Stephan Moratti

Tinnitus perception and distress is related to abnormal spontaneous brain activity as measured by magnetoencephalography

Background The neurophysiological mechanisms underlying tinnitus perception are not well understood. Surprisingly, there have been no group studies comparing abnormalities in ongoing, spontaneous neuronal activity in individuals with and without tinnitus perception. Methods and Findings Here, we show that the spontaneous neuronal activity of a group of individuals with tinnitus (n = 17) is characterised by a marked reduction in alpha (8–12 Hz) power together with an enhancement in delta (1.5–4 Hz) as compared to a normal hearing control group (n = 16). This pattern was especially pronounced for temporal regions. Moreover, correlations with tinnitus-related distress revealed strong associations with this abnormal spontaneous activity pattern, particularly in right temporal and left frontal areas. Overall, effects were stronger for the alpha than for the delta frequency band. A data stream of 5 min, recorded with a whole-head neuromagnetometer under a resting condition, was sufficient to extract the marked differences. Conclusions Despite some limitations, there are arguments that the regional pattern of abnormal spontaneous activity we found could reflect a tinnitus-related cortical network. This finding, which suggests that a neurofeedback approach could reduce the adverse effects of this disturbing condition, could have important implications for the treatment of tinnitus.

Early modulation of visual perception by emotional arousal: Evidence from steady-state visual evoked brain potentials

Allocation of processing resources to emotional picture stimuli was examined using steady-state visual evoked brain potentials (ssVEPs). Participants viewed a set of 60 colored affective pictures from the International Affective Picture System, presented in a flickering mode at 10 Hz in order to elicit ssVEPs. Phase and amplitude of the 10-Hz ssVEP were examined for six picture categories: threat and mutilation (unpleasant), families and erotica (pleasant), and household objects and persons (neutral). Self-reported affective arousal and hedonic valence of the picture stimuli were assessed by means of subjective ratings. Viewing affectively arousing (unpleasant and pleasant) pictures was associated with enhanced ssVEP amplitude at parieto-occipital recording sites, as compared with neutral stimuli. Phase information suggested increased coactivation of right occipitotemporal and frontotemporal sources during processing of affectively arousing stimuli. These findings are consistent with reentrant modulation of early visual processing by distributed networks including subcortical and neocortical structures according to a stimuluss motivational relevance.

Motivated attention in emotional picture processing is reflected by activity modulation in cortical attention networks

In the present study, we presented high (pleasant and unpleasant)- and low (neutral)-arousing emotional pictures in a steady state visual evoked field paradigm while recording the magnetoencephalogram. Applying a minimum norm estimation (MNE) technique, we determined the origin and the strength of the evoked neuromagnetic field. In addition to magnetocortical data, we examined subjective ratings, heart rate change and viewing time to obtain a multivariate data base of emotional experience related to the present paradigm. As evidenced by the MNE, pictures rated as high arousing elicited greater activity in frontoparietal cortical networks than low-arousing pictures, with a right hemispheric predominance. This effect was also observed in occipito-temporal regions but to a lesser extent. Longer viewing times for high-arousing pictures and sustained heart rate deceleration for high-arousing unpleasant pictures indicated that these stimuli were of high motivational relevance compared to neutral pictures. Taken together, we argue that activity in higher-order frontoparietal cortical attention networks is modulated by emotional arousal. In turn, this attention network influences activity in systems performing stimulus processing.

Adaptation in human visual cortex as a mechanism for rapid discrimination of aversive stimuli.

The ability to react rapidly and efficiently to adverse stimuli is crucial for survival. Neuroscience and behavioral studies have converged to show that visual information associated with aversive content is processed quickly and accurately and is associated with rapid amplification of the neural responses. In particular, unpleasant visual information has repeatedly been shown to evoke increased cortical activity during early visual processing between 60 and 120 ms following the onset of a stimulus. However, the nature of these early responses is not well understood. Using neutral versus unpleasant colored pictures, the current report examines the time course of short-term changes in the human visual cortex when a subject is repeatedly exposed to simple grating stimuli in a classical conditioning paradigm. We analyzed changes in amplitude and synchrony of large-scale oscillatory activity across 2 days of testing, which included baseline measurements, 2 conditioning sessions, and a final extinction session. We found a gradual increase in amplitude and synchrony of very early cortical oscillations in the 20-35 Hz range across conditioning sessions, specifically for conditioned stimuli predicting aversive visual events. This increase for conditioned stimuli affected stimulus-locked cortical oscillations at a latency of around 60-90 ms and disappeared during extinction. Our findings suggest that reorganization of neural connectivity on the level of the visual cortex acts to optimize early perception of specific features indicative of emotional relevance.

Hypofunction of Right Temporoparietal Cortex During Emotional Arousal in Depression

CONTEXT Neuropsychological models of depression highlight temporoparietal hypofunction associated with low emotional arousal in major depressive disorder (MDD). These models were derived from indirect measures such as neuropsychological tests and electroencephalography alpha band power. OBJECTIVE To determine if high-arousing stimuli directly modulated activity in attention and arousal-related sensory brain regions in patients with MDD. DESIGN Between-group comparison (patients with MDD vs healthy control subjects) of neuromagnetic oscillatory activity driven by flickering emotional and neutral pictures (steady-state visual evoked fields [ssVEFs]). SETTING Center of magnetoencephalography at a public university and public ambulatory mental health service. PARTICIPANTS Fifteen female low-anxious patients with MDD and 15 female controls. The groups were matched with respect to age and handedness. INTERVENTION Magnetoencephalographic recordings and self-report ratings. MAIN OUTCOME MEASURES Modulation of current source strengths obtained by frequency domain minimum norm source localization of ssVEFs. RESULTS Controls and patients with MDD showed enhanced current source strengths at ssVEF frequency in occipital and parietal cortex for high-arousing emotional pictures (P < .05 for permutation statistics). While this arousal modulation in controls was pronounced in the right temporoparietal cortex, weak arousal modulation characterized that brain region in patients with MDD (F(1,28) = 7.2, P < .05 for interaction group by quadraticcontrast). CONCLUSIONS Although emotional pictures engaged the dorsal visual stream to a greater extent than neutral pictures in both study groups, only controls showed strong arousal modulation in the right temporoparietal cortex. Because the right temporoparietal cortex is associated with the arousal dimension of emotion, subjects with depression may have difficulties in activating arousal-related brain areas, whereas basic stimulus processing related to activation of the dorsal visual stream is intact.

Prefrontal-Occipitoparietal Coupling Underlies Late Latency Human Neuronal Responses to Emotion

Enhanced late positive potentials (LPPs) evoked by highly arousing unpleasant and pleasant stimuli have been consistently observed in event-related potential experiments in humans. Although the psychological factors modulating the LPP have been studied in detail, the neurobiological underpinnings of this response remain poorly understood. Current models suggest that the LPP is a product of both an automatic facilitation of perceptual activity, as well as postperceptual processing under cognitive control. Here we applied magnetoencephalography (MEG) and beamformer analysis combined with Granger causality measures to provide a mechanistic account for LPP generation that reconciles these two models. We demonstrate that the magnetic homolog of the LPP, mLPP, is localized within bilateral occipitoparietal and right prefrontal cortex. Critically, directed functional connectivity analysis between these brain regions, indexed by Granger causality, demonstrates stronger bidirectional influences between frontal and occipitoparietal cortex for high arousing emotional relative to low arousing neutral pictures. Thus, both bottom-up and top-down accounts of the late latency response to emotion derived from psychological studies can be explained by a reciprocal codependency between activity in prefrontal and occipitoparietal cortex.

Neural mechanisms of evoked oscillations: Stability and interaction with transient events

There is increasing evidence that early event‐related potentials are a result of phase alignment of ongoing background oscillations of the electroencephalogram rather than additive amplitude modulation. Steady state visual‐evoked potentials (ssVEPs) can be recorded using an intensity modulated stimulus, resulting in an evoked brain response at a known frequency, i.e. the stimulation frequency. Given this property, the ssVEP is ideally suited for examining the relationship between single‐trial fluctuations in phase/amplitude and the evoked brain potential resulting from averaging across trials. To address this issue, the current study investigated the contribution of single trial power and intertrial phase locking to ssVEP generation by presenting a peripheral flicker. Further, transient stimuli were presented during flicker and at three increasing latency lags following flicker offset to examine (1) to what extent a stimulus can disturb the ssVEP oscillation and (2) how phase alignment during P1‐N1‐P2 time windows is affected during presence of evoked oscillations. The former assessment evaluates the stability of ssVEPs and the latter the phase alignment processes to transient stimuli under experimentally induced background oscillations. We observed that ssVEPs are a result of phase alignment rather than single trial amplitude modulation. In addition, ssVEP oscillations were not disturbed by transient stimuli. Finally, phase alignment in P1‐N1‐P2 time windows was distorted during and shortly after steady state stimulation. We conclude that ssVEPs represent strongly phase locked oscillations sharing the same generation mechanisms as early evoked potentials. Hum Brain Mapp, 2007.

A fast pathway for fear in human amygdala

A fast, subcortical pathway to the amygdala is thought to have evolved to enable rapid detection of threat. This pathways existence is fundamental for understanding nonconscious emotional responses, but has been challenged as a result of a lack of evidence for short-latency fear-related responses in primate amygdala, including humans. We recorded human intracranial electrophysiological data and found fast amygdala responses, beginning 74-ms post-stimulus onset, to fearful, but not neutral or happy, facial expressions. These responses had considerably shorter latency than fear responses that we observed in visual cortex. Notably, fast amygdala responses were limited to low spatial frequency components of fearful faces, as predicted by magnocellular inputs to amygdala. Furthermore, fast amygdala responses were not evoked by photographs of arousing scenes, which is indicative of selective early reactivity to socially relevant visual information conveyed by fearful faces. These data therefore support the existence of a phylogenetically old subcortical pathway providing fast, but coarse, threat-related signals to human amygdala.

Source distribution of neuromagnetic slow waves and MEG-delta activity in schizophrenic patients

BACKGROUND Schizophrenic patients exhibit more activity in the electroencephalographic delta and theta frequency range than do control subjects. Using magnetic source imaging (MSI) our study aimed to explore this phenomenon in the magnetoencephalogram (MEG), the distribution of its sources, and associations between symptom profiles and sources of low-frequency activity in the brain. METHODS Whole-head MEG recordings were obtained from 28 schizophrenic patients and 20 healthy control subjects during a resting condition. The generators of the focal magnetic slow waves were located employing a single moving dipole model. Distributed or multiple delta and theta sources were captured by the minimum norm estimate. RESULTS Both localization procedures showed slow wave activity to be enhanced in schizophrenic patients compared with control subjects. Focal slow wave activity differed most between groups in frontotemporal and in posterior regions. Slow wave activity was associated with symptom characteristics in that positive symptoms varied with frontal delta and theta activity. CONCLUSIONS Results indicate that activity in low-frequency bands in schizophrenic patients exceeds the activity of control subjects in distinct areas, and that this focal clustering of neuromagnetic slow waves may be related to psychopathologic characteristics.

Source distribution of neuromagnetic slow wave activity in schizophrenic and depressive patients

OBJECTIVE Focal slow waves in the delta and theta frequency range frequently appear in psychopathological conditions. Due to their focal nature they can be localized by dipole modeling. We previously reported regional clustering of slow waves in temporal and parietal cortex of schizophrenic patients whereas such activity is largely absent in normals. Here we examine, to what extent distribution of slow wave generators differentiates schizophrenic from depressive syndromes. METHODS The regional densities of generators of focal slow waves were determined during resting conditions in patients with DSM-IV diagnoses of schizophrenia (N=25) and depression (N=27) and in 18 healthy controls. RESULTS Schizophrenic patients demonstrated accentuated temporal and parietal delta and theta dipole clustering, when compared to both the control and the depressive sample. In contrast, depressive patients had reduced frontal and prefrontal delta and theta dipole density relative to both schizophrenics and controls. This pattern was not related to age. Men generally displayed somewhat higher slow wave activity than women. For the areas of most pronounced slow wave deviances activity within each group was related to symptom scores: higher left-temporal slow wave activity was associated with hallucinations in schizophrenics, suppression of left-prefrontal slow wave activity correlated with depression scores. CONCLUSIONS Results suggest that slow wave distribution may assist in differentially diagnosing psychopathological conditions.