Neural assemblies coordinated by cortical waves are associated with waking and hallucinatory brain states.

The relationship between sensory stimuli and perceptions is brain-state dependent: in wakefulness, suprathreshold stimuli evoke perceptions; under anesthesia, perceptions are abolished; and during dreaming and in dissociated states, percepts are internally generated. Here, we exploit this state dependence to identify brain activity associated with internally generated or stimulus-evoked perceptions. In awake mice, visual stimuli phase reset spontaneous cortical waves to elicit 3-6 Hz feedback traveling waves. These stimulus-evoked waves traverse the cortex and entrain visual and parietal neurons. Under anesthesia as well as during ketamine-induced dissociation, visual stimuli do not disrupt spontaneous waves. Uniquely, in the dissociated state, spontaneous waves traverse the cortex caudally and entrain visual and parietal neurons, akin to stimulus-evoked waves in wakefulness. Thus, coordinated neuronal assemblies orchestrated by traveling cortical waves emerge in states in which perception can manifest. The awake state is privileged in that this coordination is reliably elicited by external visual stimuli.

Coupling of Sharp Wave Events between Zebrafish Hippocampal and Amygdala Homologs.

The mammalian hippocampus exhibits spontaneous sharp wave events (1-30 Hz) with an often-present superimposed fast ripple oscillation (120-220 Hz) to form a sharp wave ripple (SWR) complex. During slow-wave sleep or quiet restfulness, SWRs result from the sequential spiking of hippocampal cell assemblies initially activated during learned or imagined experiences. Additional cortical/subcortical areas exhibit SWR events that are coupled to hippocampal SWRs, and studies in mammals suggest that coupling may be critical for the consolidation and recall of specific memories. In the present study, we have examined juvenile male and female zebrafish and show that SWR events are intrinsically generated and maintained within the telencephalon and that their hippocampal homolog, the anterodorsolateral lobe (ADL), exhibits SW events with ∼9% containing an embedded ripple (SWR). Single-cell calcium imaging coupled to local field potential recordings revealed that ∼10% of active cells in the dorsal telencephalon participate in any given SW event. Furthermore, fluctuations in cholinergic tone modulate SW events consistent with mammalian studies. Moreover, the basolateral amygdala (BLA) homolog exhibits SW events with ∼5% containing an embedded ripple. Computing the SW peak coincidence difference between the ADL and BLA showed bidirectional communication. Simultaneous coupling occurred more frequently within the same hemisphere, and in coupled events across hemispheres, the ADL more commonly preceded BLA. Together, these data suggest conserved mechanisms across species by which SW and SWR events are modulated, and memories may be transferred and consolidated through regional coupling.

Neural and behavioural state switching during hippocampal dentate spikes.

Distinct brain and behavioural states are associated with organized neural population dynamics that are thought to serve specific cognitive functions1-3. Memory replay events, for example, occur during synchronous population events called sharp-wave ripples in the hippocampus while mice are in an 'offline' behavioural state, enabling cognitive mechanisms such as memory consolidation and planning4-11. But how does the brain re-engage with the external world during this behavioural state and permit access to current sensory information or promote new memory formation? Here we found that the hippocampal dentate spike, an understudied population event that frequently occurs between sharp-wave ripples12, may underlie such a mechanism. We show that dentate spikes are associated with distinctly elevated brain-wide firing rates, primarily observed in higher order networks, and couple to brief periods of arousal. Hippocampal place coding during dentate spikes aligns to the mouse's current spatial location, unlike the memory replay accompanying sharp-wave ripples. Furthermore, inhibiting neural activity during dentate spikes disrupts associative memory formation. Thus, dentate spikes represent a distinct brain state and support memory during non-locomotor behaviour, extending the repertoire of cognitive processes beyond the classical offline functions.

Elevated phase amplitude coupling as a depression biomarker in epilepsy.

Depression is prevalent in epilepsy patients and their intracranial brain activity recordings can be used to determine the types of brain activity that are associated with comorbid depression. We performed case-control comparison of spectral power and phase amplitude coupling (PAC) in 34 invasively monitored drug resistant epilepsy patients' brain recordings. The values of spectral power and PAC for one-minute segments out of every hour in a patient's study were correlated with pre-operative assessment of depressive symptoms by Beck Depression Inventory-II (BDI). We identified an elevated PAC signal (theta-alpha-beta phase (5-25 Hz)/gamma frequency (80-100 Hz) band) that is present in high BDI scores but not low BDI scores adult epilepsy patients in brain regions implicated in primary depression, including anterior cingulate cortex, amygdala and orbitofrontal cortex. Our results showed the application of PAC as a network-specific, electrophysiologic biomarker candidate for comorbid depression and its potential as treatment target for neuromodulation.

Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance.

The accumulation of metabolic waste is a leading cause of numerous neurological disorders, yet we still have only limited knowledge of how the brain performs self-cleansing. Here we demonstrate that neural networks synchronize individual action potentials to create large-amplitude, rhythmic and self-perpetuating ionic waves in the interstitial fluid of the brain. These waves are a plausible mechanism to explain the correlated potentiation of the glymphatic flow1,2 through the brain parenchyma. Chemogenetic flattening of these high-energy ionic waves largely impeded cerebrospinal fluid infiltration into and clearance of molecules from the brain parenchyma. Notably, synthesized waves generated through transcranial optogenetic stimulation substantially potentiated cerebrospinal fluid-to-interstitial fluid perfusion. Our study demonstrates that neurons serve as master organizers for brain clearance. This fundamental principle introduces a new theoretical framework for the functioning of macroscopic brain waves.

Blink-Related Oscillations Provide Naturalistic Assessments of Brain Function and Cognitive Workload within Complex Real-World Multitasking Environments.

BACKGROUND: There is a significant need to monitor human cognitive performance in complex environments, with one example being pilot performance. However, existing assessments largely focus on subjective experiences (e.g., questionnaires) and the evaluation of behavior (e.g., aircraft handling) as surrogates for cognition or utilize brainwave measures which require artificial setups (e.g., simultaneous auditory stimuli) that intrude on the primary tasks. Blink-related oscillations (BROs) are a recently discovered neural phenomenon associated with spontaneous blinking that can be captured without artificial setups and are also modulated by cognitive loading and the external sensory environment-making them ideal for brain function assessment within complex operational settings. METHODS: Electroencephalography (EEG) data were recorded from eight adult participants (five F, M = 21.1 years) while they completed the Multi-Attribute Task Battery under three different cognitive loading conditions. BRO responses in time and frequency domains were derived from the EEG data, and comparisons of BRO responses across cognitive loading conditions were undertaken. Simultaneously, assessments of blink behavior were also undertaken. RESULTS: Blink behavior assessments revealed decreasing blink rate with increasing cognitive load (p < 0.001). Prototypical BRO responses were successfully captured in all participants (p < 0.001). BRO responses reflected differences in task-induced cognitive loading in both time and frequency domains (p < 0.05). Additionally, reduced pre-blink theta band desynchronization with increasing cognitive load was also observed (p < 0.05). CONCLUSION: This study confirms the ability of BRO responses to capture cognitive loading effects as well as preparatory pre-blink cognitive processes in anticipation of the upcoming blink during a complex multitasking situation. These successful results suggest that blink-related neural processing could be a potential avenue for cognitive state evaluation in operational settings-both specialized environments such as cockpits, space exploration, military units, etc. and everyday situations such as driving, athletics, human-machine interactions, etc.-where human cognition needs to be seamlessly monitored and optimized.

Pathological neurons generate ripples at the UP-DOWN transition disrupting information transfer.

OBJECTIVE: To confirm and investigate why pathological high-frequency oscillations (pHFOs), including ripples (80-200 Hz) and fast ripples (200-600 Hz), are generated during the UP-DOWN transition of the slow wave and if information transmission mediated by ripple temporal coupling is disrupted in the seizure-onset zone (SOZ). METHODS: We isolated 217 total units from 175.95 intracranial electroencephalography (iEEG) contact-hours of synchronized macro- and microelectrode recordings from 6 patients. Sleep slow oscillation (.1-2 Hz) epochs were identified in the iEEG recording. iEEG HFOs that occurred superimposed on the slow wave were transformed to phasors and adjusted by the phase of maximum firing in nearby units (i.e., maximum UP). We tested whether, in the SOZ, HFOs and associated action potentials (APs) occur more often at the UP-DOWN transition. We also examined ripple temporal correlations using cross-correlograms. RESULTS: At the group level in the SOZ, HFO and HFO-associated AP probability was highest during the UP-DOWN transition of slow wave excitability (p < < .001). In the non-SOZ, HFO and HFO-associated AP was highest during the DOWN-UP transition (p < < .001). At the unit level in the SOZ, 15.6% and 20% of units exhibited more robust firing during ripples (Cohen's d = .11-.83) and fast ripples (d = .36-.90) at the UP-DOWN transition (p < .05 f.d.r. corrected), respectively. By comparison, also in the SOZ, 6.6% (d = .14-.30) and 8.5% (d = .33-.41) of units had significantly less firing during ripples and fast ripples at the UP-DOWN transition, respectively. Additional data shows that ripple and fast ripple temporal correlations, involving global slow waves, between the hippocampus, entorhinal cortex, and parahippocampal gyrus were reduced by >50% in the SOZ compared to the non-SOZ (N = 3). SIGNIFICANCE: The UP-DOWN transition of slow wave excitability facilitates the activation of pathological neurons to generate pHFOs. Ripple temporal correlations across brain regions may be important in memory consolidation and are disrupted in the SOZ, perhaps by pHFO generation.

Investigation of Methodologies for Extracting Individual Brain Oscillations: Comparisons & Insights.

There is increasing evidence that the effects of non-invasive brain stimulation can be maximized when the applied intervention matches internal brain oscillations. Extracting individual brain oscillations is thus a necessary step for implementing personalized brain stimulation. In this context, different methods have been proposed for obtaining subject-specific spectral peaks from electrophysiological recordings. However, comparing the results obtained using different approaches is still lacking. Therefore, in the present work, we examined the following methodologies in terms of obtaining individual motor-related EEG spectral peaks: fast Fourier Transform analysis, power spectrum density analysis, wavelet analysis, and a principal component based time-frequency analysis. We used EEG data obtained when performing two different motor tasks - a hand grip task and a hand opening- and-closing task. Our results showed that both the motor task type and the specific method for performing the analysis had considerable impact on the extraction of subject-specific oscillation spectral peaks.Clinical Relevance-This exploratory study provides insights into the potential effects of using different methods to extract individual brain oscillations, which is important for designing personalized brain-machine-interfaces.

Machine learning-based classification of physiological and pathological high-frequency oscillations recorded by stereoelectroencephalography.

OBJECTIVE: High-frequency oscillations (HFOs) are an efficient indicator to locate the epileptogenic zone (EZ). However, physiological HFOs produced in the normal brain region may interfere with EZ localization. The present study aimed to build a machine learning-based classifier to distinguish the properties of each HFO event based on features in different domains. METHODS: HFOs were detected in focal epilepsy patients from two different hospitals who underwent stereoelectroencephalography and subsequent resection surgery. Subsequently, 37 features in four different domains (time, frequency and time-frequency, entropy-based and nonlinear) were extracted for each HFO. After extraction, a fast correlation-based filter (FCBF) algorithm was applied for feature selection. The machine learning classifier was trained on the feature matrix with and without FCBF and then tested on the data set from patients in another hospital. RESULTS: A dataset was compiled, consisting of 89,844 pathological HFOs and 23,613 physiological HFOs from 17 patients assigned to the training dataset. Additionally, 12,695 pathological HFOs and 5,599 physiological HFOs from 9 patients were assigned to the testing dataset. Four features (ripple band power, arithmetic mean, Petrosian fractal dimension and zero crossings) were obtained for classifier training after FCBF. The classifier showed an area under the curve (AUC) of 0.95/0.98 for FCBF/no FCBF features in the training dataset and AUC of 0.82/0.90 for FCBF/no FCBF features in the testing dataset. Our findings indicated that the classifier utilizing all features demonstrated superior performance compared to the one relying on FCBF-processed features. CONCLUSION: Our classifier could reliably differentiate pathological HFOs from physiological ones, which could promote the development of HFOs in EZ localization.

Assessing attentional task-related electroencephalogram signal variations by using mobile electroencephalogram technology: An experimental study.

BACKGROUND: A better understanding of the network responses of cortical activities during rest and cognitive tasks is necessary. Therefore, in this study, we aimed to evaluate cerebral activities during attentional tasks by using mobile electroencephalography, identifying the types of attentional components and brain waves. METHODS: In this experimental study, we enrolled 12 healthy young adults. The attentional tasks comprised parts A and B of the Trail-Making Test (TMT). Nineteen electroencephalography electrodes were placed over various brain regions. The Wilcoxon signed-rank test was used to examine the differences in power levels between the rest and TMT conditions. RESULTS: During TMT part A, the electroencephalography power level of the delta waves was significantly higher in the right frontal, left central, left occipital, left inferior frontal, right mid-temporal, right posterior temporal, and middle parietal areas (P < .05) than those during the resting state; that of the alpha waves was significantly lower in the left posterior temporal area (P = .006); and that of the high gamma waves was significantly lower in the left parietal (P = .05) and left occipital (P = .002) areas. During TMT part B, the electroencephalography power level of the beta waves was significantly higher in the right frontal area (P = .041) than that during the resting state, and that of the low gamma waves was significantly higher in the left frontal pole, right frontal, and right inferior frontal areas (P < .05). During the focused attentional task, the power level of the delta waves increased and that of the alpha waves decreased, and during the alternating attentional task, those of both the beta and gamma waves increased. The delta waves were related to the whole brain, the alpha and high gamma waves to the left posterior lobe, and the beta and low gamma waves to both frontal lobes. CONCLUSION: These findings contribute to the basic knowledge necessary to develop new attentional assessment methods for clinical situations.

Developmental atlas of phase-amplitude coupling between physiologic high-frequency oscillations and slow waves.

We investigated the developmental changes in high-frequency oscillation (HFO) and Modulation Index (MI) - the coupling measure between HFO and slow-wave phase. We generated normative brain atlases, using subdural EEG signals from 8251 nonepileptic electrode sites in 114 patients (ages 1.0-41.5 years) who achieved seizure control following resective epilepsy surgery. We observed a higher MI in the occipital lobe across all ages, and occipital MI increased notably during early childhood. The cortical areas exhibiting MI co-growth were connected via the vertical occipital fasciculi and posterior callosal fibers. While occipital HFO rate showed no significant age-association, the temporal, frontal, and parietal lobes exhibited an age-inversed HFO rate. Assessment of 1006 seizure onset sites revealed that z-score normalized MI and HFO rate were higher at seizure onset versus nonepileptic electrode sites. We have publicly shared our intracranial EEG data to enable investigators to validate MI and HFO-centric presurgical evaluations to identify the epileptogenic zone.

Cross-frequency coupling between slow harmonics via the real brainstem oscillators: An in vivo animal study.

Brain waves of discrete rhythms (gamma to delta frequency ranges) are ubiquitously recorded and interpreted with respect to probable corresponding specific functions. The most challenging idea of interpreting varied frequencies of brain waves has been postulated as a communication mechanism in which different neuronal assemblies use specific ranges of frequencies cooperatively. One promising candidate is cross-frequency coupling (CFC), in which some neuronal assemblies efficiently utilize the fastest gamma range brain waves as an information carrier (phase-amplitude CFC); however, phase-phase CFC via the slowest delta and theta waves has rarely been described to date. Moreover, CFC has rarely been reported in the animal brainstem including humans, which most likely utilizes the slowest waves (delta and theta ranges). Harmonic waves are characterized by the presence of a fundamental frequency with several overtones, multiples of the fundamental frequency. Rat brainstem waves seemed to consist of slow harmonics with different frequencies that could cooperatively produce a phase-phase CFC. Harmonic rhythms of different frequency ranges can cross-couple with each other to sustain robust and resilient consonance via real oscillators, notwithstanding any perturbations.

Virtual reality and motor imagery for early post-stroke rehabilitation.

BACKGROUND: Motor impairment is a common consequence of stroke causing difficulty in independent movement. The first month of post-stroke rehabilitation is the most effective period for recovery. Movement imagination, known as motor imagery, in combination with virtual reality may provide a way for stroke patients with severe motor disabilities to begin rehabilitation. METHODS: The aim of this study is to verify whether motor imagery and virtual reality help to activate stroke patients' motor cortex. 16 acute/subacute (< 6 months) stroke patients participated in this study. All participants performed motor imagery of basketball shooting which involved the following tasks: listening to audio instruction only, watching a basketball shooting animation in 3D with audio, and also performing motor imagery afterwards. Electroencephalogram (EEG) was recorded for analysis of motor-related features of the brain such as power spectral analysis in the [Formula: see text] and [Formula: see text] frequency bands and spectral entropy. 18 EEG channels over the motor cortex were used for all stroke patients. RESULTS: All results are normalised relative to all tasks for each participant. The power spectral densities peak near the [Formula: see text] band for all participants and also the [Formula: see text] band for some participants. Tasks with instructions during motor imagery generally show greater power spectral peaks. The p-values of the Wilcoxon signed-rank test for band power comparison from the 18 EEG channels between different pairs of tasks show a 0.01 significance of rejecting the band powers being the same for most tasks done by stroke subjects. The motor cortex of most stroke patients is more active when virtual reality is involved during motor imagery as indicated by their respective scalp maps of band power and spectral entropy. CONCLUSION: The resulting activation of stroke patient's motor cortices in this study reveals evidence that it is induced by imagination of movement and virtual reality supports motor imagery. The framework of the current study also provides an efficient way to investigate motor imagery and virtual reality during post-stroke rehabilitation.

Characterizing endogenous delta oscillations in human MEG.

Rhythmic activity in the delta frequency range (0.5-3 Hz) is a prominent feature of brain dynamics. Here, we examined whether spontaneous delta oscillations, as found in invasive recordings in awake animals, can be observed in non-invasive recordings performed in humans with magnetoencephalography (MEG). In humans, delta activity is commonly reported when processing rhythmic sensory inputs, with direct relationships to behaviour. However, rhythmic brain dynamics observed during rhythmic sensory stimulation cannot be interpreted as an endogenous oscillation. To test for endogenous delta oscillations we analysed human MEG data during rest. For comparison, we additionally analysed two conditions in which participants engaged in spontaneous finger tapping and silent counting, arguing that internally rhythmic behaviours could incite an otherwise silent neural oscillator. A novel set of analysis steps allowed us to show narrow spectral peaks in the delta frequency range in rest, and during overt and covert rhythmic activity. Additional analyses in the time domain revealed that only the resting state condition warranted an interpretation of these peaks as endogenously periodic neural dynamics. In sum, this work shows that using advanced signal processing techniques, it is possible to observe endogenous delta oscillations in non-invasive recordings of human brain dynamics.

Interacting spiral wave patterns underlie complex brain dynamics and are related to cognitive processing.

The large-scale activity of the human brain exhibits rich and complex patterns, but the spatiotemporal dynamics of these patterns and their functional roles in cognition remain unclear. Here by characterizing moment-by-moment fluctuations of human cortical functional magnetic resonance imaging signals, we show that spiral-like, rotational wave patterns (brain spirals) are widespread during both resting and cognitive task states. These brain spirals propagate across the cortex while rotating around their phase singularity centres, giving rise to spatiotemporal activity dynamics with non-stationary features. The properties of these brain spirals, such as their rotational directions and locations, are task relevant and can be used to classify different cognitive tasks. We also demonstrate that multiple, interacting brain spirals are involved in coordinating the correlated activations and de-activations of distributed functional regions; this mechanism enables flexible reconfiguration of task-driven activity flow between bottom-up and top-down directions during cognitive processing. Our findings suggest that brain spirals organize complex spatiotemporal dynamics of the human brain and have functional correlates to cognitive processing.

Breathing in waves: Understanding respiratory-brain coupling as a gradient of predictive oscillations.

Breathing plays a crucial role in shaping perceptual and cognitive processes by regulating the strength and synchronisation of neural oscillations. Numerous studies have demonstrated that respiratory rhythms govern a wide range of behavioural effects across cognitive, affective, and perceptual domains. Additionally, respiratory-modulated brain oscillations have been observed in various mammalian models and across diverse frequency spectra. However, a comprehensive framework to elucidate these disparate phenomena remains elusive. In this review, we synthesise existing findings to propose a neural gradient of respiratory-modulated brain oscillations and examine recent computational models of neural oscillations to map this gradient onto a hierarchical cascade of precision-weighted prediction errors. By deciphering the computational mechanisms underlying respiratory control of these processes, we can potentially uncover new pathways for understanding the link between respiratory-brain coupling and psychiatric disorders.