Beta‐band oscillations play an essential role in motor–auditory interactions

In the human brain, self‐generated auditory stimuli elicit smaller cortical responses compared to externally generated sounds. This sensory attenuation is thought to result from predictions about the sensory consequences of self‐generated actions that rely on motor commands. Previous research has implicated brain oscillations in this process. However, the specific role of these oscillations in motor–auditory interactions during sensory attenuation is still unclear. In this study, we aimed at addressing this question by using magnetoencephalography (MEG). We recorded MEG in 20 healthy participants during listening to passively presented and self‐generated tones. Our results show that the magnitude of sensory attenuation in bilateral auditory areas is significantly correlated with the modulation of beta‐band (15–30 Hz) amplitude in the motor cortex. Moreover, we observed a significant directional coupling (Granger causality) in beta‐band originating from the motor cortex toward bilateral auditory areas. Our findings indicate that beta‐band oscillations play an important role in mediating top–down interactions between motor and auditory cortex and, in our paradigm, suppress cortical responses to predicted sensory input.     

Neural bases of rhythmic entrainment in humans: critical transformation between cortical and lower‐level representations of auditory rhythm

The spontaneous ability to entrain to meter periodicities is central to music perception and production across cultures. There is increasing evidence that this ability involves selective neural responses to meter‐related frequencies. This phenomenon has been observed in the human auditory cortex, yet it could be the product of evolutionarily older lower‐level properties of brainstem auditory neurons, as suggested by recent recordings from rodent midbrain. We addressed this question by taking advantage of a new method to simultaneously record human EEG activity originating from cortical and lower‐level sources, in the form of slow (< 20 Hz) and fast (> 150 Hz) responses to auditory rhythms. Cortical responses showed increased amplitudes at meter‐related frequencies compared to meter‐unrelated frequencies, regardless of the prominence of the meter‐related frequencies in the modulation spectrum of the rhythmic inputs. In contrast, frequency‐following responses showed increased amplitudes at meter‐related frequencies only in rhythms with prominent meter‐related frequencies in the input but not for a more complex rhythm requiring more endogenous generation of the meter. This interaction with rhythm complexity suggests that the selective enhancement of meter‐related frequencies does not fully rely on subcortical auditory properties, but is critically shaped at the cortical level, possibly through functional connections between the auditory cortex and other, movement‐related, brain structures. This process of temporal selection would thus enable endogenous and motor entrainment to emerge with substantial flexibility and invariance with respect to the rhythmic input in humans in contrast with non‐human animals.     

Habituation of visual evoked responses in neonates and fetuses: a MEG study

In this study we aimed to develop a habituation paradigm that allows the investigation of response decrement and response recovery and examine its applicability for measuring the habituation of the visually evoked responses (VERs) in neonatal and fetal magnetoencephalographic recordings. Two paradigms, one with a long and one with a short inter-train interval (ITI), were developed and tested in separate studies. Both paradigms consisted of a train of four light flashes; each train being followed by a 500Hz burst tone. Healthy pregnant women underwent two prenatal measurements and returned with their babies for a neonatal investigation. The amplitudes of the neonatal VERs in the long-ITI condition showed within-train response decrement. An increased response to the auditory dishabituator was found confirming response recovery. In the short-ITI condition, neonatal amplitude decrement could not be demonstrated while response recovery was present. In both ITI conditions, the response rate of the cortical responses was much lower in the fetuses than in the neonates. Fetal VERs in the long-ITI condition indicate amplitude decline from the first to the second flash with no further decrease. The long-ITI paradigm might be useful to investigate habituation of the VERs in neonates and fetuses, although the latter requires precaution.     

Spectral summation and facilitation in on‐ and off‐responses for optimized representation of communication calls in mouse inferior colliculus

Selectivity for processing of species‐specific vocalizations and communication sounds has often been associated with the auditory cortex. The midbrain inferior colliculus, however, is the first center in the auditory pathways of mammals integrating acoustic information processed in separate nuclei and channels in the brainstem and, therefore, could significantly contribute to enhance the perception of species’ communication sounds. Here, we used natural wriggling calls of mouse pups, which communicate need for maternal care to adult females, and further 15 synthesized sounds to test the hypothesis that neurons in the central nucleus of the inferior colliculus of adult females optimize their response rates for reproduction of the three main harmonics (formants) of wriggling calls. The results confirmed the hypothesis showing that average response rates, as recorded extracellularly from single units, were highest and spectral facilitation most effective for both onset and offset responses to the call and call models with three resolved frequencies according to critical bands in perception. In addition, the general on‐ and/or off‐response enhancement in almost half the investigated 122 neurons favors not only perception of single calls but also of vocalization rhythm. In summary, our study provides strong evidence that critical‐band resolved frequency components within a communication sound increase the probability of its perception by boosting the signal‐to‐noise ratio of neural response rates within the inferior colliculus for at least 20% (our criterion for facilitation). These mechanisms, including enhancement of rhythm coding, are generally favorable to processing of other animal and human vocalizations, including formants of speech sounds.     

Impairment in predictive processes during auditory mismatch negativity in ScZ: Evidence from event‐related fields

Patients with schizophrenia (ScZ) show pronounced dysfunctions in auditory perception but the underlying mechanisms as well as the localization of the deficit remain unclear. To examine these questions, the current study examined whether alterations in the neuromagnetic mismatch negativity (MMNm) in ScZ‐patients could involve an impairment in sensory predictions in local sensory and higher auditory areas. Using a whole‐head MEG‐approach, we investigated the MMNm as well as P300m and N100m amplitudes during a hierarchical auditory novelty paradigm in 16 medicated ScZ‐patients and 16 controls. In addition, responses to omitted sounds were investigated, allowing for a critical test of the predictive coding hypothesis. Source‐localization was performed to identify the generators of the MMNm, omission responses as well as the P300m. Clinical symptoms were examined with the positive and negative syndrome scale. Event‐related fields (ERFs) to standard sounds were intact in ScZ‐patients. However, the ScZ‐group showed a reduction in the amplitude of the MMNm during both local (within trials) and global (across trials) conditions as well as an absent P300m at the global level. Importantly, responses to sound omissions were reduced in ScZ‐patients which overlapped both in latency and generators with the MMNm sources. Thus, our data suggest that auditory dysfunctions in ScZ involve impaired predictive processes that involve deficits in both automatic and conscious detection of auditory regularities. Hum Brain Mapp 38:5082–5093, 2017. © 2017 Wiley Periodicals, Inc.     

Pathological responses to single‐pulse electrical stimuli in epilepsy: The role of feedforward inhibition

Delineation of epileptogenic cortex in focal epilepsy patients may profit from single‐pulse electrical stimulation during intracranial EEG recordings. Single‐pulse electrical stimulation evokes early and delayed responses. Early responses represent connectivity. Delayed responses are a biomarker for epileptogenic cortex, but up till now, the precise mechanism generating delayed responses remains elusive. We used a data‐driven modelling approach to study early and delayed responses. We hypothesized that delayed responses represent indirect responses triggered by early response activity and investigated this for 11 patients. Using two coupled neural masses, we modelled early and delayed responses by combining simulations and bifurcation analysis. An important feature of the model is the inclusion of feedforward inhibitory connections. The waveform of early responses can be explained by feedforward inhibition. Delayed responses can be viewed as second‐order responses in the early response network which appear when input to a neural mass falls below a threshold forcing it temporarily to a spiking state. The combination of the threshold with noisy background input explains the typical stochastic appearance of delayed responses. The intrinsic excitability of a neural mass and the strength of its input influence the probability at which delayed responses to occur. Our work gives a theoretical basis for the use of delayed responses as a biomarker for the epileptogenic zone, confirming earlier clinical observations. The combination of early responses revealing effective connectivity, and delayed responses showing intrinsic excitability, makes single‐pulse electrical stimulation an interesting tool to obtain data for computational models of epilepsy surgery.     

Brain mapping of auditory steady‐state responses: A broad view of cortical and subcortical sources

Auditory steady‐state responses (ASSRs) are evoked brain responses to modulated or repetitive acoustic stimuli. Investigating the underlying neural generators of ASSRs is important to gain in‐depth insight into the mechanisms of auditory temporal processing. The aim of this study is to reconstruct an extensive range of neural generators, that is, cortical and subcortical, as well as primary and non‐primary ones. This extensive overview of neural generators provides an appropriate basis for studying functional connectivity. To this end, a minimum‐norm imaging (MNI) technique is employed. We also present a novel extension to MNI which facilitates source analysis by quantifying the ASSR for each dipole. Results demonstrate that the proposed MNI approach is successful in reconstructing sources located both within (primary) and outside (non‐primary) of the auditory cortex (AC). Primary sources are detected in different stimulation conditions (four modulation frequencies and two sides of stimulation), thereby demonstrating the robustness of the approach. This study is one of the first investigations to identify non‐primary sources. Moreover, we show that the MNI approach is also capable of reconstructing the subcortical activities of ASSRs. Finally, the results obtained using the MNI approach outperform the group‐independent component analysis method on the same data, in terms of detection of sources in the AC, reconstructing the subcortical activities and reducing computational load.     

Hallucination‐ and speech‐specific hypercoupling in frontotemporal auditory and language networks in schizophrenia using combined task‐based fMRI data: An fBIRN study

Hypercoupling of activity in speech‐perception‐specific brain networks has been proposed to play a role in the generation of auditory‐verbal hallucinations (AVHs) in schizophrenia; however, it is unclear whether this hypercoupling extends to nonverbal auditory perception. We investigated this by comparing schizophrenia patients with and without AVHs, and healthy controls, on task‐based functional magnetic resonance imaging (fMRI) data combining verbal speech perception (SP), inner verbal thought generation (VTG), and nonverbal auditory oddball detection (AO). Data from two previously published fMRI studies were simultaneously analyzed using group constrained principal component analysis for fMRI (group fMRI‐CPCA), which allowed for comparison of task‐related functional brain networks across groups and tasks while holding the brain networks under study constant, leading to determination of the degree to which networks are common to verbal and nonverbal perception conditions, and which show coordinated hyperactivity in hallucinations. Three functional brain networks emerged: (a) auditory‐motor, (b) language processing, and (c) default‐mode (DMN) networks. Combining the AO and sentence tasks allowed the auditory‐motor and language networks to separately emerge, whereas they were aggregated when individual tasks were analyzed. AVH patients showed greater coordinated activity (deactivity for DMN regions) than non‐AVH patients during SP in all networks, but this did not extend to VTG or AO. This suggests that the hypercoupling in AVH patients in speech‐perception‐related brain networks is specific to perceived speech, and does not extend to perceived nonspeech or inner verbal thought generation.     

Modulation of pre‐attentive spectro‐temporal feature processing in the human auditory system by HD‐tDCS

The present study examined the functional lateralization of the human auditory cortex (AC) for pre‐attentive spectro‐temporal feature processing. By using high‐definition transcranial direct current stimulation (HD‐tDCS), we systematically modulated neuronal activity of the bilateral AC. We assessed the influence of anodal and cathodal HD‐tDCS delivered over the left or right AC on auditory mismatch negativity (MMN) in response to temporal as well as spectral deviants in 12 healthy subjects. The results showed that MMN to temporal deviants was significantly enhanced by anodal HD‐tDCS applied over the left AC only. Our data indicate a left hemispheric dominance for the pre‐attentive processing of low‐level temporal information.     

Processing of binaural spatial information in human auditory cortex: Neuromagnetic responses to interaural timing and level differences

This study was designed to test two hypotheses about binaural hearing: (1) that binaural cues are primarily processed in the hemisphere contralateral to the perceived location of a sound; and (2) that the two main binaural cues, interaural timing differences and interaural level differences, are processed in separate channels in the auditory cortex. Magnetoencephalography was used to measure brain responses to dichotic pitches - a perception of pitch created by segregating a narrow band of noise from a wider band of noise - derived from interaural timing or level disparities. Our results show a strong modulation of interhemispheric M100 amplitudes by ITD cues. When these cues simulated source presentation unilaterally from the right hemispace, M100 amplitude changed from a predominant right hemisphere pattern to a bilateral pattern. In contrast, ILD cues lacked any capacity to alter the right hemispheric distribution. These data indicate that intrinsic hemispheric biases are large in comparison to any contralaterality biases in the auditory system. Importantly, both types of binaural cue elicited a circa 200 ms latency object-related negativity component, believed to reflect automatic cortical processes involved in distinguishing concurrent auditory objects. These results support the conclusion that ITDs and ILDs are processed by distinct neuronal populations to relatively late stages of cortical processing indexed by the M100. However information common to the two cues seems to be extracted for use in a subsequent stage of auditory scene segregation indexed by the object related negativity. This may place a new bound on the extent to which sound location cues are processed in separate channels of the auditory cortex.     

The anterior ectosylvian sulcal auditory field in the cat: I. An electrophysiological study of its relationship to surrounding auditory cortical fields

The extent of a region containing acoustically responsive neurons within the anterior ectosylvian sulcus and its relationship to surrounding gyral auditory cortical fields was examined in chloralose-anaesthetized cats. Multiple microelectrode penetrations were made orthogonal to the middle and anterior ectosylvian gyral surfaces, and longer penetrations were made into the dorsal and ventral banks and fundus of the anterior ectosylvian sulcus. The quantitative and qualitative auditory response characteristics of neurons and neuron clusters in the sulcal banks and surrounding regions were mapped in detail, and the degree of overlap of auditory and visual neurons within the sulcus was determined by routinely testing for responsiveness to a gross light flash. The detailed results from three animals and a summary of all penetrations into the sulcus are presented. The anterior ectosylvian sulcal field (Field AES) lay deep within the banks and fundus of the posterior three quarters of the sulcus. A combination of changes in the auditory response characteristics of neurons (i.e., in optimal stimulus, latency, and frequency tuning), and the presence of visually responsive cells, distinguished this field from surrounding fields. The distinction between the anterior ectosylvian field and extensions of the nearby tonotopic fields (i.e., primary and anterior auditory fields) into the dorsal and ventral banks of the dorsoposterior sector of the sulcus was readily made on the basis of these characteristics. The distinction between the anterior ectosylvian field and extensions of the second auditory field into the ventral bank of the middle sector of the sulcus was more difficult and there were differences between animals in the transition between these fields. Anterior ectosylvian sulcal field responses did not extend into the dorsal bank in anterior parts of the sulcus but were restricted to fundal regions, an observation consistent with the presence of the fourth somatosensory field in the dorsal bank of this sector of the sulcus. The majority of penetrations into the sulcus revealed coextensive auditory and visual activity, an observation apparently at variance with the identification of a purely visual field in this region. Barbiturate anaesthesia, which has been used in experiments demonstrating an anterior ectosylvian visual area, was found to have a depressing effect on auditory responses within the anterior ectosylvian sulcal field.     

GABA metabolism and its role in gamma‐band oscillatory activity during auditory processing: An MRS and EEG study

Gamma‐aminobutyric acid (GABA) and glutamate are believed to have inhibitory and exhibitory neuromodulatory effects that regulate the brain's response to sensory perception. Furthermore, frequency‐specific synchronization of neuronal excitability within the gamma band (30–80 Hz) is attributable to a homeostatic balance between excitation and inhibition. However, our understanding of the physiological mechanism underlying gamma rhythms is based on animal models. Investigations of the relationship between GABA concentrations, glutamate concentrations, and gamma band activity in humans were mostly restricted to the visual cortex and are conflicting. Here, we performed a multimodal imaging study combining magnetic resonance spectroscopy (MRS) with electroencephalography (EEG) in the auditory cortex. In 14 healthy subjects, we investigated the impact of individual differences in GABA and glutamate concentration on gamma band response (GBR) following auditory stimulus presentation. We explored the effects of bulk GABA on the GBR across frequency (30–200 Hz) and time (?200 to 600 ms) and found no significant relationship. Furthermore, no correlations were found between gamma peak frequency or power measures and metabolite concentrations (GABA, glutamate, and GABA/glutamate ratio). These findings suggest that, according to MRS measurements, and given the auditory stimuli used in this study, GABA and glutamate concentrations are unlikely to play a significant role in the inhibitory and excitatory drive in the generation of gamma band activity in the auditory cortex. Hum Brain Mapp 38:3975–3987, 2017 . © 2017 Wiley Periodicals, Inc.     

Modulation of early cortical processing during divided attention to non‐contiguous locations

We often face the challenge of simultaneously attending to multiple non‐contiguous regions of space. There is ongoing debate as to how spatial attention is divided under these situations. Whereas, for several years, the predominant view was that humans could divide the attentional spotlight, several recent studies argue in favor of a unitary spotlight that rhythmically samples relevant locations. Here, this issue was addressed by the use of high‐density electrophysiology in concert with the multifocal m‐sequence technique to examine visual evoked responses to multiple simultaneous streams of stimulation. Concurrently, we assayed the topographic distribution of alpha‐band oscillatory mechanisms, a measure of attentional suppression. Participants performed a difficult detection task that required simultaneous attention to two stimuli in contiguous (undivided) or non‐contiguous parts of space. In the undivided condition, the classic pattern of attentional modulation was observed, with increased amplitude of the early visual evoked response and increased alpha amplitude ipsilateral to the attended hemifield. For the divided condition, early visual responses to attended stimuli were also enhanced, and the observed multifocal topographic distribution of alpha suppression was in line with the divided attention hypothesis. These results support the existence of divided attentional spotlights, providing evidence that the corresponding modulation occurs during initial sensory processing time‐frames in hierarchically early visual regions, and that suppressive mechanisms of visual attention selectively target distracter locations during divided spatial attention.     

Dissociation of part‐based and integrated neural responses to faces by means of electroencephalographic frequency tagging

In order to isolate the repetition suppression effects for each part of a whole‐face stimulus, the left and right halves of face stimuli were flickered at different frequency rates (5.88 or 7.14 Hz), changing or not changing identity at every stimulation cycle. The human electrophysiological (electroencephalographic) responses to each face half increased in amplitude when different rather than repeated face half identities were presented at every stimulation cycle. Contrary to the repetition suppression effects for whole faces, which are usually found over the right occipito‐temporal cortex, these part‐based repetition suppression effects were found on all posterior electrode sites and were unchanged when the two face halves were manipulated by separation, lateral misalignment, or inversion. In contrast, intermodulation components (e.g. 7.14–5.88 = 1.26 Hz) were found mainly over the right occipito‐temporal cortex and were significantly reduced following the aforementioned manipulations. In addition, the intermodulation components decreased substantially for face halves belonging to different identities, which form a less coherent face than when they belong to the same face identity. These observations provide objective evidence for dissociation between part‐based and integrated (i.e. holistic/configural) responses to faces in the human brain, suggesting that only responses to integrated face parts reflect high‐level, possibly face‐specific, representations.     

The effect of task‐irrelevant visual backgrounds on human transcranial magnetic stimulation‐evoked electroencephalography responses and cortical alpha activity

Brain responses evoked by transcranial magnetic stimulation (TMS) in task‐free experimental contexts are known to depend on psychophysiological states such as sleep, vegetative state and caffeine‐induced arousal. Much less is known about how TMS‐evoked responses depend on task‐irrelevant steady perceptual input. Here, we examined ongoing alpha activity and the mean amplitude of EEG potentials in response to occipitally applied TMS as a function of task‐irrelevant visual backgrounds. Responses to TMS were robustly modulated by photographs of natural scenes and man‐made environments. These effects began as early as during the N100 and continued for several hundred milliseconds after the stimulation. There was also a more general effect of background along with other stimuli, such as blank backgrounds, sinusoidal gratings and moving dot‐patterns. This effect was observable from ongoing alpha activity as well. Based on these results we conclude that different types of steady perceptual input modulate visual cortex reactivity and/or connectivity and it is possible to measure these modulations by combining TMS with electroencephalography.     

The developmental trajectory of vocal and event‐related potential responses to frequency‐altered auditory feedback

Speech motor control develops gradually as the acoustics of speech are mapped onto the positions and movements of the articulators. In this event‐related potential (ERP) study, children and adults aged 4–30 years produced vocalizations while exposed to frequency‐altered feedback. Vocal pitch variability and the latency of vocal responses were found to differ as a function of age. ERP responses indexed by the P1–N1–P2 complex were also modulated as a function of age. P1 amplitudes decreased with age, whereas N1 and P2 amplitudes increased with age. In addition, a correlation between vocal variability and N1 amplitudes was found, suggesting a complex interaction between behavioural and neurological responses to frequency‐altered feedback. These results suggest that the neural systems that integrate auditory feedback during vocal motor control undergo robust changes with age and physiological development.     

Effect of in‐painting on cortical thickness measurements in multiple sclerosis: A large cohort study

A comprehensive analysis of the effect of lesion in‐painting on the estimation of cortical thickness using magnetic resonance imaging was performed on a large cohort of 918 relapsing‐remitting multiple sclerosis patients who participated in a phase III multicenter clinical trial. An automatic lesion in‐painting algorithm was developed and implemented. Cortical thickness was measured using the FreeSurfer pipeline with and without in‐painting. The effect of in‐painting was evaluated using FreeSurfer's paired analysis pipeline. Multivariate regression analysis was also performed with field strength and lesion load as additional factors. Overall, the estimated cortical thickness was different with in‐painting than without. The effect of in‐painting was observed to be region dependent, more significant in the left hemisphere compared to the right, was more prominent at 1.5 T relative to 3 T, and was greater at higher lesion volumes. Our results show that even for data acquired at 1.5 T in patients with high lesion load, the mean cortical thickness difference with and without in‐painting is ～2%. Based on these results, it appears that in‐painting has only a small effect on the estimated regional and global cortical thickness. Hum Brain Mapp 36:3749–3760, 2015. © 2015 Wiley Periodicals, Inc.     

The role of the cerebellum in adaptation: ALE meta‐analyses on sensory feedback error

It is widely accepted that unexpected sensory consequences of self‐action engage the cerebellum. However, we currently lack consensus on where in the cerebellum, we find fine‐grained differentiation to unexpected sensory feedback. This may result from methodological diversity in task‐based human neuroimaging studies that experimentally alter the quality of self‐generated sensory feedback. We gathered existing studies that manipulated sensory feedback using a variety of methodological approaches and performed activation likelihood estimation (ALE) meta‐analyses. Only half of these studies reported cerebellar activation with considerable variation in spatial location. Consequently, ALE analyses did not reveal significantly increased likelihood of activation in the cerebellum despite the broad scientific consensus of the cerebellum's involvement. In light of the high degree of methodological variability in published studies, we tested for statistical dependence between methodological factors that varied across the published studies. Experiments that elicited an adaptive response to continuously altered sensory feedback more frequently reported activation in the cerebellum than those experiments that did not induce adaptation. These findings may explain the surprisingly low rate of significant cerebellar activation across brain imaging studies investigating unexpected sensory feedback. Furthermore, limitations of functional magnetic resonance imaging to probe the cerebellum could play a role as climbing fiber activity associated with feedback error processing may not be captured by it. We provide methodological recommendations that may guide future studies.