Noninvasive Stimulation of the Ventromedial Prefrontal Cortex Indicates Valence Ambiguity in Sad Compared to Happy and Fearful Face Processing

The ventromedial prefrontal cortex (vmPFC) is known to be specifically involved in the processing of stimuli with pleasant, rewarding meaning to the observer. By the use of non-invasive transcranial direct current stimulation (tDCS), it was previously possible to show evidence for this valence specificity and to modulate the impact of the vmPFC on emotional network processing. Prior results showed increased neural activation during pleasant relative to unpleasant stimulus processing after excitatory compared to inhibitory vmPFC-tDCS. As dysfunctional vmPFC activation patterns are associated with major depressive disorder (MDD), tDCS of this region could render an attractive application in future therapy. Here, we investigated vmPFC-tDCS effects on sad compared to happy face processing, as sad faces are often used in the study of mood disorders. After counterbalanced inhibitory or excitatory tDCS, respectively, healthy participants viewed happy and sad faces during magnetoencephalography (MEG) recording. In addition, tDCS effects on an interpretational bias of ambiguous happy-sad face morphs and an attentional bias of a dot-probe task with happy and sad faces as emotional primes were investigated. Finally, in conjoint analyses with data from a previous sibling study (happy and fearful faces) we examined whether excitatory vmPFC-tDCS would reveal a general increase in processing of pleasant stimuli independent of the type of unpleasant stimuli applied (sad vs. fearful faces). MEG and behavioral results showed that happy faces promoted a relative positivity bias after excitatory compared to inhibitory tDCS, visible in left orbitofrontal cortex and in the emotion-primed dot-probe task. A converse pattern in the MEG data during sad face processing suggests the possible involvement of an empathy network and thus significantly differed from neuronal processing of fearful face processing. Implications for the bearing of vmPFC modulation on emotional face processing and the impact of specific unpleasant face expressions are discussed

How the Dorsolateral Prefrontal Cortex Controls Affective Processing in Absence of Visual Awareness – Insights From a Combined EEG-rTMS Study

The dorsolateral prefrontal cortex (DLPFC) plays a key role in the modulation of affective processing. However, its specific role in the regulation of neurocognitive processes underlying the interplay of affective perception and visual awareness has remained largely unclear. Using a mixed factorial design, this study investigated effects of inhibitory continuous theta-burst stimulation (cTBS) of the right DLPFC (rDLPFC) compared to an Active Control condition on behavioral (N = 48) and electroencephalographic (N = 38) correlates of affective processing in healthy Chinese participants. Event-related potentials (ERPs) in response to passively viewed subliminal and supraliminal negative and neutral natural scenes were recorded before and after cTBS application. We applied minimum-norm approaches to estimate the corresponding neuronal sources. On a behavioral level, we found evidence for reduced emotional interference by, and less negative and aroused ratings of negative supraliminal stimuli following rDLPFC inhibition. We found no evidence for stimulation effects on self-reported mood or the behavioral discrimination of subliminal stimuli. On a neurophysiological level, rDLPFC inhibition relatively enhanced occipito-parietal brain activity for both subliminal and supraliminal negative compared to neutral images (112–268 ms; 320–380 ms). The early onset and localization of these effects suggests that rDLPFC inhibition boosts automatic processes of “emotional attention” independently of visual awareness. Further, our study reveals the first available evidence for a differential influence of rDLPFC inhibition on subliminal versus supraliminal neural emotion processing. Explicitly, our findings indicate that rDLPFC inhibition selectively enhances late (292–360 ms) activity in response to supraliminal negative images. We tentatively suggest that this differential frontal activity likely reflects enhanced awareness-dependent down-regulation of negative scene processing, eventually leading to facilitated disengagement from and less negative and aroused evaluations of negative supraliminal stimuli

The causal role of prefrontal hemispheric asymmetry in valence processing of words - Insights from a combined cTBS-MEG study

Roesmann K, Dellert T, Junghoefer M, et al. The causal role of prefrontal hemispheric asymmetry in valence processing of words - Insights from a combined cTBS-MEG study. NEUROIMAGE. 2019;191:367-379.Hemispheric asymmetries play an important role in multiple cerebral functions. Asymmetries in prefrontal cortex (PFC) function have been suggested to regulate emotional processing in that right-hemispheric dominance biases towards negative affect, whereas left PFC dominance favors positive affect. This study used transcranial magnetic stimulation to test the causal role of prefrontal asymmetries in the processing of emotional stimuli. To experimentally induce hemispheric asymmetries, 21 healthy volunteers underwent two separate sessions of inhibitory continuous theta burst stimulation (cTBS) to the left versus right dorsolateral prefrontal cortex. Each stimulation was followed by magnetoencephalographic (MEG) recordings of event-related fields elicited by visually presented emotional words in a silent reading task and a subsequent behavioral emotion categorization task. The asymmetry manipulation influenced valence processing of words in early, mid-latency and late time intervals in right occipitotemporal and parietal brain regions. Left-sided cTBS (inducing right-hemispheric dominance) consistently resulted in enhanced brain responses to negative words, while right-sided cTBS (inducing left-hemispheric dominance) enhanced responses to positive words. On a behavioral level, right-hemispheric dominance resulted in more categorization matches of negative compared to positive words, while left-hemispheric dominance resulted in reverse effects. These results provide direct evidence that bottom-up valence processing is influenced by prefrontal hemispheric asymmetry

Tinnitus loudness ratings.

<p>Averaged ratings (across all three days) on a visual analog scale (VAS) of the subjectively perceived tinnitus loudness before (grey bar) and after (red bar) tailor-made notched music (TMNM) exposure for the increased spectral energy (ISEC) TMNM (left) and the classical TMNM (right) group. Error bars denote one standard error of the mean. Stars denote significance values of <i>F</i>-test depicting a significant main effect (** = <i>p</i> <. 01) of <i>Session</i> (pre vs. post music exposure) and a non-significant (<i>ns</i>) interaction effect <i>Session</i> x <i>Group</i>.</p

Power spectral density of Brownian noise filtered with both procedures.

<p>Brownian noise was chosen to illustrate the filter procedure, as it resembles the typical energy spectrum of music (lower energy in higher frequencies, 1/f behavior). Black line: frequency spectrum of Brownian noise with 3 s duration. Blue line: frequency spectrum of 3 s of Brownian noise filtered with the applied online filter for classical tailor-made notched music (TMNM). First, spectral energy was re-distributed from low to high frequency ranges (“flattening”). Second, a frequency band of 1/2 octave width centered at 6 kHz was removed from the energy spectrum of Brownian noise (classical TMNM). Green line: frequency spectrum of 3 s of Brownian noise filtered with the applied online filter for increased spectral energy contrast TMNM (ISEC-TMNM). In addition to the filtering procedure of classical TMNM, 3/8 octaves bandwidth of the edge frequency bands around the notch were amplified by 20 dB.</p

Results for the main effect <i>Session</i>.

<p>A: the right part depicts Statistical Parametric Maps of <i>F</i>-values for the main effect <i>Session</i> (pre vs. post tailor-made notched music (TMNM) exposure) in a temporal (B: parietal, C: orbitofrontal, D: occipital-temporal) cluster. Only spatiotemporal clusters which survived the cluster-based permutation test are colorized. Black cylinders reflect the source locations within the significant clusters. The right part framed with a circle disentangles the direction of the effect by depicting the mean activity evoked by the tinnitus tone before and after TMNM exposure within the significant temporal (B: parietal, C: orbitofrontal, D: occipital-temporal) cluster. Error bars denote one standard error of the mean. Stars denote significance-values of the <i>F</i>-test (** = <i>p</i> <. 01, * = <i>p</i> <. 05, <i>ns</i> = non-significant).</p

Study procedure.

<p>Tinnitus frequency was estimated before beginning of the training. The training session consisted of a hearing threshold determination for the reference tone of 500 Hz (RT). Ratings on the visual analog scale (VAS) were done before and after MEG measurements. Classical or ISEC tailor-made notched music (TMNM) was presented for 3 hours in between two VAS/MEG/VAS sessions. The training session was repeated on the next two days.</p

Global source power plot of the source waveforms averaged across all subjects.

<p>Neural activities evoked by the tinnitus tone pre (dotted line) and post (solid line) tailor-made notched music (TMNM) exposure. The a priori N1 time interval of interest (IOI) is highlighted in grey.</p

Results for the interaction effect <i>Session</i> x <i>Group</i>.

<p>A: left part depicts Statistical Parametric Maps of <i>F</i>-values for the interaction effect <i>Session</i> (pre vs. post tailor-made notched music (TMNM) exposure) x <i>Group</i> (increased spectral energy contrast (ISEC) vs. classical TMNM) in an inferior temporal (B: frontal) cluster. Only spatiotemporal clusters which survived the cluster-based permutation test are colorized. Black cylinders reflect the source locations within the significant clusters. The right part framed with a circle disentangles the direction of the interaction effect by depicting the mean activity evoked by the tinnitus tone before and after TMNM exposure within the significant inferior temporal (B: frontal) cluster for each group individually. Error bars denote one standard error of the mean. Stars denote significance values of pairwise <i>t</i>-tests disentangling the interaction effect (** = <i>p</i> <. 01, * = <i>p</i> <. 05, <i>ns</i> = non-significant).</p