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Sensitivity to repetitions in sound amplitude and frequency is crucial for sound perception. As with other aspects of sound processing, sensitivity to such patterns may change with age, and may help explain some age-related changes in hearing such as segregating speech from background sound. We recorded magnetoencephalography to characterize differences in the processing of sound patterns between younger and older adults. We presented tone sequences that either contained a pattern (made of a repeated set of tones) or did not contain a pattern. We show that auditory cortex in older, compared to younger, adults is hyperresponsive to sound onsets, but that sustained neural activity in auditory cortex, indexing the processing of a sound pattern, is reduced. Hence, the sensitivity of neural populations in auditory cortex fundamentally differs between younger and older individuals, overresponding to sound onsets, while underresponding to patterns in sounds. This may help to explain some age-related changes in hearing such as increased sensitivity to distracting sounds and difficulties tracking speech in the presence of other sound.

Optimal perception requires adaptation to sounds in the environment. Adaptation involves representing the acoustic stimulation history in neural response patterns, for example, by altering response magnitude or latency as sound-level context changes. Neurons in the auditory brainstem of rodents are sensitive to acoustic stimulation history and sound-level context (often referred to as sensitivity to stimulus statistics), but the degree to which the human brainstem exhibits such neural adaptation is unclear. In six electroencephalography experiments with over 125 participants, we demonstrate that the response latency of the human brainstem is sensitive to the history of acoustic stimulation over a few tens of milliseconds. We further show that human brainstem responses adapt to sound-level context in, at least, the last 44 ms, but that neural sensitivity to sound-level context decreases when the time window over which acoustic stimuli need to be integrated becomes wider. Our study thus provides evidence of adaptation to sound-level context in the human brainstem and of the timescale over which sound-level information affects neural responses to sound. The research delivers an important link to studies on neural adaptation in non-human animals.

Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI)

Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis , is caused by strains from the LGV biovar, most commonly represented by ompA-genotypes L2b and L2. We investigated the diversity in LGV samples across an international collection over seven years using typing and genome sequencing. LGV-positive samples (n=321) from eight countries collected between 2011 and 2017 (Spain n=97, Netherlands n=67, Switzerland n=64, Australia n=53, Sweden n=37, Hungary n=31, Czechia n=30, Slovenia n=10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA-genotype L2b. However, analysis of the ompA gene shows ompA-genotype L2b (n=83), ompA-genotype L2 (n=180) and several variants of these (n=52; 12 variant types), as well as other/mixed ompA-genotypes (n=6). To elucidate the genomic diversity, whole genome sequencing (WGS) was performed from selected samples using SureSelect target enrichment, resulting in 42 genomes, covering a diversity of ompA-genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these ompA-genotypes derive from an ompA-genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrepresented among genomic changes in these samples, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA-genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of ompA-genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the ompA-genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.

Sensitivity to sound-level statistics is crucial for optimal perception, but research has focused mostly on neurophysiological recordings, whereas behavioral evidence is sparse. We use electroencephalography (EEG) and behavioral methods to investigate how sound-level statistics affect neural activity and the detection of near-threshold changes in sound amplitude. We presented noise bursts with sound levels drawn from distributions with either a low or a high modal sound level. One participant group listened to the stimulation while EEG was recorded (Experiment I). A second group performed a behavioral amplitude-modulation detection task (Experiment II). Neural activity depended on sound-level statistical context in two different ways. Consistent with an account positing that the sensitivity of neurons to sound intensity adapts to ambient sound level, responses for higher-intensity bursts were larger in low-mode than high-mode contexts, whereas responses for lower-intensity bursts did not differ between contexts. In contrast, a concurrent slow neural response indicated prediction-error processing: The response was larger for bursts at intensities that deviated from the predicted statistical context compared to those not deviating. Behavioral responses were consistent with prediction-error processing, but not with neural adaptation. Hence, neural activity adapts to sound-level statistics, but fine-tuning of perceptual sensitivity appears to involve neural prediction-error responses.

There is a worldwide increase in macrolide-resistant Mycoplasma genitalium strains, with severe impacts on treatment. The aim of this study was to compare three real-time PCR methods for the detection of macrolide resistance: an in-house PCR described by Touati et al., ResistancePlus® MG (SpeeDx), and S-DiaMGRes™ (Diagenode Diagnostics). One hundred M. genitalium-positive patient samples collected in Sweden and a quantitated M. genitalium DNA control were analyzed. Macrolide resistance was detected in 18, 15, and 16 of the samples with the respective methods. Sequencing of the 23S rRNA gene confirmed resistance in 16 (16%) of 100 samples in which it was detected with any of the three methods. ResistancePlus® MG and S-DiaMGRes™ falsely determined one sample as macrolide-sensitive, but this sample was determined as resistant when retested. The sensitivity of the methods was comparable, although there should be awareness of possible incorrect determination of macrolide resistance, especially of low-positive samples.

Many older listeners have difficulty understanding speech in noise, when cues to speech-sound identity are less redundant. The amplitude envelope of speech fluctuates dramatically over time, and features such as the rate of amplitude change at onsets (attack) and offsets (decay) signal critical information about the identity of speech sounds. Aging is also thought to be accompanied by increases in cortical excitability, which may differentially alter sensitivity to envelope dynamics. Here, we recorded electroencephalography in younger and older human adults (of both sexes) to investigate how aging affects neural synchronization to 4-Hz amplitude-modulated noises with different envelope shapes(ramped:slow attack & sharp decay;damped:sharp attack & slow decay). We observed that subcortical responses did not differ between age groups, whereas older compared to younger adults exhibited larger cortical responses to sound onsets, consistent with an increase in auditory cortical excitability. Neural activity in older adults synchronized more strongly with rapid-onset, slow-offset (damped) envelopes, was less sinusoidal, and more peaked. Younger adults demonstrated the opposite pattern, showing stronger synchronization with slow-onset, rapid-offset (ramped) envelopes, as well as a more sinusoidal neural response shape. The current results suggest that age-related changes in the excitability of auditory cortex alter responses to envelope dynamics. This may be part of the reason why older adults experience difficulty understanding speech in noise.Significance StatementMany middle aged and older adults report difficulty understanding speech when there is background noise, which can trigger social withdrawal and negative psychosocial health outcomes. The difficulty may be related to age-related changes in how the brain processes temporal sound features. We tested younger and older people on their sensitivity to different envelope shapes, using EEG. Our results demonstrate that aging is associated with heightened sensitivity to sounds with a sharp attack and gradual decay, and sharper neural responses that deviate from the sinusoidal features of the stimulus, perhaps reflecting increased excitability in the aged auditory cortex. Altered responses to temporal sound features may be part of the reason why older adults often experience difficulty understanding speech in social situations.

Recurring structures forming regular patterns are common in sounds. Learning such patterns is thought to be crucial for accurate auditory perceptual organization (scene analysis) and efficient recognition and prediction of sounds. The current study investigated the behavioral and neural signatures of rapid perceptual learning of regular patterns in sounds. In six behavioral and EEG experiments with over 120 human participants from both sexes, we show that individuals are faster to detect regular patterns, are more sensitive to pattern deviations, and are more accurate at judging the temporal order of pattern onset relative to a visual stimulus when patterns are repeated compared to novel. Sustained neural activity indexed perceptual learning in two ways. First, sustained activity increased earlier for repeated compared to novel regular patterns when participants attended to sounds, but not when they ignored them; this earlier response increase mirrored the rapid perceptual learning we observed behaviorally. Second, the magnitude of sustained activity was reduced for repeated compared to novel patterns, independent of whether participants attended to or ignored sounds. The reduction in the magnitude of sustained activity appeared only for later stimulus presentations, suggesting it is not directly related to perceptual learning, but to processes enabled by learning. Our study thus reveals neural markers of perceptual learning of auditory patterns, and of processes that may be related to reduced novelty or better prediction of learned auditory patterns. Significance statement Perceptual learning of regular patterns in sounds may optimize perception, but not much is known about the underlying neural processes. We observed several behavioral indices of perceptual learning, including faster pattern detection and increased sensitivity to pattern deviations for repeated compared to novel patterns. Sustained neural activity – indexing pattern processing – increased earlier for repeated than novel patterns, mirroring perceptual learning observed behaviorally. The magnitude of sustained activity was reduced for repeated relative to novel patterns. This reduction appeared only for later stimulus presentations, suggesting it is not directly related to perceptual learning. Our study thus neurally characterizes the perceptual learning of auditory patterns and of subsequent processes that may index reduced novelty or increased prediction of learned auditory patterns.

Healthy aging is accompanied by listening difficulties, including decreased speech comprehension, that stem from an ill-understood combination of sensory and cognitive changes. Here, we use electroencephalography to demonstrate that auditory neural oscillations of older adults entrain less firmly and less flexibly to speech-paced (∼3 Hz) rhythms than younger adults’ during attentive listening. These neural entrainment effects are distinct in magnitude and origin from the neural response to sound per se. Non-entrained parieto-occipital alpha (8–12 Hz) oscillations are enhanced in young adults, but suppressed in older participants, during attentive listening. Entrained neural phase and task-induced alpha amplitude exert opposite, complementary effects on listening performance: higher alpha amplitude is associated with reduced entrainment-driven behavioural performance modulation. Thus, alpha amplitude as a task-driven, neuro-modulatory signal can counteract the behavioural corollaries of neural entrainment. Balancing these two neural strategies may present new paths for intervention in age-related listening difficulties., The changes that accompany age-related decreases in speech comprehension are not yet understood. Here, authors show that older adults are less able to entrain to speech-paced auditory rhythms and that the behavioural consequences can be counteracted by top-down neural modulation.

ObjectivesIn Sweden, an increasing number of tests for sexually transmitted infections are conducted. Self-sampling services are provided free of charge at the national eHealth website. Our aim was to obtain a deeper understanding of users’ beliefs and experiences of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) self-sampling services.MethodsThis qualitative study is part of the national project ‘Internet-based chlamydia and gonorrhoea self-sampling test’, conducted in Sweden. Individuals ordering a CT/NG self-sampling test at home from the eHealth website were invited to participate. Of the 114 individuals who agreed, a purposeful sample including 20 women and men aged 18–49 years (mean, 30.8 years) participated in a telephone interview in 2019.ResultsThe test service for CT/NG was highly appreciated by men and women of different ages. Round-the-clock accessibility, avoiding clinical visits, ease of use, confidentiality and a rapid test result were reasons for this appreciation. Language, uncertainty about the correct sampling procedure, unreliable postal services and concerns about handling of personal data were mentioned as barriers. Reasons for testing were checking after unprotected sex, symptoms, checking a partner’s fidelity or a regular routine—‘to be on the safe side’. Knowledge about the infections and their consequences was limited; some considered them severe, especially if they could threaten fertility, and others were less concerned. Disclosing an infection was described as emotionally stressful. Participants had high self-efficacy in relation to the test and would not hesitate to use the service again, even if it involved a cost.ConclusionsInternet-based CT/NG self-sampling at home was highly appreciated and was used for individual health reasons, but also out of concern for others’ health and for society as a whole. The benefits seem to outweigh the barriers, and the service may therefore continue to be widely offered.

The functional organization of human auditory cortex can be probed by characterizing responses to various classes of sound at different anatomical locations. Along with histological studies this approach has revealed a primary field in posteromedial Heschl’s gyrus (HG) with pronounced induced high-frequency (70-150 Hz) activity and short-latency responses that phase-lock to rapid transient sounds. Low-frequency neural oscillations are also relevant to stimulus processing and information flow, however their distribution within auditory cortex has not been established. Alpha activity (7-14 Hz) in particular has been associated with processes that may differentially engage earlier versus later levels of the cortical hierarchy, including functional inhibition and the communication of sensory predictions. These theories derive largely from the study of occipitoparietal sources readily detectable in scalp electroencephalography. To characterize the anatomical basis and functional significance of less accessible temporal-lobe alpha activity we analyzed responses to sentences in seven human adults (four female) with epilepsy who had been implanted with electrodes in superior temporal cortex. In contrast to primary cortex in posteromedial HG, a non-primary field in anterolateral HG was characterized by high spontaneous alpha activity that was strongly suppressed during auditory stimulation. Alpha-power suppression decreased with distance from anterolateral HG throughout superior temporal cortex, and was more pronounced for clear compared to degraded speech. This suppression could not be accounted for solely by a change in the slope of the power spectrum. The differential manifestation and stimulus-sensitivity of alpha oscillations across auditory fields should be accounted for in theories of their generation and function.Significance StatementTo understand how auditory cortex is organized in support of perception, we recorded from patients implanted with electrodes for clinical reasons. This allowed measurement of activity in brain regions at different levels of sensory processing. Oscillations in the alpha range (7-14 Hz) have been associated with functions including sensory prediction and inhibition of regions handling irrelevant information, but their distribution within auditory cortex is not known. A key finding was that these oscillations dominated in one particular non-primary field, anterolateral Heschl’s gyrus, and were suppressed when subjects listened to sentences. These results build on our knowledge of the functional organization of auditory cortex and provide anatomical constraints on theories of the generation and function of alpha oscillations.

Neural response adaptation plays an important role in perception and cognition. Here, we used electroencephalography to investigate how aging affects the temporal dynamics of neural adaptation in human auditory cortex. Younger (18-31 years) and older (51-70 years) normal hearing adults listened to tone sequences with varying onset-to-onset intervals. Our results show long-lasting neural adaptation such that the response to a particular tone is a nonlinear function of the extended temporal history of sound events. Most important, aging is associated with multiple changes in auditory cortex; older adults exhibit larger and less variable response magnitudes, a larger dynamic response range, and a reduced sensitivity to temporal context. Computational modeling suggests that reduced adaptation recovery times underlie these changes in the aging auditory cortex and that the extended temporal stimulation has less influence on the neural response to the current sound in older compared with younger individuals. Our human electroencephalography results critically narrow the gap to animal electrophysiology work suggesting a compensatory release from cortical inhibition accompanying hearing loss and aging.

The frequency-following response (FFR) is a measure of the brain's periodic sound encoding. It is of increasing importance for studying the human auditory nervous system due to numerous associations with auditory cognition and dysfunction. Although the FFR is widely interpreted as originating from brainstem nuclei, a recent study using MEG suggested that there is also a right-lateralized contribution from the auditory cortex at the fundamental frequency (Coffey et al., 2016b). Our objectives in the present work were to validate and better localize this result using a completely different neuroimaging modality and to document the relationships between the FFR, the onset response, and cortical activity. Using a combination of EEG, fMRI, and diffusion-weighted imaging, we show that activity in the right auditory cortex is related to individual differences in FFR–fundamental frequency (f(0)) strength, a finding that was replicated with two independent stimulus sets, with and without acoustic energy at the fundamental frequency. We demonstrate a dissociation between this FFR–f(0)-sensitive response in the right and an area in left auditory cortex that is sensitive to individual differences in the timing of initial response to sound onset. Relationships to timing and their lateralization are supported by parallels in the microstructure of the underlying white matter, implicating a mechanism involving neural conduction efficiency. These data confirm that the FFR has a cortical contribution and suggest ways in which auditory neuroscience may be advanced by connecting early sound representation to measures of higher-level sound processing and cognitive function. SIGNIFICANCE STATEMENT The frequency-following response (FFR) is an EEG signal that is used to explore how the auditory system encodes temporal regularities in sound and is related to differences in auditory function between individuals. It is known that brainstem nuclei contribute to the FFR, but recent findings of an additional cortical source are more controversial. Here, we use fMRI to validate and extend the prediction from MEG data of a right auditory cortex contribution to the FFR. We also demonstrate a dissociation between FFR–related cortical activity from that related to the latency of the response to sound onset, which is found in left auditory cortex. The findings provide a clearer picture of cortical processes for analysis of sound features.

© 2019 Elsevier Inc. Sensitivity to temporal regularity (e.g., recurring modulation in amplitude) is crucial for speech perception. Degradation of the auditory periphery due to aging and hearing loss may lead to increased responsiveness to sound in the auditory cortex, with potential consequences for the processing of temporal regularities. We used electroencephalography recorded from younger (19–33 years) and older adults (55–76 years) to investigate whether younger and older listeners differ in responsiveness to sound and sensitivity to amplitude modulation in sounds. Aging was associated with reduced adaptation in the auditory cortex, suggesting an age-related increase in responsiveness. Furthermore, neural synchronization in the auditory cortex to 4-Hz amplitude-modulated narrow-band noises was enhanced in ∼30% of older individuals. Despite enhanced responsiveness and synchronization in the auditory cortex, sustained neural activity (likely involving auditory and higher-order regions) in response to amplitude modulation was absent in older people. Aging appears to be associated with over-responsiveness to amplitude modulation in the auditory cortex, but with diminished regularity sensitivity in higher-order areas.

Increased memory load is often signified by enhanced neural oscillatory power in the alpha range (8–13 Hz), which is taken to reflect inhibition of task-irrelevant brain regions. The corresponding neural correlates of memory decay, however, are not yet well understood. In the current study, we investigated auditory short-term memory decay in humans using a delayed matching-to-sample task with pure-tone sequences. First, in a behavioral experiment, we modeled memory performance over six different delay-phase durations. Second, in a MEG experiment, we assessed alpha-power modulations over three different delay-phase durations. In both experiments, the temporal expectation for the to-be-remembered sound was manipulated so that it was either temporally expected or not. In both studies, memory performance declined over time, but this decline was weaker when the onset time of the to-be-remembered sound was expected. Similarly, patterns of alpha power in and alpha-tuned connectivity between sensory cortices changed parametrically with delay duration (i.e., decrease in occipitoparietal regions, increase in temporal regions). Temporal expectation not only counteracted alpha-power decline in heteromodal brain areas (i.e., supramarginal gyrus), but also had a beneficial effect on memory decay, counteracting memory performance decline. Correspondingly, temporal expectation also boosted alpha connectivity within attention networks known to play an active role during memory maintenance. The present data show how patterns of alpha power orchestrate short-term memory decay and encourage a more nuanced perspective on alpha power across brain space and time beyond its inhibitory role. SIGNIFICANCE STATEMENT Our sensory memories of the physical world fade quickly. We show here that this decay of short-term memory can be counteracted by so-called temporal expectation; that is, knowledge of when to expect a sensory event that an individual must remember. We also show that neural oscillations in the “alpha” (8–13 Hz) range index both the degree of memory decay (for brief sound patterns) and the respective memory benefit from temporal expectation. Spatially distributed cortical patterns of alpha power show opposing effects in auditory versus visual sensory cortices. Moreover, alpha-tuned connectivity changes within supramodal attention networks reflect the allocation of neural resources as short-term memory representations fade.

The ability to detect regularities in sound (i.e., recurring structure) is critical for effective perception, enabling, for example, change detection and prediction. Two seemingly unconnected lines of research concern the neural operations involved in processing regularities: one investigates how neural activity synchronizes with temporal regularities (e.g., frequency modulation; FM) in sounds, whereas the other focuses on increases in sustained activity during stimulation with repeating tone-frequency patterns. In three electroencephalography studies with male and female human participants, we investigated whether neural synchronization and sustained neural activity are dissociable, or whether they are functionally interdependent. Experiment I demonstrated that neural activity synchronizes with temporal regularity (FM) in sounds, and that sustained activity increases concomitantly. In Experiment II, phase coherence of FM in sounds was parametrically varied. Although neural synchronization was more sensitive to changes in FM coherence, such changes led to a systematic modulation of both neural synchronization and sustained activity, with magnitude increasing as coherence increased. In Experiment III, participants either performed a duration categorization task on the sounds, or a visual object tracking task to distract attention. Neural synchronization was observed irrespective of task, whereas the sustained response was observed only when attention was on the auditory task, not under (visual) distraction. The results suggest that neural synchronization and sustained activity levels are functionally linked: both are sensitive to regularities in sounds. However, neural synchronization might reflect a more sensory-driven response to regularity, compared with sustained activity which may be influenced by attentional, contextual, or other experiential factors.Significance statementOptimal perception requires that the auditory system detects regularities in sounds. Synchronized neural activity and increases in sustained neural activity both appear to index the detection of a regularity, but the functional interrelation of these two neural signatures is unknown. In three electroencephalography experiments, we measured both signatures concomitantly while listeners were presented with sounds containing frequency modulations that differed in their regularity. We observed that both neural signatures are sensitive to temporal regularity in sounds, although they functionally decouple when a listener is distracted by a demanding visual task. Our data suggest that neural synchronization reflects a more automatic response to regularity, compared with sustained activity which may be influenced by attentional, contextual, or other experiential factors.

Alignment of neural oscillations with temporally regular input allows listeners to generate temporal expectations. However, it remains unclear how behavior is governed in the context of temporal variability: What role do temporal expectations play, and how do they interact with the strength of neural oscillatory activity? Here, human participants detected near-threshold targets in temporally variable acoustic sequences. Temporal expectation strength was estimated using an oscillator model and pre-target neural amplitudes in auditory cortex were extracted from magnetoencephalography signals. Temporal expectations modulated target-detection performance, however, only when neural delta-band amplitudes were large. Thus, slow neural oscillations act to gate influences of temporal expectation on perception. Furthermore, slow amplitude fluctuations governed linear and quadratic influences of auditory alpha-band activity on performance. By fusing a model of temporal expectation with neural oscillatory dynamics, the current findings show that human perception in temporally variable contexts relies on complex interactions between multiple neural frequency bands.

Stimulus-specific adaptation is the phenomenon whereby neural response magnitude decreases with repeated stimulation. Inconsistencies between recent nonhuman animal recordings and computational modeling suggest dynamic influences on stimulus-specific adaptation. The present human electroencephalography (EEG) study investigates the potential role of statistical context in dynamically modulating stimulus-specific adaptation by examining the auditory cortex-generated N1 and P2 components. As in previous studies of stimulus-specific adaptation, listeners were presented with oddball sequences in which the presentation of a repeated tone was infrequently interrupted by rare spectral changes taking on three different magnitudes. Critically, the statistical context varied with respect to the probability of small versus large spectral changes within oddball sequences (half of the time a small change was most probable; in the other half a large change was most probable). We observed larger N1 and P2 amplitudes (i.e., release from adaptation) for all spectral changes in the small-change compared with the large-change statistical context. The increase in response magnitude also held for responses to tones presented with high probability, indicating that statistical adaptation can overrule stimulus probability per se in its influence on neural responses. Computational modeling showed that the degree of coadaptation in auditory cortex changed depending on the statistical context, which in turn affected stimulus-specific adaptation. Thus the present data demonstrate that stimulus-specific adaptation in human auditory cortex critically depends on statistical context. Finally, the present results challenge the implicit assumption of stationarity of neural response magnitudes that governs the practice of isolating established deviant-detection responses such as the mismatch negativity.

Perception of time and temporal change is critical for human cognition. Yet, perception of temporal change is susceptible to contextual influences such as changes of a sound's pitch. Using functional magnetic resonance imaging (fMRI), the current study aimed to investigate perception of temporal rate change and pitch-induced illusory distortions. In a 6 × 6 design, human participants (N=19) listened to frequency-modulated sounds (~ 4 Hz) that varied over time in both modulation rate and pitch. Participants judged the direction of rate change ('speeding up' vs. 'slowing down'), while ignoring changes in pitch. Behaviorally, rate judgments were strongly biased by pitch changes: Participants perceived rate to slow down when pitch decreased and to speed up when pitch increased ('rate-change illusion'). The fMRI data revealed activation increases with increasing task difficulty in pre-SMA, left putamen, and right IFG/insula. Importantly, activation in pre-SMA was linked to the perceptual sensitivity to discriminate rate changes and, together with the left putamen, to relative reductions in susceptibility to pitch-induced illusory distortions. Right IFG/insula activations, however, only scaled with task difficulty. These data offer a distinction between regions whose activations scale with perceptual sensitivity to features of time (pre-SMA) and those that more generally support behaving in difficult listening conditions (IFG/insula). Hence, the data underscore that individual differences in time perception can be related to different patterns of neurofunctional activation.

Enhanced alpha power compared with a baseline can reflect states of increased cognitive load, for example, when listening to speech in noise. Can knowledge about “when” to listen (temporal expectations) potentially counteract cognitive load and concomitantly reduce alpha? The current magnetoencephalography (MEG) experiment induced cognitive load using an auditory delayed-matching-to-sample task with 2 syllables S1 and S2 presented in speech-shaped noise. Temporal expectation about the occurrence of S1 was manipulated in 3 different cue conditions: “Neutral” (uninformative about foreperiod), “early-cued” (short foreperiod), and “late-cued” (long foreperiod). Alpha power throughout the trial was highest when the cue was uninformative about the onset time of S1 (neutral) and lowest for the late-cued condition. This alpha-reducing effect of late compared with neutral cues was most evident during memory retention in noise and originated primarily in the right insula. Moreover, individual alpha effects during retention accounted best for observed individual performance differences between late-cued and neutral conditions, indicating a tradeoff between allocation of neural resources and the benefits drawn from temporal cues. Overall, the results indicate that temporal expectations can facilitate the encoding of speech in noise, and concomitantly reduce neural markers of cognitive load.

Classically, neural adaptation refers to a reduction in response magnitude by sustained stimulation. In human electroencephalography (EEG), neural adaptation has been measured, for example, as frequency-specific response decrease by previous stimulation. Only recently and mainly based on animal studies, it has been suggested that statistical properties in the stimulation lead to adjustments of neural sensitivity and affect neural response adaptation. However, it is thus far unresolved which statistical parameters in the acoustic stimulation spectrum affect frequency-specific neural adaptation, and on which time scales the effects take place. The present human EEG study investigated the potential influence of the overall spectral range as well as the spectral spacing of the acoustic stimulation spectrum on frequency-specific neural adaptation. Tones randomly varying in frequency were presented passively and computational modeling of frequency-specific neural adaptation was used. Frequency-specific adaptation was observed for all presentation conditions. Critically, however, the spread of adaptation (i.e., degree of coadaptation) in tonotopically organized regions of auditory cortex changed with the spectral range of the acoustic stimulation. In contrast, spectral spacing did not affect the spread of frequency-specific adaptation. Therefore, changes in neural sensitivity in auditory cortex are directly coupled to the overall spectral range of the acoustic stimulation, which suggests that neural adjustments to spectral stimulus statistics occur over a time scale of multiple seconds.

Neural oscillatory dynamics are a candidate mechanism to steer perception of time and temporal rate change. While oscillator models of time perception are strongly supported by behavioral evidence, a direct link to neural oscillations and oscillatory entrainment has not yet been provided. In addition, it has thus far remained unaddressed how context-induced illusory percepts of time are coded for in oscillator models of time perception. To investigate these questions, we used magnetoencephalography and examined the neural oscillatory dynamics that underpin pitch-induced illusory percepts of temporal rate change. Human participants listened to frequency-modulated sounds that varied over time in both modulation rate and pitch, and judged the direction of rate change (decrease vs increase). Our results demonstrate distinct neural mechanisms of rate perception: Modulation rate changes directly affected listeners' rate percept as well as the exact frequency of the neural oscillation. However, pitch-induced illusory rate changes were unrelated to the exact frequency of the neural responses. The rate change illusion was instead linked to changes in neural phase patterns, which allowed for single-trial decoding of percepts. That is, illusory underestimations or overestimations of perceived rate change were tightly coupled to increased intertrial phase coherence and changes in cerebro-acoustic phase lag. The results provide insight on how illusory percepts of time are coded for by neural oscillatory dynamics.

Spectral analysis of acoustic stimuli occurs in the auditory periphery (termed frequency selectivity) as well as at the level of auditory cortex (termed frequency specificity). Frequency selectivity is commonly investigated using an auditory filter model, while frequency specificity is often investigated as neural adaptation of the N1 response in electroencephalography (EEG). However, the effects of aging on frequency-specific adaptation, and the link between peripheral frequency selectivity and neural frequency specificity have not received much attention. Here, normal hearing younger (20–31 years) and older participants (49–63 years) underwent a psychophysical notched noise experiment to estimate individual auditory filters, and an EEG experiment to investigate frequency-specific adaptation in auditory cortex. The shape of auditory filters was comparable between age groups, and thus shows intact frequency selectivity in normal aging. In auditory cortex, both groups showed N1 frequency-specific neural adaptation effects that similarly varied with the spectral variance in the stimulation, while N1 responses were overall larger for older than younger participants. Importantly, the overall N1 amplitude, but not frequency-specific neural adaptation was correlated with the pass-band of the auditory filter. Thus, the current findings show a dissociation of peripheral frequency selectivity and neural frequency specificity, but suggest that widened auditory filters are compensated for by a response gain in frequency-specific areas of auditory cortex.

In auditory cortex, activation and subsequent adaptation is strongest for regions responding best to a stimulated tone frequency and less for regions responding best to other frequencies. Previous attempts to characterize the spread of neural adaptation in humans investigated the auditory cortex N1 component of the event-related potentials. Importantly, however, more recent studies in animals show that neural response properties are not independent of the stimulation context. To link these findings in animals to human scalp potentials, we investigated whether contextual factors of the acoustic stimulation, namely, spectral variance, affect the spread of neural adaptation. Electroencephalograms were recorded while human participants listened to random tone sequences varying in spectral variance (narrow vs. wide). Spread of adaptation was investigated by modeling single-trial neural adaptation and subsequent recovery based on the spectro-temporal stimulation history. Frequency-specific neural responses were largest on the N1 component, and the modeled neural adaptation indices were strongly predictive of trial-by-trial amplitude variations. Yet the spread of adaption varied depending on the spectral variance in the stimulation, such that adaptation spread was broadened for tone sequences with wide spectral variance. Thus the present findings reveal context-dependent auditory cortex adaptation and point toward a flexibly adjusting auditory system that changes its response properties with the spectral requirements of the acoustic environment.

In language processing, the relative contribution of early sensory and higher cognitive brain areas is still an open issue. A recent controversial hypothesis proposes that sensory cortices show sensitivity to syntactic processes, whereas other studies suggest a wider neural network outside sensory regions. The goal of the current event‐related fMRI study is to clarify the contribution of sensory cortices in auditory syntactic processing in a 2 × 2 design. Two‐word utterances were presented auditorily and varied both in perceptual markedness (presence or absence of an overt word category marking “‐t”), and in grammaticality (syntactically correct or incorrect). A multivariate pattern classification approach was applied to the data, flanked by conventional cognitive subtraction analyses. The combination of methods and the 2 × 2 design revealed a clear picture: The cognitive subtraction analysis found initial syntactic processing signatures in a neural network including the left IFG, the left aSTG, the left superior temporal sulcus (STS), as well as the right STS/STG. Classification of local multivariate patterns indicated the left‐hemispheric regions in IFG, aSTG, and STS to be more syntax‐specific than the right‐hemispheric regions. Importantly, auditory sensory cortices were only sensitive to the overt perceptual marking, but not to the grammaticality, speaking against syntax‐inflicted sensory cortex modulations. Instead, our data provide clear evidence for a distinction between regions involved in pure perceptual processes and regions involved in initial syntactic processes. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

We aimed to compare conventional ompA typing of Chlamydia trachomatis with multilocus sequence typing (MLST) and multilocus variable-number tandem-repeat (VNTR) analysis (MLVA). Previously used MLST and MLVA systems were compared to modified versions that used shorter target regions and nested PCR. Heterosexual couples were selected from among persons with urogenital C. trachomatis infections visiting the sexually transmitted infection outpatient clinic in Amsterdam, The Netherlands. We identified 30 couples with a total of 65 C. trachomatis -positive samples on which MLST and MLVA for eight target regions were performed. All regions were successfully sequenced in 52 samples, resulting in a complete profile for 18 couples and 12 individuals. Nine ompA genovars from D to K, with two variants of genovar G, were found. The numbers of sequence type and MLVA type profiles were 20 for MLST and 21 for MLVA, and a combination of MLST and MLVA yielded 28 profiles, with discriminatory indexes ( D ) ranging from 0.95 to 0.99. Partners in 17 couples shared identical profiles, while partners in 1 couple had completely different profiles. Three persons had infections at multiple anatomical locations, and within each of these three individuals, all profiles were identical. The discriminatory capacity of all MLST and MLVA methods is much higher than that of ompA genotyping ( D = 0.78). No genotype variation was found within the samples of the same person or from heterosexual couples with a putative single transmission. This shows that the chlamydial genome in clinical specimens has an appropriate polymorphism to enable epidemiological cluster analysis using MLST and MLVA.

Recent auditory oddball studies using syntactic stimuli report a syntactic effect on the mismatch negativity (sMMN) around 100–200 ms. For morphosyntactic violations, this sMMN effect has been localized in the left superior temporal cortex. Independently, a recent visual sentence processing study introduced a “sensory hypothesis” which postulates that sensory cortices are sensitive to syntactic violations when these are overtly marked by closed-class morphemes, and thus contribute to early syntax-related effects in EEG and MEG. The present study aimed to test the sensory hypothesis in the auditory modality by localizing the neuronal sources of the sMMN to phrase structure violations. Using whole head magnetoencephalography, two-word utterances which were syntactically correct, uncommon or incorrect due to a word category violation were presented in an auditory oddball paradigm. In the sMMN time window (100–180 ms), incorrect phrases elicited strongest activation in the left Sylvian fissure (including the primary auditory cortex) and in the left superior temporal sulcus. Prior to this, a very early grammaticality effect (40–80 ms), focused in the left Sylvian fissure, was found. An additional grammaticality effect in a later time window (280–380 ms) was localized in the anterior part of the superior temporal gyrus, the planum polare. Processing of an uncommon phrase did not differ from processing a correct phrase in any of the time windows, indicating the genuinely syntactic nature of the sMMN effect. Our results are in line with previous studies localizing the sMMN to morphosyntactic violations and are furthermore compatible with the sensory hypothesis of closed-class morphology based syntactic processes.

A quantitative real-time polymerase chain reaction (PCR) based on the omp P6 gene was developed to detect Haemophilus influenzae. Its specificity was determined by analysis of 29 strains of 11 different Haemophilus spp. and was compared with PCR assays having other target genes: rnpB, 16S rRNA, and bexA. The method was evaluated on nasopharyngeal aspirates from 166 adult patients with community-acquired pneumonia. When 10(4) DNA copies/mL was used as cutoff limit for the method, P6 PCR had a sensitivity of 97.5% and a specificity of 96.0% compared with the culture. Of 20 culture-negative but P6 PCR-positive cases, 18 were confirmed by fucK PCR as H. influenzae. Five (5.9%) of 84 nasopharyngeal aspirates from adult controls tested PCR positive. We conclude that the P6 real-time PCR is both sensitive and specific for identification of H. influenzae in respiratory secretions. Quantification facilitates discrimination between disease-causing H. influenzae strains and commensal colonization.

Background: Genital chlamydia infection (chlamydia) is the most commonly reported sexually transmitted infection (STI) in Sweden. To guide prevention needs, we aimed to investigate factors associated with chlamydia. Methods: A cohort of visitors aged 20-40 years at an urban STI clinic in Sweden was recruited. Behavioural data were collected using a self-administered questionnaire. Self-sampled specimens were tested for chlamydia by a DNA amplification assay. Statistically significant (p

Objectives: The so-called small-world effect can have a great impact on efforts to control the incidence and prevalence of sexually transmitted infections. This is because a small number of so-called spatial bridgers (individuals who, through sexual contacts, interconnect geographically distant areas) can drastically lower the average path length in the sexual network and, as a result, make locally based intervention programs much less effective. The objectives of this study were to analyze the sociodemographic characteristics of these bridgers and to compare the result with the remaining study population. The purpose was to determine whether it is possible to identify them for targeted intervention programs. Study Design: During 2001, contact tracing was performed in approximately 98% of all cases with positive test results in Varmland County. The sexual networks obtained constituted a study population of 851 individuals. Statistical analysis was used to characterize individuals engaged in spatial bridging behavior. Results: Approximately 8% of the study population was characterized as spatial bridgers. Using multivariate analysis, we found almost no significant differences between these individuals and the rest of the study population when it came to sociodemographic variables, including education, economy, and ethnicity. Conclusion: The number of spatial bridgers is high enough to create a small-world network with links that can fuel the endemic chlamydia in Varmland County. Sociodemographic information could not be used to characterize spatial bridgers. In interventions against chlamydia, spatial bridgers shall be considered as potentially important for sustaining the disease.

BACKGROUND: Accurate information about the prevalence of Chlamydia trachomatis is needed to assess national prevention and control measures. METHODS: We systematically reviewed population-based cross-sectional studies that estimated chlamydia prevalence in European Union/European Economic Area (EU/EEA) Member States and non-European high income countries from January 1990 to August 2012. We examined results in forest plots, explored heterogeneity using the I² statistic, and conducted random effects meta-analysis if appropriate. Meta-regression was used to examine the relationship between study characteristics and chlamydia prevalence estimates. RESULTS: We included 25 population-based studies from 11 EU/EEA countries and 14 studies from five other high income countries. Four EU/EEA Member States reported on nationally representative surveys of sexually experienced adults aged 18-26 years (response rates 52-71%). In women, chlamydia point prevalence estimates ranged from 3.0-5.3%; the pooled average of these estimates was 3.6% (95% CI 2.4, 4.8, I² 0%). In men, estimates ranged from 2.4-7.3% (pooled average 3.5%; 95% CI 1.9, 5.2, I² 27%). Estimates in EU/EEA Member States were statistically consistent with those in other high income countries (I² 0% for women, 6% for men). There was statistical evidence of an association between survey response rate and estimated chlamydia prevalence; estimates were higher in surveys with lower response rates, (p = 0.003 in women, 0.018 in men). CONCLUSIONS: Population-based surveys that estimate chlamydia prevalence are at risk of participation bias owing to low response rates. Estimates obtained in nationally representative samples of the general population of EU/EEA Member States are similar to estimates from other high income countries Background: Accurate information about the prevalence of Chlamydia trachomatis is needed to assess national prevention and control measures.Methods: We systematically reviewed population-based cross-sectional studies that estimated chlamydia prevalence in European Union/European Economic Area (EU/EEA) Member States and non-European high income countries from January 1990 to August 2012. We examined results in forest plots, explored heterogeneity using the I2 statistic, and conducted random effects meta-analysis if appropriate. Meta-regression was used to examine the relationship between study characteristics and chlamydia prevalence estimates.Results: We included 25 population-based studies from 11 EU/EEA countries and 14 studies from five other high income countries. Four EU/EEA Member States reported on nationally representative surveys of sexually experienced adults aged 18–26 years (response rates 52–71%). In women, chlamydia point prevalence estimates ranged from 3.0–5.3%; the pooled average of these estimates was 3.6% (95% CI 2.4, 4.8, I2 0%). In men, estimates ranged from 2.4–7.3% (pooled average 3.5%; 95% CI 1.9, 5.2, I2 27%). Estimates in EU/EEA Member States were statistically consistent with those in other high income countries (I2 0% for women, 6% for men). There was statistical evidence of an association between survey response rate and estimated chlamydia prevalence; estimates were higher in surveys with lower response rates, (p = 0.003 in women, 0.018 in men).

Background We aimed to study if certain clinical and/or microbiological factors are associated with a high nasopharyngeal (NP) density of Streptococcus pneumoniae in pneumococcal pneumonia. In addition, we aimed to study if a high NP pneumococcal density could be useful to detect severe pneumococcal pneumonia. Methods Adult patients hospitalized for radiologically confirmed community-acquired pneumonia were included in a prospective study. NP aspirates were collected at admission and were subjected to quantitative PCR for pneumococcal DNA (Spn9802 DNA). Patients were considered to have pneumococcal etiology if S. pneumoniae was detected in blood culture and/ or culture of respiratory secretions and/or urinary antigen test. Results Of 166 included patients, 68 patients had pneumococcal DNA detected in NP aspirate. Pneumococcal etiology was noted in 57 patients (84%) with positive and 8 patients (8.2%) with negative test for pneumococcal DNA (p= 2 days prior to admission, and a medium/high serum immunoglobulin titer against the patient's own pneumococcal serotype. NP pneumococcal density was not associated with sex, age, smoking, co-morbidity, viral co-infection, pneumococcal serotype, or bacteremia. Severe pneumococcal pneumonia was noted in 28 study patients. When we studied the performance of PCR with different DNA cut-off levels for detection of severe pneumococcal pneumonia, we found sensitivities of 54-82% and positive predictive values of 37-56%, indicating suboptimal performance. Conclusions Pneumonia severity, symptom duration similar to 2 days, and a medium/high serum immunoglobulin titer against the patient's own serotype were independently associated with a high NP pneumococcal density. NP pneumococcal density has limited value for detection of severe pneumococcal pneumonia.

We studied the immunoglobulin (Ig) response to causative serotype-specific capsular polysaccharides in adult pneumococcal pneumonia patients. The serotypes were grouped according to their degree of encapsulation and invasive potential. Seventy patients with pneumococcal pneumonia, 20 of whom were bacteremic, were prospectively studied. All pneumococcal isolates from the patients were serotyped, and the Ig titers to the homologous serotype were determined in acute- and convalescent-phase sera using a serotype-specific enzyme-linked immunosorbent assay. The Ig titers were lower in bacteremic cases than in nonbacteremic cases (P< 0.042). The Ig titer ratio (convalescent/acute titer) was ≥2 in 33 patients, 1 to 1.99 in 20 patients, and P< 0.031). The patients with serotypes with a thin capsule (1, 4, 7F, 9N, 9V, and 14) and medium/high invasive potential (1, 4, 7F, 9N, 9V, 14, and 18C) had higher Ig titer ratios than did patients with serotypes with a thick capsule (3, 6B, 11A, 18C, 19A, 19F, and 23F) and low invasive potential (3, 6B, 19A, 19F, and 23F) (P< 0.05 for both comparisons after adjustment for age). Ig titer ratios of

Temporal expectations enhance neural encoding precision, reflected in optimized alignment of slow neural oscillatory phase, and facilitate subsequent stimulus processing. If an event's exact occurrence time is unknown, temporal expectations arise solely from the passage of time. Here, we show that this specific type of temporal expectation is also reflected in neural phase organization. While undergoing magnetoencephalography, participants performed an auditory-delayed matching-to-sample task with two syllables (S1, S2). Critically, S1-onset time varied in the 0.6-1.8-s (i.e., 0.6-1.7 Hz) range. Increasing S1-onset times led to increased slow-delta (0.6-0.9 Hz) phase coherence over right frontotemporal sensors during S1 encoding. Moreover, individuals with higher slow-delta coherence showed decreased alpha power (8-13 Hz) during subsequent memory retention. In sum, temporal expectations based on the passage of time optimize the precise alignment of neural oscillatory phase with an expected stimulus.

Objectives: To analyse trends in rates of genital chlamydial infection and ectopic pregnancy between 1985 and 1995 in a county in Sweden. Setting: Uppsala county where screening for chlamydial infection, treatment, and contact tracing has been widespread and where ectopic pregnancies are recorded. Methods: Rates of chlamydial infections and ectopic pregnancy between 1985 and 1995 were calculated for women aged 20-39 years. Poisson and linear regression were used to examine the association between the risk of ectopic pregnancy and the current rates of chlamydial infection and rates of chlamydial infection from up to 5 years earlier. Main outcome measures: Rates of chlamydial infection per 100 examinations, rates of ectopic pregnancy per 1000 pregnancies, rate ratios and 95% confidence intervals for an increase in chlamydial infections of 5 new cases per 100 examinations. Results: 103 870 cervical samples from women aged 15-39 years were analysed; 5648 (5.4%) were positive for chlamydia. 51 630 pregnancies were analysed; 930 (1.8%) were ectopic. Both rates declined over time. For women aged 20-24 years there was a strong correlation between the rate of ectopic pregnancy and the rate of chlamydial infection in the same year (r=0.93, P Conclusions: Declining rates of genital chlamydial infections have probably led to a fall in the rate of ectopic pregnancies. The timing of the decline in the rate of ectopic pregnancies varies with age. Among young women falling rates of chlamydial infection have been accompanied by an immediate reduction in the rate of ectopic pregnancy. Key messages The effect of measures to diagnose and treat genital chlamydial infections on the risk of ectopic pregnancy was examined in a county in Sweden Rates of chlamydial infection and ectopic pregnancy both declined between 1985 and 1995 Chlamydial infections seem to be the main cause of ectopic pregnancy in young women; the risk of ectopic pregnancy decreased concurrently with the decline in chlamydial infections In older women the associations were less pronounced

We aimed to compare sputum and nasopharyngeal aspirate (NpA) samples and the PCR gene targets lytA and Spn9802 in quantitative PCR (qPCR) assays for rapid detection of pneumococcal etiology in community-acquired pneumonia (CAP). Seventy-eight adult patients hospitalized for radiologically confirmed CAP had both good-quality sputum and NpA specimens collected at admission. These samples were subjected to lytA qPCR and Spn9802 qPCR assays with analytical times of lytA assay), 96% and 17% (sputum Spn9802 assay), 81% and 11% (NpA lytA assay), and 81% and 20% (NpA Spn9802 assay), respectively. The mean lytA and Spn9802 DNA levels were significantly higher in qPCR-positive sputum samples from cases with pneumococcal etiology than in qPCR-positive sputum samples from CAP cases without pneumococcal etiology or qPCR-positive NpA samples from cases with pneumococcal etiology ( P < 0.02 for all comparisons). For detection of pneumococcal etiology, receiver operating characteristic curve analysis showed that sputum specimens were superior to NpA specimens as the sample type ( P < 0.02 for both gene targets) and lytA tended to be superior to Spn9802 as the gene target. The best-performing test, the sputum lytA qPCR assay, showed high sensitivity (94%) and specificity (96%) with a cutoff value of 10 5 DNA copies/ml. In CAP patients with good sputum production, this test has great potential to be used for the rapid detection of pneumococcal etiology and to target penicillin therapy.

Meaningful auditory stimuli such as speech and music often vary simultaneously along multiple time scales. Thus, listeners must selectively attend to, and selectively ignore, separate but intertwined temporal features. The current study aimed to identify and characterize the neural network specifically involved in this feature-selective attention to time. We used a novel paradigm where listeners judged either the duration or modulation rate of auditory stimuli, and in which the stimulation, working memory demands, response requirements, and task difficulty were held constant. A first analysis identified all brain regions where individual brain activation patterns were correlated with individual behavioral performance patterns, which thus supported temporal judgments generically. A second analysis then isolated those brain regions that specifically regulated selective attention to temporal features: Neural responses in a bilateral fronto-parietal network including insular cortex and basal ganglia decreased with degree of change of the attended temporal feature. Critically, response patterns in these regions were inverted when the task required selectively ignoring this feature. The results demonstrate how the neural analysis of complex acoustic stimuli with multiple temporal features depends on a fronto-parietal network that simultaneously regulates the selective gain for attended and ignored temporal features.

In Uppsala County, between 1985 and 1993, examinations for Chlamydia trachomatis were being performed in a central laboratory. A change in national sexually transmitted disease legislation in 1988 encouraged screening.To analyze trends in detection rates of genital chlamydial infections by age, sex, and clinic type, and to assess the influence of the legislation change.This was an analysis of 119,892 tests, representing 95.4% of all specimens sampled. Eighty-six percent of the samples were cultured, 14% were examined by enzyme immunoassay.Seventy-nine percent of specimens came from women. 7,989 positive samples were identified. Detection rates declined from 107.2 per 1,000 in 1985 to 32.3 in 1993 in women and from 183.3 to 70.7 in men. Positivity rates were highest in sexually transmitted disease and youth clinics and lowest in private practices. Among female youths, rates leveled off in later years, but the rates increased in male youths. The legislation change reduced the probability of a positive test in men but not in women.Genital chlamydial infection generally declined. However, among youths, an increase has occurred in recent years. Continued screening and the introduction of noninvasive diagnostic methods for males is warranted, particularly in youth clinics. Selective screening may be more cost-effective in other age groups.

Patients with the monogenic disease autoimmune polyendocrine syndrome type I (APSI) develop autoimmunity against multiple endocrine organs and suffer from chronic mucocutaneous candidiasis (CMC), a paradoxical complication with an unknown mechanism. We report here that saliva from APSI patients with CMC is defective in inhibiting growth of Candida albicans in vitro and show reduced levels of a salivary protein identified as cystatin SA1. In contrast, APSI patients without CMC express salivary cystatin SA1 and can inhibit C. albicans to the same extent as healthy controls. We evaluated the anti-fungal activity of cystatin SA1 and found that synthesized full length cystatin SA1 efficiently inhibits growth of C. albicans in vitro. Moreover, APSI patients exhibit salivary IgA autoantibodies recognizing myosin-9, a protein expressed in the salivary glands, thus linking autoimmunity to cystatin SA1 deficiency and CMC. This data suggests an autoimmune mechanism behind CMC in APSI and provides rationale for evaluating cystatin SA1 in antifungal therapy.

The present magnetoencephalography study investigated whether the brain states of early syntactic and auditory-perceptual processes can be decoded from single-trial recordings with a multivariate pattern classification approach. In particular, it was investigated whether the early neural activation patterns in response to rule violations in basic auditory perception and in high cognitive processes (syntax) reflect a functional organization that largely generalizes across individuals or is subject-specific. On this account, subjects were auditorily presented with correct sentences, syntactically incorrect sentences, correct sentences including an interaural time difference change, and sentences containing both violations. For the analysis, brain state decoding was carried out within and across subjects with three pairwise classifications. Neural patterns elicited by each of the violation sentences were separately classified with the patterns elicited by the correct sentences. The results revealed the highest decoding accuracies over temporal cortex areas for all three classification types. Importantly, both the magnitude and the spatial distribution of decoding accuracies for the early neural patterns were very similar for within-subject and across-subject decoding. At the same time, across-subject decoding suggested a hemispheric bias, with the most consistent patterns in the left hemisphere. Thus, the present data show that not only auditory-perceptual processing brain states but also cognitive brain states of syntactic rule processing can be decoded from single-trial brain activations. Moreover, the findings indicate that the neural patterns in response to syntactic cognition and auditory perception reflect a functional organization that is highly consistent across individuals.

Objective When investigating auditory perceptual regularity processing, mismatch negativity (MMN) is commonly used. MMN is computed as a difference signal between the event-related potentials (ERPs) elicited by repeated standard tones and rarely occurring deviant tones. This procedure leads to an underestimation of the N1 component elicited by standards compared to the N1 to deviants which might affect the MMN. Consequently, a random control design was previously introduced. This design, however, overestimates the N1 to the deviant. Here, we developed a new paradigm that avoids previous drawbacks. Methods We designed a regular cascadic sequence as a control to the deviant. ERPs were measured while presenting conventional oddball blocks (standards, deviants), random control blocks and a cascadic control block. Results MMN was observed in each difference signal. Regarding the N1, standards elicited smallest amplitudes. The N1 for the deviant and the cascadic control was comparable. The largest N1 was elicited by the random control. Conclusion Standards underestimate N1 refractoriness effects in the responses to deviants, while random control tones overestimate. Cascadic control tones, however, provide a reasonable estimation for the N1. Significance The new cascadic control design is suitable to investigate auditory perceptual regularity processes while controlling for N1 refractoriness effects.

Neural auditory responses are known to change from childhood to adulthood. The most prominent components of the event-related potentials (ERPs) found in children are the P1 and N2, while the P1 and N1 are strongest in adults. Previous dipole localizations showed regions of the auditory cortex (AC) underlying these responses. An N1 in children, however, has only been observed in older age or under certain experimental conditions different than commonly applied in adults. The current study aimed to further elucidate on auditory processing and related components in school-aged children. To do this, MEG and EEG was recorded in adults and 9 to 10 year old children, while presenting pure tones either repetitively or randomly among tones of different pitch. Furthermore, the current paradigm was explicitly designed to not only investigate the P1 and N2 in children, but moreover to examine N1 modulations based on different refractory states caused by the two conditions. Our results are clear cut. In adults, P1(m) and N1(m) components were localized in AC regions, with the N1(m) largely attenuated for repetitive tones. The P1(m) and N2(m) components observed in children were also localized in AC regions. Most importantly, ERP modulations in the N1 time window (i.e., larger responses for random than repetitive tones) were remarkably similar for adults and children, both in amplitude and latency. This effect indicates that the N1 sub-component reflecting frequency-specific refractoriness is fully developed in 9 to 10 year old children. Thus, previous interpretations on the function and maturation of the N1 need reconsideration.

Processing syntax is believed to be a higher cognitive function involving cortical regions outside sensory cortices. In particular, previous studies revealed that early syntactic processes at around 100-200 ms affect brain activations in anterior regions of the superior temporal gyrus (STG), while independent studies showed that pure auditory perceptual processing is related to sensory cortex activations. However, syntax-related modulations of sensory cortices were reported recently, thereby adding diverging findings to the previous studies. The goal of the present magnetoencephalography study was to localize the cortical regions underlying early syntactic processes and those underlying perceptual processes using a within-subject design. Sentences varying the factors syntax (correct vs. incorrect) and auditory space (standard vs. change of interaural time difference (ITD)) were auditorily presented. Both syntactic and auditory spatial anomalies led to very early activations (40-90 ms) in the STG. Around 135 ms after violation onset, differential effects were observed for syntax and auditory space, with syntactically incorrect sentences leading to activations in the anterior STG, whereas ITD changes elicited activations more posterior in the STG. Furthermore, our observations strongly indicate that the anterior and the posterior STG are activated simultaneously when a double violation is encountered. Thus, the present findings provide evidence of a dissociation of speech-related processes in the anterior STG and the processing of auditory spatial information in the posterior STG, compatible with the view of different processing streams in the temporal cortex.

Background Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR) for detection of S. pneumoniae (9802 gene fragment), H. influenzae (omp P6 gene) and N. meningitidis (ctrA gene). The method was evaluated on bronchoalveolar lavage (BAL) samples from 156 adults with lower respiratory tract infection (LRTI) and 31 controls, and on 87 cerebrospinal fluid (CSF) samples from meningitis patients. Results The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis) in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 105 genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively. In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both bacteria. Conclusions The PCR provides increased sensitivity and the multiplex format facilitates diagnosis of S. pneumoniae, H. influenzae and N. meningitidis and the assay enable detection after antibiotic treatment has been installed. Quantification increases the specificity of the etiology for pneumonia.

Objectives In 2006 a new variant of Chlamydia trachomatis (nvCT), with a deletion in the cryptic plasmid, was reported in Sweden. This deletion included the targets for the genetic diagnostic systems used in many clinical laboratories and resulted in thousands of falsenegative results. The aim of this study was to characterise consecutive Chlamydia tissue culturepositive samples from 2006 in Orebro County, after identification of the nvCT, and to compare the results from samples collected in the same county in 1999e2000. The study also aimed to evaluate the discriminatory capacity of multilocus sequence typing (MLST) compared with ompA sequencing. Methods ompA sequencing and MLST was used to characterise 100 consecutive Chlamydia tissue culturepositive samples. Results A significant (p

In the present study, we evaluated rapid real-time PCR assays for ply, Spn9802, and lytA applied to plasma samples for the detection of Streptococcus pneumoniae in patients with community-acquired pneumonia (CAP). In a prospective study of CAP aetiology, an EDTA plasma sample was collected together with blood culture in 92 adult CAP patients and 91 adult controls. Among the 92 CAP patients, lytA PCR was positive in eight (9%), Spn9802 PCR was positive in 11 (12%) and ply PCR was positive in 19 (21%) cases. Of 91 controls, the ply PCR was positive in eight cases (9%), but no positive cases were noted by Spn9802 or lytA PCRs. Ten CAP patients had pneumococcal bacteraemia. Compared to blood culture, PCR for lytA, Spn9802 and ply had sensitivities of 70% (7/10), 60% (6/10) and 70% (7/10), and specificities of 96% (79/82), 94% (77/82) and 85% (70/82) respectively. With blood culture and/or culture of representative sputum, and/or urinary antigen detection, S. pneumoniae was identified in 31 CAP patients. Compared to these tests in combination, PCR for lytA, Spn9802 and ply showed sensitivities of 26% (8/31), 32% (10/31) and 42% (13/31), and specificities of 100% (61/61), 98% (60/61) and 90% (55/61) respectively. We conclude that Spn9802 and lytA PCRs may be useful for the rapid detection of bacteraemic pneumococcal pneumonia, whereas ply PCR is not specific enough for routine use and blood PCR with small plasma volumes is not useful for the detection of nonbacteraemic pneumococcal pneumonia.

The current shift from phenotypically toward genotypically based microbial diagnosis is not unproblematic. A novel quantitative real-time polymerase chain reaction (PCR) assay based on the Spn9802 DNA fragment was therefore developed for detection of Streptococcus pneumoniae. Out of 44 bacterial species, only S. pneumoniae and Streptococcus pseudopneumoniae were positive in Spn9802 PCR. In an evaluation on nasopharyngeal aspirates from 166 patients with community-acquired pneumonia, the assay was positive in 49 of 50 culture-positive cases. Of 19 culture-negative but Spn9802 PCR-positive cases, 12 were confirmed as S. pneumoniae by rnpB sequence analysis. With an expanded reference standard, including culture and rnpB sequencing, Spn9802 had a sensitivity of 94% and a specificity of 98%. A cutoff for clinically significant positivity was 10(4) DNA copies/mL, giving 71% sensitivity and 100% specificity. In conclusion, Spn9802 real-time PCR is highly sensitive and specific. The quantification it provides enables differentiation between pneumococcal pathogenicity and commensalism.

Two cases of the sexually transmitted infection lymphogranuloma venereum (LGV) were detected in men who have sex with men (MSM) in Sweden during 2004