Biology subjects

Mylonas, D.

Publications and source records attributed to Mylonas, D..

9 recordsLinked to original sources

bioRxiv2024

Hippocampal ripples mediate motor learning during brief rest breaks in humans

Critical aspects of motor learning and memory happen offline, during both wake and sleep. When healthy young people learn a motor sequence task, most of their performance improvement happens not while typing, but offline, during interleaved rest breaks. In contrast, the performance of patients with dense amnesia due to hippocampal damage actually gets worse over the rest breaks and improves while typing. These findings indicate that an intact hippocampus is necessary for offline motor learning during wake, but do not specify its mechanism. Here, we studied epilepsy patients (n=17) undergoing direct intracranial EEG monitoring of the hippocampus as they learned the same motor sequence task. Like healthy young people, they showed greater speed gains across rest breaks than while typing. They also showed higher hippocampal ripple rates during these rest breaks that predicted offline gains in speed. This suggests that motor learning during brief rest breaks during wake is mediated by hippocampal ripples. These results expand our understanding of the role of hippocampal ripples beyond declarative memory to include enhancing motor procedural memory. Significance StatementIn patients with epilepsy undergoing direct intracranial EEG monitoring of the hippocampus, we found a higher rate of ripples during the brief rest breaks of a motor sequence task than during task execution. These offline hippocampal ripples predicted the amount of performance improvement over the break. We conclude that the hippocampus contributes to motor learning during brief rest breaks, and propose that this offline learning is mediated by ripples.

neuroscience↗

bioRxiv2023

A spectrum of altered non-rapid eye movement sleep in schizophrenia

BackgroundMultiple facets of sleep neurophysiology, including electroencephalography (EEG) metrics such as non-rapid eye movement (NREM) spindles and slow oscillations (SO), are altered in individuals with schizophrenia (SCZ). However, beyond group-level analyses which treat all patients as a unitary set, the extent to which NREM deficits vary among patients is unclear, as are their relationships to other sources of heterogeneity including clinical factors, illness duration and ageing, cognitive profiles and medication regimens. Using newly collected high density sleep EEG data on 103 individuals with SCZ and 68 controls, we first sought to replicate our previously reported (Kozhemiako et. al, 2022) group-level mean differences between patients and controls (original N=130). Then in the combined sample (N=301 including 175 patients), we characterized patient-to-patient variability in NREM neurophysiology. ResultsWe replicated all group-level mean differences and confirmed the high accuracy of our predictive model (Area Under the ROC Curve, AUC = 0.93 for diagnosis). Compared to controls, patients showed significantly increased between-individual variability across many (26%) sleep metrics, with patterns only partially recapitulating those for group-level mean differences. Although multiple clinical and cognitive factors were associated with NREM metrics including spindle density, collectively they did not account for much of the general increase in patient-to-patient variability. Medication regimen was a greater (albeit still partial) contributor to variability, although original group mean differences persisted after controlling for medications. Some sleep metrics including fast spindle density showed exaggerated age-related effects in SCZ, and patients exhibited older predicted biological ages based on an independent model of ageing and the sleep EEG. ConclusionWe demonstrated robust and replicable alterations in sleep neurophysiology in individuals with SCZ and highlighted distinct patterns of effects contrasting between-group means versus within-group variances. We further documented and controlled for a major effect of medication use, and pointed to greater age-related change in NREM sleep in patients. That increased NREM heterogeneity was not explained by standard clinical or cognitive patient assessments suggests the sleep EEG provides novel, nonredundant information to support the goals of personalized medicine. Collectively, our results point to a spectrum of NREM sleep deficits among SCZ patients that can be measured objectively and at scale, and that may offer a unique window on the etiological and genetic diversity that underlies SCZ risk, treatment response and prognosis.

neuroscience↗

bioRxiv2023

NREM sleep oscillations and their relations with sleep-dependent memory consolidation in early course psychosis and first-degree relatives

Sleep spindles are believed to mediate sleep-dependent memory consolidation, particularly when coupled to neocortical slow oscillations. Schizophrenia is characterized by a deficit in sleep spindles that correlates with reduced overnight memory consolidation. Here, we examined sleep spindle activity, slow oscillation-spindle coupling, and both motor procedural and verbal declarative memory consolidation in early course, minimally medicated psychosis patients and non-psychotic first-degree relatives. Using a four-night experimental procedure, we observed significant deficits in spindle density and amplitude in patients relative to controls that were driven by individuals with schizophrenia. Schizophrenia patients also showed reduced sleep-dependent consolidation of motor procedural memory, which correlated with spindle density. Contrary to expectations, there were no group differences in the consolidation of declarative memory on a word pairs task. Nor did the relatives of patients differ in spindle activity or memory consolidation compared with controls, however increased consistency in the timing of SO-spindle coupling were seen in both patient and relatives. Our results extend prior work by demonstrating correlated deficits in sleep spindles and sleep-dependent motor procedural memory consolidation in early course, minimally medicated patients with schizophrenia, but not in first-degree relatives. This is consistent with other work in suggesting that impaired sleep-dependent memory consolidation has some specificity for schizophrenia and is a core feature rather than reflecting the effects of medication or chronicity. Statement of significanceWe investigated sleep neurophysiology and memory consolidation in minimally-medicated, early course psychosis patients and unaffected first-degree relatives of patients in a four-night study. Early-course schizophrenia patients had a sleep spindle deficit that correlated with reduced procedural memory consolidation. Although first-degree relatives did not show any deficit in spindles or memory consolidation, the spindles of both relatives and patients showed increased consistency of the temporal coupling of spindles with slow oscillations compared with controls. These results suggest that sleep spindle and memory consolidation deficits are a core feature of schizophrenia. Spindle deficits may be a biomarker of schizophrenia modifiable by treatment, and motivate the development of targeted novel interventions.

neuroscience↗

bioRxiv2023

Human thalamic recordings reveal that epileptic spikes block sleep spindle production during non-rapid eye movement sleep

In severe epileptic encephalopathies, epileptic activity contributes to progressive cognitive dysfunction. Several epileptic encephalopathies share the trait of spike-wave activation during non-rapid eye movement sleep (EE-SWAS), a state dominated by sleep oscillations known to coordinate offline memory consolidation. How epileptic activity impacts these thalamocortical sleep oscillations has not been directly observed in humans. Using a unique dataset of simultaneous human thalamic and cortical recordings in subjects with and without EE-SWAS, we reconcile prior conflicting observations about how epileptic spikes coordinate with sleep oscillations and provide direct evidence for epileptic spike interference of sleep spindle production. We find that slow oscillations facilitate both epileptic spikes and sleep spindles during stage 2 sleep (N2) at different phases of the slow oscillation. We show that sleep activated cortical epileptic spikes propagate to the thalamus (thalamic spike rate is increased after a cortical spike, p[~]0). Thalamic spikes increase the spindle refractory period (p<1.5e-21). In patients with EE-SWAS, the abundance of thalamic spikes result in downregulation of spindles for 30 seconds after each thalamic spike (p=3.4e-11) and decreased overall spindle rate across N2 (p=2e-7). These direct human thalamocortical observations identify a novel mechanism through which epileptiform spikes could impact cognitive function, wherein sleep-activated epileptic spikes inhibit thalamic sleep spindles in epileptic encephalopathy.

neuroscience↗

bioRxiv2021

Non-rapid eye movement sleep and wake neurophysiology in schizophrenia

Motivated by the potential of objective neurophysiological markers to index thalamocortical function in patients with severe psychiatric illnesses, we comprehensively characterized key NREM sleep parameters across multiple domains, their interdependencies, and their relationship to waking event-related potentials and symptom severity. In 130 schizophrenia (SCZ) patients and controls, we confirmed a marked reduction in sleep spindle density in SCZ and extended these findings to show that only slow spindles predicted symptom severity, and that fast and slow spindle properties were largely uncorrelated. We also describe a novel measure of slow oscillation and spindle interaction that was attenuated in SCZ. The main sleep findings were replicated in a demographically distinct sample, and a joint model, based on multiple NREM components, predicted disease status in the replication cohort. Although also altered in patients, auditory event-related potentials elicited during wake were unrelated to NREM metrics. Consistent with a growing literature implicating thalamocortical dysfunction in SCZ, our characterization identifies independent NREM and wake EEG biomarkers that may index distinct aspects of SCZ pathophysiology and point to multiple neural mechanisms underlying disease heterogeneity. This study lays the groundwork for evaluating these neurophysiological markers, individually or in combination, to guide efforts at treatment and prevention as well as identifying individuals most likely to benefit from specific interventions.

neuroscience↗

bioRxiv2021

Sources of variation in the spectral slope of the sleep EEG

Building on previous work linking changes in the electroencephalogram (EEG) spectral slope to arousal level, Lendner et al. (2021) reported that wake, non rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep exhibit progressively steeper 30-45 Hz slopes, interpreted in terms of increasing cortical inhibition. Here we sought to replicate Lendner et al.s scalp EEG findings (based on 20 individuals) in a larger sample of 11,630 individuals from multiple cohorts in the National Sleep Research Resource (NSRR). In a final analytic sample of N = 10,255 distinct recordings, there was unambiguous statistical support for the hypothesis that, within individuals, the mean spectral slope grows steeper going from wake to NREM to REM sleep. We found that the choice of mastoid referencing scheme modulated the extent to which electromyogenic or electrocardiographic artifacts were likely to bias 30-45 Hz slope estimates, as well as other sources of technical, device-specific bias. Nonetheless, within individuals, slope estimates were relatively stable over time. Both cross-sectionally and longitudinal, slopes tended to become shallower with increasing age, particularly for REM sleep; males tended to show flatter slopes than females across all states. Although conceptually distinct, spectral slope did not predict sleep state substantially better than other summaries of the high frequency EEG power spectrum (>20 Hz, in this context) including beta band power, however. Finally, to more fully describe sources of variation in the spectral slope and its relationship to other sleep parameters, we quantified state-dependent differences in the variances (both within and between individuals) of spectral slope, power and interhemispheric coherence, as well as their covariances. In contrast to the common conception of the REM EEG as relatively wake-like (i.e. paradoxical sleep), REM and wake were the most divergent states for multiple metrics, with NREM exhibiting intermediate profiles. Under a simplified modelling framework, changes in spectral slope could not, by themselves, fully account for the observed differences between states, if assuming a strict power law model. Although the spectral slope is an appealing, theoretically inspired parameterization of the sleep EEG, here we underscore some practical considerations that should be borne in mind when applying it in diverse datasets. Future work will be needed to fully characterize state-dependent changes in the aperiodic portions of the EEG power spectra, which appear to be consistent with, albeit not fully explained by, changes in the spectral slope.

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bioRxiv2020

Sleep spindles facilitate selective memory consolidation

Sleep has been shown to be critical for memory consolidation, with some research suggesting that certain memories are prioritized for consolidation. Initial strength of a memory appears to be an important boundary condition in determining which memories are consolidated during sleep. However, the role of consolidation-mediating oscillations, such as sleep spindles and slow oscillations, in this preferential consolidation has not been explored. Here, 54 human participants (76% female) studied pairs of words to three distinct encoding strengths, with recall being tested immediately following learning and again six hours later. Thirty-six had a two-hour nap opportunity following learning, whilst the remaining 18 remained awake throughout. Results showed that across six hours awake, weakly encoded memories deteriorated the fastest. In the nap group however, this effect was attenuated, with forgetting rates equivalent across encoding strengths. Within the nap group, consolidation of weakly encoded items was associated with fast sleep spindle density during non-rapid eye movement sleep. Moreover, sleep spindles that were coupled to slow oscillations predicted the consolidation of weak memories independently of uncoupled sleep spindles. These relationships were unique to weakly encoded items, with spindles not correlating with memory for intermediate or strong items. This suggests that sleep spindles facilitate memory consolidation, guided in part by memory strength. Significance statementGiven the countless pieces of information we encode each day, how does the brain select which memories to commit to long-term storage? Sleep is known to aid in memory consolidation, and it appears that certain memories are prioritized to receive this benefit. Here, we found that compared to staying awake, sleep was associated with better memory for weakly encoded information. This suggests that sleep helps attenuate the forgetting of weak memory traces. Fast sleep spindles, a hallmark oscillation of non-rapid eye movement sleep, mediate consolidation processes. We extend this to show that fast spindles were uniquely associated with the consolidation of weakly encoded memories. This provides new evidence for preferential sleep-based consolidation and elucidate a physiological correlate of this benefit.

neuroscience↗

bioRxiv2018

The Biological Basis of the Experience of Constant Colour Categories

In the work reported here, we used the Land Colour Mondrian experiments to test the degree to which subjects vary in their perception of colour categories. Twenty subjects of different ethnic and cultural backgrounds, for all but one of whom English was not the primary language, viewed 8 patches of different colour in two Mondrian displays; each patch, when viewed, was made to reflect identical ratios of long-, middle- and short-wave light. Subjects were asked to match the colour of the viewed patch with that of the Munsell chip coming closest in colour to that of the viewed patch, without using language. Overall, there was no variability in categorizing colours as red, yellow, brown and green but a small variability in categorizing them as purple, blue, orange and turquoise. In terms of hue, we found significantly less variability in matching warm hues than in cool ones. We interpret the lack of significant variability between subjects in the matches made as a pointer to similar computational mechanisms being employed in different subjects to perceive colours, thus permitting subjects to assume that their categorization of colours has universal agreement and assent.

neuroscience↗

bioRxiv2016

The Constancy of Colored After-Images

We undertook psychophysical experiments to determine whether the color of the after-image produced by viewing a colored patch which is part of a complex multi-colored scene depends on the wavelength-energy composition of the light reflected from that patch. Our results show that, just as the color of a patch which is part of a complex scene is independent of the wavelength-energy composition of the light coming from it alone, but depends as well on the wavelength-energy composition of the light coming from its surrounds, so is the color of its after-image. Hence, traditional accounts of after-images as being the result of retinal adaptation or the perceptual result of physiological opponency, are inadequate. We propose instead that the color of after-images is generated after colors themselves are generated in the visual brain.

neuroscience↗