Archives Italiennes de Biologie, 150: 185-193, 2012. Sleep-dependent consolidation of motor skills in patients with narcolepsy-cataplexy M. MAZZETTI1, G. PLAZZI2, C. CAMPI1, A. CICCHELLA1, K. MATTAROZZI1, G. TUOZZI1, S. VANDI2, L. VIGNATELLI3, C. CIPOLLI1 1 Department of Psychology, University of Bologna, Italy; 2 Department of Neurological Sciences, University of Bologna, Italy; 3 City of Bologna Local Health Trust, Bologna, Italy A bstract Background and Objectives: This study investigated whether the altered organization of post-training sleep in patients with narcolepsy-cataplexy (NC) is associated with a lower off-line improvement in the consolidation of motor skills compared with normal subjects. Study Design: Fourteen drug-naive NC patients, fulfilling the international clinical and polysomnographic diag- nostic criteria, and 14 individually-matched controls underwent training at a sequential finger tapping task (FTT) and were re-tested on the next morning (after a night with polysomnographic recording) and after another six nights (spent at home). Setting: Training and retrieval sessions were performed in a controlled laboratory setting. Results: FTT performance was worse in NC patients than controls at training and at both retrieval sessions and showed a fairly different time course (slower than in controls) of consolidation. Several sleep indices (lower values of stage-2 NREM sleep and SWS) were compatible with a lower effectiveness of sleep for consolidation of motor skills in NC patients, although no statistically significant relationship was found between such indices and improve- ment rate. Conclusion: The consolidation process of motor skills results less effective in NC patients since training and slower than in normal subjects over the week following training. The wider variations in performance scores and sleep parameters of post.-training night in NC patients relative to controls suggest that a) the lower initial consolidation may be due to a less effective encoding consequent to altered prior sleep, and b) the consolidation process over the 24 h following training is negatively influenced not only by the altered characteristics of post-training sleep, but also by the daytime sleepiness following training. Key words Narcolepsy-cataplexy • Altered sleep • Non-declarative memory • Consolidation process • Motor skills Introduction particular, non-declarative) information has shown to be negatively influenced by an acute sleep loss, A sleep-dependent effect has been consistently as well as sleep restriction and fragmentation (for observed in the consolidation process of recent review, see Diekelmann and Born, 2010). (namely, acquired in the pre-sleep period) informa- It seems thus plausible that the altered sleep of tion, regardless of their declarative or non-declar- patients with such chronic disorders as primary ative nature (i.e., “know what” and “know-how”, insomnia (PI), obstructive sleep apnoeas (OSA), and according to Squire’s taxonomy: Squire, 1993). narcolepsy-cataplexy (NC), also has a less positive Complementarily, the consolidation of new (in effect on memory consolidation. Indeed, these disor- Corresponding Author: Carlo Cipolli, Department of Psychology, University of Bologna, viale Berti Pichat 5, 40127, Bologna, Italy - Tel.: +39 51 2091816 - Fax: +39 51 243086 - Email: [email protected] 186 M. MAZZETTI ET AL. ders have often been associated with varying impair- Inclusion criteria were: excessive daytime sleepi- ments in memory tasks on both declarative and non- ness, measured by the Epworth Sleepiness Scale declarative information (in particular, perceptual and (ESS: Johns, 1991) and confirmed by the Multiple motor skills: for review, see Fulda and Schulz, 2001; Sleep Latency Test (MSLT), demonstrating a mean 2010). This makes it crucial to establish whether the sleep latency of eight minutes or less and at least postulated smaller gain provided by altered sleep in two episodes of SOREM sleep; clear-cut cataplexy; the consolidation of new information is at least partly presence of the human leukocyte antigen HLA- responsible for the memory impairment observed in DQB1*0602 (Mignot et al., 1997); right-handedness. patients with chronic sleep disorders. Exclusion criteria were: age under 18 and over 50 To date, few studies have tested this hypothesis (for years (the wide age range depending on the rarity review, see Cipolli et al., 2012). A lower post-night of the disease); less than eight years of education; a improvement in motor skills relative to normal sub- history of pharmacological treatment for sleep disor- jects has been reported in two (Nissen et al., 2006; ders; a history of psychiatric disorders or other neu- 2011) of the three studies (the other being that by rological diseases, and brain lesions (ascertained at Backhaus et al., 2006) on PI patients and in the brain magnetic resonance imaging (MRI); moderate only study on OSA patients (Kloepfer et al., 2009), or severe depression (a score higher than 18 on Beck whereas no study has so far investigated NC patients. Depression Inventory: (Beck et al., 1961), visual or Narcolepsy-cataplexy is a neurological disease asso- motor deficits, i.e. scores above the cut-off point of ciated to numerous variations in the sleep architec- mild deficit in all the psychometric tests listed below ture. Besides an excessive daytime sleepiness, NC (see Materials). patients show an increased number of awakenings and stage shifts over the night, a larger proportion Control subjects of stage-1 and lower proportions of stage 2 sleep Fourteen healthy subjects individually matched with and slow wave sleep (SWS) than normal subjects NC patients for sex, age and educational level (AASM, 2005). were selected at the Psychology Department of the We report here the results of a study on the level University of Bologna. Subjects had to sleep seven and time course of motor skills consolidation in to nine hours per night without any major disruption NC patients relative to matched healthy controls. of the sleep-wake cycle, as assessed clinically by an Consolidation level was measured by means a expert neurologist (G.P.). The exclusion criteria were sequential finger tapping task (FTT) at training, the same as those adopted for NC patients, plus a after the following night (spent in laboratory) and score of ten or more at ESS and the need to take any after a six further nights (spent at home). FTT was medication at the time of the experiment. Subjects chosen as a) sensitive to sleep-dependent variations were paid for their participation in the study. in motor learning in healthy subjects (Walker et al., The study protocol was approved by the local Ethics 2002), and b) representative of skilled sequential Committee. Informed written consent according to movements (from dialling a phone number to play- the Declaration of Helsinki was obtained from each ing the piano) at work in everyday motor behaviour participant. (Ghilardi et al., 2009; Kvint et al., 2011). Apparatus PSG recording (System 98, Micromed®; Mogliano Methods Veneto, Italy) included EEG (four channels), verti- cal and horizontal EOG (two channels), EMG (three Participants channels) for mylohyoideus and right and left ante- Patients rior tibialis muscles and ECG (one channel). EEG Fourteen first-diagnosed NC patients were enrolled electrodes were positioned according to the interna- for the study at the Sleep Disorders Centre of the tional 10-20 system on sites C3, C4, Cz, O1, with University of Bologna. NC diagnosis was based controlateral mastoid reference. Sleep stages were on the international clinical and polysomnographic classified following standard criteria (Rechtschaffen (PSG) criteria (AASM, 2005). and Kales, 1968). SLEEP AND motor SKILLS IN NARCOLEPSY 187 Materials day, the next day (after the night spent in laboratory) Psychometric Testing and after a further six nights (spent at home). All participants were examined by the same psy- The experiment was planned on non-consecutive chologist, unaware of the study aims, who admin- days with respect to the clinical routine to avoid istered Wechsler Adult Intelligence Scale - Revised making the cognitive and emotional burden too (Wechsler, 1981) for the assessment of global and arduous. specific cognitive deficits, Wechsler Memory Scale (Wechsler, 1987) for short- and long-term memory, Control subjects Baddeley Logical Reasoning Test (Baddeley, 1968) The design planned for controls was the same as for for reasoning, the forms A and B of Trail Making NC patients to balance the cognitive and emotional Test for speed of processing, flexibility and execu- demands: subjects eligible as individually-matched tive functions (Tombaugh, 2004). controls underwent psychometric assessment and a nocturnal PSG recording for adaptation to the labo- finger Tapping ratory and started the experimental routine in the FTT requires the subject to press repeatedly a following week. five element sequence (6-3-5-4-6) with the fingers None of the participants were permitted to take a nap (except thumb) of the non-dominant hand on a com- after training, in order to measure the influence of puter keyboard as fast and accurately as possible for the following night-time sleep per se on the consoli- 30-s trials interrupted by 30-s breaks. dation level. They had to avoid coffee and alcohol FTT task was carried out without visual feedback of before and after training session and after next-day the tapping as the non-dominant hand was shielded and seventh-day sessions. On the