Hippocampal barques and their manifestation as 14&6 Hz positive spikes during sleep.

OBJECTIVE: This study investigates variations in hippocampal barque occurrence during sleep and compares findings to respective variations of their scalp manifestation as 14&6/sec positive spikes. METHODS: From 11 epilepsy patients, 12 non-epileptogenic hippocampi with barques were identified for this study. Using the first seizure-free whole-night sleep stereo-encephalography (sEEG) recording, we performed sleep staging and measured the occurrence of barques and 14&6/sec positive spikes variants. RESULTS: Hippocampal barques (total count: 9,183; mean count per record: 765.2 ± 251.2) occurred predominantly during non-rapid eye movement (NREM) II sleep (total: 5,744; mean: 478.6 ± 176.1; 62.2 ± 6.0%) and slow-wave sleep (SWS) (total: 2,950; mean: 245.83 ± 92.9; 32.0 ± 6.2%), with rare to occasional occurrence in NREM I (total: 85; mean: 7.0 ± 2.8; 0.9 ± 0.4%), rapid eye movement (REM) (total: 153; mean: 12.75 ± 4.0; 1.7 ± 0.6) and wakefulness (total: 251; mean: 20.9 ± 6.3; 2.9 ± 0.9%). Barque rate increased during SWS (mean: 2.7 ± 1.0 per min) compared to NREM II (2.2 ± 1.0 per min) and other states (wakefulness: 0.1 ± 0.0 per min; NREM I: 0.3 ± 0.1 per min; REM: 0.1 ± 0.0 per min). The 14&6/sec positive spikes variant (total count: 2,406; mean: 343.7 ± 106.7) was present in NREM II (total: 2,059; mean: 249.1 ± 100.2, 84.9 ± 3.6%) and SWS (total: 347; mean: 49.5 ± 12.8, 15.0 ± 3.6%) stages, and absent from the rest of sleep and wakefulness. While all 14&6/sec positive spikes correlated with barques, only 44.7 ± 6.1% of barques manifested as 14&6/sec positive spikes. CONCLUSIONS: Hippocampal barques are predominant in NREM II and SWS, and tend to increase their presence during SWS. Their scalp manifestation as 14&6/sec positive spikes is confounded by wakefulness, REM and NREM I stages, and "masked" by the co-occurrence of NREM II and SWS slow waves, and overlapping reactive micro-arousal elements. SIGNIFICANCE: Our study highlighted the overnight profile of hippocampal barques, in relation to the respective profile of their scalp manifestation, the 14&6/sec positive spikes variant.

Sex Differences in Blood-Brain Barrier Transport of Psychotropic Drugs.

Treatment of neuropsychiatric disorders relies on the effective delivery of therapeutic molecules to the target organ, the brain. The blood-brain barrier (BBB) hinders such delivery and proteins acting as transporters actively regulate the influx and importantly the efflux of both endo- and xeno-biotics (including medicines). Neuropsychiatric disorders are also characterized by important sex differences, and accumulating evidence supports sex differences in the pharmacokinetics and pharmacodynamics of many drugs that act on the brain. In this minireview we gather preclinical and clinical findings on how sex and sex hormones can influence the activity of those BBB transporter systems and affect the brain pharmacokinetics of psychotropic medicines. It emerges that it is not well understood which psychotropics are substrates for each of the many and not well-studied brain transporters. Indeed, most evidence originates from studies performed in peripheral tissues, such as the liver and the kidneys. None withstanding, accumulated evidence supports the existence of several sex differences in expression and activity of transport proteins, and a further modulating role of gonadal hormones. It is proposed that a closer study of sex differences in the active influx and efflux of psychotropics from the brain may provide a better understanding of sex-dependent brain pharmacokinetics and pharmacodynamics of psychotropic medicines.