye closing was calculated and its cortical sources superimposed on each individual's magnetic resonance imaging (MRI) scan. The resulting functional image was converted into a Talairach-transformed anatomical brain image and group comparisons were made. We also assessed correlations between cortical ERS sources showing significant between-group differences in alpha activity and external clinical parameters, especially measures of cognitive function. RESULTS: The averaged alpha ERS after eye closing appeared dominantly in posterior brain regions in both patients with AD and healthy controls. However, there was a significant increase in alpha ERS in frontal regions, maximal over the prefrontal cortex, in patients with AD relative to controls, indicating a frontal shift of the posterior dominant MEG alpha rhythm in AD patients. This frontal ERS source in the alpha band was negatively correlated with Mini-Mental State Examination scores in the AD patient group. CONCLUSIONS: The findings indicate that a frontal shift of alpha ERS elicited by an eyes-open/eyes-closed paradigm may be an early brain electromagnetic change in patients with AD, probably representing a physiological state marker of the disease. Furthermore, the results confirm that the beamformer with group comparison analysis is a useful tool with which to explore functional processes in the brain, as indicated by oscillatory activity changes.

Frontal cortex activation associated with speeded processing of visuospatial working memory revealed by multichannel near-infrared spectroscopy during Advanced Trail Making Test performance.

Although visuospatial working memory (VSWM) is commonly used during speeded and unconscious memory processing in daily life, most neuroimaging studies on VSWM use tasks that impose motor restrictions onto the examinees to avoid movement-related artifacts. Multichannel near-infrared spectroscopy (NIRS), however, can measure cortical activation during cognitive processing without interfering with task procedure. The purpose of this study is to determine whether multichannel NIRS can detect VSWM-induced frontal cortex activation similar to that seen in VSWM performance in daily-life activity. Using NIRS, we measured relative changes in the concentration of oxygenated hemoglobin as an index of frontal activation in 52 measurement points (channels) on the frontal area during the Advanced Trail Making Test (ATMT), a tool used to assess VSWM. The ATMT consists of two tasks, R and F, with the former assessing motor factors and the latter relating to both motor and cognitive factors involved in speeded and unconscious VSWM operations. Twenty-six healthy volunteers were enrolled in this study. Channel activation during Task F performance was observed bilaterally over the dorsolateral and ventrolateral prefrontal cortex. This distribution may reflect central executive function of working memory. Channel activation during Task R was circumscribed to part of the left ventrolateral prefrontal cortex partially overlapping with areas active during Task F performance, likely representing task-related motor factor activation. Our findings suggest that multichannel NIRS during ATMT performance is an appropriate means of measuring cortical activation induced by VSWM operations during daily activity.

Post-movement beta rebound abnormality as indicator of mirror neuron system dysfunction in autistic spectrum disorder: an MEG study.

The mu rhythm is regarded as a physiological indicator of the human mirror neuron system (MNS). The dysfunctional MNS hypothesis in patients with autistic spectrum disorder (ASD) has often been tested using EEG and MEG, targeting mu rhythm suppression during action observation/execution, although with controversial results. We explored neural activity related to the MNS in patients with ASD, focusing on power increase in the beta frequency band after observation and execution of movements, known as post-movement beta rebound (PMBR). Multiple source beamformer (MSBF) and BrainVoyager QX were used for MEG source imaging and statistical group analysis, respectively. Seven patients with ASD and ten normal subjects participated in this study. During the MEG recordings, the subjects were asked to observe and later execute object-related hand actions performed by an experimenter. We found that both groups exhibited pronounced PMBR exceeding 20% when observing and executing actions with a similar topographic distribution of maximal activity. However, significantly reduced PMBR was found only during the observation condition in the patients relative to controls in cortical regions within the MNS, namely the sensorimotor area, premotor cortex and superior temporal gyrus. Reduced PMBR during the observation condition was also found in the medial prefrontal cortex. These results support the notion of a dysfunctional execution/observation matching system related to MNS impairment in patients with ASD, and the feasibility of using MEG to detect neural activity, in particular PMBR abnormalities, as an index of MNS dysfunction during performance of motor or cognitive tasks.