In this study, for the first time, hemodynamic responses induced by the motor activation during a finger tapping protocol was successfully measured with fNIRS from children with hemiparetic CP and compared with age-matched healthy controls. For both groups of the pediatric subjects, a good reproducibility of motor activation measured by fNIRS has been obtained by comparing the results from Visits 1 and 2. Our repeatable observation of ΔHbO2
activation is in good agreement with previous studies reported for replicable measurements on adult's visual cortex [33
] and prefrontal cortex [34
]. While a success rate of 60% (18 out of total 30 qualified subjects) was achieved for fNIRS measurements in this study, it is not optimal and needs to be improved if we wish to have fNIRS become a clinical tool in the near future. Two immediate causes for this rate are (1) the high attenuation of optical signals due to dark-colored hair and (2) pediatric subjects' compliance with experimental instructions. To solve the former problem, improvement of the signal to noise ratio is critically necessary. Possible solutions include to advance the coupling efficiency between the probe tip and the scalp [35
] and to optimize the range of source-detector separations [36
]. To solve the latter obstruction, a protocol with a simple or shorter activation task or without any task [38
] should be explored for pediatric subjects.
Spatiotemporal analysis was introduced to investigate the combined pattern in both temporal evolution and spatial distribution of reconstructed ΔHbO2 images of the two hemispheres stimulated by motor activation. Specific parameters, such as Vcontra, Vipsi, and L, were identified to characterize the functional participation and re-organization of the two hemispheres in the control and children with CP. This study has demonstrated that the derived parameter of L is useful to quantify the degree of brain laterality in children with hemiparetic CP because ipsilateral and bilateral activities are frequently evoked during motor task in this population. To our current knowledge, this is the first report of such analysis used in fNIRS brain imaging.
Predominant motor activation on the contralateral hemisphere was identified among the healthy children 7 years of age and older. This observation agrees with a similar fMRI study in adults during single finger movements [32
]. According to our observation, it appears that the motor function in normal children tends to be better developed at 7 years old and greater, while this observation needs to be validated with a larger subject pool. The same fMRI study has also demonstrated that the patterns of motor activation in left- and right-handers are similar in single finger movements [32
]. Therefore, although most healthy children in this study were right-handed, we expect that it would not alter the current conclusion.
The laterality of motor activation measured by fNIRS was diverse among hemiparetic children. The parameters derived from spatiotemporal analysis allow us to statistically identify the enhanced inter-hemispheric reorganization of motor function in hemiparetic children (even after excluding 6-year-old subjects). We have observed that the unaffected hemisphere functions together with the affected hemisphere for both the paretic and nonparetic hands. It is noteworthy that even though all of the hemiparetic children in this study had mild motor disorder, their brain impairments were different in terms of type, location and size. Such impairments can be identified by reviewing their MRI images; in turn, they are crucial and characteristic factors in hemispheric reorganization [40
]. Therefore, to confirm the current observations on abnormal laterality of motor function in children with CP, further study with a larger subject pool of more categorized brain impairments is needed.
In addition, by combining the data from both the healthy children and children with CP, it appears that the laterality of motor function is age-dependent in early childhood. In particular, both of the healthy children and children with CP at 6 years of age have shown significantly ipsilateral or bilateral activations. By reviewing their videotapes, we have ruled out the possibility of poor performance from these subjects; thus, it may imply an incomplete development of motor function in children at 6 years old and younger.
The unintended motion artifacts were still the most significant interferences during measurement, resulting in discontinuities in fNIRS data. A cross validation was performed to screen the fNIRS data by correlating with the videotape and surface EMG. In this way, the quality of fNIRS data was ensured to be motion-artifact free. In the study, we measured the respiration and cardiac pulsation patterns simultaneously with the fNIRS signals. In order to remove physiological noises [41
], these accessory signals were used to carry out adaptive filtering in our earlier study [18
] with a portion of the subjects. However, we have not employed the adaptive filter in this study due to the following reasons: (1) since the respiration waves have slow oscillations (0.3–0.5 Hz for children), training the adaptive filter requires a long-term, continuous baseline. It was not feasible to obtain high-quality, stable baselines in some data sets because motion artifacts often occurred within the recorded baselines. (2) It is a common procedure to average multiple stimulation epochs in each session, with which the slow-varying respiration interference is greatly reduced, as experienced in our previous work [43
]. One conclusion drawn from this part of study is that fNIRS-only measurements are simpler, easier, and still adequate to allow meaningful spatiotemporal analysis. Additional physiological measurements are complementary for better signal processing and characterization, but requiring longer and more stable measurements.
At last, it is noteworthy that several factors should be considered when interpreting the results in this study. First, we used a sparse array of optodes, as shown in , which was comfortable to the subjects. However, this optode array has a crude spatial resolution and may result in certain spatial distortion in the reconstructed Δ[HbO2
] or Δ[Hb
] image [36
]. Second, the imaged area was limited within the sensorimotor region only. Other participating cortical regions evoked by the finger tapping task, such as premotor and supplementary areas, were not optically interrogated and scanned. Third, in this study, we did not find any significant variation in manually-recorded heart rate or oxygen saturation in either the CP group or Control group. However, we assume that the tapping task was harder to children with CP than to the healthy controls and might cause systemic changes in children with CP. Such changes may occur simultaneously with the functional activation and may be inherently encoded into the functional brain measurements in some subjects [45
]. Our current results could not be completely resistant to such systemic changes, while the systemic influence is expected to be insignificant because of a short period of activation and mild motor movement of finger tapping. For future studies, a subject's heart rate and oxygen saturation may be recorded simultaneously with fNIRS so that systemic changes of the subject during the experiment can be monitored or determined. Then, appropriate compensation analysis and comparison between healthy controls and patients can be made.
In summary, we have demonstrated clearly that with the use of 3D spatiotemporal analysis and quantification of brain laterality, fNIRS has an ability to assess the cortical reorganization in children with mild CP. Specifically, the introduction of lateralization factor, L, has allowed us to reveal laterality of the brain activation derived from the fNIRS data. Such analysis may be applicable to other fNIRS applications, taking advantages of integrating both temporal and spatial information simultaneously.