Noninvasive remote activation of the ventral midbrain by transcranial direct current stimulation of prefrontal cortex.

The midbrain lies deep within the brain and has an important role in reward, motivation, movement and the pathophysiology of various neuropsychiatric disorders such as Parkinson's disease, schizophrenia, depression and addiction. To date, the primary means of acting on this region has been with pharmacological interventions or implanted electrodes. Here we introduce a new noninvasive brain stimulation technique that exploits the highly interconnected nature of the midbrain and prefrontal cortex to stimulate deep brain regions. Using transcranial direct current stimulation (tDCS) of the prefrontal cortex, we were able to remotely activate the interconnected midbrain and cause increases in participants' appraisals of facial attractiveness. Participants with more enhanced prefrontal/midbrain connectivity following stimulation exhibited greater increases in attractiveness ratings. These results illustrate that noninvasive direct stimulation of prefrontal cortex can induce neural activity in the distally connected midbrain, which directly effects behavior. Furthermore, these results suggest that this tDCS protocol could provide a promising approach to modulate midbrain functions that are disrupted in neuropsychiatric disorders.

Dynamic effects and information quantifiers of statistical memory of MEG's signals at photosensitive epilepsy.

The time series analysis of magnetoencephalographic (MEG) signals is very important both for basic brain research and for medical diagnosis and treatment. Here we discuss the crucial role of statistical memory effects (ME) in human brain functioning with photosensitive epilepsy (PSE). We study two independent statistical memory quantifiers that reflect the dynamical characteristics of neuromagnetic brain responses on a flickering stimulus of different colored combinations from a group of control subjects, which are contrasted with those from a patient with PSE. We analyze the frequency dependence of two memory measures for the neuromagnetic signals. The strong memory and the accompanying transition to a regular and robust regime of the signals' chaotic behavior in the separate areas are characteristic for a patient with PSE. This particularly interesting observation most likely identifies the regions of the protective mechanism in a human organism against occurrence of PSE.

Wavelet-crosscorrelation analysis: Non-stationary analysis of neurophysiological signals.

OBJECTIVE: Wavelet-crosscorrelation analysis is a new application of wavelet analysis used to show the propagation of epileptiform discharges and to localize the corresponding lesions. We have shown previously that this analysis can help predict brain conditions statistically (Mizuno-Matsumoto et al. 2002). Our objective was to assess whether wavelet-crosscorrelation analysis reveals the initiation and propagation of epileptiform activity in human patients. METHODS: The data obtained from three patients with simple partial seizures (SPS) using whole-head magnetoencephalography (MEG) were analyzed by the wavelet-crosscorrelation method. Wavelet-crosscorrelation coefficients (WCC), the coherent structure of each possible pair of signals from 64 MEG channels forvarious periods, and the time lag (TL) in two related signals, were ascertained. RESULTS: We clearly demonstrated both localization of the irritative zone and propagation of the epileptiform discharges. CONCLUSIONS: Wavelet-crosscorrelation analysis can help reveal and visualize the dynamic changes of brain conditions. The method of this analysis can compensate for other existing methods for the analysis of MEG, electroencephalography (EEG) or Elecotrocorticography (ECoG). SIGNIFICANCE: Our proposed method suggests that revealing and visualizing the dynamic changes of brain conditions can help clinicians and even patients themselves better understand such conditions.

The first grid for the oral and maxillofacial region and its application for speech analysis.

OBJECTIVES: Introduction of a new grid-based method for analyzing speech functions which takes into account the related information of patients' data and the oral air flow with pronouncing analyzed by computational fluid dynamics. METHODS: An on-line speech analyzer was developed for clinical use utilizing GridPort2.3.1 based on globus2.4.2, comprising several computational tools such as unified data storage, semantic data analysis, computational fluid dynamics analysis and three-dimensional visualization of calculated results from different hardware sources with various types of operation systems. RESULTS: The power transportation layer between dental clinics and computational and storage resources could be provided by using a WWW-based portal. The backend data management system could be constructed using a storage resource broker (SRB) and extensible mark up language (XML). CONCLUSIONS: The new method allows the construction of a data warehouse through this grid-based speech function analysis in order to extract the principal factors related to speech disorders.

An OGSA-based integration of life-scientific resources for drug discovery.

OBJECTIVES: The rapid progress of life-scientific research has the potential to dramatically change the paradigm of drug discovery. Efficient utilization of life-scientific resources, i.e., databases and analytic software tools, poses a challenging issue with regard to the reduction of time and cost in the drug discovery process. In this paper, a variety of heterogeneous Web-based life-scientific resources are integrated toward the improvement of drug discovery performance. METHODS: For the integration of heterogeneous life-scientific resources, a database federation technique based on three-layer architecture has been utilized. With the federation technique, life-scientific resources are integrated step by step through database layers, database integration layers and analysis layers to encapsulate complexity and heterogeneity. In this study, we have taken advantage of the latest Grid technology based on OGSA (Open Grid Services Architecture) for the implementation of our approach. RESULTS: The actual case of life-scientific resources for drug discovery demonstrates that our prototype system developed with the proposed technique works well for the identification process of candidate compounds to a target protein. In other words, the prototype system allows a researcher to retrieve candidate compounds with less effort than before. CONCLUSIONS: The usefulness of the prototypic system represents the ability of our approach to integrate heterogeneous life-scientific resources, which have the potential to dramatically improve efficiency in drug discovery, resulting in the shortening of drug development. On the other hand, the system requires further consideration from the aspect of practical use. Dynamic aggregation of the resources is one example of such a consideration.

A framework supporting the development of a Grid portal for analysis based on ROI.

OBJECTIVES: In our research on brain function analysis, users require two different simultaneous types of processing: interactive processing to a specific part of data and high-performance batch processing to an entire dataset. The difference between these two types of processing is in whether or not the analysis is for data in the region of interest (ROI). In this study, we propose a Grid portal that has a mechanism to freely assign computing resources to the users on a Grid environment according to the users' two different types of processing requirements. METHODS: We constructed a Grid portal which integrates interactive processing and batch processing by the following two mechanisms. First, a job steering mechanism controls job execution based on user-tagged priority among organizations with heterogeneous computing resources. Interactive jobs are processed in preference to batch jobs by this mechanism. Second, a priority-based result delivery mechanism that administrates a rank of data significance. RESULTS: The portal ensures a turn-around time of interactive processing by the priority-based job controlling mechanism, and provides the users with quality of services (QoS) for interactive processing. The users can access the analysis results of interactive jobs in preference to the analysis results of batch jobs. The Grid portal has also achieved high-performance computation of MEG analysis with batch processing on the Grid environment. CONCLUSION: The priority-based job controlling mechanism has been realized to freely assign computing resources to the users' requirements. Furthermore the achievement of high-performance computation contributes greatly to the overall progress of brain science. The portal has thus made it possible for the users to flexibly include the large computational power in what they want to analyze.

Usefulness of switching to cabergoline from other dopamine agonists in patients with advanced Parkinson's disease.

Problems associated with long-term treatment of advanced Parkinson's disease (PD) include motor complications and psychotic and autonomic symptoms. We switched patients from bromocriptine (BR) or pergolide (PER) to cabergoline (CB) therapy and investigated CB's usefulness in alleviating such problems. Subjects were 30 patients (mean age 68.2 years; 13 receiving BR, 17 PER) with PD complicated by effects of long-term treatment but in whom their dose of dopamine (DA) agonist was contraindicated due to adverse reactions. Patients were switched to CB over a 2-4-week period. Hoehn-Yahr and Unified Parkinson Disease Rating Scale (UPDRS) I-IV "on" and "off" scores improved in both the BR and PER groups. CB was not discontinued due to adverse reactions in any patient. In conclusion, switching to CB is useful in patients in whom it is problematic to increase their dose of DA agonist due to motor complications or psychotic symptoms of advanced PD.

Effect of sodium valproate on neuromagnetic responses to chromatic flicker: implication for photosensitivity.

The effect of oral administration of sodium valproate in normal subjects was evaluated using whole-scalp magnetoencephalography, with results compared to the effect of sodium valproate in photosensitive children. Neuromagnetic responses to 10 Hz equiluminant red-green and red-blue flicker were measured before and after 5 days of sodium valproate administration. For the red-green flicker, relative power spectra at the stimulus frequency (10 Hz) were attenuated with medication in most brain regions. However, for the red-blue flicker, the 10-Hz power in the occipital region was enhanced with medication, while it was reduced in other regions. These results qualitatively resembled those in photosensitive children. The present findings suggest that (1) combinational chromatic sensitivity can be a critical factor for cortical excitability, that (2) the effect of sodium valproate is qualitatively similar in normal and photosensitive subjects, and that (3) the effect of sodium valproate on cortical excitability is not simply to suppress the stimulus-synchronized occipital activity, but rather to inhibit the spread of cortical activity from the occipital region to other regions.

A grid computing infrastructure for MEG data analysis.

Magnetoencephalography (MEG) is widely used for studying brain functions, but clinical applications of MEG have been less prevalent. One reason is that only clinicians who have highly specialized knowledge can use MEG diagnostically, and such clinicians are found at only a few major hospitals. Another reason is that MEG data analysis is getting more and more complicated, and deals with a large amount of data, and thus requires high-performance computing. These problems can be solved by the collaboration of human and computing resources distributed in multiple facilities. A new computing infrastructure for brain scientists and clinicians in distant locations was therefore developed by the Grid technology, which provides virtual computing environments composed of geographically distributed computers and experimental devices. A prototype system connecting an MEG system at the AIST in Japan, a Grid environment composed of PC clusters at Osaka University in Japan and Nanyang Technological University in Singapore, and user terminals in Baltimore was developed. MEG data measured at the AIST were transferred in real-time through a 1-GB/s network to the PC clusters for processing by a wavelet cross-correlation method, and then monitored in Baltimore. The current system is the basic model for remote-access to MEG equipment and high-speed processing of MEG data.

Sound alters visual evoked potentials in humans.

When a single flash is accompanied by two auditory beeps, the single flash is perceived as two flashes. We investigated whether this crossmodal influence on visual perception occurs at the level of the modality-specific visual pathway or later. We compared the visual evoked potentials (VEPs) in the presence and absence of sound. Activity was modulated extensively and with short latency in trials in which an illusory flash was perceived. In addition, the brain potentials for the illusory flash were qualitatively very similar to those for a physical flash, suggesting that the same mechanism underlies the percept of both illusory and physical flashes. These results suggest that the activity in the visual cortex can be modulated by sound. This implication challenges the general belief that the visual cortical processing is independent of other modalities.

What visual perception tells us about mind and brain.

Recent studies of visual perception have begun to reveal the connection between neuronal activity in the brain and conscious visual experience. Transcranial magnetic stimulation of the human occipital lobe disrupts the normal perception of objects in ways suggesting that important aspects of visual perception are based on activity in early visual cortical areas. Recordings made with microelectrodes in animals suggest that the perception of the lightness and depth of visual surfaces develops through computations performed across multiple brain areas. Activity in earlier areas is more tightly correlated with the physical properties of objects whereas neurons in later areas respond in a manner more similar to visual perception.

Transient global amnesia (TGA) in an MEG study.

A patient who had experienced an attack of transient global amnesia (TGA) was examined using neurophysiological methods. Magnetoencephalography (MEG) was performed and the Wechsler Memory Scale-Revised (WMS-R) test was administered at 5 days and at more than a month after the TGA episode. MEG data on neuronal activity obtained while the patient was undertaking a working memory task and during rest were analyzed using the wavelet-crosscorrelation method, which reveals time-lag and information flow between related sites in the brain. The WMS-R memory scores showed dramatic improvement when the test was administered a month following the attack, although no significant changes were observed in EEG, MRI and SPECT data. The MEG study revealed that under a working memory load how the neuron works functionally and the information propagates assembly within the right hemisphere, and that these brain functions were not performed adequately shortly after the TGA attack.

Afterimage of perceptually filled-in surface.

An afterimage induced by prior adaptation to a visual stimulus is believed to be due to bleaching of photochemical pigments or neural adaptation in the retina. We report a type of afterimage that appears to require cortical adaptation. Fixating a neon-color spreading configuration led not only to negative afterimages corresponding to the inducers (local afterimages), but also to one corresponding to the perceptually filled-in surface during adaptation (global afterimage). These afterimages were mutually exclusive, undergoing monocular rivalry. The strength of the global afterimage correlated to a greater extent with perceptual filling-in during adaptation than with the strength of the local afterimages. Thus, global afterimages are not merely by-products of local afterimages, but involve adaptation at a cortical representation of surface.

Sensory modalities are not separate modalities: plasticity and interactions.

Historically, perception has been viewed as a modular function, with the different sensory modalities operating independently of each other. Recent behavioral and brain imaging studies challenge this view, by suggesting that cross-modal interactions are the rule and not the exception in perception, and that the cortical pathways previously thought to be sensory-specific are modulated by signals from other modalities.

When sound affects vision: effects of auditory grouping on visual motion perception.

Two identical visual targets moving across each other can be perceived either to bounce off or to stream through each other. A brief sound at the moment the targets coincide biases perception toward bouncing. We found that this bounce-inducing effect was attenuated when other identical sounds (auditory flankers) were presented 300 ms before and after the simultaneous sound. The attenuation occurred only when the simultaneous sound and auditory flankers had similar acoustic characteristics and the simultaneous sound was not salient. These results suggest that there is an aspect of auditory-grouping (saliency-assigning) processes that is context-sensitive and can be utilized by the visual system for solving ambiguity. Furthermore, control experiments revealed that such auditory context did not affect the perceptual qualities of the simultaneous sound. Because the attenuation effect is not manifest in the perception of acoustic characteristics of individual sound elements, we conclude that it is a genuine cross-modal effect.

Temporal and spatial characteristics of attention to facilitate manual and eye-movement responses.

Previous investigation found that the speed of saccadic eye movements is enhanced when a temporal interval (gap) is introduced between the disappearance of a foveal fixation mark and the appearance of a peripheral target (the gap paradigm). Attention was shown to be involved in the gap paradigm. Here, we investigated relevant temporal and spatial characteristics of attention, manipulating central fixation marks and peripheral targets. Results from three experiments indicate that (i) the speed of manual and eye-movement detection is accelerated when a fixation mark changes abruptly (in less than 100 ms) before its termination in the gap paradigm; (ii) the speed is further accelerated when a peripheral target location is pre-cued; (iii) sufficient time for fixation (1000 ms) is necessary for the facilitation. These results suggest that fast and transient attention at the fixation spot facilitates attentional disengagement process that urges a spatial-orienting mechanism. Sustained attention is required in the engagement process during the fixation.

Postcoincidence trajectory duration affects motion event perception.

In a two-dimensional display, identical visual targets moving toward and across each other with equal, constant speed can be perceived either to reverse their motion directions at the coincidence point (bouncing percept) or to stream through one another (streaming percept). Although there is a strong tendency to perceive the streaming percept, various factors have been reported to induce the bouncing percept, such as a sound or a visual flash at the moment of the visual target coincidence. By changing duration of the postcoincidence trajectory (PCT), we investigated how long it would take for such bounce-inducing factors to be maximally effective after the visual coincidence. With bounce-inducing factors, the percentage of the bouncing percept did not reach its maximal level immediately after the coincidence but increased as a function of PCT duration up to 150-200 msec. The results clearly reject the possibility of the cognitive-bias hypothesis about the bounce-inducing effect and suggest rather that the bounce-inducing factors have to interact with the PCT for some period after the coincidence to be maximally effective.

Pupillary response to chromatic flicker.

There is significant evidence for higher-level cortical control of pupillary responses to visual stimuli, suggesting that factors other than luminance changes may induce a pupillary response. In the present study, the pupillary responses to equiluminant flickering stimuli in a range of 3-13 Hz were examined. Flicker stimuli included color-black (luminance-modulated) and color-color (hue-modulated) flicker. Equiluminance was determined both by objective luminance measures as well as by subjective, perceptual equiluminance for each subject. For both objectively and subjectively equiluminant flicker, significant, sustained pupillary constrictions were recorded. The magnitude of these responses was sensitive to both color and frequency parameters; red-blue color-paired flicker consistently produced the strongest constrictions. These responses occurred even when the flicker was of a lower luminance, both physically and perceptually, than a preceding nonflickering color, indicating that chromatic rather than luminance-sensitive mechanisms are involved in this response. Interestingly, the color- and frequency-sensitivity of constriction parallels those of flickers which maximally stimulate photosensitive epileptic patients, raising the possibility that chromatic response may be a factor in photosensitivity.

Compression of space in visual memory.

Human observers had to point to the location of a briefly presented target by means of a mouse after a brief delay following target offset. It was found that observers systematically mislocalized the target closer to the center of gaze, and to visually salient markers in the visual display. A perceptual judgment task revealed that these errors in localization were independent of whether or not eye movements were made, and even of planning for them, thereby demonstrating that the effect was a perceptual phenomenon, not a sensorimotor one. Further experiments demonstrated clearly that the magnitude of the time interval between target presentation and judgment regarding its spatial location was the critical parameter. A longer time interval between the event and its report enhanced significantly the amplitude of compression, thus establishing this phenomenon as a visual memory effect. We conclude that visual memory of spatial location is distorted over time in a systematic, monotonic fashion as a result of the sustained fixation of the observer on a fixed location during and shortly after target presentation, or by the continual presence of stable, salient landmarks in the environment.