Steffen Gais

Tinnitus Intensity Dependent Gamma Oscillations of the Contralateral Auditory Cortex

Background Non-pulsatile tinnitus is considered a subjective auditory phantom phenomenon present in 10 to 15% of the population. Tinnitus as a phantom phenomenon is related to hyperactivity and reorganization of the auditory cortex. Magnetoencephalography studies demonstrate a correlation between gamma band activity in the contralateral auditory cortex and the presence of tinnitus. The present study aims to investigate the relation between objective gamma-band activity in the contralateral auditory cortex and subjective tinnitus loudness scores. Methods and Findings In unilateral tinnitus patients (Nu200a=u200a15; 10 right, 5 left) source analysis of resting state electroencephalographic gamma band oscillations shows a strong positive correlation with Visual Analogue Scale loudness scores in the contralateral auditory cortex (max ru200a=u200a0.73, p<0.05). Conclusion Auditory phantom percepts thus show similar sound level dependent activation of the contralateral auditory cortex as observed in normal audition. In view of recent consciousness models and tinnitus network models these results suggest tinnitus loudness is coded by gamma band activity in the contralateral auditory cortex but might not, by itself, be responsible for tinnitus perception.

Theta-gamma dysrhythmia and auditory phantom perception.

Tinnitus is considered an auditory phantom percept analogous to phantom pain. Thalamocortical dysrhythmia has been proposed as a possible pathophysiological mechanism for both tinnitus and pain. Thalamocortical dysrhythmia refers to a persistent pathological resting state theta-gamma coupling that is spatially localized at an area where normally alpha oscillations predominate. Auditory cortex stimulation via implanted electrodes has been developed to treat tinnitus, targeting an area of activation on functional MR imaging elicited by tinnitus-matched sound presentation. The authors describe a case in which clinical improvement was correlated with changes in intracranial recordings. Maximal tinnitus suppression was obtained by current delivery exactly at the blood oxygen level-dependent activation hotspot, which colocalizes with increased gamma and theta activity, in contrast to the other electrode poles, which demonstrated a normal alpha peak. These spectral changes normalized when stimulation induced tinnitus suppression, both on electrode and source-localized electroencephalography recordings. These data suggest that thetagamma coupling as proposed by the thalamocortical dysrhythmia model might be causally related to a conscious auditory phantom percept.

Contribution of norepinephrine to emotional memory consolidation during sleep

BACKGROUNDnThere is increasing evidence indicating that slow wave sleep (SWS) supports memory consolidation. This effect may in part originate from phasic noradrinergic (NE) activity occurring during SWS in the presence of tonically lowered NE levels. Here, we examined whether NE supports the consolidation of amygdala-dependent emotional memory during SWS.nnnMETHODSnIn a double-blind cross-over study, 15 men learned emotional and neutral materials (stories, pictures) in the evening before a 3-h period of early SWS-rich retention sleep, during which either placebo or clonidine, an α2-adrenoceptor agonist which blocks locus coeruleus NE release, was intravenously infused. Memory retrieval as well as affective ratings and heart rate responses to the pictures were assessed 23 h after learning.nnnRESULTSnClonidine reduced plasma NE levels but had no effect on SWS. While retention of story content words and pictures per se remained unaffected, clonidine distinctly blocked the superiority of emotional compared to neutral memory for temporal order, with this superiority of emotional over neutral memories observed only in the placebo condition. Heart rate responses to pictures were not affected, but whereas under placebo conditions familiar negative pictures were rated less arousing and with a more negative valence compared to pictures not seen before; these differences were abolished after clonidine.nnnCONCLUSIONnGiven that memory for the temporal order of events depends on the hippocampus to a greater extent than item memory, our findings suggest that NE activity during early SWS-rich sleep facilitates consolidation of memories that involve both, a strong amygdalar and hippocampal component.

The memory function of noradrenergic activity in non-rem sleep

There is a long-standing assumption that low noradrenergic activity during sleep reflects mainly the low arousal during this brain state. Nevertheless, recent research has demonstrated that the locus coeruleus, which is the main source of cortical noradrenaline, displays discrete periods of intense firing during non-REM sleep, without any signs of awakening. This transient locus coeruleus activation during sleep seems to occur in response to preceding learning-related episodes. In the present study, we manipulate noradrenergic activity during sleep in humans with either the α2-autoreceptor agonist clonidine or the noradrenaline reuptake inhibitor reboxetine. We show that reducing noradrenergic activity during sleep, but not during wakefulness, impairs subsequent memory performance in an odor recognition task. Increasing noradrenergic availability during sleep, in contrast, enhances memory retention. We conclude that noradrenergic activity during non-REM sleep interacts with other sleep-related mechanisms to functionally contribute to off-line memory consolidation.

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.

Evidence for two distinct sleep-related long-term memory consolidation processes.

Numerous studies examine the effect of a nights sleep on memory consolidation, but few go beyond this short time-scale to test long-lasting effects of sleep on memory. We investigated long-term effects of sleep on typical memory tasks. During the hours following learning, participants slept or stayed awake. We compared recall performance between wake and sleep conditions after delays of up to 6 days. Performance develops in two distinct ways. Word pair, syllable, and motor sequence learning tasks benefit from sleep during the first day after encoding, when compared with daytime or nighttime wakefulness. However, performance in the wake conditions recovers after another night of sleep, so that we observe no lasting effect of sleep. Sleep deprivation before recall does not impair performance. Thus, fatigue cannot adequately explain the lack of long-term effects. We suggest that the hippocampus might serve as a buffer during the retention interval, and consolidation occurs during delayed sleep. In contrast, a non-hippocampal mirror-tracing task benefits significantly from sleep, even when tested after a 4-day delay including recovery sleep. This indicates a dissociation between two sleep-related consolidation mechanisms, which could rely on distinct neuronal processes.

Classification based hypothesis testing in neuroscience: Below-chance level classification rates and overlooked statistical properties of linear parametric classifiers

Multivariate pattern analysis (MVPA) has recently become a popular tool for data analysis. Often, classification accuracy as quantified by correct classification rate (CCR) is used to illustrate the size of the effect under investigation. However, we show that in low sample size (LSS), low effect size (LES) data, which is typical in neuroscience, the distribution of CCRs from cross‐validation of linear MVPA is asymmetric and can show classification rates considerably below what would be expected from chance classification. Conversely, the mode of the distribution in these cases is above expected chance levels, leading to a spuriously high number of above chance CCRs. This unexpected distribution has strong implications when using MVPA for hypothesis testing. Our analyses warrant the conclusion that CCRs do not well reflect the size of the effect under investigation. Moreover, the skewness of the null‐distribution precludes the use of many standard parametric tests to assess significance of CCRs. We propose that MVPA results should be reported in terms of P values, which are estimated using randomization tests. Also, our results show that cross‐validation procedures using a low number of folds, e.g. twofold, are generally more sensitive, even though the average CCRs are often considerably lower than those obtained using a higher number of folds. Hum Brain Mapp 37:1842–1855, 2016.

Exploring the Effect of Sleep and Reduced Interference on Different Forms of Declarative Memory

STUDY OBJECTIVESnMany studies have found that sleep benefits declarative memory consolidation. However, fundamental questions on the specifics of this effect remain topics of discussion. It is not clear which forms of memory are affected by sleep and whether this beneficial effect is partly mediated by passive protection against interference. Moreover, a putative correlation between the structure of sleep and its memory-enhancing effects is still being discussed.nnnDESIGNnIn three experiments, we tested whether sleep differentially affects various forms of declarative memory. We varied verbal content (verbal/nonverbal), item type (single/associate), and recall mode (recall/recognition, cued/free recall) to examine the effect of sleep on specific memory subtypes. We compared within-subject differences in memory consolidation between intervals including sleep, active wakefulness, or quiet meditation, which reduced external as well as internal interference and rehearsal.nnnPARTICIPANTSnForty healthy adults aged 18-30 y, and 17 healthy adults aged 24-55 y with extensive meditation experience participated in the experiments.nnnRESULTSnAll types of memory were enhanced by sleep if the sample size provided sufficient statistical power. Smaller sample sizes showed an effect of sleep if a combined measure of different declarative memory scales was used. In a condition with reduced external and internal interference, performance was equal to one with high interference. Here, memory consolidation was significantly lower than in a sleep condition. We found no correlation between sleep structure and memory consolidation.nnnCONCLUSIONSnSleep does not preferentially consolidate a specific kind of declarative memory, but consistently promotes overall declarative memory formation. This effect is not mediated by reduced interference.

Sleep-Effects on Implicit and Explicit Memory in Repeated Visual Search

In repeated visual search tasks, facilitation of reaction times (RTs) due to repetition of the spatial arrangement of items occurs independently of RT facilitation due to improvements in general task performance. Whereas the latter represents typical procedural learning, the former is a kind of implicit memory that depends on the medial temporal lobe (MTL) memory system and is impaired in patients with amnesia. A third type of memory that develops during visual search is the observers’ explicit knowledge of repeated displays. Here, we used a visual search task to investigate whether procedural memory, implicit contextual cueing, and explicit knowledge of repeated configurations, which all arise independently from the same set of stimuli, are influenced by sleep. Observers participated in two experimental sessions, separated by either a nap or a controlled rest period. In each of the two sessions, they performed a visual search task in combination with an explicit recognition task. We found that (1) across sessions, MTL-independent procedural learning was more pronounced for the nap than rest group. This confirms earlier findings, albeit from different motor and perceptual tasks, showing that procedural memory can benefit from sleep. (2) Likewise, the sleep group compared with the rest group showed enhanced context-dependent configural learning in the second session. This is a novel finding, indicating that the MTL-dependent, implicit memory underlying contextual cueing is also sleep-dependent. (3) By contrast, sleep and wake groups displayed equivalent improvements in explicit recognition memory in the second session. Overall, the current study shows that sleep affects MTL-dependent as well as MTL-independent memory, but it affects different, albeit simultaneously acquired, forms of MTL-dependent memory differentially.

Rapid and independent memory formation in the parietal cortex

Significance When it comes to memory, our brain needs to deal with two opposing demands: remaining plastic to acquire new information rapidly and maintaining old information faithfully over long periods. It is assumed that two distinct brain systems are in charge of these functions: the fast-learning hippocampus and the slow-learning neocortex. The interaction between these two systems has traditionally been seen as very slow, requiring weeks or months to build a neocortical memory trace. In this study, brain activity during virtual-reality navigation shows that contributions of hippocampus and parietal neocortex to memory are changing substantially already at the time a spatial memory representation is built. Notably, we show that the posterior parietal cortex fulfills all criteria for a hippocampus-independent memory representation. Previous evidence indicates that the brain stores memory in two complementary systems, allowing both rapid plasticity and stable representations at different sites. For memory to be established in a long-lasting neocortical store, many learning repetitions are considered necessary after initial encoding into hippocampal circuits. To elucidate the dynamics of hippocampal and neocortical contributions to the early phases of memory formation, we closely followed changes in human functional brain activity while volunteers navigated through two different, initially unknown virtual environments. In one condition, they were able to encode new information continuously about the spatial layout of the maze. In the control condition, no information could be learned because the layout changed constantly. Our results show that the posterior parietal cortex (PPC) encodes memories for spatial locations rapidly, beginning already with the first visit to a location and steadily increasing activity with each additional encounter. Hippocampal activity and connectivity between the PPC and hippocampus, on the other hand, are strongest during initial encoding, and both decline with additional encounters. Importantly, stronger PPC activity related to higher memory-based performance. Compared with the nonlearnable control condition, PPC activity in the learned environment remained elevated after a 24-h interval, indicating a stable change. Our findings reflect the rapid creation of a memory representation in the PPC, which belongs to a recently proposed parietal memory network. The emerging parietal representation is specific for individual episodes of experience, predicts behavior, and remains stable over offline periods, and must therefore hold a mnemonic function.