scholarly journals Schizophrenia-associated variation at ZNF804A correlates with altered experience-dependent dynamics of sleep slow waves and spindles in healthy young adults

SLEEP ◽  
2021 ◽  
Author(s):  
Ullrich Bartsch ◽  
Laura J Corbin ◽  
Charlotte Hellmich ◽  
Michelle Taylor ◽  
Kayleigh E Easey ◽  
...  

Abstract The rs1344706 polymorphism in ZNF804A is robustly associated with schizophrenia and schizophrenia is, in turn, associated with abnormal non-rapid eye movement (NREM) sleep neurophysiology. To examine whether rs1344706 is associated with intermediate neurophysiological traits in the absence of disease, we assessed the relationship between genotype, sleep neurophysiology, and sleep-dependent memory consolidation in healthy participants. We recruited healthy adult males with no history of psychiatric disorder from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Participants were homozygous for either the schizophrenia-associated ‘A’ allele (N=22) or the alternative ‘C’ allele (N=18) at rs1344706. Actigraphy, polysomnography (PSG) and a motor sequence task (MST) were used to characterize daily activity patterns, sleep neurophysiology and sleep-dependent memory consolidation. Average MST learning and sleep-dependent performance improvements were similar across genotype groups, albeit more variable in the AA group. During sleep after learning, CC participants showed increased slow-wave (SW) and spindle amplitudes, plus augmented coupling of SW activity across recording electrodes. SW and spindles in those with the AA genotype were insensitive to learning, whilst SW coherence decreased following MST training. Accordingly, NREM neurophysiology robustly predicted the degree of overnight motor memory consolidation in CC carriers, but not in AA carriers. We describe evidence that rs1344706 polymorphism in ZNF804A is associated with changes in the coordinated neural network activity that supports offline information processing during sleep in a healthy population. These findings highlight the utility of sleep neurophysiology in mapping the impacts of schizophrenia-associated common genetic variants on neural circuit oscillations and function.

2020 ◽  
Author(s):  
Ullrich Bartsch ◽  
Laura J Corbin ◽  
Charlotte Hellmich ◽  
Michelle Taylor ◽  
Kayleigh E Easey ◽  
...  

ABSTRACTBackgroundThe rs1344706 polymorphism in ZNF804A is robustly associated with schizophrenia (SZ), yet brain and behavioral phenotypes related to this variant have not been extensively characterized. In turn, SZ is associated with abnormal non-rapid eye movement (NREM) sleep neurophysiology. To examine whether rs1344706 is associated with intermediate neurophysiological traits in the absence of disease, we assessed the relationship between genotype, sleep neurophysiology, and sleep-dependent memory consolidation in healthy participants.MethodsWe recruited healthy adult males, with no history of psychiatric disorder, from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Participants were homozygous for either the SZ-associated ‘A’ allele (N=25) or the alternative ‘C’ allele (N=22) at rs1344706. Actigraphy, polysomnography (PSG) and a motor sequencing task (MST) were used to characterize daily activity patterns, sleep neurophysiology and sleep-dependent memory consolidation.ResultsAverage MST learning and sleep-dependent performance improvements were similar across genotype groups, but with increased variability in the AA group. CC participants showed increased slow-wave and spindle amplitudes, plus augmented coupling of slow-wave activity across recording electrodes after learning. Slow-waves and spindles in those with the AA genotype were insensitive to learning, whilst slow-wave coherence decreased following MST training.ConclusionWe describe evidence that rs1344706 polymorphism in ZNF804A is associated with changes in experience- and sleep-dependent, local and distributed neural network activity that supports offline information processing during sleep in a healthy population. These findings highlight the utility of sleep neurophysiology in mapping the impacts of SZ-associated variants on neural circuit oscillations and function.


2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Ullrich Bartsch ◽  
Andrew J. Simpkin ◽  
Charmaine Demanuele ◽  
Erin Wamsley ◽  
Hugh M. Marston ◽  
...  

Abstract The slow waves (SW) of non-rapid eye movement (NREM) sleep reflect neocortical components of network activity during sleep-dependent information processing; their disruption may therefore impair memory consolidation. Here, we quantify sleep-dependent consolidation of motor sequence memory, alongside sleep EEG-derived SW properties and synchronisation, and SW–spindle coupling in 21 patients suffering from schizophrenia and 19 healthy volunteers. Impaired memory consolidation in patients culminated in an overnight improvement in motor sequence task performance of only 1.6%, compared with 15% in controls. During sleep after learning, SW amplitudes and densities were comparable in healthy controls and patients. However, healthy controls showed a significant 45% increase in frontal-to-occipital SW coherence during sleep after motor learning in comparison with a baseline night (baseline: 0.22 ± 0.05, learning: 0.32 ± 0.05); patient EEG failed to show this increase (baseline: 0.22 ± 0.04, learning: 0.19 ± 0.04). The experience-dependent nesting of spindles in SW was similarly disrupted in patients: frontal-to-occipital SW–spindle phase-amplitude coupling (PAC) significantly increased after learning in healthy controls (modulation index baseline: 0.17 ± 0.02, learning: 0.22 ± 0.02) but not in patients (baseline: 0.13 ± 0.02, learning: 0.14 ± 0.02). Partial least-squares regression modelling of coherence and PAC data from all electrode pairs confirmed distributed SW coherence and SW–spindle coordination as superior predictors of overnight memory consolidation in healthy controls but not in patients. Quantifying the full repertoire of NREM EEG oscillations and their long-range covariance therefore presents learning-dependent changes in distributed SW and spindle coordination as fingerprints of impaired cognition in schizophrenia.


2019 ◽  
Author(s):  
Ullrich Bartsch ◽  
Andrew Simpkin ◽  
Charmaine Demanuele ◽  
Erin Wamsley ◽  
Hugh Marston ◽  
...  

AbstractThe slow-waves (SW) of non-rapid eye movement sleep (NREM) reflect neocortical components of network activity during sleep-dependent information processing; their disruption may therefore contribute to impaired memory consolidation. Here, we quantify SW dynamics relative to motor sequence memory in patients suffering schizophrenia and healthy volunteers.Patients showed normal intrinsic SW properties but impaired SW coherence, which failed to exhibit the learning-dependent increases evident in healthy volunteers. SW-spindle phase amplitude coupling across distributed EEG electrodes was also dissociated from experience in patients, with long-range fronto-parietal and -occipital networks most severely affected. Partial least squares regression modelling confirmed distributed SW coherence and SW-spindle coordination as predictors of overnight memory consolidation in healthy controls, but not in patients.Quantifying the full repertoire of NREM EEG oscillations and their long-range covariance therefore presents learning-dependent changes in distributed SW and spindle coordination as fingerprints of impaired cognition in schizophrenia.


2021 ◽  
Author(s):  
Charles W Dickey ◽  
Ilya A Verzhbinsky ◽  
Xi Jiang ◽  
Burke Q Rosen ◽  
Sophie Kajfez ◽  
...  

Hippocampal ripples index the reconstruction of spatiotemporal neuronal firing patterns essential for the consolidation of memories in the cortex during non-rapid eye movement (NREM) sleep. However, it is not known whether ripples are generated in the human cortex during sleep. Here, using human intracranial recordings, we show that ~70ms long ~80Hz ripples are ubiquitous in all regions of the cortex during NREM sleep as well as waking. During waking, cortical ripples occur on local high frequency activity peaks. During sleep, cortical ripples occur during spindles on the down-to-upstate transition, with unit-firing patterns consistent with generation by pyramidal-interneuron feedback. Cortical ripples mark the recurrence of spatiotemporal activity patterns from preceding waking, and they group co-firing within the window of spike-timing-dependent plasticity. Thus, cortical ripples guided by sequential sleep waves may facilitate memory consolidation during NREM sleep in humans.


2020 ◽  
Author(s):  
Quinton M. Skilling ◽  
Brittany C. Clawson ◽  
Bolaji Eniwaye ◽  
James Shaver ◽  
Nicolette Ognjanovski ◽  
...  

SummarySleep plays a critical role in memory consolidation, although the exact mechanisms mediating this process are unknown. Combining computational and in vivo experimental approaches, we test the hypothesis that reduced cholinergic input to the hippocampus during non-rapid eye movement (NREM) sleep generates stable spike timing relationships between neurons. We find that the order of firing among neurons during a period of NREM sleep reflects their relative firing rates during prior wake, and changes as a function of prior learning. We show that learning-dependent pattern formation (e.g. “replay”) in the hippocampus during NREM, together with spike timing dependent plasticity (STDP), restructures network activity in a manner similar to that observed in brain circuits across periods of sleep. This suggests that sleep actively promotes memory consolidation by switching the network from rate-based to firing phase-based information encoding.


Author(s):  
Michelle A. Frazer ◽  
Yesenia Cabrera ◽  
Rockelle S. Guthrie ◽  
Gina R. Poe

Abstract Purpose of review This paper reviews all optogenetic studies that directly test various sleep states, traits, and circuit-level activity profiles for the consolidation of different learning tasks. Recent findings Inhibiting or exciting neurons involved either in the production of sleep states or in the encoding and consolidation of memories reveals sleep states and traits that are essential for memory. REM sleep, NREM sleep, and the N2 transition to REM (characterized by sleep spindles) are integral to memory consolidation. Neural activity during sharp-wave ripples, slow oscillations, theta waves, and spindles are the mediators of this process. Summary These studies lend strong support to the hypothesis that sleep is essential to the consolidation of memories from the hippocampus and the consolidation of motor learning which does not necessarily involve the hippocampus. Future research can further probe the types of memory dependent on sleep-related traits and on the neurotransmitters and neuromodulators required.


2021 ◽  
Vol 11 (2) ◽  
pp. 261
Author(s):  
Frank J. van Schalkwijk ◽  
Walter R. Gruber ◽  
Laurie A. Miller ◽  
Eugen Trinka ◽  
Yvonne Höller

Memory complaints are frequently reported by patients with epilepsy and are associated with seizure occurrence. Yet, the direct effects of seizures on memory retention are difficult to assess given their unpredictability. Furthermore, previous investigations have predominantly assessed declarative memory. This study evaluated within-subject effects of seizure occurrence on retention and consolidation of a procedural motor sequence learning task in patients with epilepsy undergoing continuous monitoring for five consecutive days. Of the total sample of patients considered for analyses (N = 53, Mage = 32.92 ± 13.80 y, range = 18–66 y; 43% male), 15 patients experienced seizures and were used for within-patient analyses. Within-patient contrasts showed general improvements over seizure-free (day + night) and seizure-affected retention periods. Yet, exploratory within-subject contrasts for patients diagnosed with temporal lobe epilepsy (n = 10) showed that only seizure-free retention periods resulted in significant improvements, as no performance changes were observed following seizure-affected retention. These results indicate general performance improvements and offline consolidation of procedural memory during the day and night. Furthermore, these results suggest the relevance of healthy temporal lobe functioning for successful consolidation of procedural information, as well as the importance of seizure control for effective retention and consolidation of procedural memory.


Neuroforum ◽  
2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Maryam Ghorbani ◽  
Lisa Marshall

AbstractSleep contributes actively to the consolidation of many forms of memory. This review describes the neural oscillations of non-rapid eye movement (NREM) sleep, the structures underlying these oscillations and their relation to hippocampus-dependent memory consolidation. A main focus lies on the relation between inter- and intraregional interactions and their electrophysiological representation. Methods for modulating neural oscillations with the intent of affecting memory consolidation are presented.


2010 ◽  
Vol 104 (5) ◽  
pp. 2603-2614 ◽  
Author(s):  
Michael A. Nitsche ◽  
Michaela Jakoubkova ◽  
Nivethida Thirugnanasambandam ◽  
Leonie Schmalfuss ◽  
Sandra Hullemann ◽  
...  

Motor learning and memory consolidation require the contribution of different cortices. For motor sequence learning, the primary motor cortex is involved primarily in its acquisition. Premotor areas might be important for consolidation. In accordance, modulation of cortical excitability via transcranial DC stimulation (tDCS) during learning affects performance when applied to the primary motor cortex, but not premotor cortex. We aimed to explore whether premotor tDCS influences task performance during motor memory consolidation. The impact of excitability-enhancing, -diminishing, or placebo premotor tDCS during rapid eye movement (REM) sleep on recall in the serial reaction time task (SRTT) was explored in healthy humans. The motor task was learned in the evening. Recall was performed immediately after tDCS or the following morning. In two separate control experiments, excitability-enhancing premotor tDCS was performed 4 h after task learning during daytime or immediately before conduction of a simple reaction time task. Excitability-enhancing tDCS performed during REM sleep increased recall of the learned movement sequences, when tested immediately after stimulation. REM density was enhanced by excitability-increasing tDCS and reduced by inhibitory tDCS, but did not correlate with task performance. In the control experiments, tDCS did not improve performance. We conclude that the premotor cortex is involved in motor memory consolidation during REM sleep.


1984 ◽  
Vol 57 (4) ◽  
pp. 1089-1096 ◽  
Author(s):  
A. D. Berssenbrugge ◽  
J. A. Dempsey ◽  
J. B. Skatrud

We assessed the influence of sleep state on ventilatory acclimatization to hypoxia. Ventilation, arterial O2 saturation (SaO2), and arterial acid-base status were monitored in healthy adult males during wakefulness, nonrapid-eye-movement (NREM) sleep, and rapid-eye-movement (REM) sleep in normoxia [barometric pressure (PB) = 740 Torr] and over 4 continuous days of hypobaric hypoxia (PB = 455 Torr). The relative hypoventilation observed during sleep compared with wakefulness in normoxia was also observed during all stages of hypoxic acclimatization. The characteristic time-dependent changes associated with acclimatization to chronic hypoxia were similar during wakefulness and all sleep states: 1) arterial CO2 partial pressure (PaCO2) decreased 27–31% by night 4 with approximately half of this fall occurring acutely (0.3–3 h hypoxia); 2) minute ventilation increased progressively with duration of hypoxic exposure including increased levels of hyperventilation throughout the initial night of sleep in hypoxia; 3) SaO2 was lowest acutely and gradually increased coincident with the progressive hyperventilation; and 4) pHa increased acutely and remained unchanged despite additional hyperventilation due to a compensatory reduction in [HCO3-]a. In addition, in the acclimatized subject hyperventilation persisted following acute restoration of normoxia, and this continued hyperventilation was similar in magnitude during both wakefulness and NREM sleep. These results indicate that suprapontine influences on ventilatory control associated with the state of wakefulness are not required in the process of ventilatory acclimatization to chronic hypoxia.


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