Cortical networks show characteristic recruitment patterns after somatosensory stimulation by pneumatically evoked repetitive hand movements in newborn infants.

Controlled assessment of functional cortical networks is an unmet need in the clinical research of noncooperative subjects, such as infants. We developed an automated, pneumatic stimulation method to actuate naturalistic movements of an infant's hand, as well as an analysis pipeline for assessing the elicited electroencephalography (EEG) responses and related cortical networks. Twenty newborn infants with perinatal asphyxia were recruited, including 7 with mild-to-moderate hypoxic-ischemic encephalopathy (HIE). Statistically significant corticokinematic coherence (CKC) was observed between repetitive hand movements and EEG in all infants, peaking near the contralateral sensorimotor cortex. CKC was robust to common sources of recording artifacts and to changes in vigilance state. A wide recruitment of cortical networks was observed with directed phase transfer entropy, also including areas ipsilateral to the stimulation. The extent of such recruited cortical networks was quantified using a novel metric, Spreading Index, which showed a decrease in 4 (57%) of the infants with HIE. CKC measurement is noninvasive and easy to perform, even in noncooperative subjects. The stimulation and analysis pipeline can be fully automated, including the statistical evaluation of the cortical responses. Therefore, the CKC paradigm holds great promise as a scientific and clinical tool for controlled assessment of functional cortical networks.

Neonatal somatosensory evoked potentials persist during hypothermia.

AIM: Treatment with therapeutic hypothermia has challenged the use of amplitude-integrated electroencephalography in predicting outcomes after perinatal asphyxia. In this study, we assessed the feasibility and gain of somatosensory evoked potentials (SEP) during hypothermia. METHODS: This retrospective study comprised neonates from 35 + 6 to 42 + 2 gestational weeks and treated for asphyxia or hypoxic-ischaemic encephalopathy at Helsinki University Hospital between 14 February 2007 and 23 December 2009. This period was partly before the introduction of routine therapeutic hypothermia, which enabled us to include normothermic neonates who would these days receive hypothermia treatment. We analysed SEPs from 47 asphyxiated neonates and compared the results between 23 normothermic and 24 hypothermic neonates. RESULTS: Our data showed that hypothermia led to SEP latencies lengthening by a few milliseconds, but the essential gain for predicting outcomes by SEPs was preserved during hypothermia. Of the 24 hypothermic neonates, bilaterally absent SEPs were associated with poor outcome in 2/2 neonates, normal SEPs were associated with good outcomes in 13/15 neonates and 5/7 neonates with unilaterally absent or grossly delayed SEPs had a poor outcome. CONCLUSION: Our findings indicated that SEPs were a reliable tool for evaluating the somatosensory system in asphyxiated neonates in both normothermic and hypothermic conditions.

Use of complex visual stimuli allows controlled recruitment of cortical networks in infants.

OBJECTIVE: To characterize cortical networks activated by patterned visual stimuli in infants, and to evaluate their potential for assessment of visual processing and their associations with neurocognitive development. METHODS: Three visual stimuli, orientation reversal (OR), global form (GF), and global motion (GM), were presented to cohort of five-month-old infants (N = 26). Eye tracker was used to guide the stimulation and to choose epochs for analysis. Visual responses were recorded with electroencephalography and analysed in source space using weighted phase lag index as the connectivity measure. The networks were quantified using several metrics that were compared between stimuli and correlated to cognitive outcomes. RESULTS: Responses to OR/GF/GM stimuli were observed in nearly all (96/100/100%) recordings. All stimuli recruited cortical networks that were partly condition-specific in their characteristics. The more complex GF and GM conditions recruited wider global networks than OR. Additionally, strength of the GF network showed positive association with later cognitive performance. CONCLUSIONS: Network analysis suggests that visual stimulation recruits large-scale cortical networks that extend far beyond the conventional visual streams and that differ between stimulation conditions. SIGNIFICANCE: The method allows controlled recruitment of wide cortical networks, which holds promise for the early assessment of visual processing and its related higher-order cognitive processes.

Use of eye tracking improves the detection of evoked responses to complex visual stimuli during EEG in infants.

OBJECTIVE: To improve the reliability of detecting EEG responses evoked by complex visual stimuli to the level required for clinical use by integrating an eye tracker to the EEG setup and optimizing the analysis protocol. METHODS: Infants were presented with continuous orientation reversal (OR), global form (GF), and global motion (GM) stimuli. Eye tracking was used to control stimulus presentation and exclude epochs with disoriented gaze. The spectral responses were estimated from 13 postcentral EEG channels using a circular variant of Hotelling's T2 test statistic. RESULTS: Among 39 healthy infants, statistically significant (p < 0.01) responses to OR/GF/GM stimuli were found from 92%/100%/95% recordings, respectively. The specificity test of the detection algorithm, using non-stimulated baseline EEG, did not yield any false-positive findings. Taken together, this yields 15% improvement on average in the detection performance compared to that in the current literature. CONCLUSIONS: Changes to the test protocol and incorporation of the eye tracking information improves the detection of responses to complex visual stimuli in infants. SIGNIFICANCE: This work presents a test protocol suitable for use in a clinical environment at a level of reliability that allows individual diagnostics.

Dynamic eye tracking based metrics for infant gaze patterns in the face-distractor competition paradigm.

OBJECTIVE: To develop new standardized eye tracking based measures and metrics for infants' gaze dynamics in the face-distractor competition paradigm. METHOD: Eye tracking data were collected from two samples of healthy 7-month-old (total n = 45), as well as one sample of 5-month-old infants (n = 22) in a paradigm with a picture of a face or a non-face pattern as a central stimulus, and a geometric shape as a lateral stimulus. The data were analyzed by using conventional measures of infants' initial disengagement from the central to the lateral stimulus (i.e., saccadic reaction time and probability) and, additionally, novel measures reflecting infants gaze dynamics after the initial disengagement (i.e., cumulative allocation of attention to the central vs. peripheral stimulus). RESULTS: The results showed that the initial saccade away from the centrally presented stimulus is followed by a rapid re-engagement of attention with the central stimulus, leading to cumulative preference for the central stimulus over the lateral stimulus over time. This pattern tended to be stronger for salient facial expressions as compared to non-face patterns, was replicable across two independent samples of 7-month-old infants, and differentiated between 7 and 5 month-old infants. CONCLUSION: The results suggest that eye tracking based assessments of infants' cumulative preference for faces over time can be readily parameterized and standardized, and may provide valuable techniques for future studies examining normative developmental changes in preference for social signals. SIGNIFICANCE: Standardized measures of early developing face preferences may have potential to become surrogate biomarkers of neurocognitive and social development.

Functional plasticity of the motor cortical structures demonstrated by navigated TMS in two patients with epilepsy.

BACKGROUND: Recently, navigated transcranial magnetic stimulation (nTMS) has been suggested to be useful in preoperative functional localization of motor cortex in patients having tumors close to the somatomotor cortex. Resection of tumors in anatomically predicted eloquent areas without adverse effects have emphasized functional plasticity elicited by intracranial pathology. OBJECTIVE: To describe functional plasticity of motor cortex indicated by nTMS in two patients with epilepsy. METHODS: nTMS, functional MRI (fMRI), diffusion-tensor (DT)-tractography and magnetoencephalography (MEG) were utilized to preoperatively localize motor cortical areas in the workup for epilepsy surgery. The localizations were compared with each other, with the cortical anatomical landmarks, and in one patient with invasive electrical cortical stimulation (ECS). RESULTS: In two out of 19 studied patients, nTMS identified motor cortical sites that differed from those indicated by anatomical landmarks. In one patient, nTMS activated preferentially premotor cortex rather than pathways originating from the precentral gyrus. MEG and fMRI localizations conformed with nTMS whereas ECS localized finger motor function into the precentral gyrus. Resection of the area producing motor responses in biphasic nTMS did not produce a motor deficit. In the other patient, nTMS indicated abnormal ipsilateral hand motor cortex localization and confirmed the functionality of aberrant motor cortical representations of the left foot also indicated by fMRI and DT-tractography. CONCLUSION: nTMS may reveal the functional plasticity and shifts of motor cortical function. Epileptic foci may modify cortical inhibition and the nTMS results. Therefore, in some patients with epilepsy, the nTMS results need to be interpreted with caution with regard to surgical planning.