Tiina Näsi

Spontaneous Hemodynamic Oscillations during Human Sleep and Sleep Stage Transitions Characterized with Near-Infrared Spectroscopy

Understanding the interaction between the nervous system and cerebral vasculature is fundamental to forming a complete picture of the neurophysiology of sleep and its role in maintaining physiological homeostasis. However, the intrinsic hemodynamics of slow-wave sleep (SWS) are still poorly known. We carried out 30 all-night sleep measurements with combined near-infrared spectroscopy (NIRS) and polysomnography to investigate spontaneous hemodynamic behavior in SWS compared to light (LS) and rapid-eye-movement sleep (REM). In particular, we concentrated on slow oscillations (3–150 mHz) in oxy- and deoxyhemoglobin concentrations, heart rate, arterial oxygen saturation, and the pulsation amplitude of the photoplethysmographic signal. We also analyzed the behavior of these variables during sleep stage transitions. The results indicate that slow spontaneous cortical and systemic hemodynamic activity is reduced in SWS compared to LS, REM, and wakefulness. This behavior may be explained by neuronal synchronization observed in electrophysiological studies of SWS and a reduction in autonomic nervous system activity. Also, sleep stage transitions are asymmetric, so that the SWS-to-LS and LS-to-REM transitions, which are associated with an increase in the complexity of cortical electrophysiological activity, are characterized by more dramatic hemodynamic changes than the opposite transitions. Thus, it appears that while the onset of SWS and termination of REM occur only as gradual processes over time, the termination of SWS and onset of REM may be triggered more abruptly by a particular physiological event or condition. The results suggest that scalp hemodynamic changes should be considered alongside cortical hemodynamic changes in NIRS sleep studies to assess the interaction between the autonomic and central nervous systems.

Magnetic-Stimulation-Related Physiological Artifacts in Hemodynamic Near-Infrared Spectroscopy Signals

Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be measured with near-infrared spectroscopy (NIRS). This study demonstrates that cerebral neuronal activity is not their sole contributor. We compared bilateral NIRS responses following brain stimulation to those from the shoulders evoked by shoulder stimulation and contrasted them with changes in circulatory parameters. The left primary motor cortex of ten subjects was stimulated with 8-s repetitive TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor threshold. Hemoglobin concentration changes were measured with NIRS on the stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude and heart rate were recorded as well. The left shoulder of ten other subjects was stimulated with the same protocol while the hemoglobin concentration changes in both shoulders were measured. In addition to PPG amplitude and heart rate, the pulse transit time was recorded. The brain stimulation reduced the total hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres. The shoulder stimulation reduced HbT on the stimulated shoulder but increased it contralaterally. The waveforms of the HbT responses on the stimulated hemisphere and shoulder correlated strongly with each other (r = 0.65–0.87). All circulatory parameters were also affected. The results suggest that the TMS-evoked NIRS signal includes components that do not result directly from cerebral neuronal activity. These components arise from local effects of TMS on the vasculature. Also global circulatory effects due to arousal may affect the responses. Thus, studies involving TMS-evoked NIRS responses should be carefully controlled for physiological artifacts and effective artifact removal methods are needed to draw inferences about TMS-evoked brain activity.

Cyclic alternating pattern is associated with cerebral hemodynamic variation: A near-infrared spectroscopy study of sleep in healthy humans

The cyclic alternating pattern (CAP), that is, cyclic variation of brain activity within non-REM sleep stages, is related to sleep instability and preservation, as well as consolidation of learning. Unlike the well-known electrical activity of CAP, its cerebral hemodynamic counterpart has not been assessed in healthy subjects so far. We recorded scalp and cortical hemodynamics with near-infrared spectroscopy on the forehead and systemic hemodynamics (heart rate and amplitude of the photoplethysmograph) with a finger pulse oximeter during 23 nights in 11 subjects. Electrical CAP activity was recorded with a polysomnogram. CAP was related to changes in scalp, cortical, and systemic hemodynamic signals that resembled the ones seen in arousal. Due to their repetitive nature, CAP sequences manifested as low- and very-low-frequency oscillations in the hemodynamic signals. The subtype A3+B showed the strongest hemodynamic changes. A transient hypoxia occurred during CAP cycles, suggesting that an increased CAP rate, especially with the subtype A3+B, which may result from diseases or fragmented sleep, might have an adverse effect on the cerebral vasculature.

Effect of task-related extracerebral circulation on diffuse optical tomography: experimental data and simulations on the forehead

The effect of task-related extracerebral circulatory changes on diffuse optical tomography (DOT) of brain activation was evaluated using experimental data from 14 healthy human subjects and computer simulations. Total hemoglobin responses to weekday-recitation, verbal-fluency, and hand-motor tasks were measured with a high-density optode grid placed on the forehead. The tasks caused varying levels of mental and physical stress, eliciting extracerebral circulatory changes that the reconstruction algorithm was unable to fully distinguish from cerebral hemodynamic changes, resulting in artifacts in the brain activation images. Crosstalk between intra- and extracranial layers was confirmed by the simulations. The extracerebral effects were attenuated by superficial signal regression and depended to some extent on the heart rate, thus allowing identification of hemodynamic changes related to brain activation during the verbal-fluency task. During the hand-motor task, the extracerebral component was stronger, making the separation less clear. DOT provides a tool for distinguishing extracerebral components from signals of cerebral origin. Especially in the case of strong task-related extracerebral circulatory changes, however, sophisticated reconstruction methods are needed to eliminate crosstalk artifacts.

Slow spontaneous hemodynamic oscillations during sleep measured with near-infrared spectroscopy

Spontaneous cerebral hemodynamic oscillations below 100 mHz reflect the level of cerebral activity, modulate hemodynamic responses to tasks and stimuli, and may aid in detecting various pathologies of the brain. Near-infrared spectroscopy (NIRS) is ideally suited for both measuring spontaneous hemodynamic oscillations and monitoring sleep, but little research has been performed to combine these two applications. We analyzed 30 all-night NIRS–electroencephalography (EEG) sleep recordings to investigate spontaneous hemodynamic activity relative to sleep stages determined by polysomnography.Signal power of hemodynamic oscillations in the low-frequency (LF, 40–150 mHz) and very-low-frequency (VLF, 3–40 mHz) bands decreased in slow-wave sleep (SWS) compared to light sleep (LS) and rapid-eye-movement (REM) sleep. No statistically significant (p < 0.05) differences in oscillation power between LS and REM were observed. However, the period of VLF oscillations around 8 mHz increased in REM sleep in line with earlier studies with other modalities. These results increase our knowledge of the physiology of sleep, complement EEG data, and demonstrate the applicability of NIRS to studying spontaneous hemodynamic fluctuations during sleep.

Characterizing Cerebral and Extracerebral Components in TMS-Evoked Near-Infrared Spectroscopy Signals

Near-infrared spectroscopy (NIRS) can be used to study changes in blood volume and oxygenation level due to transcranial magnetic stimulation (TMS). In previous studies, no attention has been paid to the fact that TMS also activates superficial tissue, which may confound the analysis of the NIRS signal originating from the brain. In addition, stimulation-related changes in, e.g., blood pressure and heart rate may induce global interference in the NIRS signal. We delivered TMS trains to the left primary motor cortex of healthy subjects and recorded NIRS from both ipsi- and contralateral hemispheres. In addition, the shoulder of one subject was stimulated and NIRS was recorded simultaneously above the stimulation site. Extracerebral contribution was estimated from the shoulder stimulation data, using principal component analysis (PCA) and from NIRS data corresponding to short source–detector (SD) distances (multidistance method). Motor cortex stimulation resulted in pronounced reductions in the concentration of oxygenated hemoglobin (HbO2) on the contralateral (non-stimulated) hemisphere. On the ipsilateral (stimulated) hemisphere, a less pronounced decrease of HbO2 was observed. Also the shoulder stimulation resulted in reduction of HbO2. Applying PCA resulted in smaller HbO2 reductions on the contralateral hemisphere and increased signal-to-noise ratio on both hemispheres. The multidistance method also resulted in smaller HbO2 reductions on the contralateral hemisphere. The present results suggest that some reductions of HbO2 may be due to extracerebral effects. These effects have to be taken into account when analyzing and interpreting TMS-evoked NIRS signals.

Method for assessing the contribution of systemic circulation in near-infrared spectroscopy signals

Near-infrared spectroscopy (NIRS) and diffuse optical tomography (DOT) detect changes in brain blood volume and oxygenation by measuring light that has passed through the head, including the scalp and the skull. Extracerebral and systemic circulation interfere with optical measurements of cerebral hemodynamics, especially when measuring brain responses to stimuli or tasks that evoke strong systemic circulatory changes. We studied the effect of changes in systemic circulation on NIRS responses and DOT reconstructions in thirteen subjects during a hand motor task that increased the heart rate. Both the NIRS responses and the DOT reconstructions depended on the change in the heart rate. The NIRS response amplitudes during epochs with a large change in heart rate (24.8±0.8 bpm; highest third) were significantly larger (p < 0.05) than during epochs with a smaller change in heart rate (5.8±0.5 bpm; lowest third). Accordingly, we propose that comparing epochs associated with large and small changes in heart rate serves as a method for estimating whether NIRS signals are affected by the systemic circulation, given that there is variability in the systemic circulation between epochs.

Coherences of Slow Oscillations in Near-Infrared Spectroscopy Signals and Other Cardiovascular Parameters

Cardiovascular signals were recorded from head and arm using two near-infrared spectroscopy instruments, an intra-arterial and an intravenous blood pressure monitor, and an electrocardiograph. Slow spontaneous oscillations were investigated and coherences between signals were estimated.