Entrainment echoes in the cerebellum.

Evidence accumulates that the cerebellum's role in the brain is not restricted to motor functions. Rather, cerebellar activity seems to be crucial for a variety of tasks that rely on precise event timing and prediction. Due to its complex structure and importance in communication, human speech requires a particularly precise and predictive coordination of neural processes to be successfully comprehended. Recent studies proposed that the cerebellum is indeed a major contributor to speech processing, but how this contribution is achieved mechanistically remains poorly understood. The current study aimed to reveal a mechanism underlying cortico-cerebellar coordination and demonstrate its speech-specificity. In a reanalysis of magnetoencephalography data, we found that activity in the cerebellum aligned to rhythmic sequences of noise-vocoded speech, irrespective of its intelligibility. We then tested whether these "entrained" responses persist, and how they interact with other brain regions, when a rhythmic stimulus stopped and temporal predictions had to be updated. We found that only intelligible speech produced sustained rhythmic responses in the cerebellum. During this "entrainment echo," but not during rhythmic speech itself, cerebellar activity was coupled with that in the left inferior frontal gyrus, and specifically at rates corresponding to the preceding stimulus rhythm. This finding represents evidence for specific cerebellum-driven temporal predictions in speech processing and their relay to cortical regions.

Phase-dependent word perception emerges from region-specific sensitivity to the statistics of language.

Neural oscillations reflect fluctuations in excitability, which biases the percept of ambiguous sensory input. Why this bias occurs is still not fully understood. We hypothesized that neural populations representing likely events are more sensitive, and thereby become active on earlier oscillatory phases, when the ensemble itself is less excitable. Perception of ambiguous input presented during less-excitable phases should therefore be biased toward frequent or predictable stimuli that have lower activation thresholds. Here, we show such a frequency bias in spoken word recognition using psychophysics, magnetoencephalography (MEG), and computational modelling. With MEG, we found a double dissociation, where the phase of oscillations in the superior temporal gyrus and medial temporal gyrus biased word-identification behavior based on phoneme and lexical frequencies, respectively. This finding was reproduced in a computational model. These results demonstrate that oscillations provide a temporal ordering of neural activity based on the sensitivity of separable neural populations.

Proactive or reactive? Neural oscillatory insight into the leader-follower dynamics of early infant-caregiver interaction.

We know that infants' ability to coordinate attention with others toward the end of the first year is fundamental to language acquisition and social cognition. Yet, we understand little about the neural and cognitive mechanisms driving infant attention in shared interaction: do infants play a proactive role in creating episodes of joint attention? Recording electroencephalography (EEG) from 12-mo-old infants while they engaged in table-top play with their caregiver, we examined the communicative behaviors and neural activity preceding and following infant- vs. adult-led joint attention. Infant-led episodes of joint attention appeared largely reactive: they were not associated with increased theta power, a neural marker of endogenously driven attention, and infants did not increase their ostensive signals before the initiation. Infants were, however, sensitive to whether their initiations were responded to. When caregivers joined their attentional focus, infants showed increased alpha suppression, a pattern of neural activity associated with predictive processing. Our results suggest that at 10 to 12 mo, infants are not routinely proactive in creating joint attention episodes yet. They do, however, anticipate behavioral contingency, a potentially foundational mechanism for the emergence of intentional communication.

Internal Representations Are Prioritized by Frontoparietal Theta Connectivity and Suppressed by alpha Oscillation Dynamics: Evidence from Concurrent Transcranial Magnetic Stimulation EEG and Invasive EEG.

Control over internal representations requires the prioritization of relevant information and suppression of irrelevant information. The frontoparietal network exhibits prominent neural oscillations during these distinct cognitive processes. Yet, the causal role of this network-scale activity is unclear. Here, we targeted theta-frequency frontoparietal coherence and dynamic alpha oscillations in the posterior parietal cortex using online rhythmic transcranial magnetic stimulation (TMS) in women and men while they prioritized or suppressed internally maintained working memory (WM) representations. Using concurrent high-density EEG, we provided evidence that we acutely drove the targeted neural oscillation and TMS improved WM capacity only when the evoked activity corresponded with the desired cognitive process. To suppress an internal representation, we increased the amplitude of lateralized alpha oscillations in the posterior parietal cortex contralateral to the irrelevant visual field. For prioritization, we found that TMS to the prefrontal cortex increased theta-frequency connectivity in the prefrontoparietal network contralateral to the relevant visual field. To understand the spatial specificity of these effects, we administered the WM task to participants with implanted electrodes. We found that theta connectivity during prioritization was directed from the lateral prefrontal to the superior posterior parietal cortex. Together, these findings provide causal evidence in support of a model where a frontoparietal theta network prioritizes internally maintained representations and alpha oscillations in the posterior parietal cortex suppress irrelevant representations.

Neural correlates of retrospective memory confidence during face-name associative learning.

The ability to accurately assess one's own memory performance during learning is essential for adaptive behavior, but the brain mechanisms underlying this metamemory function are not well understood. We investigated the neural correlates of memory accuracy and retrospective memory confidence in a face-name associative learning task using magnetoencephalography in healthy young adults (n = 32). We found that high retrospective confidence was associated with stronger occipital event-related fields during encoding and widespread event-related fields during retrieval compared to low confidence. On the other hand, memory accuracy was linked to medial temporal activities during both encoding and retrieval, but only in low-confidence trials. A decrease in oscillatory power at alpha/beta bands in the parietal regions during retrieval was associated with higher memory confidence. In addition, representational similarity analysis at the single-trial level revealed distributed but differentiable neural activities associated with memory accuracy and confidence during both encoding and retrieval. In summary, our study unveiled distinct neural activity patterns related to memory confidence and accuracy during associative learning and underscored the crucial role of parietal regions in metamemory.

Electrical stimulation induced self-related auditory hallucinations correlate with oscillatory power change in the default mode network.

Self-related information is crucial in our daily lives, which has led to the proposal that there is a specific brain mechanism for processing it. Neuroimaging studies have consistently demonstrated that the default mode network (DMN) is strongly associated with the representation and processing of self-related information. However, the precise relationship between DMN activity and self-related information, particularly in terms of neural oscillations, remains largely unknown. We electrically stimulated the superior temporal and fusiform areas, using stereo-electroencephalography to investigate neural oscillations associated with elicited self-related auditory hallucinations. Twenty-two instances of auditory hallucinations were recorded and categorized into self-related and other-related conditions. Comparing oscillatory power changes within the DMN between self-related and other-related auditory hallucinations, we discovered that self-related hallucinations are associated with significantly stronger positive power changes in both alpha and gamma bands compared to other-related hallucinations. To ensure the validity of our findings, we conducted controlled analyses for factors of familiarity and clarity, which revealed that the observed effects within the DMN remain independent of these factors. These results underscore the significance of the functional role of the DMN during the processing of self-related auditory hallucinations and shed light on the relationship between self-related perception and neural oscillatory activity.

Perceptual training improves audiovisual integration by enhancing alpha-band oscillations and functional connectivity in older adults.

Numerous studies on perceptual training exist, however, most have focused on the precision of temporal audiovisual perception, while fewer have concentrated on ability promotion for audiovisual integration (AVI). To investigate these issues, continuous 5-day audiovisual perceptual training was applied, during which electroencephalography was performed in response to auditory-only (A), visual-only (V) and audiovisual (AV) stimuli before and after training. The results showed that the perceptual sensitivity was greater for training group than for control group and was greater in the posttest than in the pretest. The response to the AV stimulus was significantly faster in the posttest than in the pretest for the older training group but was significantly greater for A and V stimuli for the younger training group. Electroencephalography analysis found higher P3 AVI amplitudes [AV-(A + V)] in the posttest than in the pretest for training group, which were subsequently reflected by an increased alpha (8-12 Hz) oscillatory response and strengthened global functional connectivity (weighted phase lag index). Furthermore, these facilitations were greater for older training groups than for younger training groups. These results confirm the age-related compensatory mechanism for AVI may be strengthened as audiovisual perceptual training progresses, providing an effective candidate for cognitive intervention in older adults.

Top-down and bottom-up oscillatory dynamics regulate implicit visuomotor sequence learning.

Implicit visuomotor sequence learning is crucial for acquiring skills that result in automated behaviors. The oscillatory dynamics underpinning this learning process are not well understood. To address this gap, the current study employed electroencephalography with a medium-density array (64 electrodes) to investigate oscillatory activity associated with implicit visuomotor sequence learning in the Serial Reaction Time task. In the task, participants unknowingly learn a series of finger movements. Eighty-five healthy adults participated in the study. Analyses revealed that theta activity at the vertex and alpha/beta activity over the motor areas decreased over the course of learning. No associations between alpha/beta and theta power were observed. These findings are interpreted within a dual-process framework: midline theta activity is posited to regulate top-down attentional processes, whereas beta activity from motor areas underlies the bottom-up encoding of sensory information from movement. From this model, we suggest that during implicit visuomotor sequence learning, top-down processes become disengaged (indicated by a reduction in theta activity), and modality specific bottom-up processes encode the motor sequence (indicated by a reduction in alpha/beta activity).

Serial Dependence in Perception.

Much evidence has shown that perception is biased towards previously presented similar stimuli, an effect recently termed serial dependence. Serial dependence affects nearly every aspect of perception, often causing gross perceptual distortions, especially for weak and ambiguous stimuli. Despite unwanted side-effects, empirical evidence and Bayesian modeling show that serial dependence acts to improve efficiency and is generally beneficial to the system. Consistent with models of predictive coding, the Bayesian priors of serial dependence are generated at high levels of cortical analysis, incorporating much perceptual experience, but feed back to lower sensory areas. These feedback loops may drive oscillations in the alpha range, linked strongly with serial dependence. The discovery of top-down predictive perceptual processes is not new, but the new, more quantitative approach characterizing serial dependence promises to lead to a deeper understanding of predictive perceptual processes and their underlying neural mechanisms.

Rhythmic Entrainment Echoes in Auditory Perception.

Rhythmic entrainment echoes-rhythmic brain responses that outlast rhythmic stimulation-can demonstrate endogenous neural oscillations entrained by the stimulus rhythm. Here, we tested for such echoes in auditory perception. Participants detected a pure tone target, presented at a variable delay after another pure tone that was rhythmically modulated in amplitude. In four experiments involving 154 human (female and male) participants, we tested (1) which stimulus rate produces the strongest entrainment echo and, inspired by the tonotopical organization of the auditory system and findings in nonhuman primates, (2) whether these are organized according to sound frequency. We found the strongest entrainment echoes after 6 and 8 Hz stimulation, respectively. The best moments for target detection (in phase or antiphase with the preceding rhythm) depended on whether sound frequencies of entraining and target stimuli matched, which is in line with a tonotopical organization. However, for the same experimental condition, best moments were not always consistent across experiments. We provide a speculative explanation for these differences that relies on the notion that neural entrainment and repetition-related adaptation might exercise competing opposite influences on perception. Together, we find rhythmic echoes in auditory perception that seem more complex than those predicted from initial theories of neural entrainment.SIGNIFICANCE STATEMENT Rhythmic entrainment echoes are rhythmic brain responses that are produced by a rhythmic stimulus and persist after its offset. These echoes play an important role for the identification of endogenous brain oscillations, entrained by rhythmic stimulation, and give us insights into whether and how participants predict the timing of events. In four independent experiments involving >150 participants, we examined entrainment echoes in auditory perception. We found that entrainment echoes have a preferred rate (between 6 and 8 Hz) and seem to follow the tonotopic organization of the auditory system. Although speculative, we also found evidence that several, potentially competing processes might interact to produce such echoes, a notion that might need to be considered for future experimental design.

Phase Alignment of Low-Frequency Neural Activity to the Amplitude Envelope of Speech Reflects Evoked Responses to Acoustic Edges, Not Oscillatory Entrainment.

The amplitude envelope of speech is crucial for accurate comprehension. Considered a key stage in speech processing, the phase of neural activity in the theta-delta bands (1-10 Hz) tracks the phase of the speech amplitude envelope during listening. However, the mechanisms underlying this envelope representation have been heavily debated. A dominant model posits that envelope tracking reflects entrainment of endogenous low-frequency oscillations to the speech envelope. Alternatively, envelope tracking reflects a series of evoked responses to acoustic landmarks within the envelope. It has proven challenging to distinguish these two mechanisms. To address this, we recorded MEG while participants (n = 12, 6 female) listened to natural speech, and compared the neural phase patterns to the predictions of two computational models: an oscillatory entrainment model and a model of evoked responses to peaks in the rate of envelope change. Critically, we also presented speech at slowed rates, where the spectro-temporal predictions of the two models diverge. Our analyses revealed transient theta phase-locking in regular speech, as predicted by both models. However, for slow speech, we found transient theta and delta phase-locking, a pattern that was fully compatible with the evoked response model but could not be explained by the oscillatory entrainment model. Furthermore, encoding of acoustic edge magnitudes was invariant to contextual speech rate, demonstrating speech rate normalization of acoustic edge representations. Together, our results suggest that neural phase-locking to the speech envelope is more likely to reflect discrete representation of transient information rather than oscillatory entrainment.SIGNIFICANCE STATEMENT This study probes a highly debated topic in speech perception: the neural mechanisms underlying the cortical representation of the temporal envelope of speech. It is well established that the slow intensity profile of the speech signal, its envelope, elicits a robust brain response that "tracks" these envelope fluctuations. The oscillatory entrainment model posits that envelope tracking reflects phase alignment of endogenous neural oscillations. Here the authors provide evidence for a distinct mechanism. They show that neural speech envelope tracking arises from transient evoked neural responses to rapid increases in the speech envelope. Explicit computational modeling provides direct and compelling evidence that evoked responses are the primary mechanism underlying cortical speech envelope representations, with no evidence for oscillatory entrainment.

Prospection of Potential Actions during Visual Working Memory Starts Early, Is Flexible, and Predicts Behavior.

For visual working memory to serve upcoming behavior, it is crucial that we prepare for the potential use of working-memory contents ahead of time. Recent studies have demonstrated how the prospection and planning for an upcoming manual action starts early after visual encoding, and occurs alongside visual retention. Here, we address whether such "output planning" in visual working memory flexibly adapts to different visual-motor mappings, and occurs even when an upcoming action will only potentially become relevant for behavior. Human participants (female and male) performed a visual-motor working memory task in which they remembered one or two colored oriented bars for later (potential) use. We linked, and counterbalanced, the tilt of the visual items to specific manual responses. This allowed us to track planning of upcoming behavior through contralateral attenuation of ß band activity, a canonical motor-cortical EEG signature of manual-action planning. The results revealed how action encoding and subsequent planning alongside visual working memory (1) reflect anticipated task demands rather than specific visual-motor mappings, (2) occur even for actions that will only potentially become relevant for behavior, and (3) are associated with faster performance for the encoded item, at the expense of performance to other working-memory content. This reveals how the potential prospective use of visual working memory content is flexibly planned early on, with consequences for the speed of memory-guided behavior.SIGNIFICANCE STATEMENT It is increasingly studied how visual working memory helps us to prepare for the future, in addition to how it helps us to hold onto the past. Recent studies have demonstrated that the planning of prospective actions occurs alongside encoding and retention in working memory. We show that such early "output planning" flexibly adapts to varying visual-motor mappings, occurs both for certain and potential actions, and predicts ensuing working-memory guided behavior. These results highlight the flexible and future-oriented nature of visual working memory, and provide insight into the neural basis of the anticipatory dynamics that translate visual representations into adaptive upcoming behavior.

Spontaneous α Brain Dynamics Track the Episodic "When".

Across species, neurons track time over the course of seconds to minutes, which may feed the sense of time passing. Here, we asked whether neural signatures of time-tracking could be found in humans. Participants stayed quietly awake for a few minutes while being recorded with magnetoencephalography (MEG). They were unaware they would be asked how long the recording lasted (retrospective time) or instructed beforehand to estimate how long it will last (prospective timing). At rest, rhythmic brain activity is nonstationary and displays bursts of activity in the alpha range (α: 7-14 Hz). When participants were not instructed to attend to time, the relative duration of α bursts linearly predicted individuals' retrospective estimates of how long their quiet wakefulness lasted. The relative duration of α bursts was a better predictor than α power or burst amplitude. No other rhythmic or arrhythmic activity predicted retrospective duration. However, when participants timed prospectively, the relative duration of α bursts failed to predict their duration estimates. Consistent with this, the amount of α bursts was discriminant between prospective and retrospective timing. Last, with a control experiment, we demonstrate that the relation between α bursts and retrospective time is preserved even when participants are engaged in a visual counting task. Thus, at the time scale of minutes, we report that the relative time of spontaneous α burstiness predicts conscious retrospective time. We conclude that in the absence of overt attention to time, α bursts embody discrete states of awareness constitutive of episodic timing.SIGNIFICANCE STATEMENT The feeling that time passes is a core component of consciousness and episodic memory. A century ago, brain rhythms called "α" were hypothesized to embody an internal clock. However, rhythmic brain activity is nonstationary and displays on-and-off oscillatory bursts, which would serve irregular ticks to the hypothetical clock. Here, we discovered that in a given lapse of time, the relative bursting time of α rhythms is a good indicator of how much time an individual will report to have elapsed. Remarkably, this relation only holds true when the individual does not attend to time and vanishes when attending to it. Our observations suggest that at the scale of minutes, α brain activity tracks episodic time.

Fast and Slow Rhythms of Naturalistic Reading Revealed by Combined Eye-Tracking and Electroencephalography.

Neural oscillations are thought to support speech and language processing. They may not only inherit acoustic rhythms, but might also impose endogenous rhythms onto processing. In support of this, we here report that human (both male and female) eye movements during naturalistic reading exhibit rhythmic patterns that show frequency-selective coherence with the EEG, in the absence of any stimulation rhythm. Periodicity was observed in two distinct frequency bands: First, word-locked saccades at 4-5 Hz display coherence with whole-head theta-band activity. Second, fixation durations fluctuate rhythmically at ∼1 Hz, in coherence with occipital delta-band activity. This latter effect was additionally phase-locked to sentence endings, suggesting a relationship with the formation of multi-word chunks. Together, eye movements during reading contain rhythmic patterns that occur in synchrony with oscillatory brain activity. This suggests that linguistic processing imposes preferred processing time scales onto reading, largely independent of actual physical rhythms in the stimulus.SIGNIFICANCE STATEMENT The sampling, grouping, and transmission of information are supported by rhythmic brain activity, so-called neural oscillations. In addition to sampling external stimuli, such rhythms may also be endogenous, affecting processing from the inside out. In particular, endogenous rhythms may impose their pace onto language processing. Studying this is challenging because speech contains physical rhythms that mask endogenous activity. To overcome this challenge, we turned to naturalistic reading, where text does not require the reader to sample in a specific rhythm. We observed rhythmic patterns of eye movements that are synchronized to brain activity as recorded with EEG. This rhythmicity is not imposed by the external stimulus, which indicates that rhythmic brain activity may serve as a pacemaker for language processing.

Speech Reception in Young Children with Autism Is Selectively Indexed by a Neural Oscillation Coupling Anomaly.

Communication difficulties are one of the core criteria in diagnosing autism spectrum disorder (ASD), and are often characterized by speech reception difficulties, whose biological underpinnings are not yet identified. This deficit could denote atypical neuronal ensemble activity, as reflected by neural oscillations. Atypical cross-frequency oscillation coupling, in particular, could disrupt the joint tracking and prediction of dynamic acoustic stimuli, a dual process that is essential for speech comprehension. Whether such oscillatory anomalies already exist in very young children with ASD, and with what specificity they relate to individual language reception capacity is unknown. We collected neural activity data using electroencephalography (EEG) in 64 very young children with and without ASD (mean age 3; 17 females, 47 males) while they were exposed to naturalistic-continuous speech. EEG power of frequency bands typically associated with phrase-level chunking (δ, 1-3 Hz), phonemic encoding (low-γ, 25-35 Hz), and top-down control (ß, 12-20 Hz) were markedly reduced in ASD relative to typically developing (TD) children. Speech neural tracking by δ and θ (4-8 Hz) oscillations was also weaker in ASD compared with TD children. After controlling gaze-pattern differences, we found that the classical θ/γ coupling was replaced by an atypical ß/γ coupling in children with ASD. This anomaly was the single most specific predictor of individual speech reception difficulties in ASD children. These findings suggest that early interventions (e.g., neurostimulation) targeting the disruption of ß/γ coupling and the upregulation of θ/γ coupling could improve speech processing coordination in young children with ASD and help them engage in oral interactions.SIGNIFICANCE STATEMENT Very young children already present marked alterations of neural oscillatory activity in response to natural speech at the time of autism spectrum disorder (ASD) diagnosis. Hierarchical processing of phonemic-range and syllabic-range information (θ/γ coupling) is disrupted in ASD children. Abnormal bottom-up (low-γ) and top-down (low-ß) coordination specifically predicts speech reception deficits in very young ASD children, and no other cognitive deficit.

The role of parietal beta-band activity in the resolution of visual crowding.

Visual crowding is the difficulty in identifying an object when surrounded by neighbouring flankers, representing a bottleneck for object perception. Crowding arises not only from the activity of visual areas but also from parietal areas and fronto-parietal network activity. Parietal areas would provide the dorsal-to-ventral guidance for object identification and the fronto-parietal network would modulate the attentional resolution. Several studies highlighted the relevance of beta oscillations (15-25 Hz) in these areas for visual crowding and other connatural visual phenomena. In the present study, we investigated the differential contribution of beta oscillations in the parietal cortex and fronto-parietal network in the resolution of visual crowding. During a crowding task with letter stimuli, high-definition transcranial Alternating Current Stimulation (tACS) in the beta band (18 Hz) was delivered bilaterally on parietal sites, on the right fronto-parietal network, and in a sham regime. Resting-state EEG was recorded before and after stimulation to measure tACS-induced aftereffects. The influence of crowding was reduced only when tACS was delivered bilaterally on parietal sites. In this condition, beta power was reduced after the stimulation. Furthermore, the magnitude of tACS-induced aftereffects varied as a function of individual differences in beta oscillations. Results corroborate the link between parietal beta oscillations and visual crowding, providing fundamental insights on brain rhythms underlying the dorsal-to-ventral guidance in visual perception and suggesting that beta tACS can induce plastic changes in these areas. Remarkably, these findings open new possibilities for neuromodulatory interventions for disorders characterised by abnormal crowding, such as dyslexia.

How mind wandering influences motor control: The modulating role of movement difficulty.

It has been found that mind wandering can impair motor control. However, it remains unclear whether the impact of mind wandering on motor control is modulated by movement difficulty and its associated neural mechanisms. To address this issue, we manipulated movement difficulty using handedness and finger dexterity separately in two signal-response tasks with identical experiment designs, in which right-handed participants performed key-pressing and key-releasing movements with the specified fingers, and they had to intermittently report whether their attention was "On task" or "Off task." Key-releasing with the right index finger (RI) had a faster reaction time and stronger contralateral delta-theta (1-7 Hz) functional connectivity than with the left index (LI) in Experiment 1, and mind wandering only reduced the contralateral delta-theta functional connectivity and midfrontal delta-theta activity for key-releasing with RI. Key-pressing with right index and middle fingers (RIR) had a faster reaction time and stronger midfrontal delta-theta activity than with right index and ring fingers (RIR) in Experiment 2, and mind wandering only reduced the midfrontal delta-theta activity for key-pressing with RIM. Theta oscillations are vital in motor control. These findings suggest that mind wandering only impairs the motor control of relatively simple movements without affecting the difficult ones. It supports the notion that mind wandering competes for executive resources with the primary task. Moreover, the quantity of executive resources recruited for a task and how these resources are allocated is contingent upon the task difficulty, which may determine whether mind wandering would interfere with motor control.

Theta and alpha oscillatory signatures of auditory sensory and cognitive loads during complex listening.

The neuronal signatures of sensory and cognitive load provide access to brain activities related to complex listening situations. Sensory and cognitive loads are typically reflected in measures like response time (RT) and event-related potentials (ERPs) components. It's, however, strenuous to distinguish the underlying brain processes solely from these measures. In this study, along with RT- and ERP-analysis, we performed time-frequency analysis and source localization of oscillatory activity in participants performing two different auditory tasks with varying degrees of complexity and related them to sensory and cognitive load. We studied neuronal oscillatory activity in both periods before the behavioral response (pre-response) and after it (post-response). Robust oscillatory activities were found in both periods and were differentially affected by sensory and cognitive load. Oscillatory activity under sensory load was characterized by decrease in pre-response (early) theta activity and increased alpha activity. Oscillatory activity under cognitive load was characterized by increased theta activity, mainly in post-response (late) time. Furthermore, source localization revealed specific brain regions responsible for processing these loads, such as temporal and frontal lobe, cingulate cortex and precuneus. The results provide evidence that in complex listening situations, the brain processes sensory and cognitive loads differently. These neural processes have specific oscillatory signatures and are long lasting, extending beyond the behavioral response.

Quantifying local field potential dynamics with amplitude and frequency stability between ON and OFF medication and stimulation in Parkinson's disease.

Neural oscillations are critical to understanding the synchronisation of neural activities and their relevance to neurological disorders. For instance, the amplitude of beta oscillations in the subthalamic nucleus has gained extensive attention, as it has been found to correlate with medication status and the therapeutic effects of continuous deep brain stimulation in people with Parkinson's disease. However, the frequency stability of subthalamic nucleus beta oscillations, which has been suggested to be associated with dopaminergic information in brain states, has not been well explored. Moreover, the administration of medicine can have inverse effects on changes in frequency and amplitude. In this study, we proposed a method based on the stationary wavelet transform to quantify the amplitude and frequency stability of subthalamic nucleus beta oscillations and evaluated the method using simulation and real data for Parkinson's disease patients. The results suggest that the amplitude and frequency stability quantification has enhanced sensitivity in distinguishing pathological conditions in Parkinson's disease patients. Our quantification shows the benefit of combining frequency stability information with amplitude and provides a new potential feedback signal for adaptive deep brain stimulation.

Granule cells perform frequency-dependent pattern separation in a computational model of the dentate gyrus.

Mnemonic discrimination (MD) may be dependent on oscillatory perforant path input frequencies to the hippocampus in a "U"-shaped fashion, where some studies show that slow and fast input frequencies support MD, while other studies show that intermediate frequencies disrupt MD. We hypothesize that pattern separation (PS) underlies frequency-dependent MD performance. We aim to study, in a computational model of the hippocampal dentate gyrus (DG), the network and cellular mechanisms governing this putative "U"-shaped PS relationship. We implemented a biophysical model of the DG that produces the hypothesized "U"-shaped input frequency-PS relationship, and its associated oscillatory electrophysiological signatures. We subsequently evaluated the network's PS ability using an adapted spatiotemporal task. We undertook systematic lesion studies to identify the network-level mechanisms driving the "U"-shaped input frequency-PS relationship. A minimal circuit of a single granule cell (GC) stimulated with oscillatory inputs was also used to study potential cellular-level mechanisms. Lesioning synapses onto GCs did not impact the "U"-shaped input frequency-PS relationship. Furthermore, GC inhibition limits PS performance for fast frequency inputs, while enhancing PS for slow frequency inputs. GC interspike interval was found to be input frequency dependent in a "U"-shaped fashion, paralleling frequency-dependent PS observed at the network level. Additionally, GCs showed an attenuated firing response for fast frequency inputs. We conclude that independent of network-level inhibition, GCs may intrinsically be capable of producing a "U"-shaped input frequency-PS relationship. GCs may preferentially decorrelate slow and fast inputs via spike timing reorganization and high frequency filtering.