BACKGROUND: Fear extinction is a fundamental component of exposure-based therapies for anxiety-related disorders. The renewal of fear in a different context after extinction highlights the importance of contextual factors. In this study, we aimed to investigate the causal role of the left inferior frontal gyrus (LiFG) in the context-dependency of fear extinction learning via administration of transcranial direct current stimulation (tDCS) over this area.
METHODS: 180 healthy subjects were assigned to 9 groups: 3 tDCS conditions (anodal, cathodal, and sham) × 3 context combinations (AAA, ABA, and ABB). The fear conditioning/extinction task was conducted over three consecutive days: acquisition, extinction learning, and extinction recall. tDCS (2 mA, 10min) was administered during the extinction learning phase over the LiFG via a 4-electrode montage. Skin conductance response (SCR) data and self-report assessments were collected.
RESULTS: During the extinction learning phase, groups with excitability-enhancing anodal tDCS showed a significantly higher fear response to the threat cues compared to cathodal and sham stimulation conditions, irrespective of contextual factors. This effect was stable until the extinction recall phase. Additionally, excitability-reducing cathodal tDCS caused a significant decrease of the response difference between the threat and safety cues during the extinction recall phase. The self-report assessments showed no significant differences between the conditions throughout the experiment.
CONCLUSIONS: Independent of the context, excitability enhancement of the LiFG did impair fear extinction, and led to preservation of fear memory. In contrast, excitability reduction of this area enhanced fear extinction retention. These findings imply that the LiFG plays a role in the fear extinction network, which seems to be however context-independent.

Mismatch negativity (MMN) or its magnetic counterpart (MMNm) is a neurophysiological signal to reflect the automatic change-detection ability. However, MMN studies in patients with panic disorder (PD) showed contrasting results using electroencephalographic (EEG) recordings. The present study attempted to overcome the limitations of EEG methodology by means of a whole-head magnetoencephalography (MEG) combined with the depth-weighted minimum norm estimate method to conduct an in-depth investigation on the MMNm at the cortical level in patients with PD.
We recruited 22 healthy controls (HC) and 20 patients with PD to perform auditory oddball paradigm during MEG recordings. The cortical MMNm amplitudes and latencies in the superior temporal gyrus, inferior parietal lobule, and inferior frontal gyrus (IFG) were compared between the HC and PD groups. The correlations between MMNm responses and clinical measurement were also examined.
Compared with the HC group, the PD group demonstrated significantly reduced MMNm amplitudes in the IFG. Furthermore, higher trait scores of the State-Trait Anxiety Inventory were associated with lower MMNm amplitudes of the right IFG among patients with PD.
Generalization of the current results to other settings or samples should be made cautiously due to the use of different medication regimens and presence of comorbidities in our patients.
Our data suggest dysfunctional pre-attentive change-detection ability in patients with PD, particularly in the IFG.

Objective: Pain and affective disorders have clear clinical relevance; however, very few studies have investigated the association between pain and bipolar disorder. This study investigated the brain activity of patients with bipolar disorder (BPs) undergoing tonic pain and assessed the interaction between pain and emotion. Methods: Ten BPs and ten healthy controls (HCs) were exposed to emotional pictures (positive, neutral, or negative), tonic pain only (pain session), and emotional pictures along with tonic pain (combined session). A moderate tonic pain was induced by the infusion of hypertonic saline (5% NaCl) into the right masseter muscle with a computer-controlled system. Whole-brain blood oxygenation level dependent (BOLD) signals were acquired using 3T functional resonance imaging (fMRI). Results: Ten BPs and ten healthy participants were included in the final analysis. During the pain session, BPs accepted more saline, but showed lower pain rating scores than HCs. When experiencing pain, BPs showed a significant decrease in the BOLD signal in the bilateral insula, left inferior frontal gyrus (IFG), and left cerebellum as compared with HCs. In the combined session, the activated regions for positive mood (pain with positive mood > baseline) in BPs were the left cerebellum, right temporal gyrus, and left occipital gyrus; the activated regions for negative mood (pain with negative mood > baseline) were the right occipital gyrus, left insula, left IFG, and bilateral precentral gyrus. Conclusions: This study presents the preliminary finding of the interaction between pain and emotion in BPs. BPs exhibited lower sensitivity to pain, and the activation of insula and IFG may reflect the interaction between emotion and pain stimulus.

Repetitive thinking styles such as rumination are considered to be a key factor in the development and maintenance of mental disorders. Different situational triggers (e.g., social stressors) have been shown to elicit rumination in subjects exhibiting such habitual thinking styles. At the same time, the process of rumination influences the adaption to stressful situations. The study at hand aims to investigate the effect of trait rumination on neuronal activation patterns during the Trier Social Stress Test (TSST) as well as the physiological and affective adaptation to this high-stress situation.
A sample of 23 high and 22 low ruminators underwent the TSST and two control conditions while their cortical hemodynamic reactions were measured with functional near-infrared spectroscopy (fNIRS). Additional behavioral, physiological and endocrinological measures of the stress response were assessed.
Subjects showed a linear increase from non-stressful control conditions to the TSST in cortical activity of the cognitive control network (CCN) and dorsal attention network (DAN), comprising the bilateral dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus (IFG) and superior parietal cortex/somatosensory association cortex (SAC). During stress, high ruminators showed attenuated cortical activity in the right IFG, whereby deficits in IFG activation mediated group differences in post-stress state rumination and negative affect.
Aberrant activation of the CCN and DAN during social stress likely reflects deficits in inhibition and attention with corresponding negative emotional and cognitive consequences. The results shed light on possible neuronal underpinnings by which high trait rumination may act as a risk factor for the development of clinical syndromes.

Recent studies have suggested that functional abnormalities in Broca\'s area, which is important in language production (speech and thoughts before speech), play an important role in the pathophysiology of schizophrenia. While multi-modal approaches have proved useful in revealing the specific pathophysiology of psychosis, the association of functional abnormalities with gray matter volume (GMV) here in subjects with an ultra-high risk (UHR) of schizophrenia, those with first-episode schizophrenia (FES), and healthy controls has yet to be clarified. Therefore, the relationship between cortical activity measured using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task, and GMV in the Broca\'s area assessed using a manual tracing in magnetic resonance imaging (MRI), which considers individual structural variation, was examined for 57 subjects (23 UHR/18 FES/16 controls). The UHR and FES group showed significantly reduced brain activity compared to control group in the left pars triangularis (PT) (P=.036, .003, respectively). Furthermore in the FES group, the reduced brain activity significantly positively correlated with the volume in the left PT (B=0.29, P=.027), while significant negative association was evident for all subjects (B=-0.18, P=.010). This correlation remained significant after adjusting for antipsychotics dosage, and voxel-wise analysis could not detect any significant correlation between impaired cortical activity and volume. The significant relationship between neural activity and GMV in the left PT may reflect a specific pathophysiology related to the onset of schizophrenia.