Magnetoencephalography as a tool in psychiatric research: current status and perspective

The application of neuroimaging to provide mechanistic insights into circuit dysfunctions in major psychiatric conditions and the development of biomarkers are core challenges in current psychiatric research. In this review, we propose that recent technological and analytic advances in Magnetoencephalography (MEG), a technique which allows the measurement of neuronal events directly and non-invasively with millisecond resolution, provides novel opportunities to address these fundamental questions. Because of its potential in delineating normal and abnormal brain dynamics, we propose that MEG provides a crucial tool to advance our understanding of pathophysiological mechanisms of major neuropsychiatric conditions, such as Schizophrenia, Autism Spectrum Disorders, and the dementias. In our paper, we summarize the mechanisms underlying the generation of MEG signals and the tools available to reconstruct generators and underlying networks using advanced source-reconstruction techniques. We then survey recent studies that have utilized MEG to examine aberrant rhythmic activity in neuropsychiatric disorders. This is followed by links with preclinical research, which have highlighted possible neurobiological mechanisms, such as disturbances in excitation/inhibition parameters, which could account for measured changes in neural oscillations. In the final section of the paper, challenges as well as novel methodological developments are discussed which could pave the way for a widespread application of MEG in translational research with the aim of developing biomarkers for early detection and diagnosis

Deficits in high- (>60 Hz) gamma-band oscillations during visual processing in schizophrenia

Current theories of the pathophysiology of schizophrenia have focused on abnormal temporal coordination of neural activity. Oscillations in the gamma-band range (>25 Hz) are of particular interest as they establish synchronization with great precision in local cortical networks. However, the contribution of high gamma (>60 Hz) oscillations toward the pathophysiology is less established. To address this issue, we recorded magnetoencephalographic (MEG) data from 16 medicated patients with chronic schizophrenia and 16 controls during the perception of Mooney faces. MEG data were analysed in the 25–150 Hz frequency range. Patients showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces while responses to inverted stimuli were intact. Impaired processing of Mooney faces in schizophrenia patients was accompanied by a pronounced reduction in spectral power between 60–120 Hz (effect size: d = 1.26) which was correlated with disorganized symptoms (r = −0.72). Our findings demonstrate that deficits in high gamma-band oscillations as measured by MEG are a sensitive marker for aberrant cortical functioning in schizophrenia, suggesting an important aspect of the pathophysiology of the disorder

Long-range coupling of prefrontal cortex and visual (MT) or polysensory (STP) cortical areas in motion perception

To investigate how, where and when moving auditory cues interact with the perception of object-motion during self-motion, we conducted psychophysical, MEG, and fMRI experiments in which the subjects viewed nine textured objects during simulated forward self-motion. On each trial, one object was randomly assigned its own looming motion within the scene. Subjects reported which of four labeled objects had independent motion within the scene in two conditions: (1) visual information only and (2) with additional moving- auditory cue. In MEG, comparison of the two conditions showed: (i) MT activity is similar across conditions, (ii) late after the stimulus presentation there is additional activity in the auditory cue condition ventral to MT, (iii) with the auditory cue, the right auditory cortex (AC) shows early activity together with STS, (iv) these two activities have different time courses and the STS signals occur later in the epoch together with frontal activity in the right hemisphere, (v) for the visual-only condition activity in PPC (posterior parietal cortex) is stronger than in the auditory-cue condition. fMRI conducted for visual-only condition reveals activations in a network of parietal and frontal areas and in MT. In addition, Dynamic Granger Causality analysis showed for auditory cues a strong connection of the AC with STP but not with MT suggesting binding of visual and auditory information at STP. Also, while in the visual-only condition PFC is connected with MT, in the auditory-cue condition PFC is connected to STP (superior temporal polysensory) area. These results indicate that PFC allocates attention to the “object” as a whole, in STP to a moving visual-auditory object, and in MT to a moving visual object.Accepted manuscrip

Influence of metallic artifact filtering on MEG signals for source localization during interictal epileptiform activity

Objective. Medical intractable epilepsy is a common condition that affects 40% of epileptic patients that generally have to undergo resective surgery. Magnetoencephalography (MEG) has been increasingly used to identify the epileptogenic foci through equivalent current dipole (ECD) modeling, one of the most accepted methods to obtain an accurate localization of interictal epileptiform discharges (IEDs). Modeling requires that MEG signals are adequately preprocessed to reduce interferences, a task that has been greatly improved by the use of blind source separation (BSS) methods. MEG recordings are highly sensitive to metallic interferences originated inside the head by implanted intracranial electrodes, dental prosthesis, etc and also coming from external sources such as pacemakers or vagal stimulators. To reduce these artifacts, a BSS-based fully automatic procedure was recently developed and validated, showing an effective reduction of metallic artifacts in simulated and real signals (Migliorelli et al 2015 J. Neural Eng. 12 046001). The main objective of this study was to evaluate its effects in the detection of IEDs and ECD modeling of patients with focal epilepsy and metallic interference. Approach. A comparison between the resulting positions of ECDs was performed: without removing metallic interference; rejecting only channels with large metallic artifacts; and after BSS-based reduction. Measures of dispersion and distance of ECDs were defined to analyze the results. Main results. The relationship between the artifact-to-signal ratio and ECD fitting showed that higher values of metallic interference produced highly scattered dipoles. Results revealed a significant reduction on dispersion using the BSS-based reduction procedure, yielding feasible locations of ECDs in contrast to the other two approaches. Significance. The automatic BSS-based method can be applied to MEG datasets affected by metallic artifacts as a processing step to improve the localization of epileptic foci.Postprint (published version

The mechanisms of tinnitus: perspectives from human functional neuroimaging

In this review, we highlight the contribution of advances in human neuroimaging to the current understanding of central mechanisms underpinning tinnitus and explain how interpretations of neuroimaging data have been guided by animal models. The primary motivation for studying the neural substrates of tinnitus in humans has been to demonstrate objectively its representation in the central auditory system and to develop a better understanding of its diverse pathophysiology and of the functional interplay between sensory, cognitive and affective systems. The ultimate goal of neuroimaging is to identify subtypes of tinnitus in order to better inform treatment strategies. The three neural mechanisms considered in this review may provide a basis for TI classification. While human neuroimaging evidence strongly implicates the central auditory system and emotional centres in TI, evidence for the precise contribution from the three mechanisms is unclear because the data are somewhat inconsistent. We consider a number of methodological issues limiting the field of human neuroimaging and recommend approaches to overcome potential inconsistency in results arising from poorly matched participants, lack of appropriate controls and low statistical power

Physiology of Higher Central Auditory Processing and Plasticity

Binaural cue processing requires central auditory function as damage to the auditory cortex and other cortical regions impairs sound localization. Sound localization cues are initially extracted by brainstem nuclei, but how the cerebral cortex supports spatial sound perception remains unclear. This chapter reviews the evidence that spatial encoding within and beyond the auditory cortex supports sound localization, including the integration of information across sound frequencies and localization cues. In particular, this chapter discusses the role of brain regions across the cerebral cortex that may be specialized for extracting and transforming the spatial aspects of sounds and extends from sensory to parietal and prefrontal cortices. The chapter considers how the encoding of spatial information changes with attention and how spatial processing fits within the broader context of auditory scene analysis by cortical networks. The importance of neural plasticity in binaural processing is outlined, including a discussion of how changes in the mapping of localization cues to spatial position allow listeners to adapt to changes in auditory input throughout life and after hearing loss. The chapter ends by summarizing some of the open questions about the central processing of binaural cues and how they may be answered