Maturation of Sensori-Motor Functional Responses in the Preterm Brain.

Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level-dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults.

An exploration of task based fMRI in neonates using echo-shifting to allow acquisition at longer TE without loss of temporal efficiency.

Optimal contrast to noise ratio of the BOLD signal in neonatal and foetal fMRI has been hard to achieve because of the much longer T2(⁎) values in developing brain tissue in comparison to those in the mature adult brain. The conventional approach of optimizing fMRI sequences would suggest matching the echo time (TE) and the T2(⁎) of the neonatal and foetal brain. However, the use of a long echo time would typically increase the minimum repetition time (TR) resulting in inefficient sampling. Here we apply the concept of echo shifting to task based neonatal fMRI in order to achieve an improved contrast to noise ratio and efficient data sampling at the same time. Echo shifted EPI (es-EPI) is a modification of a standard 2D-EPI sequence which enables echo times longer than the time between consecutive excitations (TE>TS=TRNS, where NS is the number of acquired slices and TS the inter-slice repetition time). The proposed method was tested on neonatal subjects using a passive sensori-motor task paradigm. Dual echo EPI datasets with an identical readout structure to es-EPI were also acquired and used as control data to assess BOLD activation. From the results of the latter analysis, an average increase of 78±41% in contrast to noise ratio was observable when comparing late to short echoes. Furthermore, es-EPI allowed the acquisition of data with an identical contrast to the late echo, but more efficiently since a higher number of slices could be acquired in the same amount of time.

Development of BOLD signal hemodynamic responses in the human brain.

In the rodent brain the hemodynamic response to a brief external stimulus changes significantly during development. Analogous changes in human infants would complicate the determination and use of the hemodynamic response function (HRF) for functional magnetic resonance imaging (fMRI) in developing populations. We aimed to characterize HRF in human infants before and after the normal time of birth using rapid sampling of the blood oxygen level dependent (BOLD) signal. A somatosensory stimulus and an event related experimental design were used to collect data from 10 healthy adults, 15 sedated infants at term corrected post menstrual age (PMA) (median 41+1 weeks), and 10 preterm infants (median PMA 34+4 weeks). A positive amplitude HRF waveform was identified across all subject groups, with a systematic maturational trend in terms of decreasing time-to-peak and increasing positive peak amplitude associated with increasing age. Application of the age-appropriate HRF models to fMRI data significantly improved the precision of the fMRI analysis. These findings support the notion of a structured development in the brain's response to stimuli across the last trimester of gestation and beyond.

Technology-aided assessment of sensorimotor function in early infancy.

There is a pressing need for new techniques capable of providing accurate information about sensorimotor function during the first 2 years of childhood. Here, we review current clinical methods and challenges for assessing motor function in early infancy, and discuss the potential benefits of applying technology-assisted methods. We also describe how the use of these tools with neuroimaging, and in particular functional magnetic resonance imaging (fMRI), can shed new light on the intra-cerebral processes underlying neurodevelopmental impairment. This knowledge is of particular relevance in the early infant brain, which has an increased capacity for compensatory neural plasticity. Such tools could bring a wealth of knowledge about the underlying pathophysiological processes of diseases such as cerebral palsy; act as biomarkers to monitor the effects of possible therapeutic interventions; and provide clinicians with much needed early diagnostic information.