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Abstract: Localization of sound sources is a considerable computational challenge for the human brain. Whereas the visual system can process basic spatial information in parallel, the auditory system lacks a straightforward correspondence between external spatial locations and sensory receptive fields. Consequently, the question how different acoustic features supporting spatial hearing are represented in the central nervous system is still open. Functional neuroimaging studies in humans have provided evidence for a posterior auditory “where” pathway that encompasses non-primary auditory cortex areas, including the planum temporale (PT) and posterior superior temporal gyrus (STG), which are strongly activated by horizontal sound direction changes, distance changes, and movement. However, these areas are also activated by a wide variety of other stimulus features, posing a challenge for the interpretation that the underlying areas are purely spatial. This review discusses behavioral and neuroimaging studies on sound localization, and some of the competing models of representation of auditory space in humans. This article is part of a Special Issue entitled . [Copyright &y& Elsevier]

Converging lines of evidence suggest that auditory system short-term plasticity can enable several perceptual and cognitive functions that have been previously considered as relatively distinct phenomena. Here we review recent findings suggesting that auditory stimulation, auditory selective attention and cross-modal effects of visual stimulation each cause transient excitatory and (surround) inhibitory modulations in the auditory cortex. These modulations might adaptively tune hierarchically organized sound feature maps of the auditory cortex (e.g. tonotopy), thus filtering relevant sounds during rapidly changing environmental and task demands. This could support auditory sensory memory, pre-attentive detection of sound novelty, enhanced perception during selective attention, influence of visual processing on auditory perception and longer-term plastic changes associated with perceptual learning. [Copyright &y& Elsevier]

Background: Information on the inheritance of neurophysiological abnormalities might help elucidate the molecular genetic basis of schizophrenia. We used magnetoencephalography (MEG) and electroencephalography (EEG) to investigate the inheritance of auditory-cortical deficiencies in twin pairs discordant for schizophrenia. Methods: Auditory EEG/MEG responses to frequent standard and occasional deviant tones were measured in mono- and dizygotic (MZ and DZ) twin pairs discordant for schizophrenia and demographically matched healthy twin pairs, recruited from a total population cohort. The MEG/EEG results were regressed against the genetic resemblance to patients with schizophrenia across the patients’ unaffected MZ/DZ co-twins and control subjects (with genetic correlations of 1, .5, and 0 to schizophrenia patients, respectively). Results: The EEG responses P50, N100, and mismatch negativity (MMN), as well as the MEG response P50m, were reduced in the schizophrenic patients. P50 and N100 were significantly decreased also in their unaffected co-twins, as compared with the control subjects. Importantly, the P50 and N100 decrease correlated with the unaffected subjects’ genetic resemblance to schizophrenia patients. Conclusions: Our results suggest inherited abnormalities in cortical auditory processing in schizophrenia, reflected by the decreased P50/P50m and N100 amplitudes, whereas the MMN abnormalities might reflect predominantly state-dependent neurodegeneration. [Copyright &y& Elsevier]

Objective: Scopolamine, a muscarinic receptor antagonist, can produce temporary cognitive impairments as well as electroencephalographic changes that partially resemble those observed in Alzheimer''s disease. In order to test the sensitivity of spectral power and hemispheric coherence to changes in cholinergic transmission, we evaluated quantitative magnetoencephalogram (MEG) after intravenous injection of scopolamine.Methods: MEG of 8 elderly healthy subjects (59–80 years) were measured with a whole-head magnetometer after intravenous injection of scopolamine. An injection of glycopyrrolate, a peripheral muscarinic antagonist, was used as the placebo in a double-blind, randomized, cross-over design. Spectral power and coherence were computed over 7 brain regions in 3 frequency bands.Results: Scopolamine administration increased theta activity (4–8 Hz) and resulted in the abnormal pattern of MEG desynchronization in eyes-open vs. eyes-closed conditions in the alpha band (8–13 Hz). These effects were most prominent over the posterior regions. Interhemispheric and left intrahemispheric coherence was significantly decreased in the theta band (4–8 Hz).Conclusions: Spontaneous cortical activity at the theta and alpha range and functional coupling in the theta band are modulated by the cholinergic system. MEG may provide a tool for monitoring brain dynamics in neurological disorders associated with cholinergic abnormalities. [Copyright &y& Elsevier]

To elucidate serotonin modulation of selective attention, 13 volunteers (21–30 years) were studied in two sessions, 5 h after either acute tryptophan depletion (ATD) that decreases brain serotonin synthesis, or control-mixture ingestion (randomized, double-blind, cross-over design). Simultaneous electroencephalogram and magnetoencephalogram were measured during dichotic listening of two concurrent trains of standard and deviant tones. Subjects counted the deviants presented to one ear and ignored those presented to the other ear. ATD lowered plasma total tryptophan by 75% and free tryptophan by 39%. ATD suppressed the amplitude enhancement of P50 and N1 to selectively attended tones, but did not affect the later aspects of processing negativity. The P50 latencies were increased after ATD, irrespective of attention. In conclusion, serotonin may regulate attentional modulation of early cortical stimulus processing. [Copyright &y& Elsevier]

Objective: Dopaminergic function has been closely associated with attentional performance, but its precise role has remained elusive.Methods: Electrophysiological and behavioral methods were used to assess the effects of dopamine D2-receptor antagonist haloperidol on involuntary attention shifting using a randomized, double-blind, placebo-controlled cross-over design. Eleven subjects were instructed to discriminate equiprobable 200 and 400 ms tones in a forced-choice reaction-time (RT) task during simultaneous measurement of whole-head magnetoencephalography and high-resolution electroencephalography.Results: Occasional changes in task-irrelevant tone frequency (10% increase or decrease) caused marked distraction on behavioral performance, as shown by significant RT increases to deviant stimuli and subsequent standard tones. Furthermore, while the standard tones elicited distinct P1–N1–P2–N2–P3 waveforms, deviant tones elicited additional mismatch negativity (MMN), P3a, and reorienting negativity (RON) responses, indexing brain events associated with involuntary attention shifting. While haloperidol did not affect the source loci of the responses of magnetic N1 and MMN, the amplitude of the electric P3a and that of RON were significantly reduced and the latency of magnetic RON were delayed following haloperidol administration.Conclusions: The present results suggest that dopamine modulates involuntary attention shifting to task-irrelevant deviant events. It appears that dopamine may disrupt the subsequent re-orienting efforts to the relevant task after distraction. [Copyright &y& Elsevier]

Neuronal oscillations are suggested to play an important role in auditory working memory (WM), but their contribution to content-specific representations has remained unclear. Here, we measure magnetoencephalography during a retro-cueing task with parametric ripple-sound stimuli, which are spectrotemporally similar to speech but resist non-auditory memory strategies. Using machine learning analyses, with rigorous between-subject cross-validation and non-parametric permutation testing, we show that memorized sound content is strongly represented in phase-synchronization patterns between subregions of auditory and frontoparietal cortices. These phase-synchronization patterns predict the memorized sound content steadily across the studied maintenance period. In addition to connectivity-based representations, there are indices of more local, "activity silent" representations in auditory cortices, where the decoding accuracy of WM content significantly increases after task-irrelevant "impulse stimuli." Our results demonstrate that synchronization patterns across auditory sensory and association areas orchestrate neuronal coding of auditory WM content. This connectivity-based coding scheme could also extend beyond the auditory domain. [Display omitted] • How neurons in human brain store transient working memories (WMs) is debated • We hypothesize that interregional phase synchronization supports WM maintenance • We decode auditory memories from magnetoencephalograms to test this hypothesis • Synchronization patterns across sensory and higher areas reveal content held in WM Mamashli et al. use machine learning analyses of human magnetoencephalography (MEG) recordings to study "working memory," maintenance of information in mind over brief periods of time. Their results show that the human brain maintains working memory content in transient functional connectivity patterns across sensory and association areas. [ABSTRACT FROM AUTHOR]

Abstract.: We introduce a method of combing MEG and fMRI to generate estimates of synchronized oscillations on the cortex. This method suppresses locations without concordant fMRI activity to avoid over estimation of phase-locking values. Simulations suggest 80% fMRI provides optimal detection power. We demonstrate this method in human somatomotor data to characterize beta-band oscillations. [Copyright &y& Elsevier]

Abstract: Mild cognitive impairment (MCI) is a memory disorder often preceding Alzheimer''s disease (AD). AD has been shown to be associated with abnormal generation of spontaneous electromagnetic activity. We investigated whether the cortical generation of spontaneous brain oscillations in MCI shows changes resembling those observed in AD. A minimum current estimates algorithm was applied to identify cortical sources of magnetoencephalographic (MEG) spontaneous brain oscillations in male MCI patients with a clear memory disorder and in healthy elderly controls. This data was subsequently compared to a male subsample of AD patients from an earlier study. While there were clear oscillatory abnormalities in AD patients, there was no evidence of significant changes in the alpha source distribution in MCI patients as compared to healthy controls. Deficits in the distribution of oscillatory sources in the resting state are thus likely to occur at later stages of cognitive impairment than MCI. [Copyright &y& Elsevier]

Abstract: Objective: Previous studies have reported abnormalities in both spontaneous and evoked electromagnetic brain activity in Alzheimer’s disease (AD). We studied the auditory steady-state response (SSR) which represents the net effect of entrained background activity and superimposed cortical evoked responses, in AD patients and healthy controls. Methods: Whole-head magnetoencephalography (MEG) was used to measure SSR to monaural 40-Hz stimulation in AD patients and age-matched controls. Equivalent current dipoles (ECD) of the SSR were modeled in each hemisphere, and source amplitudes were compared between the two groups using time-varying ECD models. Results: Our results indicate that the SSR is significantly increased in AD patients with mild to moderate cognitive deterioration in comparison with healthy elderly subjects. Conclusions: Goal-directed functioning requires optimization of inhibitory and excitatory inputs in the cortex, allowing the adaptation of responsiveness to repetitive stimulation with low relevance. The present results suggest that this balance is impaired in AD, manifesting itself in decreased inhibition in cortical auditory processing and impaired adaptation of the stimulus-locked activity, probably due to abnormalities in cholinergic modulation. Significance: MEG appears to be a sensitive tool to detect abnormalities of auditory processing already in early stages of AD. [Copyright &y& Elsevier]

Abstract: Cognitive dysfunctions may be a significant factor in drug-seeking behavior, reducing the efficiency of rehabilitation in opioid dependence. Neurophysiological basis of these dysfunctions is poorly understood. 21 opioid-dependent patients and 15 healthy controls with no experience of illicit drugs were studied with simultaneous electroencephalography (EEG) and magnetoencephalography (MEG). Among opioid dependents 15 were benzodiazepine co-dependent. In a passive oddball paradigm, a train of 700-Hz standard tones (80%), presented to the left ear, was occasionally interrupted by infrequent deviants, which were either 600-Hz or 400-Hz pure tones or complex novel sounds. The auditory evoked potentials (AEP) and fields (AEF) were analyzed. The strength of the N1m dipoles was enhanced in patients with benzodiazepine co-dependence, but the latency of the response or the source location was not changed. A delay of mismatch negativity (MMN) response of novel tones in EEG, and delay of P3am response on the contralateral hemisphere to stimulated ear in MEG in opioid-dependent patients were observed. There were no differences in source locations or strengths of the dipoles for P1m, MMNm, and P3am determined using equivalent current dipoles. There were no group differences in EEG amplitude measures. In conclusion, our results suggest delayed pre-attentive auditory processing of novel information in opioid dependence. Benzodiazepine co-dependence modulated N1m response. [Copyright &y& Elsevier]

Abstract: Neurochemical mechanisms mediating the interaction between emotional and cognitive processing are not yet fully understood. Here, we utilized acute tryptophan depletion (ATD) to reduce the brain synthesis of serotonin (5-HT), which is thought to have a central role in regulation of emotions and mood in humans. ATD effects on event-related potentials and magnetic fields were studied using a passive odd-ball paradigm in a randomized, double-blinded, controlled, cross-over design. Auditory responses were recorded simultaneously with high-resolution magnetoencephalography (MEG) and electroencephalography (EEG) in 14 healthy subjects, 5 h after ATD or a control condition. ATD significantly increased depressed mood and lowered plasma tryptophan concentration (total tryptophan decreased by 75%, free tryptophan decreased by 39%). As compared with the control condition, ATD increased the amplitudes of mismatch negativity (MMN) to duration and frequency changes and decreased the latencies of magnetic MMN to frequency changes in the hemisphere ipsilateral to the ear stimulated. Further, ATD modulated N1m latencies and decreased P2m source activity. ATD increased the interhemispheric latency difference of MMNm to frequency changes. No effects on P50 were observed. The present results suggest serotonergic modulation of preattentive auditory change detection, suggested to initiate involuntary attention shifting in the human brain. [Copyright &y& Elsevier]