Rehearsal initiates systems memory consolidation, sleep makes it last.

After encoding, memories undergo a transitional process termed systems memory consolidation. It allows fast acquisition of new information by the hippocampus, as well as stable storage in neocortical long-term networks, where memory is protected from interference. Whereas this process is generally thought to occur slowly over time and sleep, we recently found a rapid memory systems transition from hippocampus to posterior parietal cortex (PPC) that occurs over repeated rehearsal within one study session. Here, we use fMRI to demonstrate that this transition is stabilized over sleep, whereas wakefulness leads to a reset to naïve responses, such as observed during early encoding. The role of sleep therefore seems to go beyond providing additional rehearsal through memory trace reactivation, as previously thought. We conclude that repeated study induces systems consolidation, while sleep ensures that these transformations become stable and long lasting. Thus, sleep and repeated rehearsal jointly contribute to long-term memory consolidation.

Fast track to the neocortex: A memory engram in the posterior parietal cortex.

Models of systems memory consolidation postulate a fast-learning hippocampal store and a slowly developing, stable neocortical store. Accordingly, early neocortical contributions to memory are deemed to reflect a hippocampus-driven online reinstatement of encoding activity. In contrast, we found that learning rapidly engenders an enduring memory engram in the human posterior parietal cortex. We assessed microstructural plasticity via diffusion-weighted magnetic resonance imaging as well as functional brain activity in an object-location learning task. We detected neocortical plasticity as early as 1 hour after learning and found that it was learning specific, enabled correct recall, and overlapped with memory-related functional activity. These microstructural changes persisted over 12 hours. Our results suggest that new traces can be rapidly encoded into the parietal cortex, challenging views of a slow-learning neocortex.

Decoding material-specific memory reprocessing during sleep in humans.

Neuronal learning activity is reactivated during sleep but the dynamics of this reactivation in humans are still poorly understood. Here we use multivariate pattern classification to decode electrical brain activity during sleep and determine what type of images participants had viewed in a preceding learning session. We find significant patterns of learning-related processing during rapid eye movement (REM) and non-REM (NREM) sleep, which are generalizable across subjects. This processing occurs in a cyclic fashion during time windows congruous to critical periods of synaptic plasticity. Its spatial distribution over the scalp and relevant frequencies differ between NREM and REM sleep. Moreover, only the strength of reprocessing in slow-wave sleep influenced later memory performance, speaking for at least two distinct underlying mechanisms between these states. We thus show that memory reprocessing occurs in both NREM and REM sleep in humans and that it pertains to different aspects of the consolidation process.

Neurology and psychiatry: waking up to opportunities of sleep. : State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.

Evaluation of the vascular integrity of free flaps based on microcirculation imaging techniques.

BACKGROUND: A free-flap graft refers to the free transfer of tissue to cover tissue defects caused by trauma or malperfusion in plastic surgery. The basic principle, which makes a free flap working is an adequate blood flow. We applied new techniques which are able to detect the blood flow of the anastomosis and of dermal and subdermal tissue layers in a reliable way. METHODS: To this end we applied innovative Ultrasound-techniques (contrast enhanced high resolution Ultrasound (US), color coded Doppler sonography (CCDS), Cross Beamtrade mark, Power Doppler, Tissue Harmonic Imagingtrade mark (THI), Speckle Reduction Imagingtrade mark (SRI)), as well as the Indocyanine Green (ICG) fluorescence angiography to evaluate the vascular integrity of 15 parascapular flaps implanted to the fore foot over a period of four years. The age of the subjects ranged from 16 to 60 years. The US machine (GE Logiq 9) was equipped with a Logiq 9L transducer (6-9 MHz) and the modalities of CHI (Contrast Harmonic Imaging) and True Agent Detection (dual view of B-Mode and contrast mode). RESULTS: The borders of the investigated flaps could be best detected using Cross Beamtrade mark Technology with SRItrade mark and THItrade mark. Power Doppler was able to detect anastomotic vessels even if they were twisted or elongated. Reduced perfusion curves were seen in cases with low anastomotic flow in CCDS. The CHItrade mark allowed dynamic flow detection of the microcirculation of the tissue graft over a depth of up to 3 cm including quantitative perfusion curves of tissue microcirculation by using TICtrade mark analysis. There is a strong correlation between the perfusion indices measured by ICG fluorescence angiography and CHItrade mark. Furthermore the ICG showed a remarkable enhancement of fluorescence in the flap borders, which need to be explored in future investigations. CONCLUSION: These new applications provide useful and effective methods for improved postoperative monitoring of free flaps in plastic surgery and can lead to substantial reduction in the overall risk of flap failure.

Contrast harmonic ultrasound and indocyanine-green fluorescence video angiography for evaluation of dermal and subdermal microcirculation in free parascapular flaps.

PURPOSE: Contrast harmonic ultrasound (CHI) with a linear transducer is a new diagnostic approach that allows dynamic and quantitative flow detection of tissue perfusion in microsurgery. The aim of the study was the evaluation of perfusion of the dermal and subdermal layers of microvascular tissue transplants with CHI in comparison to ICG-fluorescence angiography. MATERIAL AND METHOD: In a prospective clinical study indocyanine-green fluorescence video angiography and contrast enhanced high resolution ultrasound (5-10 MHz; linear transducer; Logiq 9; GE) were used for evaluation of the microcirculation in 10 transplanted free parascapular flaps. Two regions were analysed, the centre of the flap and the region of the anastomosis. The perfusion patterns of both methods were compared. RESULTS: The perfusion indexes measured by ICG-fluorescence angiography correlated very precisely in all patients with the quantitative perfusion curves of contrast-enhanced US with CHI. Two flaps with slow filling and low dye intensity showed low contrast enhancement in CHI with modified perfusion curves with slow increase. In two cases a reduced perfusion and filling were found. There were no statistical differences between the two diagnostic methods (p>0.01). CONCLUSION: CHI improves US detections of dermal and subdermal microcirculation in comparison to ICG fluorescence angiography. CHI is a new diagnostic method for postoperative monitoring of free flaps.

Hemodynamic cerebral correlates of sleep spindles during human non-rapid eye movement sleep.

In humans, some evidence suggests that there are two different types of spindles during sleep, which differ by their scalp topography and possibly some aspects of their regulation. To test for the existence of two different spindle types, we characterized the activity associated with slow (11-13 Hz) and fast (13-15 Hz) spindles, identified as discrete events during non-rapid eye movement sleep, in non-sleep-deprived human volunteers, using simultaneous electroencephalography and functional MRI. An activation pattern common to both spindle types involved the thalami, paralimbic areas (anterior cingulate and insular cortices), and superior temporal gyri. No thalamic difference was detected in the direct comparison between slow and fast spindles although some thalamic areas were preferentially activated in relation to either spindle type. Beyond the common activation pattern, the increases in cortical activity differed significantly between the two spindle types. Slow spindles were associated with increased activity in the superior frontal gyrus. In contrast, fast spindles recruited a set of cortical regions involved in sensorimotor processing, as well as the mesial frontal cortex and hippocampus. The recruitment of partially segregated cortical networks for slow and fast spindles further supports the existence of two spindle types during human non-rapid eye movement sleep, with potentially different functional significance.

Wavelength-dependent modulation of brain responses to a working memory task by daytime light exposure.

In addition to classical visual effects, light elicits nonvisual brain responses, which profoundly influence physiology and behavior. These effects are mediated in part by melanopsin-expressing light-sensitive ganglion cells that, in contrast to the classical photopic system that is maximally sensitive to green light (550 nm), is very sensitive to blue light (470-480 nm). At present, there is no evidence that blue light exposure is effective in modulating nonvisual brain activity related to complex cognitive tasks. Using functional magnetic resonance imaging, we show that, while participants perform an auditory working memory task, a short (18 min) daytime exposure to blue (470 nm) or green (550 nm) monochromatic light (3 x 10(13) photons/cm2/s) differentially modulates regional brain responses. Blue light typically enhanced brain responses or at least prevented the decline otherwise observed following green light exposure in frontal and parietal cortices implicated in working memory, and in the thalamus involved in the modulation of cognition by arousal. Our results imply that monochromatic light can affect cognitive functions almost instantaneously and suggest that these effects are mediated by a melanopsin-based photoreceptor system.

Differential adaptation of neurocognitive brain functions to recurrent hypoglycemia in healthy men.

Antecedent hypoglycemia is known to attenuate hormonal and symptomatic responses to subsequent hypoglycemia. Whether this pertains also to hypoglycemia-induced cognitive dysfunction is controversially discussed. Neurocognitive adaptation might essentially depend on the type of function. Here, we compared the influence of recurrent hypoglycemia in 15 healthy men on counterregulatory hormones, subjective symptoms of hypoglycemia, short-term memory performance (word recall), and performance on an auditory attention task (oddball). The attention task was also used to record event-related brain potential (ERP) indicators of stimulus processing. In each subject, three consecutive hypoglycemic clamps were performed, two on day 1 and the third on day 2. Neurocognitive testing was performed during baseline and at two different hypoglycemic plateaus (2.8 and 2.5 mmol/l) during the first and last clamp. As expected, hormonal responses were significantly reduced to the last as compared to the first hypoglycemia indicating adaptation. Subjective symptoms also decreased in response to recurrent hypoglycemia. Short-term memory performance deteriorated distinctly on the first hypoglycemic clamp, but maintained the normal level on the last clamp (P=0.006). Likewise, the impairment in reaction time (P=0.022) and response accuracy (P=0.005) was distinctly smaller on the last than first hypoglycemia. In parallel, the hypoglycemia-induced decrease in P3 amplitude (P=0.019) and the increase in P3 latency (P=0.049) were diminished with recurrent hypoglycemia, indicating that late stages of controlled stimulus processing likewise adapted. In contrast, the distinct decrease in amplitudes of the N1 and P2 components of the ERP (preceding the P3) was closely comparable in response to the first and last hypoglycemia (P>0.3). Together results indicate an adaptation to recurrent hypoglycemia for signs of controlled stimulus processing presumably involving hippocampo-prefrontocortical circuitry, while earlier automatic stages of processing appear to be spared.

NPY attenuates positive cortical DC-potential shift upon food intake in man.

Previous studies have shown that the regulation of hunger and satiety is accompanied by coordinate changes in cortical excitability. Starved subjects show a transient negative shift in the scalp-recorded cortical direct current (DC-)potential in the beginning of eating, indicating increased cortical excitability. With increasing satiety, the DC negativity becomes soon replaced by a reward related positive potential shift. Neuropeptide Y (NPY) is known from animal studies to increase food intake and induce weight gain, which might result from increasing hunger drive or reducing satiety. Here we investigated whether NPY affects the cortical sequelae of hunger and satiety regulation as reflected by cortical DC-potentials in man. DC-potentials were recorded over frontal (Fz, F3, F4), central (Cz, C3, C4) and parietal (Pz, P3, P4) electrode positions in 14 subjects who had abstained from eating for 15 h and who were intranasally administered 50 nmol of NPY and placebo 20 min prior to recordings. After a 3-min baseline epoch, subjects consumed 400 ml of liquid food within 5 min. Recordings ended 7 min after food consumption. In the placebo condition during food intake, with some delay a positive DC-potential shift developed which was most pronounced over frontal and central areas and reached maximum values 0-3 min after food consumption. NPY reduced this satiation associated positive shift (p<0.05) over all areas except P3 and Pz. Data suggest that NPY exerts its orexigenic influence by attenuating mechanisms of satiation.

Emotional memory formation is enhanced across sleep intervals with high amounts of rapid eye movement sleep.

Recent studies indicated a selective activation during rapid eye movement (REM) sleep of the amygdala known to play a decisive role in the processing of emotional stimuli. This study compared memory retention of emotional versus neutral text material over intervals covering either early sleep known to be dominated by nonREM slow wave sleep (SWS) or late sleep, in which REM sleep is dominant. Two groups of men were tested across 3-h periods of early and late sleep (sleep group) or corresponding retention intervals filled with wakefulness (wake group). Sleep was recorded polysomnographically. Cortisol concentrations in saliva were monitored at acquisition and retrieval testing. As expected, the amount of REM sleep was about three times greater during late than during early retention sleep, whereas a reversed pattern was observed for SWS distribution (P < 0.001). Sleep improved retention, compared with the effects of wake intervals (P < 0.02). However, this effect was substantial only in the late night (P < 0.005), during which retention was generally worse than during the early night (P < 0.02). Late sleep particularly enhanced memory for emotional texts. This effect was highly significant in comparison with memory for neutral texts (P < 0.01) and in comparison with memory after late and early wake intervals (P < 0.001). Cortisol concentration differed between early and late retention intervals but not between sleep and wake conditions. Results are consonant with a supportive function of REM sleep predominating late sleep for the formation of emotional memory in humans.

Early sleep triggers memory for early visual discrimination skills.

Improvement after practicing visual texture discrimination does not occur until several hours after practice has ended. We show that this improvement strongly depends on sleep. To specify the process responsible for sleep-related improvement, we compared the effects of 'early' and 'late' sleep, dominated respectively by slow-wave and rapid eye movement (REM) sleep. Discrimination skills significantly improved over early sleep, improved even more over a whole night's sleep, but did not improve after late sleep alone. These findings suggest that procedural memory formation is prompted by slow-wave sleep-related processes. Late REM sleep may promote memory formation at a second stage, only after periods of early sleep have occurred.