Abnormal, affect-specific modulatory effects on early auditory processing in schizophrenia: magnetoencephalographic evidence.

Abnormalities in the perception and identification of emotions have frequently been reported in schizophrenia. Hemodynamic neuroimaging studies found functional abnormalities in cortical and subcortical brain circuits that are involved in normal affective processing, but the temporal dynamics of abnormal emotion processing in schizophrenia remain largely elusive. To investigate this issue, we recorded early auditory evoked field components by means of whole-head magnetoencephalography that were in response to emotion-associated tones in seventeen patients with schizophrenia and in seventeen healthy, matched controls. Forty-two click-like tones (conditioned stimuli; CS) acquired differential emotional meaning through an affective associative learning procedure by pairing each CS three times with either pleasant, unpleasant or neutral auditory scenes. As expected, differential affect-specific modulation in patients vs. controls was evident, starting at the auditory N1m onset latency of approximately 70ms, extending to 230ms. While controls showed the expected enhanced processing of emotion associated CS, patients revealed an inverted pattern with reduced processing of arousal, when compared to neutral stimuli, in the right prefrontal cortex. The present finding suggests impairments in the prioritization of emotionally salient vs. non-salient stimuli in patients with schizophrenia. Dysfunction in higher cognitive processes and behavior in schizophrenia may therefore reflect dysfunction in fundamental, early emotion processing stages.

Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex modulates early affective processing.

The dorsolateral prefrontal cortex (dlPFC) has often been suggested as a key modulator of emotional stimulus appraisal and regulation. Therefore, in clinical trials, it is one of the most frequently targeted regions for non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS). In spite of various encouraging reports that demonstrate beneficial effects of rTMS in anxiety disorders, psychophysiological studies exploring the underlying neural mechanisms are sparse. Here we investigated how inhibitory rTMS influences early affective processing when applied over the right dlPFC. Before and after rTMS or sham stimulation, subjects viewed faces with fearful or neutral expressions while whole-head magnetoencephalography (MEG) was recorded. Due to the disrupted functioning of the right dlPFC, visual processing in bilateral parietal, temporal, and occipital areas was amplified starting at around 90 ms after stimulus onset. Moreover, increased fear-specific activation was found in the right TPJ area in a time-interval between 110 and 170 ms. These neurophysiological effects were reflected in slowed reaction times for fearful, but not for neutral faces in a facial expression identification task while there was no such effect on a gender discrimination control task. Our study confirms the specific and important role of the dlPFC in regulation of early emotional attention and encourages future clinical research to use minimal invasive methods such as transcranial magnetic (TMS) or direct current stimulation (tDCS).

Rapid and highly resolving associative affective learning: convergent electro- and magnetoencephalographic evidence from vision and audition.

Various pathway models for emotional processing suggest early prefrontal contributions to affective stimulus evaluation. Yet, electrophysiological evidence for such rapid modulations is still sparse. In a series of four MEG/EEG studies which investigated associative learning in vision and audition using a novel MultiCS Conditioning paradigm, many different neutral stimuli (faces, tones) were paired with aversive and appetitive events in only two to three learning instances. Electrophysiological correlates of neural activity revealed highly significant amplified processing for conditioned stimuli within distributed prefrontal and sensory cortical networks. In both, vision and audition, affect-specific responses occurred in two successive waves of rapid (vision: 50-80 ms, audition: 25-65 ms) and mid-latency (vision: >130 ms, audition: >100 ms) processing. Interestingly, behavioral measures indicated that MultiCS Conditioning successfully prevented contingency awareness. We conclude that affective processing rapidly recruits highly elaborate and widely distributed networks with substantial capacity for fast learning and excellent resolving power.

Preferential responses to extinguished face stimuli are preserved in frontal and occipito-temporal cortex at initial but not later stages of processing.

Magnetoencephalographic correlates of rapid emotional responses (50-80 ms) in frontal and occipito-temporal regions have recently been reported using a novel MultiCS Conditioning paradigm with odor-conditioned faces. As those short-latency responses were supposed to partially reflect initial access to nonextinguished emotional memories, it could be predicted that they outlast the extinction phase. To test this hypothesis, appetitively and aversively odor-conditioned faces were frequently presented during extinction while event-related magnetic fields were recorded. Affect-specific responses in frontal and occipito-temporal areas were found in the early (50-80 ms) but not in the later (130-190 ms) time interval following extinction learning. These results suggest that previously acquired emotional memories can be accessed at initial processing stages but become ineffective in modulating processing at later stages as extinction proceeds.

Affect-specific modulation of the N1m to shock-conditioned tones: magnetoencephalographic correlates.

Despite its fundamental relevance for representing the emotional world surrounding us, human affective neuroscience research has widely neglected the auditory system, at least in comparison to the visual domain. Here, we have investigated the spatiotemporal dynamics of human affective auditory processing using time-sensitive whole-head magnetoencephalography. A novel and highly challenging affective associative learning procedure, 'MultiCS conditioning', involving multiple conditioned stimuli (CS) per affective category, was adopted to test whether previous findings from intramodal conditioning of multiple click-tones with an equal number of auditory emotional scenes (Bröckelmann et al., 2011 J. Neurosci., 31, 7801) would generalise to crossmodal conditioning of multiple click-tones with an electric shock as single aversive somatosensory unconditioned stimulus (UCS). Event-related magnetic fields were recorded in response to 40 click-tones before and after four contingent pairings of 20 CS with a shock and the other half remaining unpaired. In line with previous findings from intramodal MultiCS conditioning we found an affect-specific modulation of the auditory N1m component 100-150 ms post-stimulus within a distributed frontal-temporal-parietal neural network. Increased activation for shock-associated tones was lateralised to right-hemispheric regions, whereas unpaired safety-signalling tones were preferentially processed in the left hemisphere. Participants did not show explicit awareness of the contingent CS-UCS relationship, yet behavioural conditioning effects were indicated on an indirect measure of stimulus valence. Our findings imply converging evidence for a rapid and highly differentiating affect-specific modulation of the auditory N1m after intramodal as well crossmodal MultiCS conditioning and a correspondence of the modulating impact of emotional attention on early affective processing in vision and audition.

The impact of acute psychosocial stress on magnetoencephalographic correlates of emotional attention and exogenous visual attention.

Stress-induced acute activation of the cerebral catecholaminergic systems has often been found in rodents. However, little is known regarding the consequences of this activation on higher cognitive functions in humans. Theoretical inferences would suggest increased distractibility in the sense of increased exogenous attention and emotional attention. The present study investigated the influence of acute stress responses on magnetoencephalographic (MEG) correlates of visual attention. Healthy male subjects were presented emotional and neutral pictures in three subsequent MEG recording sessions after being exposed to a TSST-like social stressor, intended to trigger a HPA-response. The subjects anticipation of another follow-up stressor was designed to sustain the short-lived central catecholaminergic stress reactions throughout the ongoing MEG recordings. The heart rate indicates a stable level of anticipatory stress during this time span, subsequent cortisol concentrations and self-report measures of stress were increased. With regard to the MEG correlates of attentional functions, we found that the N1m amplitude remained constantly elevated during stressor anticipation. The magnetic early posterior negativity (EPNm) was present but, surprisingly, was not at all modulated during stressor anticipation. This suggests that a general increase of the influence of exogenous attention but no specific effect regarding emotional attention in this time interval. Regarding the time course of the effects, an influence of the HPA on these MEG correlates of attention seems less likely. An influence of cerebral catecholaminergic systems is plausible, but not definite.

Emotion-associated tones attract enhanced attention at early auditory processing: magnetoencephalographic correlates.

Emotionally significant objects and events in our environment attract attention based on their motivational relevance for survival. Such kind of emotional attention is thought to lead to affect-specific amplified processing that closely resembles effects of directed attention. Although there has been extensive research on prioritized processing of visual emotional stimuli, the spatio-temporal dynamics of motivated attention mechanisms in auditory processing are less clearly understood. We investigated modulatory effects of emotional attention at early auditory processing stages using time-sensitive whole-head magnetoencephalography. A novel associative learning procedure involving multiple conditioned stimuli (CSs) per affective category was introduced to specifically test whether affect-specific modulation can proceed in a rapid and highly differentiating fashion in humans. Auditory evoked fields (AEFs) were recorded in response to 42 different ultrashort, click-like sounds before and after affective conditioning with pleasant, unpleasant, or neutral auditory scenes. As hypothesized, emotional attention affected neural click tone processing at time intervals of the P20-50m (20-50 ms) and the N1m (100-130 ms), two early AEF components sensitive to directed selective attention (Woldorff et al., 1993). Distributed source localization revealed amplified processing of tones associated with aversive or pleasant compared with neutral auditory scenes at auditory sensory, frontal and parietal cortex regions. Behavioral tests did not indicate any awareness for the contingent CS-UCS (unconditioned stimulus) relationships in the participants, suggesting affective associative learning in absence of contingency awareness. Our findings imply early and highly differentiating affect-specific modulation of auditory stimulus processing supported by neural mechanisms and circuitry comparable with those reported for directed auditory attention.

Acute stress alters auditory selective attention in humans independent of HPA: a study of evoked potentials.

BACKGROUND: Acute stress is a stereotypical, but multimodal response to a present or imminent challenge overcharging an organism. Among the different branches of this multimodal response, the consequences of glucocorticoid secretion have been extensively investigated, mostly in connection with long-term memory (LTM). However, stress responses comprise other endocrine signaling and altered neuronal activity wholly independent of pituitary regulation. To date, knowledge of the impact of such "paracorticoidal" stress responses on higher cognitive functions is scarce. We investigated the impact of an ecological stressor on the ability to direct selective attention using event-related potentials in humans. Based on research in rodents, we assumed that a stress-induced imbalance of catecholaminergic transmission would impair this ability. METHODOLOGY/PRINCIPAL FINDINGS: The stressor consisted of a single cold pressor test. Auditory negative difference (Nd) and mismatch negativity (MMN) were recorded in a tonal dichotic listening task. A time series of such tasks confirmed an increased distractibility occurring 4-7 minutes after onset of the stressor as reflected by an attenuated Nd. Salivary cortisol began to rise 8-11 minutes after onset when no further modulations in the event-related potentials (ERP) occurred, thus precluding a causal relationship. This effect may be attributed to a stress-induced activation of mesofrontal dopaminergic projections. It may also be attributed to an activation of noradrenergic projections. Known characteristics of the modulation of ERP by different stress-related ligands were used for further disambiguation of causality. The conjuncture of an attenuated Nd and an increased MMN might be interpreted as indicating a dopaminergic influence. The selective effect on the late portion of the Nd provides another tentative clue for this. CONCLUSIONS/SIGNIFICANCE: Prior studies have deliberately tracked the adrenocortical influence on cognition, as it has proven most influential with respect to LTM. However, current cortisol-optimized study designs would have failed to detect the present findings regarding attention.