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•Non-invasive indices in the human cortex of net synaptic strength are decreased after a nap.•Indices of inducibility of LTP-like plasticity are increased after a nap.•The findings show that even a brief daytime nap is sufficient to restore synaptic plasticity.•The findings provide a mechanistic link to the benefits of naps observed on behavioral levels. Nighttime sleep renormalizes net synaptic strength (homeostatic plasticity) and the inducibility of long-term potentiation (LTP)-like plasticity (associative plasticity) in the cortex. However, whether an afternoon nap is sufficient for this process remains to be characterized. Twenty healthy adults participated in a repeated measures sleep laboratory study with an adaptation and two experimental sessions – nap and wake (1:15–2:15 pm). After the nap or wake session, non-invasive indices of net synaptic strength (indexed by transcranial magnetic stimulation, TMS-probed corticospinal excitability and wake EEG theta activity) and inducibility of LTP-like plasticity (indexed by TMS-induced motor evoked potentials, MEPs, following paired associative stimulation, PAS) were assessed. We observed indices of reduced net synaptic strength after sleep compared to wakefulness, evidenced by a higher TMS intensity needed to induce MEPs and reduced wake EEG theta activity. Additionally, we observed an increase in the inducibility of associative synaptic plasticity after sleep, as evidenced by a greater increase in TMS-induced MEPs in response to PAS. The study reinforces the restorative effect of sleep for homeostatic and associative synaptic plasticity in the human cortex and demonstrates that even a short nap can promote this process.

Sleep is ubiquitous in animals and humans, but its function remains to be further determined. The synaptic homeostasis hypothesis of sleep–wake regulation proposes a homeostatic increase in net synaptic strength and cortical excitability along with decreased inducibility of associative synaptic long-term potentiation (LTP) due to saturation after sleep deprivation. Here we use electrophysiological, behavioural and molecular indices to non-invasively study net synaptic strength and LTP-like plasticity in humans after sleep and sleep deprivation. We demonstrate indices of increased net synaptic strength (TMS intensity to elicit a predefined amplitude of motor-evoked potential and EEG theta activity) and decreased LTP-like plasticity (paired associative stimulation induced change in motor-evoked potential and memory formation) after sleep deprivation. Changes in plasma BDNF are identified as a potential mechanism. Our study indicates that sleep recalibrates homeostatic and associative synaptic plasticity, believed to be the neural basis for adaptive behaviour, in humans. Sleep deprivation is believed to lead to homeostatic increases in synaptic strength and reduced inducibility of associative LTP, based mainly on findings from animal studies. Here, Kuhn et al . demonstrate similar sleep-dependent synaptic plasticity changes in humans along with altered plasma BDNF levels.

The neuroplasticity hypothesis of major depressive disorder proposes that a dysfunction of synaptic plasticity represents a basic pathomechanism of the disorder. Animal models of depression indicate enhanced plasticity in a ventral emotional network, comprising the amygdala. Here, we investigated fear extinction learning as a non-invasive probe for amygdala-dependent synaptic plasticity in patients with major depressive disorder and healthy controls. Differential fear conditioning was measured in 37 inpatients with severe unipolar depression (International Classification of Diseases, 10th revision, criteria) and 40 healthy controls. The eye-blink startle response, a subcortical output signal that is modulated by local synaptic plasticity in the amygdala in fear acquisition and extinction learning, was recorded as the primary outcome parameter. After robust and similar fear acquisition in both groups, patients with major depressive disorder showed significantly enhanced fear extinction learning in comparison to healthy controls, as indicated by startle responses to conditioned stimuli. The strength of extinction learning was positively correlated with the total illness duration. The finding of enhanced fear extinction learning in major depressive disorder is consistent with the concept that the disorder is characterized by enhanced synaptic plasticity in the amygdala and the ventral emotional network. Clinically, the observation emphasizes the potential of successful extinction learning, the basis of exposure therapy, in anxiety-related disorders despite the frequent comorbidity of major depressive disorder.

Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a 'top-down' cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal 'activation', cathodal 'deactivation', and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the 'top-down' pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep.

The synaptic plasticity hypothesis of major depressive disorder (MDD) posits that alterations in synaptic plasticity represent a final common pathway underlying the clinical symptoms of the disorder. This study tested the hypotheses that patients with MDD show an attenuation of cortical synaptic long-term potentiation (LTP)-like plasticity in comparison with healthy controls, and that this attenuation recovers after remission. Cortical synaptic LTP-like plasticity was measured using a transcranial magnetic stimulation protocol, ie, paired associative stimulation (PAS), in 27 in-patients with MDD according to ICD-10 criteria and 27 sex- and age-matched healthy controls. The amplitude of motor-evoked potentials was measured before and after PAS. Patients were assessed during the acute episode and at follow-up to determine the state- or trait-character of LTP-like changes. LTP-like plasticity, the PAS-induced increase in motor-evoked potential amplitudes, was significantly attenuated in patients with an acute episode of MDD compared with healthy controls. Patients with remission showed a restoration of synaptic plasticity, whereas the deficits persisted in patients without remission, indicative for a state-character of impaired LTP-like plasticity. The results provide first evidence for a state-dependent partial occlusion of cortical LTP-like plasticity in MDD. This further identifies impaired LTP-like plasticity as a potential pathomechanism and treatment target of the disorder.

The protein brain-derived neurotrophic factor (BDNF) promotes neural plasticity of the central nervous system and plays an important role for learning and memory. A single nucleotide polymorphism (rs6265) at position 66 in the pro-region of the human BDNF gene, resulting in a substitution of the amino acid valine (val) with methionine (met), leads to attenuated BDNF secretion and has been associated with reduced neurocognitive function. Inhomogeneous results have been found regarding the effect of the BDNF genotype on behavior. We determined the BDNF genotype and performance on the Compound Remote Associate (CRA) task as a common measure of creativity in 76 healthy university students. In our main analyses, we did not find significant differences between met-carriers (n = 30) and non-met carriers (n = 46). In a secondary analysis, we found that met-carriers had a slower solution time (medium effect size) for items of medium difficulty. Our results suggest that met-carriers and non-met-carriers do not generally differ regarding their creativity, but non-met-carriers may have a certain advantage when it comes to moderately difficult problems. The wider literature suggests that both genetic variants come with advantages and disadvantages. Future research needs to sharpen our understanding of the disadvantages and, potentially, advantages met allele carriers may have.

Animals and humans spend on average one third of their lives in sleep, but its functions remain to be specified. Distinct lines of research propose that sleep promotes local strengthening of information-bearing synapses (plasticity) and global downscaling of synaptic strength (stability) in neural networks-prerequisites for adaptive behavior in a changing environment. However, the potential orchestration of these processes, particularly in humans, needs to be further characterized. Here, we use electrophysiological, behavioral, and molecular indices to noninvasively study cortical plasticity and network stability in humans. We observe indices of local strengthening of prior induced long-term potentiation-like plasticity (paired associative stimulation induced change in motor-evoked potential) and global network stabilization (homeostatic regulation of wake EEG theta activity) after brief periods of nonrapid eye movement sleep compared with wakefulness. The interplay of local sleep slow oscillations and spindle activity, previously related to synaptic refinements during sleep, is identified as a potential mechanism. Our findings are consistent with the notion that sleep-specific brain activity patterns reduce the plasticity-stability dilemma by orchestrating local plasticity and global stability of neural assemblies in the human cortex. Future studies are needed to further decipher the neural mechanisms underlying our indirect observations.

Zusammenfassung Hintergrund Die neurobiologische Augmentation von Psychotherapie gewinnt in den letzten Jahren in der Psychotherapieforschung zunehmend an Bedeutung. In diesem Zusammenhang ist die Beeinflussung von Schlaf, dessen begünstigende Wirkung für Gedächtnisbildung und zugrunde liegende neuronale Plastizität vielfach gezeigt wurde, als nichtinvasive Intervention besonders interessant. Fragestellung Welchen Einfluss hat Schlaf und dessen gezielte Manipulation auf die Wirksamkeit von Psychotherapie und wie kann Schlaf als Intervention zur Augmentation von Lernprozessen in der Psychotherapie eingesetzt werden? Methoden Wichtige Studien, die die Auswirkung von Schlaf auf Prozesse der Gedächtnisbildung und Psychotherapie untersuchen, werden vorgestellt und diskutiert. Ergebnisse Zur Augmentation von Psychotherapie ist Schlaf ein aussichtsreicher Ansatzpunkt. Schlafmuster sind dabei sowohl vor als auch nach Psychotherapie relevant. Zudem besteht die Möglichkeit, Schlaf und assoziierte neuronale Prozesse zu manipulieren, z. B. durch transkranielle Gleichstromstimulation (tDCS) oder Medikamente, und somit Lernvorgänge und neuronale Plastizität im Kontext von Psychotherapie zu beeinflussen. Diskussion Schlaf ist ein vielversprechender Ansatz zur Augmentation von Psychotherapie. Weitere Studien sind notwendig, um die Grundlagen besser zu verstehen und zu prüfen, ob der Ansatz in den therapeutischen Alltag integriert werden kann.