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Humans perceive continuous speech signals as discrete sequences. To clarify the temporal segmentation window of speech information processing in the human auditory cortex, the relationship between speech perception and cortical responses was investigated using auditory evoked magnetic fields (AEFs). AEFs were measured while participants heard synthetic Japanese words /atataka/. There were eight types of /atataka/ with different speech rates. The durations of the words ranged from 75 to 600 ms. The results revealed a clear correlation between the AEFs and syllables. Specifically, when the durations of the words were between 375 and 600 ms, the evoked responses exhibited four clear responses from the superior temporal area, M100, that corresponded not only to the onset of speech but also to each group of consonant/vowel syllable units. The number of evoked M100 responses was correlated to the duration of the stimulus as well as the number of perceived syllables. The approximate range of the temporal segmentation window limit of speech perception was considered to be between 75 and 94 ms. This finding may contribute to optimizing the temporal performance of high-speed synthesized speech generation systems. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Paired‐pulse stimulation provides clinically useful information regarding sensory inhibition. When supraorbital nerve stimulation is repeated within a short interval, the response to the second stimulation is reduced to varying degrees. This magnitude of change in stimulation response can be monitored by electromyogram (EMG) or by mechanomyogram (MMG) as in this report. MMG has some advantages such as being less time consuming and lacking stimulus artifact. We compared the use of MMG and EMG to validate MMG as an effective method of assessing blink reflex paired‐pulse inhibition. Methods: Eight volunteers participated. Participants received electrical stimulation to the supraorbital nerve of each side. A paired‐pulse paradigm was employed, varying the conditioning‐test interval between 5 and 800 ms. The R1 component of the induced blink reflex was simultaneously recorded by EMG using a pair of electrodes placed on the lower eyelid and by MMG using an accelerometer placed between the electrodes. Results: The correlation coefficient of the R1 amplitude between MMG and EMG of the grand‐averaged waveforms was 0.99. The average participant r value was.91 (range.76–.99). Similar analyses were performed for the amplitude variation of the second response relative to the first response. Results correlated well, yielding r values of.97 and.86 for the grand‐averaged waveform and the average for each subject. Discussion: The present results demonstrate that MMG could be an alternative to EMG in assessing paired‐pulse inhibition of the electrical blink reflex R1 component. [ABSTRACT FROM AUTHOR]

Epilepsy is considered to be related to deficits in suppression function and is also known to be associated with specific character traits. In this study, we used paired-pulse suppression of change-related cortical responses and the Bear-Fedio personality inventory (BFI) in 34 healthy adults. With a continuous sound duration of 2,000 ms, change-related responses were elicited twice at 1,100 and 1,700 ms. The P50/N100 amplitude was used to calculate the degree of paired-pulse suppression. Results showed that the suppression rate was negatively correlated with the total BFI score (r = − 0.50, p = 0.004) as well as 9 of the 18 subscales (− 0.5 < r ≤ − 0.3). A significant negative correlation was also found between the amplitude of the response to the first stimulus and the total BFI score (r = − 0.64, p = 8.8*10− 5). These findings suggest that inhibitory function is linked to epilepsy personality traits as indexed by the BFI. [ABSTRACT FROM AUTHOR]

An ultimate goal of materials science is to deliver materials with desired properties at will. Solving the inverse problem to obtain an appropriate Hamiltonian directly from the desired properties has the potential to reach qualitatively new principles, but most research to date has been limited to quantitative determination of parameters within known models. Here, we develop a general framework that can automatically design a Hamiltonian with desired physical properties by using automatic differentiation. In the application to the quantum anomalous Hall effect, our framework can not only construct the Haldane model automatically but also generate Hamiltonians that exhibit a six-times larger anomalous Hall effect. In addition, the application to the photovoltaic effect gives an optimal Hamiltonian for electrons moving on a noncoplanar spin texture, which can generate ~ 700 Am−2 under solar radiation. This framework would accelerate materials exploration by automatic construction of models and principles. Obtaining a Hamiltonian that produces desired physical properties is important in materials design, that is, however, a highly nontrivial process since the parameter space is usually unknown a priori. Here, the authors present a general theoretical framework based on the inverse problem that uses automatic differentiation to construct a Hamiltonian with the desired physical properties. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that change-related cortical responses are phenomena similar to the onset response and could be applied to the loudness dependence of auditory evoked potential (LDAEP) paradigm. In the present study, we examined the relationship between LDAEP and the change-related response using electroencephalography findings in 50 healthy subjects. There were five conditions (55, 65, 75, 85, and 95 dB) for LDAEP and five similar conditions (abrupt sound pressure increase from 70 to 75, 80, 85, 90, and 95 dB) for the change-related response. Both the onset and abrupt sound pressure increase evoked a triphasic response with peaks at approximately 50 (P50), 100 (N100), and 200 (P200) ms. We calculated the peak-to-peak amplitudes for P50/N100 and N100/P200. Medians and slopes for P50/N100 and N100/P200 amplitudes were calculated and compared between the two measures. Results revealed a significant correlation for both the slope and median for P50/N100 (r = 0.36, 0.37, p = 1.0 × 10−2, 7.9 × 10−3), N100/P200 (r = 0.40, 0.34, p = 4.0 × 10−3, 1.6 × 10−2), and P50/N100/P200 (r = 0.36, 0.35, p = 1.0 × 10−2, 1.3 × 10−2). These results suggested that the change-related response and LDAEP shared generation mechanisms at least partially. [ABSTRACT FROM AUTHOR]

Paired pulse suppression is an electrophysiological method used to evaluate sensory suppression and often applied to patients with psychiatric disorders. However, it remains unclear whether the suppression comes from specific inhibitory mechanisms, refractoriness, or fatigue. In the present study, to investigate mechanisms of suppression induced by an auditory paired pulse paradigm in 19 healthy subjects, magnetoencephalography was employed. The control stimulus was a train of 25-ms pure tones of 65 dB SPL for 2500 ms. In order to evoke a test response, the sound pressure of two consecutive tones at 2200 ms in the control sound was increased to 80 dB (Test stimulus). Similar sound pressure changes were also inserted at 1000 (CS2) and 1600 (CS1) ms as conditioning stimuli. Four stimulus conditions were used; (1) Test alone, (2) Test + CS1, (3) Test + CS1 + CS2, and (4) Test + CS2, with the four sound stimuli randomly presented and cortical responses averaged at least 100 times for each condition. The baseline-to-peak and peak-to-peak amplitudes of the P50m, N100m, and P200m components of the test response were compared among the four conditions. In addition, the response to CS1 was compared between conditions (2) and (3). The results showed significant test response suppression by CS1. While the response to CS1 was significantly suppressed when CS2 was present, it did not affect suppression of the test response by CS1. It was thus suggested that the amplitude of the response to a conditioning stimulus is not a factor to determine the inhibitory effects of the test response, indicating that suppression is due to an external influence on the excitatory pathway. [ABSTRACT FROM AUTHOR]

Wind-up like pain or temporal summation of pain is a phenomenon in which pain sensation is increased in a frequency-dependent manner by applying repeated noxious stimuli of uniform intensity. Temporal summation in humans has been studied by observing the increase in pain or flexion reflex by repetitive electrical or thermal stimulations. Nonetheless, because the measurement is accompanied by severe pain, a minimally invasive method is desirable. Gradual augmentation of flexion reflex and pain induced by repetitive stimulation of the sural nerve was observed using three stimulation methods—namely, bipolar electrical, magnetic, and monopolar electrical stimulation, with 11 healthy male subjects in each group. The effects of frequency, intensity, and number of repetitive stimuli on the increase in the magnitude of flexion reflex and pain rating were compared among the three methods. The reflex was measured using electromyography (EMG) from the short head of the biceps femoris. All three methods produced a frequency- and intensity-dependent progressive increase in reflex and pain; pain scores were significantly lower for magnetic and monopolar stimulations than for bipolar stimulation (P < 0.05). The slope of increase in the reflex was steep during the first 4–6 stimuli but became gentler thereafter. In the initial phase, an increase in the reflex during the time before signals of C-fibers arrived at the spinal cord was observed in experiments using high-frequency stimulation, suggesting that wind-up was caused by inputs of A-fibers without the involvement of C-fibers. Magnetic and monopolar stimulations are minimally invasive and useful methods for observing the wind-up of the flexion reflex in humans. Monopolar stimulation is convenient because it does not require special equipment. There is at least a partial mechanism underlying the wind-up of the flexion reflex that does not require C-fibers. [ABSTRACT FROM AUTHOR]

Electrical stimulation of specific small fibers (Aδ- and C-fibers) is used in basic studies on nociception and neuropathic pain and to diagnose neuropathies. For selective stimulation of small fibers, the optimal stimulation waveform parameters are an important aspect together with the study of electrode design. However, determining an optimal stimulation condition is challenging, as it requires the characterization of the response of the small fibers to electrical stimulation. The perception thresholds are generally characterized using single-pulse stimulation based on the strength-duration curve. However, this does not account for the temporal effects of the different waveforms used in practical applications. In this study, we designed an experiment to characterize the effects of multiple pulse stimulation and proposed a computational model that considers electrostimulation of fibers and synaptic effects in a multiscale model. The measurements of perception thresholds showed that the pulse dependency of the threshold was an exponential decay with a maximum reduction of 55%. In addition, the frequency dependence of the threshold showed a U-shaped response with a reduction of 25% at 30 Hz. Moreover, the computational model explained the synaptic effects, which were also confirmed by evoked potential recordings. This study further characterized the activation of small fibers and clarified the synaptic effects, demonstrating the importance of waveform selection. [ABSTRACT FROM AUTHOR]

Sensory processing is disrupted in several psychiatric disorders, including schizophrenia, bipolar disorder, and autism spectrum disorder. In this review, we focus on the electrophysiological auditory steady-state response (ASSR) driven by high-frequency stimulus trains as an index for disease-associated sensory processing deficits. The ASSR amplitude is suppressed within the gamma band (≥30 Hz) among these patients, suggesting an imbalance between GABAergic and N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission. The reduced power and synchronization of the 40-Hz ASSR are robust in patients with schizophrenia. In recent years, similar ASSR deficits at gamma frequencies have also been reported in patients with bipolar disorder and autism spectrum disorder. We summarize ASSR abnormalities in each of these psychiatric disorders and suggest that the observed commonalities reflect shared pathophysiological mechanisms. We reviewed studies on phase resetting in which a salient sensory stimulus affects ASSR. Phase resetting induces the reduction of both the amplitude and phase of ASSR. Moreover, phase resetting is also affected by rare auditory stimulus patterns or superimposed stimuli of other modalities. Thus, sensory memory and multisensory integration can be investigated using phase resetting of ASSR. Here, we propose that ASSR amplitude, phase, and resetting responses are sensitive indices for investigating sensory processing dysfunction in psychiatric disorders. [ABSTRACT FROM AUTHOR]

Electrical stimulation of small fibres is gaining attention in the diagnosis of peripheral neuropathies, such as diabetes mellitus, and pain research. However, it is still challenging to characterise the electrical characteristics of axons in small fibres (Aδ and C fibres). In particular, in vitro measurement for human Aδ-fibre is difficult due to the presence of myelin and ethical reason. In this study, we investigate the in vivo electrical characteristics of the human Aδ-fibre to derive strength–duration (S–D) curves from the measurement. The Aδ-fibres are stimulated using coaxial planar electrodes with intraepidermal needle tip. For human volunteer experiments, the S–D curve of Aδ-fibre is obtained in terms of injected electrical current. With the computational analysis, the standard deviation of the S–D curve is mostly attributed to the thickness of the stratum corneum and depth of the needle tip, in addition to the fibre thickness. Then, we derive electrical parameters of the axon in the Aδ-fibre based on a conventional fibre model. The parameters derived here would be important in exploring the optimal stimulation condition of Aδ-fibres. [ABSTRACT FROM AUTHOR]

Haptic memory briefly retains somatosensory information for later use; however, how and which cortical areas are affected by haptic memory remain unclear. We used change‐related cortical responses to investigate the relationship between the somatosensory cortex and haptic memory objectively. Electrical pulses, at 50 Hz with a duration of 500 ms, were randomly applied to the second, third, and fourth fingers of the right and left hands at an even probability every 800 ms. Each stimulus was labeled as D (preceded by a different side) or S (preceded by the same side). The D stimuli were further classified into 1D, 2D, and 3D, according to the number of different preceding stimuli. The S stimuli were similarly divided into 1S and 2S. The somatosensory‐evoked magnetic fields obtained were divided into four components via a dipole analysis, and each component's amplitudes were measured using the source strength waveform. The results showed that the preceding event did not affect the amplitude of the earliest 20–30 ms response in the primary somatosensory cortex. However, in the subsequent three components, the cortical activity amplitude was largest in 3D, followed by 2D, 1D, and S. These results indicate that such modulatory effects occurred somewhere in the somatosensory processing pathway higher than Brodmann's area 3b. To the best of our knowledge, this is the first study to demonstrate the existence of haptic memory for somatosensory laterality and its impact on the somatosensory cortex using change‐related cortical responses without contamination from peripheral effects. [ABSTRACT FROM AUTHOR]

In the sensory cortex, cross-modal interaction occurs during the early cortical stages of processing; however, its effect on the speed of neuronal activity remains unclear. In this study, we used magnetoencephalography (MEG) to investigate whether tactile stimulation influences auditory steady-state responses (ASSRs). To this end, a 0.5-ms electrical pulse was randomly presented to the dorsum of the left or right hand of 12 healthy volunteers at 700 ms while a train of 25-ms pure tones were applied to the left or right side at 75 dB for 1,200 ms. Peak latencies of 40-Hz ASSR were measured. Our results indicated that tactile stimulation significantly shortened subsequent ASSR latency. This cross-modal effect was observed from approximately 50 ms to 125 ms after the onset of tactile stimulation. The somatosensory information that appeared to converge on the auditory system may have arisen during the early processing stages, with the reduced ASSR latency indicating that a new sensory event from the cross-modal inputs served to increase the speed of ongoing sensory processing. Collectively, our findings indicate that ASSR latency changes are a sensitive index of accelerated processing. [ABSTRACT FROM AUTHOR]

Rapid detection of sensory changes is important for survival. We have previously used change-related cortical responses to study the change detection system and found that the generation of a change-related response was based on sensory memory and comparison processes. However, it remains unclear whether change-related cortical responses reflect processing speed. In the present study, we simultaneously recorded the auditory steady-state response (ASSR) and change-related response using magnetoencephalography to investigate the acceleration effects of sensory change events. Overall, 13 healthy human subjects (four females and nine males) completed an oddball paradigm with a sudden change in sound pressure used as the test stimulus, i.e., the control stimulus was a train of 25-ms pure tones at 75 dB for 1,200 ms, whereas the 29th sound at 700 ms of the test stimulus was replaced with a 90-dB tone. Thereafter, we compared the latency of ASSR among four probabilities of test stimulus (0, 25, 75, and 100%). For both the control and test stimulus, stronger effects of acceleration on ASSR were observed when the stimulus was rarer. This finding indicates that ASSR and change-related cortical response depend on physical changes as well as sensory memory and comparison processes. ASSR was modulated without changes in peripheral inputs, and brain areas higher than the primary cortex could be involved in exerting acceleration effects. Furthermore, the reduced latency of ASSR clearly indicated that a new sensory event increased the speed of ongoing sensory processing. Therefore, changes in the latency of ASSR are a sensitive index of accelerated processing. [ABSTRACT FROM AUTHOR]

Paired-pulse suppression refers to attenuation of neural activity in response to a second stimulus and has a pivotal role in inhibition of redundant sensory inputs. Previous studies have suggested that cortical responses to a somatosensory stimulus are modulated not only by a preceding same stimulus, but also by stimulus from a different submodality. Using magnetoencephalography, we examined somatosensory suppression induced by three different conditioning stimuli. The test stimulus was a train of electrical pulses to the dorsum of the left hand at 100 Hz lasting 1500 ms. For the pulse train, the intensity of the stimulus was abruptly increased at 1200 ms. Cortical responses to the abrupt intensity change were recorded and used as the test response. Conditioning stimuli were presented at 600 ms as pure tones, either innocuous or noxious electrical stimulation to the right foot. Four stimulus conditions were used: (1) Test alone, (2) Test + auditory stimulus, (3) Test + somatosensory stimulus, and (4) Test + nociceptive stimulus. Our results showed that the amplitude of the test response was significantly smaller for conditions (3) and (4) in the secondary somatosensory cortex contralateral (cSII) and ipsilateral (iSII) to the stimulated side as compared to the response to condition (1), whereas the amplitude of the response in the primary somatosensory cortex did not differ among the conditions. The auditory stimulus did not have effects on somatosensory change-related response. These findings show that somatosensory suppression was induced by not only a conditioning stimulus of the same somatosensory submodality and the same cutaneous site to the test stimulus, but also by that of a different submodality in a remote area. [ABSTRACT FROM AUTHOR]

We consider the general n-factor Heath, Jarrow, and Morton model (1992) and provide a sufficient condition on the volatility structure for the spot rate process to be Markovian with 2n state variables. The price of a discount bond is also Markovian with the same state variables and, hence, claims against the term structure can be efficiently priced using standard simulation techniques. Our results extend earlier works such as Ritchken and Sankara-subramanian (1995) where the one-factor model is treated, and Carverhill (1994), where the volatility structure is non-random. Numerical experiments show that our model can explain the volatility smile observed in the interest rate options-market and also overcome the biases noted by Flesaker (1993). [ABSTRACT FROM AUTHOR]

Photophobia is a common condition in which bright light causes an unpleasant feeling due to increased sensitivity to light. In addition to discomfort, photophobia may be accompanied by visual dysfunction. The present study was conducted in order to examine whether visual evoked cortical responses contribute to the assessment of visual dysfunction due to bright light. Visual evoked magnetic fields (VEFs) following the presentation of a uniform bright light of 200–3700 cd/m2 in the lower visual field were recorded in 10 healthy volunteers and the effects of five color lenses: yellow, blue, gray, green, and colorless, were examined. VEFs were subjected to a multi-dipole analysis that resulted in the separation of several source activities, including the retina, V1, V2, V6, and fusiform gyrus. Source activity in the retina corresponding to the ERG b-wave exhibited a reduced amplitude and elongated peak latency with the yellow lens. Its latency strongly correlated with transmittance at 450 nm. On the other hand, cortical activities in V1 and the fusiform gyrus were stronger with the yellow lens than with the other color and colorless lenses. Only blue-light blocking showed significant effects. The result showing that the yellow lens enhanced V1 and fusiform activities indicated that processing in these areas was improved when subjects used this lens. The combination of delayed retinal activity and increased visual cortex activity may be an objective indicator of the effects of a color lens on visual function. [ABSTRACT FROM AUTHOR]

Sensory suppression is a mechanism that attenuates selective information. As for long-latency suppression in auditory and somatosensory systems, paired-pulse suppression, observed as 2 identical stimuli spaced by approximately 500 ms, is widely known, though its mechanism remains to be elucidated. In the present study, we investigated the relationship between auditory and somatosensory long-latency suppression of change-related cortical responses using magnetoencephalography. Somatosensory change-related responses were evoked by an abrupt increase in stimulus strength in a train of current-constant square wave pulses at 100 Hz to the left median nerve at the wrist. Furthermore, auditory change-related responses were elicited by an increase in sound pressure by 15 dB in a continuous sound composed of a train of 25-ms pure tones. Binaural stimulation was used in Experiment 1, while monaural stimulation was used in Experiment 2. For both somatosensory and auditory stimuli, the conditioning and test stimuli were identical, and inserted at 2400 and 3000 ms, respectively. The results showed clear suppression of the test response in the bilateral parisylvian region, but not in the postcentral gyrus of the contralateral hemisphere in the somatosensory system. Similarly, the test response in the bilateral supratemporal plane (N100m) was suppressed in the auditory system. Furthermore, there was a significant correlation between suppression of right N100m and right parisylvian activity, suggesting that similar mechanisms are involved in both. Finally, a high test-retest reliability for suppression was seen with both modalities. Suppression revealed in the present study is considered to reflect sensory inhibition ability in individual subjects. [ABSTRACT FROM AUTHOR]

Despite their essential roles in signal processing in the brain, the functions of interneurons currently remain unclear in humans. We recently developed a method using the prepulse inhibition of sensory evoked cortical responses for functional measurements of interneurons. When a sensory feature is abruptly changed in a continuous sensory stimulus, change-related cortical responses are recorded using MEG. By inserting a weak change stimulus (prepulse) before the test change stimulus, it is possible to observe the inhibition of the test response. By manipulating the prepulse–test interval (PTI), several peaks appear in inhibition, suggesting the existence of temporally distinct mechanisms. We herein attempted to separate these components through the oral administration of diazepam and baclofen. The test stimulus and prepulse were an abrupt increase in sound pressure in a continuous click train of 10 and 5 dB, respectively. The results obtained showed that the inhibition at PTIs of 10 and 20 ms was significantly greater with diazepam than with the placebo administration, suggesting increased GABAA-mediated inhibition. Baclofen decreased inhibition at PTIs of 40 and 50 ms, which may have been due to the activation of GABAB autoreceptors. Therefore, the present study separated at least two inhibitory mechanisms pharmacologically. [ABSTRACT FROM AUTHOR]

Sensory gating is a mechanism of sensory processing used to prevent an overflow of irrelevant information, with some indexes, such as prepulse inhibition (PPI) and P50 suppression, often utilized for its evaluation. In addition, those are clinically important for diseases such as schizophrenia. In the present study, we investigated long-latency paired-pulse suppression of change-related cortical responses using magnetoencephalography. The test change-related response was evoked by an abrupt increase in sound pressure by 15 dB in a continuous sound composed of a train of 25-ms pure tones at 65 dB. By inserting a leading change stimulus (prepulse), we observed suppression of the test response. In Experiment 1, we examined the effects of conditioning-test intervals (CTI) using a 25-ms pure tone at 80 dB as both the test and prepulse. Our results showed clear suppression of the test response peaking at a CTI of 600 ms, while maximum inhibition was approximately 30%. In Experiment 2, the effects of sound pressure on prepulse were examined by inserting prepulses 600 ms prior to the test stimulus. We found that a paired-pulse suppression greater than 25% was obtained by prepulses larger than 77 dB, i.e., 12 dB louder than the background, suggesting that long latency suppression requires a relatively strong prepulse to obtain adequate suppression, different than short-latency paired-pulse suppression reported in previous studies. In Experiment 3, we confirmed similar levels of suppression using electroencephalography. These results suggested that two identical change stimuli spaced by 600 ms were appropriate for observing the long-latency inhibition. The present method requires only a short inspection time and is non-invasive. [ABSTRACT FROM AUTHOR]

Despite their indispensable roles in sensory processing, little is known about inhibitory interneurons in humans. Inhibitory postsynaptic potentials cannot be recorded non-invasively, at least in a pure form, in humans. We herein sought to clarify whether prepulse inhibition (PPI) in the auditory cortex reflected inhibition via interneurons using magnetoencephalography. An abrupt increase in sound pressure by 10 dB in a continuous sound was used to evoke the test response, and PPI was observed by inserting a weak (5 dB increase for 1 ms) prepulse. The time course of the inhibition evaluated by prepulses presented at 10–800 ms before the test stimulus showed at least two temporally distinct inhibitions peaking at approximately 20–60 and 600 ms that presumably reflected IPSPs by fast spiking, parvalbumin-positive cells and somatostatin-positive, Martinotti cells, respectively. In another experiment, we confirmed that the degree of the inhibition depended on the strength of the prepulse, but not on the amplitude of the prepulse-evoked cortical response, indicating that the prepulse-evoked excitatory response and prepulse-evoked inhibition reflected activation in two different pathways. Although many diseases such as schizophrenia may involve deficits in the inhibitory system, we do not have appropriate methods to evaluate them; therefore, the easy and non-invasive method described herein may be clinically useful. [ABSTRACT FROM AUTHOR]

Previous studies showed that the amplitude and latency of the auditory offset cortical response depended on the history of the sound, which implicated the involvement of echoic memory in shaping a response. When a brief sound was repeated, the latency of the offset response depended precisely on the frequency of the repeat, indicating that the brain recognized the timing of the offset by using information on the repeat frequency stored in memory. In the present study, we investigated the temporal resolution of sensory storage by measuring auditory offset responses with magnetoencephalography (MEG). The offset of a train of clicks for 1 s elicited a clear magnetic response at approximately 60 ms (Off-P50m). The latency of Off-P50m depended on the inter-stimulus interval (ISI) of the click train, which was the longest at 40 ms (25 Hz) and became shorter with shorter ISIs (2.5∼20 ms). The correlation coefficient r2 for the peak latency and ISI was as high as 0.99, which suggested that sensory storage for the stimulation frequency accurately determined the Off-P50m latency. Statistical analysis revealed that the latency of all pairs, except for that between 200 and 400 Hz, was significantly different, indicating the very high temporal resolution of sensory storage at approximately 5 ms. [ABSTRACT FROM AUTHOR]

Psychophysical and visual evoked potential (VEP) studies have shown that spatial frequency of a visual stimulus affects contrast sensitivity and VEPs in humans. However, it is not clear whether and how the effect of spatial frequency varies among cortical areas. Considering that all visual inputs to the retina could be expressed as a sum of sinusoidal gratings of different spatial frequencies, the effect of spatial frequency must be clarified to separate the brain activity specific to each visual stimulus. In order to examine the effect of spatial frequency on different cortical areas, the present study compared cortical responses to sinusoidal gratings of seven different spatial frequencies using magnetoencephalography (MEG). MEG waveforms of twelve healthy adults in response to sinusoidal gratings of 0.3-18.1 cycles per degree were subjected to a multi-dipole analysis. As a result, the effect of spatial frequency was significant on the first peak latency and amplitude of the source activity around V1 and V2 but not on the source activity around V3 and V6, indicating that the effect of spatial frequency varies across different visual areas in the human brain. Our results also suggest that the responses in V1 and V2 that have a peak around 90 ms and that of V6 peaking around 120 ms should be separated to investigate the stimulus-specific cortical response, particularly when examining effects of spatial frequency on the response latency. [ABSTRACT FROM AUTHOR]

Aim Posterior slow waves of youth have a well-known electroencephalographic pattern that peaks in adolescence and usually disappears in adulthood. In general, posterior slow waves of youth are regarded as normal, but some reports have suggested that their presence is related to immature personalities or inappropriate social behavior. The physiological significance of this electroencephalographic pattern, however, remains unclear. The purpose of this study was to investigate the neural origins of posterior slow waves of youth using dipole source modeling. Methods Electroencephalographic epochs, including clear posterior slow waves of youth, were visually selected from electroencephalograms obtained from six normal adolescents using 25 scalp electrodes. The selected epochs were then averaged by arranging the negative peak of the slow waves at the occipital area of each epoch on the time axis. The averaged waveforms consisting of six right and one left posterior slow waves of youth were used for dipole source analysis. A single equivalent current dipole was estimated for the averaged waveforms. Results The best equivalent current dipoles were estimated to be located in or around the fusiform and middle occipital gyrus ipsilateral to the posterior slow waves of youth. Conclusions The location of the estimated dipoles of posterior slow waves of youth was on the so-called ventral visual pathway. Further research is required to clarify the physiological significance of posterior slow waves of youth with respect to their origin. [ABSTRACT FROM AUTHOR]

Rationale and objective: Nicotine is known to have enhancing effects on some aspects of attention and cognition. The purpose of the present study was to elucidate the effects of nicotine on pre-attentive change-related cortical activity. Methods: Change-related cortical activity in response to an abrupt increase (3 dB) and decrease (6 dB) in sound pressure in a continuous sound was recorded by using magnetoencephalography. Nicotine was administered with a nicotine gum (4 mg of nicotine). Eleven healthy nonsmokers were tested with a double-blind and placebo-controlled design. Effects of nicotine on the main component of the onset response peaking at around 50 ms (P50m) and the main component of the change-related response at around 120 ms (Change-N1m) were investigated. Results: Nicotine failed to affect P50m, while it significantly increased the amplitude of Change-N1m evoked by both auditory changes. The magnitude of the amplitude increase was similar among subjects regardless of the magnitude of the baseline response, which resulted in the percent increase of Change-N1m being greater for subjects with Change-N1m of smaller amplitude. Conclusions: Since Change-N1m represents a pre-attentive automatic process to encode new auditory events, the present results suggest that nicotine can exert beneficial cognitive effects without a direct impact on attention. [ABSTRACT FROM AUTHOR]

The choice of a system specific stimulus is difficult when investigating the human nociceptive system, in contrast with the tactile, auditory and visual systems, because it should be noxious but not actually damage the tissue. The discomfort accompanying system specific stimulation must be kept to a minimum for ethical reasons. In this review, recent progress made in the study of human pain perception using intraepidermal electrical stimulation (IES) is described. Also, whether IES is a viable alternative to laser stimulation is discussed. IES selectively activates A&dgr; nociceptors, elicits a sharp pricking sensation with minimal discomfort and evokes cortical responses almost identical to those produced by laser stimulation. As IES does not require expensive equipment, and is easy to control, it would seem useful for pain research as well as clinical tests. [ABSTRACT FROM AUTHOR]

Background: Frontal intermittent rhythmic delta activity (FIRDA) on electroencephalography (EEG) consists of a run of rhythmic delta waves with frontal predominance. Although FIRDA is a relatively common abnormal EEG finding, the underlying mechanisms that produce FIRDA remain unclear. The aim of this study was to investigate the cortical source of FIRDA using dipole source modeling. Methods: We selected EEG epochs, including typical FIRDAs, from EEG recordings obtained using 25 scalp electrodes on 5 subjects. We averaged these epochs by arranging the negative peaks of the delta waves at the Fp electrodes and estimated dipoles for nine averaged waveforms. Results: Averaged waveforms were explained by a single-dipole model in seven FIRDAs and by a two-dipole model in the remaining two FIRDAs with high reliability. Estimated dipoles had a radial orientation with respect to the frontal pole and were located in the medial frontal region. The anterior cingulate cortex was the most common dipole location. Conclusions: This is the first study to approach the fundamental FIRDA mechanism by dipole source modeling and to clarify that FIRDA may be generated from the medial frontal region, particularly from the anterior cingulate cortex. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We recorded cortical activity in response to the onset, offset, and frequency change of a pure tone using magnetencephalograms (MEGs) to clarify the physiological significance of N1m relating to the detection of changes. Four interstimulus intervals (ISIs) (0.5, 1.5, 3, and 6 s) were used for each of the three auditory events. Results showed that (i) all three auditory events elicited N1m with a similar topography and similar temporal profile, (ii) the source of N1m was located in the superior temporal gyrus (STG) for all events under all ISI conditions, (iii) the amplitude of the STG activity as a function of the duration of the steady state preceding the change was similar among the three events, and (iv) there was a significant positive correlation in amplitude between on-N1m and off-N1m and between on-N1m and change-N1m. These results suggested that N1m for the three events has a similar physiological significance relating to the detection of changes. [ABSTRACT FROM AUTHOR]

In this study, the cortical dynamics of the visual change detection process were investigated using an oddball paradigm similar to that used in auditory mismatch negativity studies. When subjects watched a silent movie, color stimuli were presented using 280 dual color LEDs arranged along the frame of the video screen. Task-irrelevant red and blue color stimuli were presented randomly at a probability of 10% and 90%, respectively, in one session and vice versa for the other one, and we traced brain responses using magnetoencephalography. Results show that activation in the middle occipital gyrus (MOG) was significantly enhanced for the infrequent stimulus, while early activities in Brodmann's area 17/18 were comparable for the frequent and infrequent stimuli. These results suggest that automatic visual change detection is associated with the MOG activity. [ABSTRACT FROM AUTHOR]

Background: The rapid detection of sensory change is important to survival. The process should relate closely to memory since it requires that the brain separate a new stimulus from an ongoing background or past event. Given that sensory memory monitors current sensory status and works to pick-up changes in real-time, any change detected by this system should evoke a change-related cortical response. To test this hypothesis, we examined whether the single presentation of a sound is enough to elicit a change-related cortical response, and therefore, shape a memory trace enough to separate a subsequent stimulus. Results: Under a paradigm where two pure sounds 300 ms in duration and 800 or 840 Hz in frequency were presented in a specific order at an even probability, cortical responses to each sound were measured with magnetoencephalograms. Sounds were grouped to five events regardless of their frequency, 1D, 2D, and 3D (a sound preceded by one, two, or three different sounds), and 1S and 2S (a sound preceded by one or two same sounds). Whereas activation in the planum temporale did not differ among events, activation in the superior temporal gyrus (STG) was clearly greater for the different events (1D, 2D, 3D) than the same event (1S and 2S). Conclusions: One presentation of a sound is enough to shape a memory trace for comparison with a subsequent physically different sound and elicits change-related cortical responses in the STG. The STG works as a real-time sensory gate open to a new event. [ABSTRACT FROM AUTHOR]

Background: The detection of any abrupt change in the environment is important to survival. Since memory of preceding sensory conditions is necessary for detecting changes, such a change-detection system relates closely to the memory system. Here we used an auditory change-related N1 subcomponent (change-N1) of event-related brain potentials to investigate cortical mechanisms underlying change detection and echoic memory. Results: Change-N1 was elicited by a simple paradigm with two tones, a standard followed by a deviant, while subjects watched a silent movie. The amplitude of change-N1 elicited by a fixed sound pressure deviance (70 dB vs. 75 dB) was negatively correlated with the logarithm of the interval between the standard sound and deviant sound (1, 10, 100, or 1000 ms), while positively correlated with the logarithm of the duration of the standard sound (25, 100, 500, or 1000 ms). The amplitude of change-N1 elicited by a deviance in sound pressure, sound frequency, and sound location was correlated with the logarithm of the magnitude of physical differences between the standard and deviant sounds. Conclusions: The present findings suggest that temporal representation of echoic memory is non-linear and Weber- Fechner law holds for the automatic cortical response to sound changes within a suprathreshold range. Since the present results show that the behavior of echoic memory can be understood through change-N1, change-N1 would be a useful tool to investigate memory systems. [ABSTRACT FROM AUTHOR]

We recorded cortical activities in response to the onset and offset of a pure tone of long duration (LONG) and a train of brief pulses of a pure tone with an interstimulus interval of 50 ms (ISI–50 ms) or 100 ms (ISI–100 ms) by use of magnetoencephalograms in 11 healthy volunteers to clarify temporal and spatial profiles of the auditory on- and off-cortical response. Results showed that a region around the superior temporal gyrus (STG) of both hemispheres responded to both the onset and offset of the stimulus. The location of the source responsible for the main activity (N1m) was not significantly different between the on- and off-responses for any of the three tones. The peak latency of on-N1m was similar under the three conditions, while the peak latency of off-N1m was precisely determined by the ISI, which suggested that off-N1m is based on short-term memory of the stimulus frequency. In addition, there was a positive correlation of the N1m amplitude of N1m between the on- and off-responses among the subjects. The present results suggested that auditory on-N1m and off-N1m have similar physiological significance involved in responding to abrupt changes. [ABSTRACT FROM AUTHOR]

Mucolipidosis (ML) II alpha/beta and III alpha/beta are autosomal recessive diseases caused by a deficiency of α and/or β subunits of the enzyme N-acetylglucosamine-1-phosphotransferase, which is encoded by the GNPTAB gene. We analyzed the GNPTAB gene in 25 ML II and 15 ML III Japanese patients. In most ML II patients, the clinical conditions ‘stand alone’, ‘walk without support’ and ‘speak single words’ were impaired; however, the frequency of ‘heart murmur’, ‘inguinal hernia’ and ‘hepatomegaly and/or splenomegaly’ did not differ between ML II and III patients. We detected mutations in GNPTAB in 73 of 80 alleles. Fourteen new mutations were c.914_915insA, c.2089_2090insC, c.2427delC, c.2544delA, c.2693delA, c.3310delG, c.3388_3389insC+c.3392C>T, c.3428_3429insA, c.3741_3744delAGAA, p.R334L, p.F374L, p.H956Y, p.N1153S and duplication of exon 2. Previously reported mutations were p.Q104X, p.W894X, p.R1189X and c.2715+1G>A causing skipping of exon 13. Homozygotes or compound heterozygotes of nonsense and frameshift mutations contributed to the severe phenotype. p.F374L, p.N1153S and splicing mutations contributed to the attenuated phenotype, although coupled with nonsense mutation. These results show the effective molecular diagnosis of ML II and III and also provide phenotypic prediction. This is the first and comprehensive report of molecular analysis for ML patients of Japanese origin.Journal of Human Genetics (2009) 54, 145–151; doi:10.1038/jhg.2009.3; published online 6 February 2009 [ABSTRACT FROM AUTHOR]

Background: To segregate luminance-related, face-related and non-specific components involved in spatio-temporal dynamics of cortical activations to a face stimulus, we recorded cortical responses to face appearance (Onset), disappearance (Offset), and change (Change) using magnetoencephalography. Results: Activity in and around the primary visual cortex (V1/V2) showed luminance-dependent behavior. Any of the three events evoked activity in the middle occipital gyrus (MOG) at 150 ms and temporo-parietal junction (TPJ) at 250 ms after the onset of each event. Onset and Change activated the fusiform gyrus (FG), while Offset did not. This FG activation showed a triphasic waveform, consistent with results of intracranial recordings in humans. Conclusion: Analysis employed in this study successfully segregated four different elements involved in the spatio-temporal dynamics of cortical activations in response to a face stimulus. The results show the responses of MOG and TPJ to be associated with non-specific processes, such as the detection of abrupt changes or exogenous attention. Activity in FG corresponds to a face-specific response recorded by intracranial studies, and that in V1/V2 is related to a change in luminance. [ABSTRACT FROM AUTHOR]

Quick detection of changes in the sensory environment is very important for survival, resulting in automatic shifts of attention to the event and the facilitation of subsequent processes to execute appropriate behaviors. The abrupt onset or offset of a sensory stimulus should also activate the neural network detecting changes. To test this hypothesis, we compared cortical on- and off-responses using somatosensory-evoked potentials (SEPs) elicited by a train of electrical pulses delivered to the right hand in eight healthy volunteers. SEPs were recorded from 15 electrodes on the scalp at three different interstimulus intervals (ISIs, 50, 20, and 10 ms) under two sets of conditions (attended and unattended). Both the onset and offset of stimulation evoked two similar components, P100 and N140, in the attended and unattended conditions. The latency of P100 and N140 in response to stimulus onset did not differ among the three ISIs, while the latency of both components in response to stimulus offset was significantly longer for the longer ISI; that is, detection of the cessation of the stimulation was based on short-term memory of the stimulus frequency. The present results supported a cortical network triggered by both the onset and offset of sensory stimulation. In this network, the change is automatically detected using a memory trace by comparing the abrupt event (on or off) with the preceding condition (silent or repetitive stimuli). [ABSTRACT FROM AUTHOR]

Background: Temporal low-voltage irregular δ-waves (TLID) are often found in elderly subjects. The physiological significance of TLID has not been clarified; however, our previous studies suggest that TLID are associated with mild cerebrovascular dysfunction. Objective: The present study aimed to reveal the origin of TLID and their neural mechanisms by dipole source modeling. Methods: From electroencephalography records taken from 21 scalp electrodes, clear and typical TLID of 6 elderly subjects (mean age, 69 ± 6.2 years) were selected. Among these, we selected and averaged 7–12 clear TLID on the left side in each subject, and estimated a single equivalent current dipole for the averaged TLID. Results: The best equivalent current dipoles were estimated to be located in the medial part of the temporal lobe in or near the parahippocampal gyrus in the hemisphere ipsilateral to the TLID, with a high reliability in all subjects. Conclusions: Considering the source localization of TLID, TLID seem to indicate certain dysfunctions of the hippocampus or adjacent regions. This is the first study to report the cerebral origin of TLID and suggest its physiological significance. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Lasers can selectively activate the nociceptors of A-delta fibers. Since nociceptors in the skin are activated via temperature conduction by the laser beam, a latency jittering of cortical responses among trials would affect results obtained with a conventional averaging (C-AVE) technique. We therefore used a new method, latency-adjusted averaging (L-AVE), to investigate cortical responses to noxious laser stimulation in normal subjects. L-AVE was done by averaging trials after adjusting the latency so that the peak latency of an activity in the temporal region of all trials matched on the time axis. Both in C-AVE and in L-AVE, clear activations were found in the contralateral primary somatosensory cortex (SI) and bilateral parasylvian regions, whose activities peaked 163–181 ms after the stimulation. In addition to these three main activities, weak activities peaking at around 109–119 ms could be identified in only L-AVE in similar cortical regions. Since the direction of the source differed between early and main activities, we considered that the early weak activities were cancelled out by the later main activities with an opposite orientation. The results suggested that early cortical processing of noxious information occurs earlier than previous neurophysiological studies have estimated and that the temporal sequence of activations should be reconsidered. [ABSTRACT FROM AUTHOR]

Background: Cytokines do not only mediate responses to infection, but are also involved in behavioral and physiological responses to psychological stressors. IL-6 has received special attention in relation to the development of posttraumatic stress disorders and depression. Objective: We tested effects of prior injection of rat recombinant IL-6 (rrIL-6) on behaviors induced by the forced swim (FS) stressor, and central and peripheral responses of IL-6 to FS. Methods: Rats were injected intraperitoneally with either rrIL-6 (250 ng/0.5 ml) or equal-volume sterile saline twice within an interval of 24 h. One hour after each injection, the rats were exposed to FS or remained at the home cage (control). Results: Injection of rrIL-6 did not affect immobility, swimming or climbing behaviors during FS compared with the saline control. Although FS was not a significant factor for hypothalamic and midbrain IL-6 mRNA and plasma IL-6 responses, FS with prior administration of rrIL-6 significantly increased hypothalamic IL-6 contents in response to FS compared with the saline injection-FS condition. Conclusions: Our results suggested that stressor alone had no influence on plasma IL-6 levels and IL-6 mRNA expression levels in midbrain and hypothalamus, but administration of rrIL-6 followed by FS significantly increased hypothalamic IL-6. Our results support the notion that the interaction between IL-6 and stressor might have implications for the pathophysiology of IL-6-induced depressive symptoms. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]