This study aimed to evaluate a novel rTMS protocol for treatment-resistant depression (TRD), using an EEG 10–20 system guided dual-target accelerated approach of right lateral orbitofrontal cortex (lOFC) inhibition followed by left dorsolateral prefrontal cortex (dlPFC) excitation, along with comparing 20 Hz dlPFC accelerated TMS v. sham.

Seventy five patients participated in this trial consisting of 20 sessions over 5 consecutive days comparing dual-site (cTBS of right lOFC followed sequentially by 20 Hz rTMS of left dlPFC), active control (sham right lOFC followed by 20 Hz rTMS of left dlPFC) and sham control (sham for both targets). Resting-state fMRI was acquired prior to and following treatment.

Hamilton Rating Scale for Depression (HRSD-24) scores were similarly significantly improved at 4 weeks in both the Dual and Single group relative to Sham. Planned comparisons immediately after treatment highlighted greater HRSD-24 clinical responders (Dual: 47.8% v. Single:18.2% v. Sham:4.3%, χ2 = 13.0, p = 0.002) and in PHQ-9 scores by day 5 in the Dual relative to Sham group. We further showed that accelerated 20 Hz stimulation targeting the left dlPFC (active control) is significantly better than sham at 4 weeks. Dual stimulation decreased lOFC-subcallosal cingulate functional connectivity. Greater baseline lOFC-thalamic connectivity predicted better therapeutic response, while decreased lOFC-thalamic connectivity correlated with better response.

Our novel accelerated dual TMS protocol shows rapid clinically relevant antidepressant efficacy which may be related to state-modulation. This study has implications for community-based accessible TMS without neuronavigation and rapid onset targeting suicidal ideation and accelerated discharge from hospital.

Inflammation might play a role in bipolar disorder (BD), but it remains unclear the relationship between inflammation and brain structural and functional abnormalities in patients with BD. In this study, we focused on the alterations of functional connectivity (FC), peripheral pro-inflammatory cytokines and their correlations to investigate the role of inflammation in FC in BD depression.

In this study, 42 unmedicated patients with BD II depression and 62 healthy controls (HCs) were enrolled. Resting-state-functional magnetic resonance imaging was performed in all participants and independent component analysis was used. Serum levels of Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were measured in all participants. Correlation between FC values and IL-6 and IL-8 levels in BD was calculated.

Compared with the HCs, BD II patients showed decreased FC in the left orbitofrontal cortex (OFC) implicating the limbic network and the right precentral gyrus implicating the somatomotor network. BD II showed increased IL-6 (p = 0.039), IL-8 (p = 0.002) levels. Moreover, abnormal FC in the right precentral gyrus were inversely correlated with the IL-8 (r = −0.458, p = 0.004) levels in BD II. No significant correlation was found between FC in the left OFC and cytokines levels.

Our findings that serum IL-8 levels are associated with impaired FC in the right precentral gyrus in BD II patients suggest that inflammation might play a crucial role in brain functional abnormalities in BD.

Individuals with internet gaming disorder (IGD) are generally characterized by impaired executive control, persistent game-craving, and excessive reward-seeking behaviors. However, the causal interactions within the frontostriatal circuits underlying these problematic behaviors remain unclear. Here, spectral dynamic causal modeling (spDCM) was implemented to explore this issue.

Resting-state functional magnetic resonance imaging data from 317 online game players (148 IGD subjects and 169 recreational game users (RGUs)) were collected. Using independent component analysis, we determined six region of interests within frontostriatal circuits for further spDCM analysis, and further statistical analyses based on the parametric empirical Bayes framework were performed.

Compared with RGUs, IGD subjects showed inhibitory effective connectivity from the right orbitofrontal cortex (OFC) to the right caudate and from the right dorsolateral prefrontal cortex to the left OFC; at the same time, excitatory effective connectivity was observed from the thalamus to the left OFC. Correlation analyses results showed that the directional connection from the right OFC to the right caudate was negatively associated with addiction severity.

These results suggest that the disrupted causal interactions between specific regions might contribute to dysfunctions within frontostriatal circuits in IGD, and the pathway from the right OFC to the right caudate could serve as a target for brain modulation in future IGD interventions.

Tobacco smoking remains one of the leading causes of preventable illness and death and is heritable with complex underpinnings. Converging evidence suggests a contribution of the polygenic risk for smoking to the use of tobacco and other substances. Yet, the underlying brain mechanisms between the genetic risk and tobacco smoking remain poorly understood.

Genomic, neuroimaging, and self-report data were acquired from a large cohort of adolescents from the IMAGEN study (a European multicenter study). Polygenic risk scores (PGRS) for smoking were calculated based on a genome-wide association study meta-analysis conducted by the Tobacco and Genetics Consortium. We examined the interrelationships among the genetic risk for smoking initiation, brain structure, and the number of occasions of tobacco use.

A higher smoking PGRS was significantly associated with both an increased number of occasions of tobacco use and smaller cortical volume of the right orbitofrontal cortex (OFC). Furthermore, reduced cortical volume within this cluster correlated with greater tobacco use. A subsequent path analysis suggested that the cortical volume within this cluster partially mediated the association between the genetic risk for smoking and the number of occasions of tobacco use.

Our data provide the first evidence for the involvement of the OFC in the relationship between smoking PGRS and tobacco use. Future studies of the molecular mechanisms underlying tobacco smoking should consider the mediation effect of the related neural structure.

Abnormalities of orbitofrontal cortex (OFC) sulcogyral patterns have been reported in schizophrenia, but it is not known if these predate psychosis.

Hundred and forty-six subjects at high genetic risk of schizophrenia, 34 first episode of schizophrenia patients (SZ) and 36 healthy controls were scanned and clinically assessed. Utilising the classification system proposed by Chiavaras, we categorised OFC patterns and compared their distribution between the groups, as well as between those high risk subjects who did, and did not develop schizophrenia. The relationship between OFC pattern and schizotypy was explored in high risk subjects.

We refined Chiavaras’ classification system, with the identification of a previously unreported variant of OFC surface structure. There were significant differences in distribution of OFC patterns between high risk subjects who did or did not develop schizophrenia as well as between the first episode of schizophrenia group and healthy controls. Within the high risk group, possession of OFC Type III was associated with higher ratings on the Structured Inventory for Schizotypy (SIS) psychotic factor.

Our results suggest that OFC Type III is associated with psychotic features before the development of schizophrenia. Characterisation of OFC morphology may have a role in the identification of those at greatest risk of developing schizophrenia.

Borderline personality disorder (BPD) presents with symptoms across different domains, whose neurobiology is poorly understood.

We applied voxel-based morphometry on high-resolution magnetic resonance imaging scans of 19 female BPD patients and 50 matched female controls.

Group comparison showed bilateral orbitofrontal gray matter loss in patients, but no significant changes in the hippocampus. Voxel-wise correlation of gray matter with symptom severity scores from the Borderline Symptom List (BSL-95) showed overall negative correlation in bilateral prefrontal, right inferior temporal/fusiform and occipital cortices, and left thalamus. Significant (negative) correlations with BSL-95 subscores within the patient cohort linked autoaggression to left lateral prefrontal and insular cortices, right inferior temporal/temporal pole, and right orbital cortex; dysthymia/dysphoria to right orbitofrontal cortex; self-perception to left postcentral, bilateral inferior/middle temporal, right orbitofrontal, and occipital cortices. Schema therapy-based Young Schema Questionnaire (YSQ-S2) scores of early maladaptive schemas on emotional deprivation were linked to left medial temporal lobe gray matter reductions.

Our results confirm orbitofrontal structural deficits in BPD, while providing a framework and preliminary findings on identifying structural correlates of symptom dimensions in BPD, especially with dorsolateral and orbitofrontal cortices.

Cognitive–behavioral therapy (CBT) is thought to be useful for chronic pain, with the pathology of the latter being closely associated with cognitive–emotional components. However, there are few resting-state functional magnetic resonance imaging (R-fMRI) studies. We used the independent component analysis method to examine neural changes after CBT and to assess whether brain regions predict treatment response.

We performed R-fMRI on a group of 29 chronic pain (somatoform pain disorder) patients and 30 age-matched healthy controls (T1). Patients were enrolled in a weekly 12-session group CBT (T2). We assessed selected regions of interest that exhibited differences in intrinsic connectivity network (ICN) connectivity strength between the patients and controls at T1, and compared T1 and T2. We also examined the correlations between treatment effects and rs-fMRI data.

Abnormal ICN connectivity of the orbitofrontal cortex (OFC) and inferior parietal lobule within the dorsal attention network (DAN) and of the paracentral lobule within the sensorimotor network in patients with chronic pain normalized after CBT. Higher ICN connectivity strength in the OFC indicated greater improvements in pain intensity. Furthermore, ICN connectivity strength in the dorsal posterior cingulate cortex (PCC) within the DAN at T1 was negatively correlated with CBT-related clinical improvements.

We conclude that the OFC is crucial for CBT-related improvement of pain intensity, and that the dorsal PCC activation at pretreatment also plays an important role in improvement of clinical symptoms via CBT.

Obsessive–compulsive disorder (OCD) has been associated with abnormal cognitive and emotional functions and these dysfunctions may be dependent on the disruption of dynamic interactions within neuronal circuits associated with emotion regulation. Although several studies have shown the aberrant cognitive–affective processing in OCD patients, little is known about how to characterize effective connectivity of the disrupted neural interactions. In the present study, we applied effective connectivity analysis using dynamic causal modeling to explore the disturbed neural interactions in OCD patients.

A total of 20 patients and 21 matched healthy controls performed a delayed-response working memory task under emotional or non-emotional distraction while undergoing functional magnetic resonance imaging.

During the delay interval under negative emotional distraction, both groups showed similar patterns of activations in the amygdala. However, under negative emotional distraction, the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) exhibited significant differences between groups. Bayesian model averaging indicated that the connection from the DLPFC to the OFC was negatively modulated by negative emotional distraction in patients, when compared with healthy controls (p < 0.05, Bonferroni-corrected).

Exaggerated recruitment of the DLPFC may induce the reduction of top-down prefrontal control input over the OFC, leading to abnormal cortico-cortical interaction. This disrupted cortico-cortical interaction under negative emotional distraction may be responsible for dysfunctions of cognitive and emotional processing in OCD patients and may be a component of the pathophysiology associated with OCD.

Although both emotion and response inhibition are thought to be important in attention-deficit/hyperactivity disorder (ADHD), little is known about the neural mechanisms that underlie the interaction between these two processes in patients with this disorder. This study aimed at examining how emotional contexts affect inhibitory control in children with ADHD.

A total of 24 ADHD children and 24 healthy comparison subjects performed a modified go/no-go task during three different emotionally laden contexts: negative, neutral and positive. To explore the timing and the underlying neural substrates of emotion-modulated response inhibition, event-related potentials were measured and further analysed both at the scalp and at the voxel level.

Patients with ADHD showed greater activation of inhibition-related neural mechanisms (i.e. no-go P3 amplitudes and orbitofrontal cortex activity) to maintain a similar level of performance as healthy comparison subjects, especially during the emotionally arousing contexts (negative and positive).

This study provides plausible neural mechanisms for the difficulty that ADHD children have in controlling their behaviour in highly emotional situations. Such emotional contexts might increase the need for top-down inhibitory control and put ADHD children at greater risk for impulsive behaviours and emotional dysregulation.

Cognitive behavioural therapy (CBT) is a successful treatment of obsessive compulsive disorder (OCD). It is known to induce changes in cerebral metabolism; however, the dynamics of these changes and their relation to clinical change remain largely unknown, precluding the identification of individualized response biomarkers.

In order to study the dynamics of treatment response, we performed systematic clinical and functional magnetic resonance imaging (fMRI) evaluation of 35 OCD patients immediately before a 3-month course of CBT, halfway through and at its end, as well as 6 months after. To sensitize fMRI probing, we used an original exposure task using neutral, generic and personalized obsession-inducing images.

As expected, CBT produced a significant improvement in OCD. This improvement was continuous over the course of the therapy; therefore, outcome could be predicted by response at mid-therapy (r2 = 0.67, p < 0.001). Haemodynamic response to the task was located in the anterior cingulate and orbitofrontal cortices and was stronger during exposure to personalized obsession-inducing images. In addition, both the anxiety ratings and the haemodynamic response to the obsession-inducing images in the anterior cingulate and the left but not the right orbitofrontal clusters decreased with symptom improvement. Interestingly, haemodynamic activity continued to decrease after stabilization of clinical symptoms.

Using an innovative and highly sensitive exposure paradigm in fMRI, we showed that clinical and haemodynamic phenotypes have similar time courses during CBT. Our results, which suggest that the initial CBT sessions are crucial, prompt us to investigate the anatomo-functional modifications underlying the very first weeks of the therapy.