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.

The structure of human language is inherently hierarchical. The left posterior inferior frontal gyrus (LpIFG) is proposed to be a core region for constructing syntactic hierarchies. However, it remains unclear whether LpIFG plays a causal role in syntactic processing in Mandarin Chinese and whether its contribution depends on syntactic complexity, working memory, or both. We addressed these questions by applying inhibitory continuous theta-burst stimulation (cTBS) over LpIFG. Thirty-two participants processed sentences containing embedded relative clauses (i.e., complex syntactic processing), syntactically simpler coordinated sentences (i.e., simple syntactic processing), and non-hierarchical word lists (i.e., word list processing) after receiving real or sham cTBS. We found that cTBS significantly increased the coefficient of variation, a representative index of processing stability, in complex syntactic processing (esp., when subject relative clause was embedded) but not in the other two conditions. No significant changes in d\' and reaction time were detected in these conditions. The findings suggest that (a) inhibitory effect of cTBS on the LpIFG might be prominent in perturbing the complex syntactic processing stability but subtle in altering the processing quality; and (b) the causal role of the LpIFG seems to be specific for syntactic processing rather than working memory capacity, further evidencing their separability in LpIFG. Collectively, these results support the notion of the LpIFG as a core region for complex syntactic processing across languages.

Internal forward models hypothesize functional links between motor and sensory systems for predicting the consequences of actions. Recently, the cascaded theory proposes that somatosensory estimation in the inferior parietal lobe (IPL) can be a relay computational structure, converting motor signals into predictions of auditory consequences in a serial processing manner during speech production. The study used fMRI with functional connectivity (FC) analyses to investigate the proposed cascaded processes using three speech tasks: overt articulation (OA), silent articulation (SA) and imagined articulation (IA). The FC results showed that connectivity between aIPL and STG was increased in OA compared with SA, suggesting that the relationship between somatosensory and auditory estimations can be modulated by speech tasks. Moreover, stronger connectivity between IFGoper and pIPL, and between pIPL and STG were observed in SA and IA compared with OA. These results are consistent with a cascaded process in the internal forward models.

Verbal working memory (VWM) involves visual and auditory verbal information. Neuroimaging studies have shown significant modality effects for VWM in the left posterior parietal cortex (PPC). The left inferior frontal gyrus (IFG) is more sensitive to auditory and phonological information. However, much less is known about the effects of transcranial direct current stimulation (tDCS) over the left PPC and IFG on different sensory modalities of VWM (auditory vs. visual). Therefore, the present study aimed to examine whether tDCS over the left PPC and IFG affects visual and auditory VWM updating performance using a single-blind design. Fifty-one healthy participants were randomly assigned to three tDCS groups (left PPC/left IFG/sham) and were asked to complete both the visual and auditory letter 3-back tasks. Results showed that stimulating the left PPC enhanced the response efficiency of visual, but not auditory, VWM compared with the sham condition. Anodal stimulation to the left IFG improved the response efficiency of both tasks. The present study revealed a modality effect of VWM in the left PPC, while the left IFG had a causal role in VWM updating of different sensory modalities.

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.

The right inferior frontal gyrus (IFG) is involved in intention understanding during interpersonal interactions. To examine how prior experience of cooperation and competition affects one\'s right IFG activation in the subsequent interaction, using near-infrared spectroscopy (NIRS) we simultaneously measured paired participants\' bilateral IFG activations during a turn-taking game. Participant pairs were assigned to either one of two roles: a Builder taking the initial move to copy a target disk-pattern on monitor and the Partner taking the second move to aid in (cooperation) or to obstruct (competition) the Builder. The experiment consisted of two sessions. One participant (B-P) played as a Builder (B-) in session 1 and changed the role to the Partner (-P) in session 2, and vice versa for the paired participant (P-B). NIRS data in competition demonstrated that the Builder (B-) being obstructed in session 1 showed higher right IFG activation when (s)he took a role of obstructor (-P) in session 2 (the obstructed effect), whereas \"the cooperated effect\" was not revealed in cooperation. These results suggest that prior experience of being obstructed may facilitate understanding of the Builder and/or the obstructor\'s tactical move, thereby increasing his/her right IFG activation when one is meant to obstruct in subsequent competitions.