Naps reliably estimate nocturnal sleep spindle density in health and schizophrenia.

Sleep spindles, defining oscillations of non-rapid eye movement stage 2 sleep (N2), mediate memory consolidation. Spindle density (spindles/minute) is a stable, heritable feature of the sleep electroencephalogram. In schizophrenia, reduced spindle density correlates with impaired sleep-dependent memory consolidation and is a promising treatment target. Measuring sleep spindles is also important for basic studies of memory. However, overnight sleep studies are expensive, time consuming and require considerable infrastructure. Here we investigated whether afternoon naps can reliably and accurately estimate nocturnal spindle density in health and schizophrenia. Fourteen schizophrenia patients and eight healthy controls had polysomnography during two overnights and three afternoon naps. Although spindle density was lower during naps than nights, the two measures were highly correlated. For both groups, naps and nights provided highly reliable estimates of spindle density. We conclude that naps provide an accurate, reliable and more scalable alternative to measuring spindle density overnight.

Age-related Changes in the Sleep-dependent Reorganization of Declarative Memories.

Consolidation of declarative memories has been associated with slow wave sleep in young adults. Previous work suggests that, in spite of changes in sleep, sleep-dependent consolidation of declarative memories may be preserved with aging, although reduced relative to young adults. Previous work on young adults shows that, with consolidation, retrieval of declarative memories gradually becomes independent of the hippocampus. To investigate whether memories are similarly reorganized over sleep at the neural level, we compared functional brain activation associated with word pair recall following a nap and equivalent wake in young and older adults. SWS during the nap predicted better subsequent memory recall and was negatively associated with retrieval-related hippocampal activation in young adults. In contrast, in older adults there was no relationship between sleep and memory performance or with retrieval-related hippocampal activation. Furthermore, compared with young adults, postnap memory retrieval in older adults required strong functional connectivity of the hippocampus with the PFC, whereas there were no differences between young and older adults in the functional connectivity of the hippocampus following wakefulness. These results suggest that, although neural reorganization takes place over sleep in older adults, the shift is unique from that seen in young adults, perhaps reflecting memories at an earlier stage of stabilization.

Sleep benefits consolidation of visuo-motor adaptation learning in older adults.

Sleep is beneficial for performance across a range of memory tasks in young adults, but whether memories are similarly consolidated in older adults is less clear. Performance benefits have been observed following sleep in older adults for declarative learning tasks, but this benefit may be reduced for non-declarative, motor skill learning tasks. To date, studies of sleep-dependent consolidation of motor learning in older adults are limited to motor sequence tasks. To examine whether reduced sleep-dependent consolidation in older adults is generalizable to other forms of motor skill learning, we examined performance changes over intervals of sleep and wake in young (n = 62) and older adults (n = 61) using a mirror-tracing task, which assesses visuo-motor adaptation learning. Participants learned the task either in the morning or in evening, and performance was assessed following a 12-h interval containing overnight sleep or daytime wake. Contrary to our prediction, both young adults and older adults exhibited sleep-dependent gains in visuo-motor adaptation. There was a correlation between performance improvement over sleep and percent of the night in non-REM stage 2 sleep. These results indicate that motor skill consolidation remains intact with increasing age although this relationship may be limited to specific forms of motor skill learning.

Age-Related Changes in Sleep and Its Implications for Cognitive Decline in Aging Persons With Schizophrenia: A Critical Review.

BACKGROUND AND HYPOTHESIS: Cognitive impairment is a core feature of schizophrenia that worsens with aging and interferes with quality of life. Recent work identifies sleep as an actionable target to alleviate cognitive deficits. Cardinal non-rapid eye movement (NREM) sleep oscillations such as sleep spindles and slow oscillations are critical for cognition. People living with schizophrenia (PLWS) and their first-degree relatives have a specific reduction in sleep spindles and an abnormality in their temporal coordination with slow oscillations that predict impaired memory consolidation. While NREM oscillatory activity is reduced in typical aging, it is not known how further disruption in these oscillations contributes to cognitive decline in older PLWS. Another understudied risk factor for cognitive deficits among older PLWS is obstructive sleep apnea (OSA) which may contribute to cognitive decline. STUDY DESIGN: We conducted a narrative review to examine the published literature on aging, OSA, and NREM sleep oscillations in PLWS. STUDY RESULTS: Spindles are propagated via thalamocortical feedback loops, and this circuitry shows abnormal hyperconnectivity in schizophrenia as revealed by structural and functional MRI studies. While the risk and severity of OSA increase with age, older PLWS are particularly vulnerable to OSA-related cognitive deficits because OSA is often underdiagnosed and undertreated, and OSA adds further damage to the circuitry that generates NREM sleep oscillations. CONCLUSIONS: We highlight the critical need to study NREM sleep in older PWLS and propose that identifying and treating OSA in older PLWS will provide an avenue to potentially mitigate and prevent cognitive decline.

Sleep spindle activity is associated with state- and trait-based emotion in healthy school-aged children.

BACKGROUND: While connections between children's sleep and their daytime functioning are well established, less is known about the microstructural features of sleep that support emotional wellbeing. Investigating these relationships in healthy children may provide insight into adaptive emotional development. We therefore examined associations between non-rapid eye movement (N2) sleep spindles and both state- and trait-based measures of emotion. METHODS: A sample of 30 children (7-11 years) without psychiatric disorders completed a baseline assessment, one night of at-home polysomnography (PSG), and an in-lab emotional state assessment the next day including self-reported arousal in response to affective images. Trait-based measures of anxiety and depression as well as savoring, a positive emotion regulatory strategy, were also completed. N2 sleep spindle parameters, including spindle density (number/min) and peak frequency in central regions, were detected using an automated algorithm. RESULTS: Greater spindle density was significantly associated with decreased state-based emotional arousal towards negative affective images, and greater spindle peak frequency was associated with greater trait-based use of savoring. However, neither spindle parameter was associated with child anxiety or depressive symptoms. CONCLUSIONS: Findings align with and expand on prior research to suggest that N2 sleep spindles support adaptive emotional functioning in school-aged children.

Self-focused brain predictors of cognitive behavioral therapy response in a transdiagnostic sample.

BACKGROUND: Effective biomarkers of cognitive behavioral therapy (CBT) response provide information beyond available behavioral or self-report measures and may optimize treatment selection for patients based on likelihood of benefit. No single biomarker reliably predicts CBT response. In this study, we evaluated patterns of brain connectivity associated with self-focused attention (SFA) as biomarkers of CBT response for anxiety and obsessive-compulsive disorders. We hypothesized that pre-treatment as well as pre-to post-treatment changes in functional connectivity would be associated with improvement during CBT in a transdiagnostic sample. METHODS: Twenty-seven patients with primary social anxiety disorder (n = 14) and primary body dysmorphic disorder (n = 13) were scanned before and after 12 sessions of CBT targeting their primary disorder. Eligibility was based on elevated trait SFA scores on the Public Self-Consciousness Scale. Seed-based resting state functional connectivity associated with symptom improvement was computed using a seed in the posterior cingulate cortex of the default mode network. RESULTS: At pre-treatment, stronger positive connectivity of the seed with the cerebellum, and stronger negative connectivity with the putamen, were associated with greater clinical improvement. Between pre-to post-treatment, greater anticorrelation between the seed and postcentral gyrus, extending into the inferior parietal lobule and precuneus/superior parietal lobule was associated with clinical improvement, although this did not survive thresholding. CONCLUSIONS: Pre-treatment functional connectivity with the default mode network was associated with CBT response. Behavioral and self-report measures of SFA did not contribute to predictions, thus highlighting the value of neuroimaging-based measures of SFA. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT02808702 https://clinicaltrials.gov/ct2/show/NCT02808702.

Processing of emotional reactivity and emotional memory over sleep.

Sleep enhances memories, particularly emotional memories. As such, it has been suggested that sleep deprivation may reduce posttraumatic stress disorder. This presumes that emotional memory consolidation is paralleled by a reduction in emotional reactivity, an association that has not yet been examined. In the present experiment, we used an incidental memory task in humans and obtained valence and arousal ratings during two sessions separated either by 12 h of daytime wake or 12 h including overnight sleep. Recognition accuracy was greater following sleep relative to wake for both negative and neutral pictures. While emotional reactivity to negative pictures was greatly reduced over wake, the negative emotional response was relatively preserved over sleep. Moreover, protection of emotional reactivity was associated with greater time in REM sleep. Recognition accuracy, however, was not associated with REM. Thus, we provide the first evidence that sleep enhances emotional memory while preserving emotional reactivity.

COMT Val158Met polymorphism and executive functions in obsessive-compulsive disorder.

This study investigated the association between the catechol-O-methyl transferase (COMT) Val158Met polymorphism and executive functions in 101 patients with obsessive-compulsive disorder (OCD) and 100 healthy-control subjects (HS). Results showed that there was no significant difference for the genotype distributions between the OCD and HS groups. OCD-Met carrier subgroup's TMT B-A difference and lexical fluency scores were found to be significantly poorer than both HS subgroups. These findings suggest that lower activity of COMT associated with the Met allele, leading to higher levels of dopamine in the prefrontal cortex, lead to poorer executive function in OCD.

Increased resting-state thalamocortical functional connectivity in children and young adults with autism spectrum disorder.

There is converging evidence that abnormal thalamocortical interactions contribute to attention deficits and sensory sensitivities in autism spectrum disorder (ASD). However, previous functional MRI studies of thalamocortical connectivity in ASD have produced inconsistent findings in terms of both the direction (hyper vs. hypoconnectivity) and location of group differences. This may reflect, in part, the confounding effects of head motion during scans. In the present study, we investigated resting-state thalamocortical functional connectivity in 8-25 year-olds with ASD and their typically developing (TD) peers. We used pre-scan training, on-line motion correction, and rigorous data quality assurance protocols to minimize motion confounds. ASD participants showed increased thalamic connectivity with temporal cortex relative to TD. Both groups showed similar age-related decreases in thalamic connectivity with occipital cortex, consistent with a process of circuit refinement. Findings of thalamocortical hyperconnectivity in ASD are consistent with other evidence that decreased thalamic inhibition leads to increase and less filtered sensory information reaching the cortex where it disrupts attention and contributes to sensory sensitivity. This literature motivates studies of mechanisms, functional consequences, and treatment of thalamocortical circuit dysfunction in ASD.

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.

Self-Focused Brain Predictors of Cognitive Behavioral Therapy Response in a Transdiagnostic Sample.

Background: Effective biomarkers of cognitive behavioral therapy (CBT) response provide information beyond available behavioral or self-report measures and may optimize treatment selection for patients based on likelihood of benefit. No single biomarker reliably predicts CBT response. In this study, we evaluated patterns of brain connectivity associated with self-focused attention (SFA) as biomarkers of CBT response for anxiety and obsessive-compulsive disorders. We hypothesized that pre-treatment as well as pre- to post-treatment changes in functional connectivity would be associated with improvement during CBT in a transdiagnostic sample. Methods: Twenty-seven patients with primary social anxiety disorder (n=14) and primary body dysmorphic disorder (n=13) were scanned before and after 12 sessions of CBT targeting their primary disorder. Eligibility was based on elevated trait SFA scores on the Public Self-Consciousness Scale. Seed-based resting state functional connectivity associated with symptom improvement was computed using a seed in the posterior cingulate cortex/precuneus that delineated a self-other functional network. Results: At pre-treatment, stronger positive connectivity of the seed with the cerebellum, insula, middle occipital gyrus, postcentral gyrus, and precuneus/superior parietal lobule, and stronger negative connectivity with the putamen, were associated with greater clinical improvement. Between pre- to post-treatment, greater anticorrelation between the seed and precuneus/superior parietal lobule was associated with clinical improvement, although this did not survive thresholding. Conclusions: Pre-treatment functional connectivity between regions involved in attentional salience, self-generated thoughts, and external attention predicted greater CBT response. Behavioral and self-report measures of SFA did not contribute to predictions, thus highlighting the value of neuroimaging-based measures of SFA. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT02808702 https://clinicaltrials.gov/ct2/show/NCT02808702.

Neuropsychological function in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic disease characterized by repetitive, unwanted intrusive thoughts and ritualistic behaviors. Studies of neuropsychological functions in OCD have documented deficits in several cognitive domains, particularly with regard to visuospatial abilities, executive functioning, and motor speed. The objective of the present study was to investigate systematically the cognitive functioning of OCD patients who were free of medication and comorbid psychiatric disorders. In the present study, 72 OCD patients were compared with 54 healthy controls on their performance in a comprehensive neuropsychological battery. The Yale-Brown Obsessive Compulsive Scale and the Hamilton Depression Rating Scale were administered to the patients, and a semistructured interview form was used to evaluate the demographic features of the patients and control subjects. Overall, widespread statistically significant differences were found in tests related to verbal memory, global attention and psychomotor speed, and visuospatial and executive functions indicating a poorer performance of the OCD group. A closer scrutiny of these results suggests that the OCD group has difficulty in using an effective learning strategy that might be partly explained by their insufficient mental flexibility and somewhat poor planning abilities.

Brain-derived neurotrophic factor gene Val66Met polymorphism and cognitive function in obsessive-compulsive disorder.

In the present study, we have tested the hypothesis that brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism is associated with obsessive-compulsive disorder (OCD) and also investigated the association between the BDNF Val66Met polymorphism and the performance on tests measuring executive functions in a sample of patients with OCD. A total of 100 patients diagnosed with OCD according to DSM-IV criteria and 110 control subjects were included in this study. Single nucleotide polymorphism (G/A) leading to Val to Met substitution at codon 66 in BDNF was screened in the DNA samples of all participants. The genotype frequencies of BDNF Val66Met polymorphism were compared in OCD patients and healthy controls. The four subgroups of OCD and healthy control subjects, determined according to being Val homozygous or carrying a Met allele, were also compared according to their performance in a battery of neuropsychological tests of executive functions and verbal memory. There was no significant difference for the allele and genotype distributions of BDNF Val66Met polymorphism between the OCD and healthy control groups. Compared to the other three subgroups, OCD-Met carriers were slower on Trail-Making Test part A (TMT A), part B (TMT B) score and its speed-corrected score (TMT B-A). OCD-Met carriers had also poor performance on verbal fluency tasks and several CVLT measures compared only to the healthy control-Met carriers. These results demonstrate that the BDNF Val66Met polymorphism does not appear to be a risk factor for OCD. However, the presence of a BDNF Met allele, which is a known attenuator of BDNF activity, may be associated with a poorer executive functioning in OCD.

Maladaptive self-focused attention and default mode network connectivity: a transdiagnostic investigation across social anxiety and body dysmorphic disorders.

Maladaptive self-focused attention (SFA) is a bias toward internal thoughts, feelings and physical states. Despite its role as a core maintaining factor of symptoms in cognitive theories of social anxiety and body dysmorphic disorders (BDDs), studies have not examined its neural basis. In this study, we hypothesized that maladaptive SFA would be associated with hyperconnectivity in the default mode network (DMN) in self-focused patients with these disorders. Thirty patients with primary social anxiety disorder or primary BDD and 28 healthy individuals were eligible and scanned. Eligibility was determined by scoring greater than 1SD or below 1SD of the Public Self-Consciousness Scale normative mean, respectively, for each group. Seed-to-voxel functional connectivity was computed using a DMN posterior cingulate cortex (PCC) seed. There was no evidence of increased DMN functional connectivity in patients compared to controls. Patients (regardless of diagnosis) showed reduced functional connectivity of the PCC with several brain regions, including the bilateral superior parietal lobule (SPL), compared to controls, which was inversely correlated with maladaptive SFA but not associated with social anxiety, body dysmorphic, depression severity or rumination. Abnormal PCC-SPL connectivity may represent a transdiagnostic neural marker of SFA that reflects difficulty shifting between internal versus external attention.

REM-dependent repair of competitive memory suppression.

Memories are enhanced during sleep through memory consolidation processes. A recent study reported that sleep increases competitive forgetting in the absence of sleep-dependent consolidation of the target memory (Racsmany et al. in Psychol Sci 21:80-85, 2010). Here, using a modified retrieval-induced forgetting task, we examined whether sleep-dependent modulation of forgetting occurs concurrently with the consolidation of related target memories. Participants encoded a word-pair list and then practiced retrieving a portion of these pairs. Following a break with sleep or wake, recall of all pairs was tested. As expected, recall for practiced pairs was greater following sleep relative to wake. Contrary to Racsmany et al. (Psychol Sci 21:80-85, 2010), competitive forgetting decreased following sleep. Moreover, recall for practiced pairs correlated with slow wave sleep (SWS) while forgetting of competing targets correlated negatively with REM, suggesting a novel function of these sequential brain states on memory processing.

The effects of eszopiclone on sleep spindles and memory consolidation in schizophrenia: a randomized clinical trial.

Sleep spindles, defining oscillations of stage 2 non-rapid eye movement sleep (N2), mediate memory consolidation. Schizophrenia is characterized by reduced spindle activity that correlates with impaired sleep-dependent memory consolidation. In a small, randomized, placebo-controlled pilot study of schizophrenia, eszopiclone (Lunesta®), a nonbenzodiazepine sedative hypnotic, increased N2 spindle density (number/minute) but did not significantly improve memory. This larger double-blind crossover study that included healthy controls investigated whether eszopiclone could both increase N2 spindle density and improve memory. Twenty-six medicated schizophrenia outpatients and 29 healthy controls were randomly assigned to have a placebo or eszopiclone (3 mg) sleep visit first. Each visit involved two consecutive nights of high density polysomnography with training on the Motor Sequence Task (MST) on the second night and testing the following morning. Patients showed a widespread reduction of spindle density and, in both groups, eszopiclone increased spindle density but failed to enhance sleep-dependent procedural memory consolidation. Follow-up analyses revealed that eszopiclone also affected cortical slow oscillations: it decreased their amplitude, increased their duration, and rendered their phase locking with spindles more variable. Regardless of group or visit, the density of coupled spindle-slow oscillation events predicted memory consolidation significantly better than spindle density alone, suggesting that they are a better biomarker of memory consolidation. In conclusion, sleep oscillations are promising targets for improving memory consolidation in schizophrenia, but enhancing spindles is not enough. Effective therapies also need to preserve or enhance cortical slow oscillations and their coordination with thalamic spindles, an interregional dialog that is necessary for sleep-dependent memory consolidation.

Increased Thalamocortical Connectivity in Schizophrenia Correlates With Sleep Spindle Deficits: Evidence for a Common Pathophysiology.

BACKGROUND: Converging evidence implicates abnormal thalamocortical interactions in the pathophysiology of schizophrenia. This evidence includes consistent findings of increased resting-state functional connectivity of the thalamus with somatosensory and motor cortex during wake and reduced spindle activity during sleep. We hypothesized that these abnormalities would be correlated, reflecting a common mechanism: reduced inhibition of thalamocortical neurons by the thalamic reticular nucleus (TRN). The TRN is the major inhibitory nucleus of the thalamus and is abnormal in schizophrenia. Reduced TRN inhibition would be expected to lead to increased and less filtered thalamic relay of sensory and motor information to the cortex during wake and reduced burst firing necessary for spindle initiation during sleep. METHODS: Overnight polysomnography and resting-state functional connectivity magnetic resonance imaging were performed in 26 outpatients with schizophrenia and 30 demographically matched healthy individuals. We examined the relations of sleep spindle density during stage 2 non-rapid eye movement sleep with connectivity of the thalamus to the cortex during wakeful rest. RESULTS: As in prior studies, patients with schizophrenia exhibited increased functional connectivity of the thalamus with bilateral somatosensory and motor cortex and reduced sleep spindle density. Spindle density inversely correlated with thalamocortical connectivity, including in somotosensory and motor cortex, regardless of diagnosis. CONCLUSIONS: These findings link two biomarkers of schizophrenia-the sleep spindle density deficit and abnormally increased thalamocortical functional connectivity-and point to deficient TRN inhibition as a plausible mechanism. If TRN-mediated thalamocortical dysfunction increases risk for schizophrenia and contributes to its manifestations, understanding its mechanism could guide the development of targeted interventions.

Spared and impaired sleep-dependent memory consolidation in schizophrenia.

OBJECTIVE: Cognitive deficits in schizophrenia are the strongest predictor of disability and effective treatment is lacking. This reflects our limited mechanistic understanding and consequent lack of treatment targets. In schizophrenia, impaired sleep-dependent memory consolidation correlates with reduced sleep spindle activity, suggesting sleep spindles as a potentially treatable mechanism. In the present study we investigated whether sleep-dependent memory consolidation deficits in schizophrenia are selective. METHODS: Schizophrenia patients and healthy individuals performed three tasks that have been shown to undergo sleep-dependent consolidation: the Word Pair Task (verbal declarative memory), the Visual Discrimination Task (visuoperceptual procedural memory), and the Tone Task (statistical learning). Memory consolidation was tested 24 h later, after a night of sleep. RESULTS: Compared with controls, schizophrenia patients showed reduced overnight consolidation of word pair learning. In contrast, both groups showed similar significant overnight consolidation of visuoperceptual procedural memory. Neither group showed overnight consolidation of statistical learning. CONCLUSION: The present findings extend the known deficits in sleep-dependent memory consolidation in schizophrenia to verbal declarative memory, a core, disabling cognitive deficit. In contrast, visuoperceptual procedural memory was spared. These findings support the hypothesis that sleep-dependent memory consolidation deficits in schizophrenia are selective, possibly limited to tasks that rely on spindles. These findings reinforce the importance of deficient sleep-dependent memory consolidation among the cognitive deficits of schizophrenia and suggest sleep physiology as a potentially treatable mechanism.

Diffusion-weighted imaging evidence of altered white matter development from late childhood to early adulthood in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is thought to reflect disrupted development of brain connectivity characterized by white matter abnormalities and dyscoordination of activity across brain regions that give rise to core features. But there is little consensus about the nature, timing and location of white matter abnormalities as quantified with diffusion-weighted MRI. Inconsistent findings likely reflect small sample sizes, motion confounds and sample heterogeneity, particularly different age ranges across studies. We examined the microstructural integrity of major white matter tracts in relation to age in 38 high functioning ASD and 35 typically developing (TD) participants, aged 8-25, whose diffusion-weighted scans met strict data-quality criteria and survived group matching for motion. While there were no overall group differences in diffusion measures, the groups showed different relations with age. Only the TD group showed the expected positive correlations of fractional anisotropy with age. In parallel, axial diffusivity was unrelated to age in TD, but showed inverse correlations with age in ASD. Younger participants with ASD tended to have higher fractional anisotropy and axial diffusivity than their TD peers, while the opposite was true for older participants. Most of the affected tracts - cingulum bundle, inferior and superior longitudinal fasciculi - are association bundles related to cognitive, social and emotional functions that are abnormal in ASD. The manifestations of abnormal white matter development in ASD as measured by diffusion-weighted MRI depend on age and this may contribute to inconsistent findings across studies. We conclude that ASD is characterized by altered white matter development from childhood to early adulthood that may underlie abnormal brain function and contribute to core features.

Coordination of Slow Waves With Sleep Spindles Predicts Sleep-Dependent Memory Consolidation in Schizophrenia.

Study Objectives: Schizophrenia patients have correlated deficits in sleep spindle density and sleep-dependent memory consolidation. In addition to spindle density, memory consolidation is thought to rely on the precise temporal coordination of spindles with slow waves (SWs). We investigated whether this coordination is intact in schizophrenia and its relation to motor procedural memory consolidation. Methods: Twenty-one chronic medicated schizophrenia patients and 17 demographically matched healthy controls underwent two nights of polysomnography, with training on the finger tapping motor sequence task (MST) on the second night and testing the following morning. We detected SWs (0.5-4 Hz) and spindles during non-rapid eye movement (NREM) sleep. We measured SW-spindle phase-amplitude coupling and its relation with overnight improvement in MST performance. Results: Patients did not differ from controls in the timing of SW-spindle coupling. In both the groups, spindles peaked during the SW upstate. For patients alone, the later in the SW upstate that spindles peaked and the more reliable this phase relationship, the greater the overnight MST improvement. Regression models that included both spindle density and SW-spindle coordination predicted overnight improvement significantly better than either parameter alone, suggesting that both contribute to memory consolidation. Conclusion: Schizophrenia patients show intact spindle-SW temporal coordination, and these timing relationships, together with spindle density, predict sleep-dependent memory consolidation. These relations were seen only in patients suggesting that their memory is more dependent on optimal spindle-SW timing, possibly due to reduced spindle density. Interventions to improve memory may need to increase spindle density while preserving or enhancing the coordination of NREM oscillations.