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Background and hypothesesImpaired interference control is a potential prognostic and endophenotypic marker of schizophrenia (SZ) and bipolar disorder (BP). Assessing children with familial high-risk (FHR) of SZ or BP enables characterization of early risk markers and we hypothesize that they express impaired interference control as well as aberrant brain activation compared to population-based control (PBC) children.Study designUsing a flanker task, we examined interference control together with functional magnetic resonance imaging (fMRI) in 11-to-12-year-old children with FHR of SZ (FHR-SZ) or FHR of BP (FHR-BP) and population-based control (PBC) children as part of a register-based, prospective cohort-study; The Danish High Risk and Resilience study – VIA 11.Study resultsWe included 85 (44 % female) FHR-SZ, 63 (52 % female) FHR-BP and 98 (50 % female) PBC in the analyses. Interference effects, caused by the spatial visuomotor conflict, showed no differences between groups. Bayesian ANOVA of reaction time (RT) variability, quantified by the coefficient of variation (CVRT), revealed a group effect with similarly higher CVRTin FHR-BP and FHR-SZ compared to PBC (BF10= 6.82). The fMRI analyses revealed no evidence for between-group differences in task-related brain activation. Post-hoc analyses excluding children with psychiatric illness yielded same results.ConclusionFHR-SZ and FHR-BP at age 11-to-12 show intact ability to resolve a spatial visuo-motor conflict and neural efficacy. The increased variability in RT may reflect difficulties in maintaining sustained attention. Since variability in RT was independent of existing psychiatric illness, it may reflect a potential endophenotypic marker of risk.

Background: Parkinson's disease (PD) causes a loss of neuromelanin-positive, noradrenergic neurons in the locus coeruleus (LC), which has been implicated in nonmotor dysfunction. Objectives: We used "neuromelanin sensitive" magnetic resonance imaging (MRI) to localize structural disintegration in the LC and its association with nonmotor dysfunction in PD. Methods: A total of 42 patients with PD and 24 age-matched healthy volunteers underwent magnetization transfer weighted (MTw) MRI of the LC. The contrast-to-noise ratio of the MTw signal (CNRMTw) was used as an index of structural LC integrity. We performed slicewise and voxelwise analyses to map spatial patterns of structural disintegration, complemented by principal component analysis (PCA). We also tested for correlations between regional CNRMTw and severity of nonmotor symptoms. Results: Mean CNRMTw of the right LC was reduced in patients relative to controls. Voxelwise and slicewise analyses showed that the attenuation of CNRMTw was confined to the right mid-caudal LC and linked regional CNRMTw to nonmotor symptoms. CNRMTw attenuation in the left mid-caudal LC was associated with the orthostatic drop in systolic blood pressure, whereas CNRMTw attenuation in the caudal most portion of right LC correlated with apathy ratings. PCA identified a bilateral component that was more weakly expressed in patients. This component was characterized by a gradient in CNRMTw along the rostro-caudal and dorso-ventral axes of the nucleus. The individual expression score of this component reflected the overall severity of nonmotor symptoms. Conclusion: A spatially heterogeneous disintegration of LC in PD may determine the individual expression of specific nonmotor symptoms such as orthostatic dysregulation or apathy. © 2022 International Parkinson and Movement Disorder Society

BackgroundElectrical stimulation of the hand can suppress the motor evoked potential (MEP) elicited by transcranial magnetic stimulation (TMS) of the primary motor hand area (M1-HAND) when the afferent stimulus arrives in M1-HAND at the time of TMS. The magnitude of short-latency afferent inhibition (SAI) is expressed as the ratio between the conditioned and unconditioned MEP and is widely used to probe sensorimotor interactions in human physiological studies.Objective/HypothesisWe hypothesized that corticospinal excitability and SAI are influenced by the recent history of peripheral electrical stimulation.MethodsIn twenty healthy participants, we recorded MEPs from the right first dorsal interosseus muscle. MEPs were evoked by single-pulse TMS of the left M1-HAND alone (unconditioned TMS) or by TMS preceded by electrical stimulation of the right index finger (“homotopic” conditioning) or little finger (“heterotopic” conditioning). The three conditions were pseudo-randomly intermixed or delivered in blocks in which a single condition was repeated five or ten times. MEP amplitudes and SAI magnitudes were compared using linear mixed effect models.ResultsAll stimulation protocols consistently produced SAI, which was stronger after homotopic stimulation. Randomly intermingling the three stimulation conditions reduced the relative magnitude of homotopic and heterotopic SAI as opposed to blocked stimulation. The apparent attenuation of SAI was caused by a suppression of the unconditioned but not the conditioned MEP amplitude during the randomly intermixed condition.Conclusion(s)The recent history of afferent stimulation modulates corticospinal excitability. This “history effect” impacts on the relative magnitude of SAI depending on how conditioned and unconditioned responses are intermixed and needs to be taken into consideration when probing afferent inhibition and corticospinal excitability.

When selectively attending to a speech stream in multi-talker scenarios, low-frequency cortical activity is known to synchronize selectively to fluctuations in the attended speech signal. Older listeners with age-related sensorineural hearing loss (presbycusis) often struggle to understand speech in such situations, even when wearing a hearing aid. Yet, it is unclear whether a peripheral hearing loss degrades the attentional modulation of cortical speech tracking. Here, we used psychoacoustics and electroencephalography (EEG) in male and female human listeners to examine potential effects of hearing loss on EEG correlates of speech envelope synchronization in cortex. Behaviorally, older hearing-impaired (HI) listeners showed degraded speech-in-noise recognition and reduced temporal acuity compared with age-matched normal-hearing (NH) controls. During EEG recordings, we used a selective attention task with two spatially separated simultaneous speech streams where NH and HI listeners both showed high speech recognition performance. Low-frequency (SIGNIFICANCE STATEMENTPeople with age-related sensorineural hearing loss often struggle to follow speech in the presence of competing talkers. It is currently unclear whether hearing impairment may impair the ability to use selective attention to suppress distracting speech in situations when the distractor is well segregated from the target. Here, we report amplified envelope-entrained cortical EEG responses to attended speech and to simple tones modulated at speech rates (4 Hz) in listeners with age-related hearing loss. Critically, despite increased self-reported listening difficulties, cortical synchronization to speech mixtures was robustly modulated by selective attention in listeners with hearing loss. This allowed the attended talker to be classified from single-trial EEG responses with high accuracy in both older hearing-impaired listeners and age-matched normal-hearing controls.

BackgroundParkinson’s disease (PD) leads to a loss of neuromelanin positive, noradrenergic neurons in the locus coeruleus (LC) which has been implicated in non-motor dysfunction. “Neuromelanin sensitive” magnetic resonance imaging (MRI) has emerged as a promising tool for mapping the structural integrity of LC in vivo.ObjectivesTo identify spatial patterns of structural LC disintegration in PD and regions in the LC where structural disintegration is associated with specific non-motor dysfunctions.Methods42 patients with PD and 24 age-matched healthy volunteers underwent ultra-high field MRI of the LC using a “neuromelanin sensitive” magnetization transfer weighted (MTw) sequence. The contrast-to-noise ratio of the MTw signal (CNRMTw) served as an estimate of structural integrity, slice- and voxel-wise analyses of CNRMTw were performed to map the spatial pattern of structural disintegration, complemented by Principal Component Analysis (PCA). We also tested for correlations between CNRMTw and the severity of non-motor symptoms.ResultsMean CNRMTw of LC was reduced in patients relative to controls. The attenuation of CNRMTw was not uniformly expressed in LC, but confined to the middle and caudal LC. CNRMTw attenuation in caudal LC scaled with the orthostatic drop in systolic blood pressure and apathy ratings. PCA identified a bilaterally expressed component that was more weakly expressed in patients. This component was characterized by a gradual change in CNRMTw along the rostro-caudal and dorso-ventral axes of the nucleus. The individual expression score of this component reflected the overall severity of non-motor symptoms.ConclusionPD related structural disintegration of LC mainly affects its caudal part and may determine the individual expression of specific non-motor symptoms such as orthostatic dysregulation or apathy.

Objective. An auditory stimulus can be related to the brain response that it evokes by a stimulus-response model fit to the data. This offers insight into perceptual processes within the brain and is also of potential use for devices such as brain computer interfaces (BCIs). The quality of the model can be quantified by measuring the fit with a regression problem, or by applying it to a classification task and measuring its performance. Approach. Here we focus on a match-mismatch (MM) task that entails deciding whether a segment of brain signal matches, via a model, the auditory stimulus that evoked it. Main results. Using these metrics, we describe a range of models of increasing complexity that we compare to methods in the literature, showing state-of-the-art performance. We document in detail one particular implementation, calibrated on a publicly-available database, that can serve as a robust reference to evaluate future developments. Significance. The MM task allows stimulus-response models to be evaluated in the limit of very high model accuracy, making it an attractive alternative to the more commonly used task of auditory attention detection. The MM task does not require class labels, so it is immune to mislabeling, and it is applicable to data recorded in listening scenarios with only one sound source, thus it is cheap to obtain large quantities of training and testing data. Performance metrics from this task, associated with regression accuracy, provide complementary insights into the relation between stimulus and response, as well as information about discriminatory power directly applicable to BCI applications.

Neuronal oscillations are thought to play an important role in working memory (WM) and speech processing. Listening to speech in real‐life situations is often cognitively demanding but it is unknown whether WM load influences how auditory cortical activity synchronizes to speech features. Here, we developed an auditory n‐back paradigm to investigate cortical entrainment to speech envelope fluctuations under different degrees of WM load. We measured the electroencephalogram, pupil dilations and behavioural performance from 22 subjects listening to continuous speech with an embedded n‐back task. The speech stimuli consisted of long spoken number sequences created to match natural speech in terms of sentence intonation, syllabic rate and phonetic content. To burden different WM functions during speech processing, listeners performed an n‐back task on the speech sequences in different levels of background noise. Increasing WM load at higher n‐back levels was associated with a decrease in posterior alpha power as well as increased pupil dilations. Frontal theta power increased at the start of the trial and increased additionally with higher n‐back level. The observed alpha–theta power changes are consistent with visual n‐back paradigms suggesting general oscillatory correlates of WM processing load. Speech entrainment was measured as a linear mapping between the envelope of the speech signal and low‐frequency cortical activity (, We used an auditory n‐back task to asses the effect of working memory (WM) load on cortical speech entrainment. Consistent with visual n‐back tasks, posterior alpha band power (8–13 Hz) decreased while frontal theta power (4–7 Hz) increased with WM load. At the same time, auditory cortical entrainment (

Brain signals recorded with electroencephalography (EEG), magnetoencephalography (MEG) and related techniques often have poor signal-to-noise ratio due to the presence of multiple competing sources and artifacts. A common remedy is to average over repeats of the same stimulus, but this is not applicable for temporally extended stimuli that are presented only once (speech, music, movies, natural sound). An alternative is to average responses over multiple subjects that were presented with the same identical stimuli, but differences in geometry of brain sources and sensors reduce the effectiveness of this solution. Multiway canonical correlation analysis (MCCA) brings a solution to this problem by allowing data from multiple subjects to be fused in such a way as to extract components common to all. This paper reviews the method, offers application examples that illustrate its effectiveness, and outlines the caveats and risks entailed by the method.

The decoding of selective auditory attention from noninvasive electroencephalogram (EEG) data is of interest in brain computer interface and auditory perception research. The current state-of-the-art approaches for decoding the attentional selection of listeners are based on temporal response functions (TRFs). In the current context, a TRF is a function that facilitates a mapping between features of sound streams and EEG responses. It has been shown that when the envelope of attended speech and EEG responses are used to derive TRF mapping functions, the TRF model predictions can be used to discriminate between attended and unattended talkers. However, the predictive performance of the TRF models is dependent on how the TRF model parameters are estimated. There exist a number of TRF estimation methods that have been published, along with a variety of datasets. It is currently unclear if any of these methods perform better than others, as they have not yet been compared side by side on a single standardized dataset in a controlled fashion. Here, we present a comparative study of the ability of different TRF estimation methods to classify attended speakers from multi-channel EEG data. The performance of the TRF estimation methods is evaluated using different performance metrics on a set of labeled EEG data from 18 subjects listening to mixtures of two speech streams.

Selectively attending to one speaker in a multi-speaker scenario is thought to synchronize low-frequency cortical activity to the attended speech signal. In recent studies, reconstruction of speech from single-trial electroencephalogram (EEG) data has been used to decode which talker a listener is attending to in a two-talker situation. It is currently unclear how this generalizes to more complex sound environments. Behaviorally, speech perception is robust to the acoustic distortions that listeners typically encounter in everyday life, but it is unknown whether this is mirrored by a noise-robust neural tracking of attended speech. Here we used advanced acoustic simulations to recreate real-world acoustic scenes in the laboratory. In virtual acoustic realities with varying amounts of reverberation and number of interfering talkers, listeners selectively attended to the speech stream of a particular talker. Across the different listening environments, we found that the attended talker could be accurately decoded from single-trial EEG data irrespective of the different distortions in the acoustic input. For highly reverberant environments, speech envelopes reconstructed from neural responses to the distorted stimuli resembled the original clean signal more than the distorted input. With reverberant speech, we observed a late cortical response to the attended speech stream that encoded temporal modulations in the speech signal without its reverberant distortion. Single-trial attention decoding accuracies based on 40-50s long blocks of data from 64 scalp electrodes were equally high (80-90% correct) in all considered listening environments and remained statistically significant using down to 10 scalp electrodes and short (

Single-trial EEG measures of selective auditory attention have recently suggested the perspective of decoding who a listener is focusing on in multi-talker scenarios. Here, we report results from work within the COCOHA (Cognitive Control of a Hearing Aid) project investigating the possibility of integrating EEG into neuro-steered hearing instruments. Our EEG decoding strategy relies on measuring cortical activity entrained to envelope fluctuations in the attended speech signal. Currently, a major challenge has been to obtain robust EEG measures of selective attention in older hearing-impaired (HI) listeners. We report our recent COCOHA attempts to decode selective attention from the EEG of hearing-impaired (HI) listeners. Aided HI listeners and age-matched normal-hearing controls were presented with competing talkers at 0 dB target-to-masker ratio and instructed to attend to one talker. We show that single-trial decoding accuracies similar to those reported for younger listeners can be obtained with both groups of older listeners (70–100% correct single-trial classification). Importantly, we did not find differences in decoding accuracies between the NH and the aided HI listeners. Although numerous other challenges involved in integrating EEG signals in hearing instruments are evident, our results suggest that single-trial attention decoding is possible with hearing impaired listeners.

Glass is ubiquitous, yet our understanding of its structure-function relationships remains far from complete and limits technology. For example, while compression is an important tool in the synthesis of crystalline materials, comparable breakthroughs in preparing bulk glasses are still largely lacking. This work reveals the striking linear dependence of the plastic compressibility of borosilicate glasses on both initial trigonal boron content and relative change in hardness with pressure, with important implications for manufacturing tailored damage-resistant glassy materials.