Masako Okamoto

Three-dimensional probabilistic anatomical cranio-cerebral correlation via the international 10–20 system oriented for transcranial functional brain mapping

The recent advent of multichannel near-infrared spectroscopy (NIRS) has expanded its technical potential for human brain mapping. However, NIRS measurement has a technical drawback in that it measures cortical activities from the head surface without anatomical information of the object to be measured. This problem is also found in transcranial magnetic stimulation (TMS) that transcranially activates or inactivates the cortical surface. To overcome this drawback, we examined cranio-cerebral correlation using magnetic resonance imaging (MRI) via the guidance of the international 10-20 system for electrode placement, which had originally been developed for electroencephalography. We projected the 10-20 standard cranial positions over the cerebral cortical surface. After examining the cranio-cerebral correspondence for 17 healthy adults, we normalized the 10-20 cortical projection points of the subjects to the standard Montreal Neurological Institute (MNI) and Talairach stereotactic coordinates and obtained their probabilistic distributions. We also expressed the anatomical structures for the 10-20 cortical projection points probabilistically. Next, we examined the distance between the cortical surface and the head surface along the scalp and created a cortical surface depth map. We found that the locations of 10-20 cortical projection points in the standard MNI or Talairach space could be estimated with an average standard deviation of 8 mm. This study provided an initial step toward establishing a three-dimensional probabilistic anatomical platform that enables intra- and intermodal comparisons of NIRS and TMS brain imaging data.

Virtual spatial registration of stand-alone fNIRS data to MNI space.

The registration of functional brain data to common stereotaxic brain space facilitates data sharing and integration across different subjects, studies, and even imaging modalities. Thus, we previously described a method for the probabilistic registration of functional near-infrared spectroscopy (fNIRS) data onto Montreal Neurological Institute (MNI) coordinate space that can be used even when magnetic resonance images of the subjects are not available. This method, however, requires the careful measurement of scalp landmarks and fNIRS optode positions using a 3D-digitizer. Here we present a novel registration method, based on simulations in place of physical measurements for optode positioning. First, we constructed a holder deformation algorithm and examined its validity by comparing virtual and actual deformation of holders on spherical phantoms and real head surfaces. The discrepancies were negligible. Next, we registered virtual holders on synthetic heads and brains that represent size and shape variations among the population. The registered positions were normalized to MNI space. By repeating this process across synthetic heads and brains, we statistically estimated the most probable MNI coordinate values, and clarified errors, which were in the order of several millimeters across the scalp, associated with this estimation. In essence, the current method allowed the spatial registration of completely stand-alone fNIRS data onto MNI space without the use of supplementary measurements. This method will not only provide a practical solution to the spatial registration issues in fNIRS studies, but will also enhance cross-modal communications within the neuroimaging community.

Acute moderate exercise elicits increased dorsolateral prefrontal activation and improves cognitive performance with Stroop test

A growing number of human studies have reported the beneficial influences of acute as well as chronic exercise on cognitive functions. However, neuroimaging investigations into the neural substrates of the effects of acute exercise have yet to be performed. Using multichannel functional near-infrared spectroscopy (fNIRS), we sought cortical activation related to changes in the Stroop interference test, elicited by an acute bout of moderate exercise, in healthy volunteers (N=20). The compactness and portability of fNIRS allowed on-site cortical examination in a laboratory with a cycle ergometer, enabling strict control of the exercise intensity of each subject by assessing their peak oxygen intake (VO2peak). We defined moderate exercise intensity as 50% of a subjects peak oxygen uptake (50%VO2peak). An acute bout of moderate exercise caused significant improvement of cognitive performance reflecting Stroop interference as measured by reaction time. Consistent with previous functional neuroimaging studies, we detected brain activation due to Stroop interference (incongruent minus neutral) in the lateral prefrontal cortices in both hemispheres. This Stroop-interference-related activation was significantly enhanced in the left dorsolateral prefrontal cortex due to the acute bout of moderate exercise. The enhanced activation significantly coincided with the improved cognitive performance. This suggests that the left dorsolateral prefrontal cortex is likely the neural substrate for the improved Stroop performance elicited by an acute bout of moderate exercise. fNIRS, which allows physiological monitoring and functional neuroimaging to be combined, proved to be an effective tool for examining the cognitive effects of exercise.

Multimodal assessment of cortical activation during apple peeling by NIRS and fMRI

An intriguing application of neuroimaging is directly measuring actual human brain activities during daily living. To this end, we investigated cortical activation patterns during apple peeling. We first conducted a pilot study to assess the activation pattern of the whole lateral cortical surface during apple peeling by multichannel near-infrared spectroscopy (NIRS) and detected substantial activation in the prefrontal region in addition to expected activations extending over the motor, premotor and supplementary motor areas. We next examined cortical activation during mock apple peeling by simultaneous measurement using multichannel NIRS and functional magnetic resonance imaging (fMRI) in four subjects. We detected activations extending over the motor, premotor and supplementary motor areas, but not in the prefrontal cortex. Thus, we finally focused on the prefrontal cortex and examined its activation during apple peeling in 12 subjects using a multichannel NIRS. We subsequently found that regional concentrations of oxygenated hemoglobin significantly increased in the measured region, which encompassed portions of the dorsolateral, ventrolateral and frontopolar areas of the prefrontal cortex. The current study demonstrated that apple peeling as practiced in daily life recruited the prefrontal cortex but that such activation might not be detected for less laborious mock apple peeling that can be performed in an fMRI environment. We suggest the importance of cortical study of an everyday task as it is but not as a simplified form; we also suggest the validity of NIRS for this purpose. Studies on everyday tasks may serve as stepping stone toward understanding human activities in terms of cortical activations.

Automated cortical projection of head-surface locations for transcranial functional brain mapping

Recent advancements in two noninvasive transcranial neuroimaging techniques, near-infrared spectroscopy (NIRS) and transcranial magnetic stimulation (TMS), signify the increasing importance of establishing structural compatibility between transcranial methods and conventional tomographic methods, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). The transcranial data obtained from the head surface should be projected onto the cortical surface to present the transcranial brain-mapping data on the same platform as tomographic methods. Thus, we developed two transcranial projection algorithms that project given head-surface points onto the cortical surface in structural images, and computer programs based on them. The convex-hull algorithm features geometric handling of the cortical surface, while the balloon-inflation algorithm is faster, and better reflects the local cortical structure. The automatic cortical projection methods proved to be as effective as the manual projection method described in our previous study. These methods achieved perfect correspondence between any given point on the head surface or a related nearby point in space, and its cortical projection point. Moreover, we developed a neighbor-reference method that enables transcranial cortical projection of a given head-surface point in reference to three neighboring points and one additional standard point, even when no structural image of the subject is available. We also calculated an error factor associated with these probabilistic estimations. The current study presents a close topological link between transcranial and tomographic brain-mapping modalities, which could contribute to inter-modal data standardization.

Prefrontal activity during taste encoding: an fNIRS study.

To elucidate the function of the lateral prefrontal cortex (LPFC) in taste encoding, it is worth applying to taste, the psychological paradigms of intentional memorization that have been used with other extensively studied senses, and thus updating current models for LPFC functions to include a taste modality. Using multichannel functional near-infrared spectroscopy (fNIRS), we examined the LPFCs of healthy volunteers (N = 18) during the intentional memorization of a basic taste. In order to minimize the confounding effects of verbal processes that are known to employ the left LPFC, we used quaternary taste mixtures that were difficult to verbalize, and confined analysis to those who did not use a verbal strategy during memorization (N = 10). In order to examine the results in association with data in the literature, the location of activity was probabilistically estimated and anatomically labeled in the Montreal Neurological Institute (MNI) standard brain space. By contrasting the cortical activation under encoding conditions with that under control conditions without memory requirement, we found activation in the bilateral ventro-LPFC and the right posterior portion of the LPFC. The activation pattern was consistent with previous studies on the encoding of nonverbal materials using other senses. This suggests that models for LPFC functions that derive from previous studies can be generalized to intentional encoding processes of taste information, at least at a macro-structural level. The current study also demonstrates that, by using fNIRS, LPFC functions on taste can be examined with experimental paradigms relevant to those used for other senses.

Virtual 10-20 measurement on MR images for inter-modal linking of transcranial and tomographic neuroimaging methods.

It is important to create a link between stereotaxic coordinates and head-surface-based positioning systems in order to share data between tomographic and transcranial brain mapping studies. In our previous studies, we established the probabilistic correspondence of the international 10-20 positions to the standard stereotaxic coordinate systems and made a reference database. However, its expansion required the physical marking of the 10-20 positions and the subsequent acquisition of MR images. To avoid such tedious procedures, we developed a virtual 10-20 measurement algorithm that can be applied to re-analyze any structural MR image that covers the whole head. As in the physical 10-20 measurements, with the reference points given, the algorithm automatically determines each 10-20 position step by step. Using the virtual 10-20 measurement method, we re-analyzed the MR images of 17 healthy subjects for whom we had determined 10-20 positions by physical marking in our previous study. The acquired 10-20 positions were normalized to the Montreal Neurological Institute (MNI) stereotactic coordinates and compared with the positions previously determined by physical measurements. 10-20 positions determined using the virtual and physical methods were roughly consistent. Average standard deviations for virtual and physical methods were 7.7 mm and 9.0 mm, respectively. There was a systematic shift in the virtual method, likely due to the absence of hair interference. We corrected the shift with affine transformation. The virtual 10-20 measurement method proved to be an effective alternative to physical marking. This method will serve as an essential tool for expanding the reference database and will further strengthen the link between tomographic and transcranial brain mapping methods.

Identification of death-associated protein kinases inhibitors using structure-based virtual screening.

Death-associated protein kinases (DAPKs) function in the early stages of eukaryotic programmed cell death. DAPKs are now emerging as targets for drug discovery in novel therapeutic approaches for ischemic diseases in the brain, heart, kidney, and other organs. Using a structure-based virtual screening approach, we discovered potent and selective DAPKs inhibitors. 6 was found to be the most potent inhibitor with enzyme selectivity (IC(50) = 69 nM for DAPK1).

Clinically-oriented monitoring of acute effects of methylphenidate on cerebral hemodynamics in ADHD children using fNIRS

OBJECTIVE Attention Deficit Hyperactivity Disorder (ADHD), a common developmental syndrome with inattention, hyperactivity, and impulsivity, is typically treated with the psychostimulant drug, methylphenidate (MPH). We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to search for a clinically implementable biological marker for the acute MPH effect on ADHD children. METHODS Following an MPH washout period, twelve ADHD children performed a go/no-go task before and 1.5 h after MPH intake. fNIRS was used to monitor the lateral prefrontal cortical hemodynamics of ADHD children performing a go/no-go task. RESULTS There was no significant activation in the lateral prefrontal cortices examined before MPH intake. However, after MPH intake, significant MPH-elicited activation (oxygenated hemoglobin signal increase) was detected in the right lateral prefrontal cortex (LPFC) implicated with response inhibition functions. There was a large significant correlation between increases in task performance and activation in the right LPFC. CONCLUSIONS The improved cognitive performance was associated with activation in the right LPFC, which might serve as a biological marker to monitor the effect of MPH in ADHD children. SIGNIFICANCE MPH-effect assessment in ADHD children using fNIRS can be performed within a 3 h stay at a hospital during a single visit, and thus may be integrated into clinical practice.

Structure–activity relationship of novel DAPK inhibitors identified by structure-based virtual screening

Death-associated protein kinase (DAPK) is a serine/threonine protein kinase implicated in diverse programmed cell death pathways. DAPK is a promising target protein for the treatment of ischemic diseases. We identified novel potent and selective DAPK inhibitors efficiently by structure-based virtual screening, then further developed the hit compounds. In this paper, we describe the development of the hit compounds and the structure-activity relationship studies of the DAPK inhibitors in detail, including calculation of the solvated interaction energy (SIE), and verification of selectivity using a kinase panel.