http://www.nmr.mgh.harvard.edu/manoachlab/pubs/Manoach_endophenotype_reviewBP15.pdf

Reduced Sleep Spindles in Schizophrenia: A Treatable Endophenotype That Links Risk Genes to Impaired Cognition?

There is overwhelming evidence that sleep is crucial for memory consolidation. Patients with schizophrenia and their unaffected relatives have a specific deficit in sleep spindles, a defining oscillation of non-rapid eye movement (NREM) Stage 2 sleep that, in coordination with other NREM oscillations, mediate memory consolidation. In schizophrenia, the spindle deficit correlates with impaired sleep-dependent memory consolidation, positive symptoms, and abnormal thalamocortical connectivity. These relations point to dysfunction of the thalamic reticular nucleus (TRN), which generates spindles, gates the relay of sensory information to the cortex, and modulates thalamocortical communication. Genetic studies are beginning to provide clues to possible neurodevelopmental origins of TRN-mediated thalamocortical circuit dysfunction and to identify novel targets for treating the related memory deficits and symptoms. By forging empirical links in causal chains from risk genes to thalamocortical circuit dysfunction, spindle deficits, memory impairment, symptoms, and diagnosis, future research can advance our mechanistic understanding, treatment, and prevention of schizophrenia.

Abnormal Sleep Spindles, Memory Consolidation, and Schizophrenia

Reduced sleep spindle activity point to a TRN-MD thalamus-PFC circuit dysfunction in schizophrenia

The effect of selective REM-sleep deprivation on the consolidation and affective evaluation of emotional memories.

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.

/pdf/coordination-of-slow-waves-with-sleep-spindles-predicts-2wlcezpiw0.pdf

Anna Graf

Papers

Impairment of sleep-related memory consolidation in schizophrenia: relevance of sleep spindles?