Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease.

BACKGROUND: The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. METHODS: Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. RESULTS: After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [- 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001). CONCLUSIONS: The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.

Evaluation of the brain hemodynamic response by means of near-infrared spectroscopy (NIRS) monitoring in patients with atherosclerotic carotid disease undergoing endarterectomy.

BACKGROUNDS: Near-infrared spectroscopy (NIRS) is non-invasive technique that detects hemodynamic alterations in tissues. It enables continuous monitoring of intracerebral vascular physiologic information. Due to its portable nature, NIRS may be used bedside or in the operating room. OBJECTIVES: To evaluate use of NIRS for intraoperative monitoring of the brain hemodynamic response, during carotid endarterectomy. METHODS: 10 patients with atherosclerotic carotid disease scheduled for endarterectomy were evaluated. After patients had been selected, they answered a questionnaire on epidemiological data and information about comorbidities and then carotid disease was confirmed with diagnostic methods. NRIS monitoring was used during the surgical procedure. The variables analyzed before, during and after carotid clamping were oxygen saturation (SatO2), total hemoglobin (THb), reduced hemoglobin (RHb), and oxyhemoglobin (OHb). A p value of <0.05 was considered statistically significant. RESULTS: The results obtained from NIRS show that RHb and SatO2 vary during the different stages of surgery. RHb levels are higher during clamping, when compared with the other two surgical stages. On the other hand, SatO2 is lower during clamping. CONCLUSIONS: During carotid endarterectomy, NIRS is a feasible, real-time, and non-invasive intracranial monitoring method that accurately and reliably measures the changes in intracerebral capillary hemodynamic conditions.

Cerebral Blood Flow Response During Bolus Normal Saline Infusion After Ischemic Stroke.

GOALS: We quantified cerebral blood flow response to a 500 cc bolus of 0.9%% normal saline (NS) within 96 hours of acute ischemic stroke (AIS) using diffuse correlation spectroscopy (DCS). MATERIALS AND METHODS: Subjects with AIS in the anterior, middle, or posterior cerebral artery territory were enrolled within 96 hours of symptom onset. DCS measured relative cerebral blood flow (rCBF) in the bilateral frontal lobes for 15 minutes at rest (baseline), during a 30-minute infusion of 500 cc NS (bolus), and for 15 minutes after completion (post-bolus). Mean rCBF for each time period was calculated for individual subjects and median rCBF for the population was compared between time periods. Linear regression was used to evaluate for associations between rCBF and clinical features. RESULTS: Among 57 subjects, median rCBF (IQR) increased relative to baseline in the ipsilesional hemisphere by 17% (-2.0%, 43.1%), P< 0.001, and in the contralesional hemisphere by 13.3% (-4.3%, 36.0%), P < .004. No significant associations were found between ipsilesional changes in rCBF and age, race, infarct size, infarct location, presence of large vessel stenosis, NIH stroke scale, or symptom duration. CONCLUSION: A 500 cc bolus of .9% NS produced a measurable increase in rCBF in both the affected and nonaffected hemispheres. Clinical features did not predict rCBF response.

Transcranial Optical Monitoring of Cerebral Hemodynamics in Acute Stroke Patients during Mechanical Thrombectomy.

INTRODUCTION: Mechanical thrombectomy is revolutionizing treatment of acute stroke due to large vessel occlusion (LVO). Unfortunately, use of the modified Thrombolysis in Cerebral Infarction score (mTICI) to characterize recanalization of the cerebral vasculature does not address microvascular perfusion of the distal parenchyma, nor provide more than a vascular "snapshot." Thus, little is known about tissue-level hemodynamic consequences of LVO recanalization. Diffuse correlation spectroscopy (DCS) and diffuse optical spectroscopy (DOS) are promising methods for continuous, noninvasive, contrast-free transcranial monitoring of cerebral microvasculature. METHODS: Here, we use a combined DCS/DOS system to monitor frontal lobe hemodynamic changes during endovascular treatment of 2 patients with ischemic stroke due to internal carotid artery (ICA) occlusions. RESULTS AND DISCUSSION: The monitoring instrument identified a recanalization-induced increase in ipsilateral cerebral blood flow (CBF) with little or no concurrent change in contralateral CBF and extracerebral blood flow. The results suggest that diffuse optical monitoring is sensitive to intracerebral hemodynamics in patients with ICA occlusion and can measure microvascular responses to mechanical thrombectomy.

HIF modulation of Wnt signaling regulates skeletal myogenesis in vivo.

Deeper insight into the molecular pathways that orchestrate skeletal myogenesis should enhance our understanding of, and ability to treat, human skeletal muscle disease. It is now widely appreciated that nutrients, such as molecular oxygen (O2), modulate skeletal muscle formation. During early stages of development and regeneration, skeletal muscle progenitors reside in low O2 environments before local blood vessels and differentiated muscle form. Moreover, low O2 availability (hypoxia) impedes progenitor-dependent myogenesis in vitro through multiple mechanisms, including activation of hypoxia inducible factor 1α (HIF1α). However, whether HIF1α regulates skeletal myogenesis in vivo is not known. Here, we explored the role of HIF1α during murine skeletal muscle development and regeneration. Our results demonstrate that HIF1α is dispensable during embryonic and fetal myogenesis. However, HIF1α negatively regulates adult muscle regeneration after ischemic injury, implying that it coordinates adult myogenesis with nutrient availability in vivo. Analyses of Hif1a mutant muscle and Hif1a-depleted muscle progenitors further suggest that HIF1α represses myogenesis through inhibition of canonical Wnt signaling. Our data provide the first evidence that HIF1α regulates skeletal myogenesis in vivo and establish a novel link between HIF and Wnt signaling in this context.

Fiber-optic Monitoring of Spinal Cord Hemodynamics in Experimental Aortic Occlusion.

BACKGROUND: Spinal cord ischemia occurs frequently during thoracic aneurysm repair. Current methods based on electrophysiology techniques to detect ischemia are indirect, non-specific, and temporally slow. In this article, the authors report the testing of a spinal cord blood flow and oxygenation monitor, based on diffuse correlation and optical spectroscopies, during aortic occlusion in a sheep model. METHODS: Testing was carried out in 16 Dorset sheep. Sensitivity in detecting spinal cord blood flow and oxygenation changes during aortic occlusion, pharmacologically induced hypotension and hypertension, and physiologically induced hypoxia/hypercarbia was assessed. Accuracy of the diffuse correlation spectroscopy measurements was determined via comparison with microsphere blood flow measurements. Precision was assessed through repeated measurements in response to pharmacologic interventions. RESULTS: The fiber-optic probe can be placed percutaneously and is capable of continuously measuring spinal cord blood flow and oxygenation preoperatively, intraoperatively, and postoperatively. The device is sensitive to spinal cord blood flow and oxygenation changes associated with aortic occlusion, immediately detecting a decrease in blood flow (-65 ± 32%; n = 32) and blood oxygenation (-17 ± 13%, n = 11) in 100% of trials. Comparison of spinal cord blood flow measurements by the device with microsphere measurements led to a correlation of R = 0.49, P < 0.01, and the within-sheep coefficient of variation was 9.69%. Finally, diffuse correlation spectroscopy is temporally more sensitive to ischemic interventions than motor-evoked potentials. CONCLUSION: The first-generation spinal fiber-optic monitoring device offers a novel and potentially important step forward in the monitoring of spinal cord ischemia.

Cerebral hemodynamics at altitude: effects of hyperventilation and acclimatization on cerebral blood flow and oxygenation.

OBJECTIVE: Alterations in cerebral blood flow (CBF) and cerebral oxygenation are implicated in altitude-associated diseases. We assessed the dynamic changes in CBF and peripheral and cerebral oxygenation engendered by ascent to altitude with partial acclimatization and hyperventilation using a combination of near-infrared spectroscopy, transcranial Doppler ultrasound, and diffuse correlation spectroscopy. METHODS: Peripheral (Spo2) and cerebral (Scto2) oxygenation, end-tidal carbon dioxide (ETCO2), and cerebral hemodynamics were studied in 12 subjects using transcranial Doppler and diffuse correlation spectroscopy (DCS) at 75 m and then 2 days and 7 days after ascending to 4559 m above sea level. After obtaining baseline measurements, subjects hyperventilated to reduce baseline ETCO2 by 50%, and a further set of measurements were obtained. RESULTS: Cerebral oxygenation and peripheral oxygenation showed a divergent response, with cerebral oxygenation decreasing at day 2 and decreasing further at day 7 at altitude, whereas peripheral oxygenation decreased on day 2 before partially rebounding on day 7. Cerebral oxygenation decreased after hyperventilation at sea level (Scto2 from 68.8% to 63.5%; P<.001), increased after hyperventilation after 2 days at altitude (Scto2 from 65.6% to 69.9%; P=.001), and did not change after hyperventilation after 7 days at altitude (Scto2 from 62.2% to 63.3%; P=.35). CONCLUSIONS: An intensification of the normal cerebral hypocapnic vasoconstrictive response occurred after partial acclimatization in the setting of divergent peripheral and cerebral oxygenation. This may help explain why hyperventilation fails to improve cerebral oxygenation after partial acclimatization as it does after initial ascent. The use of DCS is feasible at altitude and provides a direct measure of CBF indices with high temporal resolution.

Optical bedside monitoring of cerebral blood flow in acute ischemic stroke patients during head-of-bed manipulation.

BACKGROUND AND PURPOSE: A primary goal of acute ischemic stroke (AIS) management is to maximize perfusion in the affected region and surrounding ischemic penumbra. However, interventions to maximize perfusion, such as flat head-of-bed (HOB) positioning, are currently prescribed empirically. Bedside monitoring of cerebral blood flow (CBF) allows the effects of interventions such as flat HOB to be monitored and may ultimately be used to guide clinical management. METHODS: Cerebral perfusion was measured during HOB manipulations in 17 patients with unilateral AIS affecting large cortical territories in the anterior circulation. Simultaneous measurements of frontal CBF and arterial flow velocity were performed with diffuse correlation spectroscopy and transcranial Doppler ultrasound, respectively. Results were analyzed in the context of available clinical data and a previous study. RESULTS: Frontal CBF, averaged over the patient cohort, decreased by 17% (P=0.034) and 15% (P=0.011) in the ipsilesional and contralesional hemispheres, respectively, when HOB was changed from flat to 30°. Significant (cohort-averaged) changes in blood velocity were not observed. Individually, varying responses to HOB manipulation were observed, including paradoxical increases in CBF with increasing HOB angle. Clinical features, stroke volume, and distance to the optical probe could not explain this paradoxical response. CONCLUSIONS: A lower HOB angle results in an increase in cortical CBF without a significant change in arterial flow velocity in AIS, but there is variability across patients in this response. Bedside CBF monitoring with diffuse correlation spectroscopy provides a potential means to individualize interventions designed to optimize CBF in AIS.

Continuous optical monitoring of cerebral hemodynamics during head-of-bed manipulation in brain-injured adults.

INTRODUCTION: Head-of-bed manipulation is commonly performed in the neurocritical care unit to optimize cerebral blood flow (CBF), but its effects on CBF are rarely measured. This pilot study employs a novel, non-invasive instrument combining two techniques, diffuse correlation spectroscopy (DCS) for measurement of CBF and near-infrared spectroscopy (NIRS) for measurement of cerebral oxy- and deoxy-hemoglobin concentrations, to monitor patients during head-of-bed lowering. METHODS: Ten brain-injured patients and ten control subjects were monitored continuously with DCS and NIRS while the head-of-bed was positioned first at 30° and then at 0°. Relative CBF (rCBF) and concurrent changes in oxy- (ΔHbO2), deoxy- (ΔHb), and total-hemoglobin concentrations (ΔTHC) from left/right frontal cortices were monitored for 5 min at each position. Patient and control response differences were assessed. RESULTS: rCBF, ΔHbO2, and ΔTHC responses to head lowering differed significantly between brain-injured patients and healthy controls (P < 0.02). For patients, rCBF changes were heterogeneous, with no net change observed in the group average (0.3 ± 28.2 %, P = 0.938). rCBF increased in controls (18.6 ± 9.4 %, P < 0.001). ΔHbO2, ΔHb, and ΔTHC increased with head lowering in both groups, but to a larger degree in brain-injured patients. rCBF correlated moderately with changes in cerebral perfusion pressure (R = 0.40, P < 0.001), but not intracranial pressure. CONCLUSION: DCS/NIRS detected differences in CBF and oxygenation responses of brain-injured patients versus controls during head-of-bed manipulation. This pilot study supports the feasibility of continuous bedside measurement of cerebrovascular hemodynamics with DCS/NIRS and provides the rationale for further investigation in larger cohorts.

Special Section Guest Editorial: Thirty Years of Functional Near-Infrared Spectroscopy.

Functional Near-Infrared Spectroscopy (fNIRS) is a non-invasive optical technique that measures cerebral hemodynamics across multiple regions of interest, and thereby characterises brain functional activation. Since its first description in 1993, fNIRS has undergone substantial developments in hardware, analysis techniques, and applications. Thirty years later, this technique is significantly enchancing our understanding in diverse areas of neuroscience research such as neurodevelopment, cognitive neuroscience, psychiatric disorders, neurodegenerative conditions, and brain injury management in intensive care settings. This special issue outlines the latest progress in instrumentation and analysis techniques and showcases some applications within the expanding field of fNIRS over the past decade.

Optimizing a two-layer method for hybrid diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy cerebral measurements in adults.

Significance: The sensitivity to extracerebral tissues is a well-known confounder of diffuse optics. Two-layer (2L) head models can separate cerebral signals from extracerebral artifacts, but they also carry the risk of crosstalk between fitting parameters. Aim: We aim to implement a constrained 2L head model for hybrid diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy (FD-DOS) data and to characterize errors in cerebral blood flow and tissue absorption with the proposed model. Approach: The algorithm uses the analytical solution of a 2L cylinder and an a priori extracerebral layer thickness to fit multidistance FD-DOS (0.8 to 4 cm) and DCS (0.8 and 2.5 cm) data, assuming homogeneous tissue reduced scattering. We characterized the algorithm's accuracy for simulated data with noise generated using a 2L slab and realistic adult head geometries and for in vitro phantom data. Results: Our algorithm recovered the cerebral flow index with 6.3 [2.8, 13.2]% and 34 [30, 42]% (median absolute percent error [interquartile range]) for slab and head geometries, respectively. Corresponding errors in the cerebral absorption coefficient were 5.0 [3.0, 7.9]% and 4.6 [2.4, 7.2]% for the slab and head geometries and 8 [5, 12]% for our phantom experiment. Our results were minimally sensitive to second-layer scattering changes and were robust to cross-talk between fitting parameters. Conclusions: In adults, the constrained 2L algorithm promises to improve FD-DOS/DCS accuracy compared with the conventional semi-infinite approach.

Revealing the spatiotemporal requirements for accurate subject identification with resting-state functional connectivity: a simultaneous fNIRS-fMRI study.

Significance: Brain fingerprinting refers to identifying participants based on their functional patterns. Despite its success with functional magnetic resonance imaging (fMRI), brain fingerprinting with functional near-infrared spectroscopy (fNIRS) still lacks adequate validation. Aim: We investigated how fNIRS-specific acquisition features (limited spatial information and nonneural contributions) influence resting-state functional connectivity (rsFC) patterns at the intra-subject level and, therefore, brain fingerprinting. Approach: We performed multiple simultaneous fNIRS and fMRI measurements in 29 healthy participants at rest. Data were preprocessed following the best practices, including the removal of motion artifacts and global physiology. The rsFC maps were extracted with the Pearson correlation coefficient. Brain fingerprinting was tested with pairwise metrics and a simple linear classifier. Results: Our results show that average classification accuracy with fNIRS ranges from 75% to 98%, depending on the number of runs and brain regions used for classification. Under the right conditions, brain fingerprinting with fNIRS is close to the 99.9% accuracy found with fMRI. Overall, the classification accuracy is more impacted by the number of runs and the spatial coverage than the choice of the classification algorithm. Conclusions: This work provides evidence that brain fingerprinting with fNIRS is robust and reliable for extracting unique individual features at the intra-subject level once relevant spatiotemporal constraints are correctly employed.

Can tactile reactivity in preterm born infants be explained by an immature cortical response to tactile stimulation in the first year? A pilot study.

This study aimed to compare preterm (PT) and full-term (FT) infants' adaptive behavior and functional cortical response to tactile stimulus, as measured by Test of Sensory Functions in Infants and functional Near-Infrared Spectroscopy (fNIRS). Outcome measures were taken at 6 (PT = 26/FT = 21 infants) and 12 months (PT = 15/FT = 14 infants). At 6 months, poorer tactile reactivity was observed in PT, but not confirmed at 12 months. At 6 months, cortical response to tactile stimulus was found in the primary sensorimotor cortex and differences between groups did not reach significance. At 12 months, cortical response was found in the primary sensorimotor cortex and premotor area and in the somatosensory associative area, with significant less frequent response in premotor area in PT. The findings reinforce fNIRS as a tool to complement the knowledge of tactile adaptive behaviors in PT in early life.

Quantification of the Tissue Oxygenation Delay Induced by Breath-Holding in Patients with Carotid Atherosclerosis.

Carotid artery stenosis (CAS) is a common vascular disease with long-term consequences for the brain. Although CAS is strongly associated with impaired cerebral hemodynamics and neurodegeneration, the mechanisms underlying hemodynamic impairment in the microvasculature remain unknown. In this work, we employed functional near-infrared spectroscopy (fNIRS) to introduce a methodological approach for quantifying the temporal delay of the evoked hemodynamic response. The method was validated during a vasodilatory task (breath-holding) in 50 CAS patients and 20 controls. Our results suggest that the hemodynamic response to breath-holding can be delayed by up to 6 s in the most severe patients, a significant increase from the median 4 s measured for the control group (p = 0.01). In addition, the fraction of brain regions that responded to the task decreased as the CAS severity increased, from a median of 90% in controls to 73% in the most severe CAS group (p = 0.04). The presence of collateral circulation increases the response to breath-holding and decreases the average time delays across the brain, although the number of communicating arteries alone cannot predict these fNIRS-based hemodynamic variables (p > 0.09). Overall, this work proposes a method to quantitatively assess impaired cerebral hemodynamics in CAS patients.

Differences in brain activity between fast and slow responses on psychomotor vigilance task: an fNIRS study.

Attention is a basic human function underlying every other cognitive process. It is demonstrated in the functional Magnetic Resonance Imaging literature that frontoparietal networks are involved with attentive performance while default mode networks are involved with inattentive performance. Yet, it is still not clear whether similar results would be found with functional Near-Infrared Spectroscopy. The goal of our study was to investigate differences in hemodynamic activity measured by functional Near-Infrared Spectroscopy between fast and slow responses on a simple sustained attention task both before and after stimulus onset. Thirty healthy adults took part in the study. Our results have shown differences between fast and slow responses only on channels over medial frontal cortex and inferior parietal cortex (p < 0,05). These differences were observed both before and after stimulus presentation. It is discussed that functional Near-Infrared Spectroscopy is a good tool to investigate the frontoparietal network and its relationship with performance in attention tasks; it could be used to further investigate other approaches on attention, such as the dual network model of cognitive control and brain states views based on complex systems analysis; and finally, it could be used to investigate attention in naturalistic settings.

Effects of Systemic Physiology on Mapping Resting-State Networks Using Functional Near-Infrared Spectroscopy.

Resting-state functional connectivity (rsFC) has gained popularity mainly due to its simplicity and potential for providing insights into various brain disorders. In this vein, functional near-infrared spectroscopy (fNIRS) is an attractive choice due to its portability, flexibility, and low cost, allowing for bedside imaging of brain function. While promising, fNIRS suffers from non-neural signal contaminations (i.e., systemic physiological noise), which can increase correlation across fNIRS channels, leading to spurious rsFC networks. In the present work, we hypothesized that additional measurements with short channels, heart rate, mean arterial pressure, and end-tidal CO2 could provide a better understanding of the effects of systemic physiology on fNIRS-based resting-state networks. To test our hypothesis, we acquired 12 min of resting-state data from 10 healthy participants. Unlike previous studies, we investigated the efficacy of different pre-processing approaches in extracting resting-state networks. Our results are in agreement with previous studies and reinforce the fact that systemic physiology can overestimate rsFC. We expanded on previous work by showing that removal of systemic physiology decreases intra- and inter-subject variability, increasing the ability to detect neural changes in rsFC across groups and over longitudinal studies. Our results show that by removing systemic physiology, fNIRS can reproduce resting-state networks often reported with functional magnetic resonance imaging (fMRI). Finally, the present work details the effects of systemic physiology and outlines how to remove (or at least ameliorate) their contributions to fNIRS signals acquired at rest.

Optical imaging and spectroscopy for the study of the human brain: status report.

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions.

Neurophotonic tools for microscopic measurements and manipulation: status report.

Neurophotonics was launched in 2014 coinciding with the launch of the BRAIN Initiative focused on development of technologies for advancement of neuroscience. For the last seven years, Neurophotonics' agenda has been well aligned with this focus on neurotechnologies featuring new optical methods and tools applicable to brain studies. While the BRAIN Initiative 2.0 is pivoting towards applications of these novel tools in the quest to understand the brain, this status report reviews an extensive and diverse toolkit of novel methods to explore brain function that have emerged from the BRAIN Initiative and related large-scale efforts for measurement and manipulation of brain structure and function. Here, we focus on neurophotonic tools mostly applicable to animal studies. A companion report, scheduled to appear later this year, will cover diffuse optical imaging methods applicable to noninvasive human studies. For each domain, we outline the current state-of-the-art of the respective technologies, identify the areas where innovation is needed, and provide an outlook for the future directions.

Upcoming Neurophotonics Status Report.

Forthcoming status report articles provide updates on microscopy and on diffuse optical imaging in neurophotonics.

Hearing brain evaluated using near-infrared spectroscopy in congenital toxoplasmosis.

Congenital toxoplasmosis (CT) is a known cause of hearing loss directly caused by Toxoplasma gondii. Hearing loss might result from sensory, neural, or sensorineural lesions. Early treated infants rarely develop hearing loss, but retinochoroidal lesions, intracranial calcifications and hydrocephalus are common. In this study, we aimed to evaluate the brain evoked hemodynamic responses of CT and healthy infants during four auditory stimuli: mother infant directed speech, researcher infant directed speech, mother reading and researcher recorded. Children underwent Transitionally Evoked Otoacoustic Emission Auditory Testing and Automated Brainstem Auditory Response tests with normal auditory results, but with a tendency for greater latencies in the CT group compared to the control group. We assessed brain hemodynamics with functional near-infrared spectroscopy (fNIRS) measurements from 61 infants, and we present fNIRS results as frequency maps of activation and deactivation for each stimulus. By evaluating infants in the three first months of life, we observed an individual heterogeneous brain activation pattern in response to all auditory stimuli for both groups. Each channel was activated or deactivated in less than 30% of children for all stimuli. There is a need of prospective studies to evaluate if the neurologic or auditory changes course with compromise of children outcomes.