2.1.

Wearable Optical Topography System and Optical Topography Measurements

The WOT system has been developed to be small, light, and wearable.²² It consists of a probe unit, a processing unit, and the WOT’s computer. The probe unit has a $2\times 8$ alternating arrangement of irradiation and detection positions covering the entire forehead, with 22 measurement points [Fig. 1 ]. The separation of each pair of irradiation and detection positions was set to $30\mathrm{mm}$ , giving the probe unit a coverage area of $30\times 210{\mathrm{mm}}^2$ on the subject’s forehead, including the bilateral temples. This arrangement enables us to monitor the cortical activations mainly in the dorsolateral prefrontal cortex (DLPFC) and the rostral prefrontal area. The probe unit has a flexible pad with irradiation and detection positions to fit the subject’s head [Fig. 1]. Vertical-cavity surface emitting laser diodes with two wavelengths (790 and $850\mathrm{nm}$ ) were used as light sources to emit light onto the scalp at each irradiation position, and silicon photodiodes were located at each detection position to detect multiply-scattered light in the biological tissue.

Fig. 1

(a) Configuration of irradiation and detection positions and of measurement points in the probe unit. White and black squares represent irradiation and detection positions, respectively. White circles represent measurement points; numbers are measurement channel numbers. The probe unit has a $2\times 8$ alternating arrangement of irradiation and detection positions with 22 measurement points. The separation of each pair of irradiation and detection positions was set to $30\mathrm{mm}$ , giving the probe unit a coverage area of $30\times 210{\mathrm{mm}}^2$ on the subject’s forehead. (b) Photograph of the probe unit. The probe unit has a flexible pad with eight irradiation positions and eight detection positions. The probe unit can be worn on the subject’s head.

The processing unit is connected to the probe unit through a flexible cable bundle for controlling OT measurements and accumulating $5\text{-}\mathrm{Hz}$ sampling data into a flash memory inside the processing unit. The processing unit also sends data to the WOT’s computer via wireless communication connections, the maximum distance of which is about $100\mathrm{m}$ . Measurement data are constantly recorded into the flash memory to avoid lack of data by disconnection and are loaded by the WOT’s computer. The probe and processing units, which are respectively worn on the subject’s head and waist, weigh about $1\mathrm{kg}$ . Thus, these units are easily carried by healthy adults, which means that the WOT system enables measurement in more natural conditions than possible with conventional systems.

The WOT’s computer sends configuration information to the processing unit and receives OT measurement data from the unit, which can then be displayed and analyzed. In this study, we used a modified WOT system that has laser diodes with two wavelengths (754 and $830\mathrm{nm}$ ) as light sources in the probe unit, because Sato suggested that noise levels in Hb changes decreased when using wavelengths shorter than $782\mathrm{nm}$ paired with $830\mathrm{nm}$ , although the detected power appears to be weaker the shorter the wavelength.²³ We selected $754\mathrm{nm}$ from such a wavelength range for optimizing our system in consideration of signal-to-noise ratio and the level of detected power.

OT measurements for behavioral tasks were executed with the modified WOT system and a personal computer (PC) for presenting sounds (see Fig. 2 ). The PC memorized a procedure for presenting sounds from the start to the end of each measurement. The WOT’s computer and the PC were connected with an RS232C cable, through which the PC sent trigger signals to the WOT’s computer for starting measurement, changing conditions, and stopping measurement.

Fig. 2

Experimental setup of OT measurements for behavioral task. The subjects wore the probe unit on their heads and the processing unit on their waists. The PC presented a sound to show the subjects the walking and turning pace. It also sent trigger signals to start measurement, change the condition, and stop the measurement to the WOT’s computer. The WOT’s computer sent configuration information to the processing unit and received OT measurement data from the unit via wireless communication connections.

While the subjects performed the behavioral tasks, we measured the oxy- and deoxy-Hb signals in their prefrontal cortices using the WOT system. The subjects wore the probe unit on their heads and the processing unit on their waists. Gain values for digital potentiometers in the probe unit were optimized depending on the detected light power before the OT measurements.

2.2.

Behavioral Task

The behavioral task performed by the subjects while walking was an AD task that requires executive functions in natural walking. This was a ball-carrying task with two conditions (task and control conditions, see Fig. 3 ), which were controlled by sounds presented by a PC. A session including the two conditions commenced when a warning sound was presented by the PC. For each condition, the subjects performed two sets of alternating walking and turning periods. In the first walking period of $10\mathrm{s}$ , a low-pitched sound was presented every second by the PC, and the subject stepped with his/her right foot hitting the ground in time with the sound while balancing a ball on a card or holding a ball in the task and control conditions, respectively. The sound presented by the PC produced a $2\text{-}\mathrm{Hz}$ step by both feet as the subjects’ walking pace. When a high-pitched sound was presented at every second in a turning period of $3\mathrm{s}$ , the subjects turned around at the same walking pace. After walking in the return direction in the second walking period of $10\mathrm{s}$ , the subjects changed the way the ball was carried, alternating the condition. Each session included five task conditions and six control conditions, where the subjects were required to gaze at the ball while performing the ball-carrying task. In this task paradigm, subjects consistently stepped with their feet hitting the ground at the same pace from the start to the end of the experiments. Thus, we considered the control condition period as a walking period without the AD task, and the task condition period as that with the AD task.

Fig. 3

Behavioral task and procedure. (a) Ball-carrying tasks while walking with two conditions: task condition, where a subject balances a ball on a card held between his/her right thumb and index finger, and control condition, where the subject holds the ball between his/her right thumb and index finger as it rests on the card in his/her hand. (b) Subject’s eye direction in behavioral task. Subjects were required to gaze at the ball from the start to the end of an experimental session. (c) Task procedure. Subjects stood still in the rest period for about $20\mathrm{s}$ , then by stepping with the right foot in time to a sound presented every $1\mathrm{s}$ by a PC, walked straight for $10\mathrm{s}$ and executed a turn over $3\mathrm{s}$ . They then walked in the return direction for $10\mathrm{s}$ at the same pace and changed the way the ball was carried during the next turn executed over $3\mathrm{s}$ .

OT measurements for the behavioral task were conducted in a gymnastic hall that was large enough for subjects to walk in both directions. Before OT measurements, subjects attended a practice session, including two pairs of the task and control conditions, so the subjects could be familiar with the ball-carrying task. In the OT measurement, only one subject dropped the ball during the first task condition period and restarted the experiment.

2.3.

Subjects

Six healthy adults (4 males and 2 females aged between 25 and $34\text{years}$ , mean age of $29.7\pm$ 3.3 SD) participated in this study. All were right-handed and had no neurological abnormalities. Informed consent was obtained from each subject.

2.4.

Data Analysis

To analyze the optical data, changes in the product of the concentration and the effective optical path length for oxy- and deoxy-Hb were calculated using the modified Beer-Lambert law:⁵

We defined a period from $5\mathrm{s}$ prior to each task condition period to the end of the following control condition period as the analysis block. Each session consisted of five analysis blocks. Then, we applied linear regression by the least squares method to the data in each analysis block during the first $5\text{-}\mathrm{s}$ period and the last $1\text{-}\mathrm{s}$ period to determine the linear trend of the baseline unrelated to the behavioral task. After correcting the baseline by removing the trend, we averaged the baseline-corrected data in all the analysis blocks.

The Hb signals were statistically assessed. Assuming that the hemodynamic changes induced by the AD task were delayed $6\mathrm{s}$ from the task onset, the shifted period of the task condition period was defined as the activation period,²³ and a $5\text{-}\mathrm{s}$ period prior to each task condition period was defined as the pretask period (Fig. 4 ). Using the averaged Hb signals ( $\Delta C_{\mathrm{oxy}}^{\prime }$ , $\Delta C_{\mathrm{deoxy}}^{\prime }$ ) during the pretask period and those during the activation period for each analysis block, we calculated the $t$ value (paired $t$ test) between the averaged Hb signals in the pretask periods of five analysis blocks, and the Hb signals in the activation periods of the same five blocks.

Fig. 4

Pretask and activation periods in the analysis block. Assuming that the hemodynamic changes induced by the task were delayed $6\mathrm{s}$ from the task onset, the shifted period of the task condition period was defined as the activation period. A $5\text{-}\mathrm{s}$ period prior to each task condition period was defined as the pretask period. Mean values during the pretask period and the activation period were used for statistical analysis.

We used the probabilistic estimation method²⁴ to register the OT measurement data of the Montreal Neurological Institute (MNI) standard brain space. Irradiation and detection positions, together with several scalp landmarks, were digitized using a 3-D magnetic space digitizer (Isotrak II Polhemus, Colchester, Vermont). We obtained the mean estimate for the location of measurement points for ten volunteers (5 males and 5 females, including 6 subjects for OT measurement).

3.1.

Time Course of Oxy- and Deoxyhemoglobin Concentrations

The time course of oxy- and deoxy-Hb signals ( $\Delta C_{\mathrm{oxy}}^{\prime }$ and $\Delta C_{\mathrm{deoxy}}^{\prime }$ , respectively) obtained from channel 8 (Fig. 1) for a representative subject are shown in Fig. 5 . During the task condition periods, $\Delta C_{\mathrm{oxy}}^{\prime }$ increased and $\Delta C_{\mathrm{deoxy}}^{\prime }$ decreased a little, which shows task-related and reproducible changes of $\Delta C_{\mathrm{oxy}}^{\prime }$ . To assess the task-related and step-related changes, power spectra of the data were calculated [Fig. 5]. In the $\Delta C_{\mathrm{oxy}}^{\prime }$ spectrum, the task-related frequency is 1.92E-2 $(=1∕52)\mathrm{Hz}$ , because one cycle of a task condition and a control condition is $52\mathrm{s}$ , and the step-related frequency is $2\mathrm{Hz}$ . The power at the former frequency is $26\mathrm{dB}$ larger than that at the latter, which is low enough to obtain the task-related changes. By use of the moving-averaged data, the power at the step-related frequency becomes $61\mathrm{dB}$ smaller than that at the data before the moving average, so the step-related changes are small enough to be negligible. The same can be said for $\Delta C_{\mathrm{deoxy}}^{\prime }$ .

Fig. 5

(a) Time-series data of oxy- and deoxy-Hb signals obtained from channel 8 [Fig. 1] for a representative subject. Light and dark gray lines represent the oxy- and deoxy-Hb signals ( $\Delta C_{\mathrm{oxy}}^{\prime }$ and $\Delta C_{\mathrm{deoxy}}^{\prime }$ ), respectively, and thick lines represent moving-averaged data for $5\mathrm{s}$ . Vertical dashed lines show the onset of a condition change. T: task condition and C: control condition. (b) Power spectra of the oxy- and deoxy Hb signals shown in (a). Arrows show the task-related and step-related frequencies. MA is the moving-averaged data.

To examine the task-related changes in $\Delta C_{\mathrm{oxy}}^{\prime }$ and $\Delta C_{\mathrm{deoxy}}^{\prime }$ , we corrected the baseline to remove low-frequency fluctuations caused by laser drifts or biological metabolism for each analysis block, then we averaged the baseline-corrected data of all the blocks without low signal-to-noise ratio blocks. The mean time courses of block-averaged $\Delta C_{\mathrm{oxy}}^{\prime }$ and $\Delta C_{\mathrm{deoxy}}^{\prime }$ for each channel obtained from all the subjects are shown in Fig. 6 . Large changes in $\Delta C_{\mathrm{oxy}}^{\prime }$ during the task condition period were observed in channels 3 through 16, which were positioned from the center to the right part of the prefrontal area [Fig. 1], and small changes in $\Delta C_{\mathrm{deoxy}}^{\prime }$ were observed as reported in the previous studies.^{15, 16, 17} To assess the task-related changes in $\Delta C_{\mathrm{oxy}}^{\prime }$ and $\Delta C_{\mathrm{deoxy}}^{\prime }$ statistically, we calculated the $t$ value (paired $t$ test) between the mean changes in those Hb signals in the pretask periods and those in the activation periods (Fig. 4). Significant $t$ values (two-tailed $t$ test, $p<0.001$ ) were obtained in $\Delta C_{\mathrm{oxy}}^{\prime }$ in channels 5 through 10, 13, and 15 (Fig. 7 ), but no significant $t$ values were obtained in $\Delta C_{\mathrm{deoxy}}^{\prime }$ . We identified the measurement points with significant $t$ values in $\Delta C_{\mathrm{oxy}}^{\prime }$ as activation channels.

Fig. 6

Mean time-series data of all subjects for block-averaged oxy- and deoxy-Hb signals for each measurement channel. Thin and thick lines represent oxy- and deoxy-Hb signals, respectively. Vertical dashed lines represent task condition periods.

Fig. 7

Measurement channels showing significant $\Delta C_{\mathrm{oxy}}^{\prime }$ (two-tailed $t$ test, $p<0.001$ ). Black circles show significant channels.