Metabolic cues impact non-oscillatory intergeniculate leaflet and ventral lateral geniculate nucleus: standard versus high-fat diet comparative study.

The intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/VLG) are subcortical structures involved in entrainment of the brain's circadian system to photic and non-photic (e.g. metabolic and arousal) cues. Both receive information about environmental light from photoreceptors, exhibit infra-slow oscillations (ISO) in vivo, and connect to the master circadian clock. Although current evidence demonstrates that the IGL/VLG communicate metabolic information and are crucial for entrainment of circadian rhythms to time-restricted feeding, their sensitivity to food intake-related peptides has not been investigated yet. We examined the effect of metabolically relevant peptides on the spontaneous activity of IGL/VLG neurons. Using ex vivo and in vivo electrophysiological recordings as well as in situ hybridisation, we tested potential sensitivity of the IGL/VLG to anorexigenic and orexigenic peptides, such as cholecystokinin, glucagon-like peptide 1, oxyntomodulin, peptide YY, orexin A and ghrelin. We explored neuronal responses to these drugs during day and night, and in standard vs. high-fat diet conditions. We found that IGL/VLG neurons responded to all the substances tested, except peptide YY. Moreover, more neurons responded to anorexigenic drugs at night, while a high-fat diet affected the IGL/VLG sensitivity to orexigenic peptides. Interestingly, ISO neurons responded to light and orexin A, but did not respond to the other food intake-related peptides. In contrast, non-ISO cells were activated by metabolic peptides, with only some being responsive to light. Our results show for the first time that peptides involved in the body's energy homeostasis stimulate the thalamus and suggest functional separation of the IGL/VLG cells. KEY POINTS: The intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/VLG) of the rodent thalamus process various signals and participate in circadian entrainment. In both structures, cells exhibiting infra-slow oscillatory activity as well as non-rhythmically firing neurons being observed. Here, we reveal that only one of these two groups of cells responds to anorexigenic (cholecystokinin, glucagon-like peptide 1 and oxyntomodulin) and orexigenic (ghrelin and orexin A) peptides. Neuronal responses vary depending on the time of day (day vs. night) and on the diet (standard vs. high-fat diet). Additionally, we visualised receptors to the tested peptides in the IGL/VLG using in situ hybridisation. Our results suggest that two electrophysiologically different subpopulations of IGL/VLG neurons are involved in two separate functions: one related to the body's energy homeostasis and one associated with the subcortical visual system.

Brain Activity Fluctuations Propagate as Waves Traversing the Cortical Hierarchy.

The brain exhibits highly organized patterns of spontaneous activity as measured by resting-state functional magnetic resonance imaging (fMRI) fluctuations that are being widely used to assess the brain's functional connectivity. Some evidence suggests that spatiotemporally coherent waves are a core feature of spontaneous activity that shapes functional connectivity, although this has been difficult to establish using fMRI given the temporal constraints of the hemodynamic signal. Here, we investigated the structure of spontaneous waves in human fMRI and monkey electrocorticography. In both species, we found clear, repeatable, and directionally constrained activity waves coursed along a spatial axis approximately representing cortical hierarchical organization. These cortical propagations were closely associated with activity changes in distinct subcortical structures, particularly those related to arousal regulation, and modulated across different states of vigilance. The findings demonstrate a neural origin of spatiotemporal fMRI wave propagation at rest and link it to the principal gradient of resting-state fMRI connectivity.

Exploring alterations in sensory pathways in migraine.

BACKGROUND: Migraine is a neurological disorder characterized by intense, debilitating headaches, often coupled with nausea, vomiting and sensitivity to light and sound. Whilst changes in sensory processes during a migraine attack have been well-described, there is growing evidence that even between migraine attacks, sensory abilities are disrupted in migraine. Brain imaging studies have investigated altered coupling between areas of the descending pain modulatory pathway but coupling between somatosensory processing regions between migraine attacks has not been properly studied. The aim of this study was to determine if ongoing functional connectivity between visual, auditory, olfactory, gustatory and somatosensory cortices are altered during the interictal phase of migraine. METHODS: To explore the neural mechanisms underpinning interictal changes in sensory processing, we used functional magnetic resonance imaging to compare resting brain activity patterns and connectivity in migraineurs between migraine attacks (n = 32) and in healthy controls (n = 71). Significant differences between groups were determined using two-sample random effects procedures (p < 0.05, corrected for multiple comparisons, minimum cluster size 10 contiguous voxels, age and gender included as nuisance variables). RESULTS: In the migraine group, increases in infra-slow oscillatory activity were detected in the right primary visual cortex (V1), secondary visual cortex (V2) and third visual complex (V3), and left V3. In addition, resting connectivity analysis revealed that migraineurs displayed significantly enhanced connectivity between V1 and V2 with other sensory cortices including the auditory, gustatory, motor and somatosensory cortices. CONCLUSIONS: These data provide evidence for a dysfunctional sensory network in pain-free migraine patients which may be underlying altered sensory processing between migraine attacks.

Infra-slow modulation of fast beta/gamma oscillations in the mouse visual system.

KEY POINTS: Neurophysiological activity in the subcortical visual system fluctuates in both infra-slow and fast oscillatory ranges, but the level of co-occurrence and potential functional interaction of these rhythms is unknown. Analysing dark-adapted spontaneous activity in the mouse subcortical visual system, we find that these two types of oscillation interact uniquely through a population of neurons expressing both rhythms. Genetic ablation of rod/cone signalling potentiates infra-slow and abolishes fast beta/gamma oscillations while genetic ablation of melanopsin substantially diminishes the interaction between these two rhythms. Our results indicate that in an intact visual system the phase of infra-slow modulates fast beta/gamma oscillations. Thus one possible impact of infra-slow oscillations in vision is to guide visual processing by interacting with fast narrowband oscillations. ABSTRACT: Infra-slow (<0.02 Hz) and fast beta/gamma (20-100 Hz) oscillations in neurophysiological activity have been widely found in the subcortical visual system. While it is well established that fast beta/gamma oscillations are involved in visual processing, the role (if any) of infra-slow oscillations is currently unknown. One possibility is that infra-slow oscillations exert influence by modulating the amplitude of fast oscillations, yet the extent to which these different oscillations arise independently and interact remains unknown. We addressed these questions by recording in vivo spontaneous activity from the subcortical visual system of visually intact mice, and animals whose retinal network was disrupted by advanced rod/cone degeneration (rd/rd cl) or melanopsin loss (Opn4-/- ). We found many neurons expressing only one type of oscillation, and indeed fast oscillations were absent in rd/rd cl. Conversely, neurons co-expressing the two oscillations were also common, and were encountered more often than expected by chance in visually intact but not Opn4-/- mice. Finally, where they co-occurred we found that beta/gamma amplitude was modulated by the infra-slow rhythm. Our data thus reveal that: (1) infra-slow and beta-gamma oscillations are separable phenomena; and (2) that they actively co-occur in a subset of neurones in which the phase of infra-slow oscillations defines beta-gamma oscillations amplitude. These findings suggest that infra-slow oscillations could influence vision by modulating beta-gamma oscillations, and raise the possibility that disruptions in these oscillatory behaviours contribute to vision dysfunction in retinal dystrophy.

Organization of Propagated Intrinsic Brain Activity in Individual Humans.

Spontaneous infra-slow (<0.1 Hz) fluctuations in functional magnetic resonance imaging (fMRI) signals are temporally correlated within large-scale functional brain networks, motivating their use for mapping systems-level brain organization. However, recent electrophysiological and hemodynamic evidence suggest state-dependent propagation of infra-slow fluctuations, implying a functional role for ongoing infra-slow activity. Crucially, the study of infra-slow temporal lag structure has thus far been limited to large groups, as analyzing propagation delays requires extensive data averaging to overcome sampling variability. Here, we use resting-state fMRI data from 11 extensively-sampled individuals to characterize lag structure at the individual level. In addition to stable individual-specific features, we find spatiotemporal topographies in each subject similar to the group average. Notably, we find a set of early regions that are common to all individuals, are preferentially positioned proximal to multiple functional networks, and overlap with brain regions known to respond to diverse behavioral tasks-altogether consistent with a hypothesized ability to broadly influence cortical excitability. Our findings suggest that, like correlation structure, temporal lag structure is a fundamental organizational property of resting-state infra-slow activity.

Electrically coupled inhibitory interneurons constrain long-range connectivity of cortical networks.

Spontaneous infra-slow brain activity (ISA) exhibits a high degree of temporal synchrony, or correlation, between distant brain regions. The spatial organization of ISA synchrony is not explained by anatomical connections alone, suggesting that active neural processes coordinate spontaneous activity. Inhibitory interneurons (IINs) form electrically coupled connections via the gap junction protein connexin 36 (Cx36) and networks of interconnected IINs are known to influence neural synchrony over short distances. However, the role of electrically coupled IIN networks in regulating spontaneous correlation over the entire brain is unknown. In this study, we performed OIS imaging on Cx36-/- mice to examine the role of this gap junction in ISA correlation across the entire cortex. We show that Cx36 deletion increased long-distance intra-hemispheric anti-correlation and inter-hemispheric correlation in spontaneous ISA. This suggests that electrically coupled IIN networks modulate ISA synchrony over long cortical distances.

Altered resting activity patterns and connectivity in individuals with complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder that typically occurs in the limbs, usually the upper limb. CRPS usually develops from a peripheral event but its maintenance relies on changes within the central nervous system. While functional abnormalities in the thalamus and primary somatosensory cortex (S1) of the brain are some of the most consistently reported brain findings in CRPS, the mechanisms are yet to be explored in full, not least of all how these two regions interact and how they might relate to clinical deficits, such as the commonly reported poor tactile acuity in this condition. This study recruited 15 upper-limb CRPS subjects and 30 healthy controls and used functional magnetic resonance imaging (fMRI) to investigate infra-slow oscillations (ISOs) in critical pain regions of the brain in CRPS. As hypothesised, we found CRPS was associated with increases in resting signal intensity ISOs (0.03-0.06 Hz) in the thalamus contralateral to the painful limb in CRPS subjects. Interestingly, there was no such difference between groups in S1, however CRPS subjects displayed stronger thalamo-S1 functional connectivity than controls, and this was related to pain. As predicted, CRPS subjects displayed poor tactile acuity on the painful limb which, interestingly, was also related to thalamo-S1 functional connectivity strength. Our findings provide novel evidence of altered patterns of resting activity and connectivity in CRPS which may underlie altered thalamocortical loop dynamics and the constant perception of pain.

Dynamics of sleep oscillations is coupled to brain temperature on multiple scales.

KEY POINTS: Sleep spindle frequency positively, duration negatively correlates with brain temperature. Local heating of the thalamus produces similar effects in the heated area. Thalamic network model corroborates temperature dependence of sleep spindle frequency. Brain temperature shows spontaneous microfluctuations during both anesthesia and natural sleep. Larger fluctuations are associated with epochs of REM sleep. Smaller fluctuations correspond to the alteration of spindling and delta epochs of infra-slow oscillation. ABSTRACT: Every form of neural activity depends on temperature, yet its relationship to brain rhythms is poorly understood. In this work we examined how sleep spindles are influenced by changing brain temperatures and how brain temperature is influenced by sleep oscillations. We employed a novel thermoelectrode designed for measuring temperature while recording neural activity. We found that spindle frequency is positively correlated and duration negatively correlated with brain temperature. Local heating of the thalamus replicated the temperature dependence of spindle parameters in the heated area only, suggesting biophysical rather than global modulatory mechanisms, a finding also supported by a thalamic network model. Finally, we show that switches between oscillatory states also influence brain temperature on a shorter and smaller scale. Epochs of paradoxical sleep as well as the infra-slow oscillation were associated with brain temperature fluctuations below 0.2°C. Our results highlight that brain temperature is massively intertwined with sleep oscillations on various time scales.

Synchronous Infra-Slow Bursting in the Mouse Accessory Olfactory Bulb Emerge from Interplay between Intrinsic Neuronal Dynamics and Network Connectivity.

Rhythmic neuronal activity of multiple frequency bands has been described in many brain areas and attributed to numerous brain functions. Among these, little is known about the mechanism and role of infra-slow oscillations, which have been demonstrated recently in the mouse accessory olfactory bulb (AOB). Along with prolonged responses to stimuli and distinct network connectivity, they inexplicably affect the AOB processing of social relevant stimuli. Here, we show that assemblies of AOB mitral cells are synchronized by lateral interactions through chemical and electrical synapses. Using a network model, we demonstrate that the synchronous oscillations in these assemblies emerge from interplay between intrinsic membrane properties and network connectivity. As a consequence, the AOB network topology, in which each mitral cell receives input from multiple glomeruli, enables integration of chemosensory stimuli over extended time scales by interglomerular synchrony of infra-slow bursting. These results provide a possible functional significance for the distinct AOB physiology and topology. Beyond the AOB, this study presents a general model for synchronous infra-slow bursting in neuronal networks.SIGNIFICANCE STATEMENT Infra-slow rhythmic neuronal activity with a very long (>10 s) duration has been described in many brain areas, but little is known about the role of this activity and the mechanisms that produce it. Here, we combine experimental and computational methods to show that synchronous infra-slow bursting activity in mitral cells of the mouse accessory olfactory bulb (AOB) emerges from interplay between intracellular dynamics and network connectivity. In this novel mechanism, slow intracellular Na+ dynamics endow AOB mitral cells with a weak tendency to burst, which is further enhanced and stabilized by chemical and electrical synapses between them. Combined with the unique topology of the AOB network, infra-slow bursting enables integration and binding of multiple chemosensory stimuli over a prolonged time scale.

Gamma and infra-slow oscillations shape neuronal firing in the rat subcortical visual system.

KEY POINTS: Neuronal oscillations observed in sensory systems are physiological carriers of information about stimulus features. Rhythm in the infra-slow range, originating from the retina, was previously found in the firing of subcortical visual system nuclei involved in both image and non-image forming functions. The present study shows that the firing of neurons in the lateral geniculate nucleus is also governed by gamma oscillation (∼35 Hz) time-locked to high phase of infra-slow rhythm that codes the intensity of transient light stimulation. We show that both physiological rhythms are synchronized within and between ipsilateral nuclei of the subcortical visual system and are dependent on retinal activity. The present study shows that neurophysiological oscillations characterized by various frequencies not only coexist in the subcortical visual system, but also are subjected to complex interference and synchronization processes. ABSTRACT: The physiological function of rhythmic firing in the neuronal networks of sensory systems has been linked with information coding. Also, neuronal oscillations in different frequency bands often change as a signature of brain state or sensory processing. Infra-slow oscillation (ISO) in the neuronal firing dependent on the retinal network has been described previously in the structures of the subcortical visual system. In the present study, we show for the first time that firing of ISO neurons in the lateral geniculate nucleus is also characterized by a harmonic discharge pattern (i.e. action potentials are separated by the intervals governed by fundamental frequency in the gamma range: ∼35 Hz). A similar phenomenon was recently described in the suprachiasmatic nuclei of the hypothalamus: the master biological clock. We found that both gamma and ISO rhythms were synchronized within and between ipsilateral nuclei of the subcortical visual system and were dependent on the retinal activity of the contralateral eye. These oscillatory patterns were differentially influenced by transient and prolonged light stimulation with respect to both frequency change direction and sustainability. The results of the present study show that the firing pattern of neurons in the subcortical visual system is shaped by oscillations from infra-slow and gamma frequency bands that are plausibly generated by the retinal network. Additionally, the results demonstrate that both rhythms are not a distinctive feature of image or non-image forming visual systems but, instead, they comprise two channels carrying distinctive properties of photic information.

Deep in the brain: Changes in subcortical function immediately preceding a migraine attack.

The neural mechanism responsible for migraine remains unclear. While the role of an external trigger in migraine initiation remains vigorously debated, it is generally assumed that migraineurs display altered brain function between attacks. This idea stems from relatively few brain imaging studies with even fewer studies exploring changes in the 24 h period immediately prior to a migraine attack. Using functional magnetic resonance imaging, we measured infra-slow oscillatory activity, regional homogeneity, and connectivity strengths of resting activity in migraineurs directly before (n = 8), after (n = 11), and between migraine attacks (n = 26) and in healthy control subjects (n = 78). Comparisons between controls and each migraine group and between migraine groups were made for each of these measures. Directly prior to a migraine, increased infra-slow oscillatory activity occurred in brainstem and hypothalamic regions that also display altered activity during a migraine itself, that is, the spinal trigeminal nucleus, dorsal pons, and hypothalamus. Furthermore, these midbrain and hypothalamic sites displayed increased connectivity strengths and regional homogeneity directly prior to a migraine. Remarkably, these resting oscillatory and connectivity changes did not occur directly after or between migraine attacks and were significantly different to control subjects. These data provide evidence of altered brainstem and hypothalamic function in the period immediately before a migraine and raise the prospect that such changes contribute to the expression of a migraine attack.

Fluctuations of the EEG-fMRI correlation reflect intrinsic strength of functional connectivity in default mode network.

Both functional magnetic resonance imaging (fMRI) and electrophysiological recordings have revealed that resting-state functional connectivity is temporally variable in human brain. Combined full-band electroencephalography-fMRI (fbEEG-fMRI) studies have shown that infraslow (<.1 Hz) fluctuations in EEG scalp potential are correlated with the blood-oxygen-level-dependent (BOLD) fMRI signals and that also this correlation appears variable over time. Here, we used simultaneous fbEEG-fMRI to test the hypothesis that correlation dynamics between BOLD and fbEEG signals could be explained by fluctuations in the activation properties of resting-state networks (RSNs) such as the extent or strength of their activation. We used ultrafast magnetic resonance encephalography (MREG) fMRI to enable temporally accurate and statistically robust short-time-window comparisons of infra-slow fbEEG and BOLD signals. We found that the temporal fluctuations in the fbEEG-BOLD correlation were dependent on RSN connectivity strength, but not on the mean signal level or magnitude of RSN activation or motion during scanning. Moreover, the EEG-fMRI correlations were strongest when the intrinsic RSN connectivity was strong and close to the pial surface. Conversely, weak fbEEG-BOLD correlations were attributable to periods of less coherent or spatially more scattered intrinsic RSN connectivity, or RSN activation in deeper cerebral structures. The results thus show that the on-average low correlations between infra-slow EEG and BOLD signals are, in fact, governed by the momentary coherence and depth of the underlying RSN activation, and may reach systematically high values with appropriate source activities. These findings further consolidate the notion of slow scalp potentials being directly coupled to hemodynamic fluctuations.

Chronic Neuropathic Pain: It's about the Rhythm.

The neural mechanisms underlying the development and maintenance of chronic neuropathic pain remain unclear. Evidence from human investigations suggests that neuropathic pain is associated with altered thalamic burst firing and thalamocortical dysrhythmia. Additionally, experimental animal investigations show that neuropathic pain is associated with altered infra-slow (<0.1 Hz) frequency oscillations within the dorsal horn and somatosensory thalamus. The aim of this investigation was to determine whether, in humans, neuropathic pain was also associated with altered infra-slow oscillations within the ascending "pain" pathway. Using resting-state functional magnetic resonance imaging, we found that individuals with orofacial neuropathic pain have increased infra-slow oscillatory activity throughout the ascending pain pathway, including within the spinal trigeminal nucleus, somatosensory thalamus, thalamic reticular nucleus, and primary somatosensory cortex. Furthermore, these infra-slow oscillations were temporally coupled across these multiple sites and occurred at frequencies similar to calcium waves in activated astrocytes. The region encompassing the spinal trigeminal nucleus also displayed increased regional homogeneity, consistent with a local spread of neural activity by astrocyte activation. In contrast, no increase in oscillatory behavior within the ascending pain pathway occurred during acute noxious stimuli in healthy individuals. These data reveal increased oscillatory activity within the ascending pain pathway that likely underpins increased thalamocortical oscillatory activity, a self-sustaining thalamocortical dysrhythmia, and the constant perception of pain. Significance statement: Chronic neuropathic pain is associated with altered thalamic firing and thalamocortical dysrhythmia. The mechanisms responsible for these changes remain unknown. In this study, we report in individuals with neuropathic pain increased oscillatory neural activity within the ascending pain pathway with evidence that these changes result from altered neural-astrocyte coupling. We propose a series of neural and glial events after nerve injury that result in the generation of altered thalamocortical activity and a persistent neuropathic pain state. Defining the underlying mechanisms responsible for neuropathic pain is critical if we are to develop more effective treatment regimens.

Infra-slow EEG fluctuations are correlated with resting-state network dynamics in fMRI.

Ongoing neuronal activity in the CNS waxes and wanes continuously across widespread spatial and temporal scales. In the human brain, these spontaneous fluctuations are salient in blood oxygenation level-dependent (BOLD) signals and correlated within specific brain systems or "intrinsic-connectivity networks." In electrophysiological recordings, both the amplitude dynamics of fast (1-100 Hz) oscillations and the scalp potentials per se exhibit fluctuations in the same infra-slow (0.01-0.1 Hz) frequency range where the BOLD fluctuations are conspicuous. While several lines of evidence show that the BOLD fluctuations are correlated with fast-amplitude dynamics, it has remained unclear whether the infra-slow scalp potential fluctuations in full-band electroencephalography (fbEEG) are related to the resting-state BOLD signals. We used concurrent fbEEG and functional magnetic resonance imaging (fMRI) recordings to address the relationship of infra-slow fluctuations (ISFs) in scalp potentials and BOLD signals. We show here that independent components of fbEEG recordings are selectively correlated with subsets of cortical BOLD signals in specific task-positive and task-negative, fMRI-defined resting-state networks. This brain system-specific association indicates that infra-slow scalp potentials are directly associated with the endogenous fluctuations in neuronal activity levels. fbEEG thus yields a noninvasive, high-temporal resolution window into the dynamics of intrinsic connectivity networks. These results support the view that the slow potentials reflect changes in cortical excitability and shed light on neuronal substrates underlying both electrophysiological and behavioral ISFs.

Meditation-type specific reduction in infra-slow activity of electroencephalogram.

Purpose: Meditation is renowned for its positive effects on cognitive abilities and stress reduction. It has been reported that the amplitude of electroencephalographic (EEG) infra-slow activity (ISA, < 0.1 Hz) is reduced as the stress level decreases. Consequently, we aimed to determine if EEG ISA amplitude decreases as a result of meditation practice across various traditions. Methods: To this end, we analyzed an open dataset comprising EEG data acquired during meditation sessions from experienced practitioners in the Vipassana tradition-which integrates elements of focused attention and open monitoring, akin to mindfulness meditation-and in the Himalayan Yoga and Isha Shoonya traditions, which emphasize focused attention and open monitoring, respectively. Results: A general trend was observed where EEG ISA amplitude tended to decrease in experienced meditators from these traditions compared to novices, particularly significant in the 0.03-0.08 Hz band for Vipassana meditators. Therefore, our analysis focused on this ISA frequency band. Specifically, a notable decrease in EEG ISA amplitude was observed in Vipassana meditators, predominantly in the left-frontal region. This reduction in EEG ISA amplitude was also accompanied by a decrease in phase-amplitude coupling (PAC) between the ISA phase and alpha band (8-12 Hz) amplitude, which implied decreased neural excitability fluctuations. Conclusion: Our findings suggest that not only does EEG ISA amplitude decrease in experienced meditators from traditions that incorporate both focused attention and open monitoring, but this decrease may also signify a diminished influence of neural excitability fluctuations attributed to ISA.

Directed physiological networks in the human prefrontal cortex at rest and post transcranial photobiomodulation.

Cerebral infra-slow oscillation (ISO) is a source of vasomotion in endogenic (E; 0.005-0.02 Hz), neurogenic (N; 0.02-0.04 Hz), and myogenic (M; 0.04-0.2 Hz) frequency bands. In this study, we quantified changes in prefrontal concentrations of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome c oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics, and electroencephalogram (EEG) powers as electrophysiological activity, using concurrent measurements of 2-channel broadband near-infrared spectroscopy and EEG on the forehead of 22 healthy participants at rest. After preprocessing, the multi-modality signals were analyzed using generalized partial directed coherence to construct unilateral neurophysiological networks among the three neurophysiological metrics (with simplified symbols of HbO, CCO, and EEG) in each E/N/M frequency band. The links in these networks represent neurovascular, neurometabolic, and metabolicvascular coupling (NVC, NMC, and MVC). The results illustrate that the demand for oxygen by neuronal activity and metabolism (EEG and CCO) drives the hemodynamic supply (HbO) in all E/N/M bands in the resting prefrontal cortex. Furthermore, to investigate the effect of transcranial photobiomodulation (tPBM), we performed a sham-controlled study by delivering an 800-nm laser beam to the left and right prefrontal cortex of the same participants. After performing the same data processing and statistical analysis, we obtained novel and important findings: tPBM delivered on either side of the prefrontal cortex triggered the alteration or reversal of directed network couplings among the three neurophysiological entities (i.e., HbO, CCO, and EEG frequency-specific powers) in the physiological network in the E and N bands, demonstrating that during the post-tPBM period, both metabolism and hemodynamic supply drive electrophysiological activity in directed network coupling of the prefrontal cortex (PFC). Overall, this study revealed that tPBM facilitates significant modulation of the directionality of neurophysiological networks in electrophysiological, metabolic, and hemodynamic activities.

Association of brain-autonomic activities and task accuracy under cognitive load: a pilot study using electroencephalogram, autonomic activity measurements, and arousal level estimated by machine learning.

The total amount of mental activity applied to working memory at a given point in time is called cognitive load, which is an important factor in various activities in daily life. We have proposed new feature quantities that reflect the time-series changes in the power of typical frequency bands in electroencephalogram (EEG) for use in examining the relationship between brain activity and behavior under cognitive load. We also measured heart rate variability (HRV) and spontaneous skin conductance responses (SCR) to examine functional associations among brain activity, autonomic activity, and behavior under cognitive load. Additionally, we applied our machine learning model previously developed using EEG to the estimation of arousal level to interpret the brain-autonomic-behavior functional association under cognitive load. Experimental data from 12 healthy undergraduate students showed that participants with higher levels of infra-slow fluctuations of alpha power have more cognitive resources and thus can process information under cognitive load more efficiently. In addition, HRV reflecting parasympathetic activity correlated with task accuracy. The arousal level estimated using our machine learning model showed its robust relationship with EEG. Despite the limitation of the sample size, the results of this pilot study suggest that the information processing efficiency of the brain under cognitive load is reflected by time-series fluctuations in EEG, which are associated with an individual's task performance. These findings can contribute to the evaluation of the internal state of humans associated with cognitive load and the prediction of human behaviors in various situations under cognitive load.

Directed physiological networks in the human prefrontal cortex at rest and post transcranial photobiomodulation.

Cerebral infra-slow oscillation (ISO) is a source of vasomotion in endogenic (E; 0.005-0.02 Hz), neurogenic (N; 0.02-0.04 Hz), and myogenic (M; 0.04-0.2 Hz) frequency bands. In this study, we quantified changes in prefrontal concentrations of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome c oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics, and electroencephalogram (EEG) powers as electrophysiological activity, using concurrent measurements of 2-channel broadband near-infrared spectroscopy and EEG on the forehead of 22 healthy participants at rest. After preprocessing, the multi-modality signals were analyzed using generalized partial directed coherence to construct unilateral neurophysiological networks among the three neurophysiological metrics (with simplified symbols of HbO, CCO, and EEG) in each E/N/M frequency band. The links in these networks represent neurovascular, neurometabolic, and metabolicvascular coupling (NVC, NMC, and MVC). The results illustrate that the demand for oxygen by neuronal activity and metabolism (EEG and CCO) drives the hemodynamic supply (HbO) in all E/N/M bands in the resting prefrontal cortex. Furthermore, to investigate the effect of transcranial photobiomodulation (tPBM), we performed a sham-controlled study by delivering an 800-nm laser beam to the left and right prefrontal cortex of the same participants. After performing the same data processing and statistical analysis, we obtained novel and important findings: tPBM delivered on either side of the prefrontal cortex triggered the alteration or reversal of directed network couplings among the three neurophysiological entities (i.e., HbO, CCO, and EEG frequency-specific powers) in the physiological network in the E and N bands, demonstrating that during the post-tPBM period, both metabolism and hemodynamic supply drive electrophysiological activity in directed network coupling of the PFC. Overall, this study revealed that tPBM facilitates significant modulation of the directionality of neurophysiological networks in electrophysiological, metabolic, and hemodynamic activities.

Recording electrical activity from the brain of behaving octopus.

Octopuses, which are among the most intelligent invertebrates,1,2,3,4 have no skeleton and eight flexible arms whose sensory and motor activities are at once autonomous and coordinated by a complex central nervous system.5,6,7,8 The octopus brain contains a very large number of neurons, organized into numerous distinct lobes, the functions of which have been proposed based largely on the results of lesioning experiments.9,10,11,12,13 In other species, linking brain activity to behavior is done by implanting electrodes and directly correlating electrical activity with observed animal behavior. However, because the octopus lacks any hard structure to which recording equipment can be anchored, and because it uses its eight flexible arms to remove any foreign object attached to the outside of its body, in vivo recording of electrical activity from untethered, behaving octopuses has thus far not been possible. Here, we describe a novel technique for inserting a portable data logger into the octopus and implanting electrodes into the vertical lobe system, such that brain activity can be recorded for up to 12 h from unanesthetized, untethered octopuses and can be synchronized with simultaneous video recordings of behavior. In the brain activity, we identified several distinct patterns that appeared consistently in all animals. While some resemble activity patterns in mammalian neural tissue, others, such as episodes of 2 Hz, large amplitude oscillations, have not been reported. By providing an experimental platform for recording brain activity in behaving octopuses, our study is a critical step toward understanding how the brain controls behavior in these remarkable animals.

Site-specific effects of 800- and 850-nm forehead transcranial photobiomodulation on prefrontal bilateral connectivity and unilateral coupling in young adults.

Significance: Transcranial photobiomodulation (tPBM) is a noninvasive neuromodulation method that facilitates the improvement of human cognition. However, limited information is available in the literature on the wavelength- and site-specific effects of prefrontal tPBM. Moreover, 2-channel broadband near-infrared spectroscopy (2-bbNIRS) is a new approach for quantifying infra-slow oscillations (ISO; 0.005 to 0.2 Hz) of neurophysiological networks in the resting human brain in vivo. Aim: We aim to prove the hypothesis that the hemodynamic and metabolic activities of the resting prefrontal cortex are significantly modulated by tPBM and that the modulation is wavelength- and site-specific in different ISO bands. Approach: Noninvasive 8-min tPBM with an 800- or 850-nm laser or sham was delivered to either side of the forehead of 26 healthy young adults. A 2-bbNIRS unit was used to record prefrontal ISO activity 7 min before and after tPBM/sham. The measured time series were analyzed in the frequency domain to determine the coherence of hemodynamic and metabolic activities at each of the three ISO frequency bands. Sham-controlled coherence values represent tPBM-induced effects on neurophysiological networks. Results: Prefrontal tPBM by either wavelength and on either lateral side of the forehead (1) increased ipsilateral metabolic-hemodynamic coupling in the endogenic band and (2) desynchronized bilateral activity of metabolism in the neurogenic band and vascular smooth-muscle hemodynamics in the myogenic band. Site-specific effects of laser tPBM were also observed with significant enhancement of bilateral hemodynamic and metabolic connectivity by the right prefrontal 800-nm tPBM. Conclusions: Prefrontal tPBM can significantly modulate neurophysiological networks bilaterally and coupling unilaterally in the human prefrontal cortex. Such modulation effects are site- and wavelength-specific for each ISO band.