The influence of anterior cingulate GABA+ and glutamate on emotion regulation and reactivity in adolescents and adults.

During adolescence, emotion regulation and reactivity are still developing and are in many ways qualitatively different from adulthood. However, the neurobiological processes underpinning these differences remain poorly understood, including the role of maturing neurotransmitter systems. We combined magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (dACC) and self-reported emotion regulation and reactivity in a sample of typically developed adolescents (n = 37; 13-16 years) and adults (n = 39; 30-40 years), and found that adolescents had higher levels of glutamate to total creatine (tCr) ratio in the dACC than adults. A glutamate Í age group interaction indicated a differential relation between dACC glutamate levels and emotion regulation in adolescents and adults, and within-group follow-up analyses showed that higher levels of glutamate/tCr were related to worse emotion regulation skills in adolescents. We found no age-group differences in gamma-aminobutyric acid+macromolecules (GABA+) levels; however, emotion reactivity was positively related to GABA+/tCr in the adult group, but not in the adolescent group. The results demonstrate that there are developmental changes in the concentration of glutamate, but not GABA+, within the dACC from adolescence to adulthood, in accordance with previous findings indicating earlier maturation of the GABA-ergic than the glutamatergic system. Functionally, glutamate and GABA+ are positively related to emotion regulation and reactivity, respectively, in the mature brain. In the adolescent brain, however, glutamate is negatively related to emotion regulation, and GABA+ is not related to emotion reactivity. The findings are consistent with synaptic pruning of glutamatergic synapses from adolescence to adulthood and highlight the importance of brain maturational processes underlying age-related differences in emotion processing.

A Japanese translation of the Swedish Universities Scales of Personality.

Background: The Swedish Universities Scales of Personality (SSP) is a personality measurement tool with a short test battery of high psychometric quality, previously not availiable in Japanese. Methods: We translated the SSP into Japanese and administered it to 103 Japanese nationals. For 11 of the 13 SSP scales in the Japanese version of the SSP (SSP-J11), the Cronbach's alpha ranged from 0.50 to 0.82 with good internal scale reliability. Results: A principal factor analysis replicated the previous work by identifying the same three principal dimensions of Neuroticism, Aggression, and Extraversion factors. Conclusion: The resulting three-factor SSP-J11 shows acceptable reliability and should provide informative insights about personality traits in research and clinical practice in a Japanese context.

Directed causal effect with PCMCI in hyperscanning EEG time series.

Social activities are likely to cause effects or reactivity in the brains of the people involved in collaborative social situations. This study assesses a new method, Tigramite, for time domain analysis of directed causality between the prefrontal cortex (PFC) of persons in such situations. An experimental situation using hyperscanning EEG was applied while individuals led and followed each other in finger-tapping rhythms. This structured task has a long duration and a high likelihood of inter-brain causal reactions in the prefrontal cortices. Tigramite is a graph-based causal discovery method to identify directed causal relationships in observational time series. Tigramite was used to analyze directed causal connections within and between the PFC. Significantly directed causality within and between brains could be detected during the social interactions. This is the first empirical evidence the Tigramite can reveal inter- and intra-brain-directed causal effects in hyperscanning EEG time series. The findings are promising for further studies of causality in neural networks during social activities using Tigramite on EEG in the time domain.

Blinding integrity of dorsomedial prefrontal intermittent theta burst stimulation in depression

Background: The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) is partly placebo, making blinding integrity important. Blinding of high-frequency rTMS and intermittent theta burst stimulation (iTBS) has been reported as successful at study end. However, blinding integrity at study start is rarely reported. The aim of this study was to investigate blinding integrity during a treatment course of iTBS over the dorsomedial prefrontal cortex (DMPFC) in depression. Methods: Forty-nine patients with depression from a double-blind-designed randomized controlled trial (NCT02905604) were included. Patients received either active or sham iTBS over the DMPFC with a placebo coil. The sham group received iTBS-synchronized transcutaneous electrical nerve stimulation. Results: After one session, 74% of participants were able to correctly guess their treatment allocation. This was above chance level (p = 0.001). The percentage dropped to 64% and 56% after the fifth and last sessions. Belonging to the active group influenced the choice to guess “active” (odds ratio: 11.7, 95% CI 2.5–53.7). A higher treatment intensity of the sham treatment increased the probability to guess “active”, but pain did not influence the choice. Conclusions: Blinding integrity in iTBS trials must be investigated at study start to avoid uncontrolled confounding. Better sham methods are needed. (AU)

Triple network model of brain connectivity changes related to adverse mood effects in an oral contraceptive placebo-controlled trial.

Combined oral contraceptives (COC) are among the most commonly used contraceptive methods worldwide, and mood side effects are the major reason for discontinuation of treatment. We here investigate the directed connectivity patterns associated with the mood side effects of an androgenic COC in a double-blind randomized, placebo-controlled trial in women with a history of affective COC side effects (n = 34). We used spectral dynamic causal modeling on a triple network model consisting of the default mode network (DMN), salience network (SN) and executive control network (ECN). Within this framework, we assessed the treatment-related changes in directed connectivity associated with adverse mood side effects. Overall, during COC use, we found a pattern of enhanced connectivity within the DMN and decreased connectivity within the ECN. The dorsal anterior cingulate cortex (SN) mediates an increased recruitment of the DMN by the ECN during treatment. Mood lability was the most prominent COC-induced symptom and also arose as the side effect most consistently related to connectivity changes. Connections that were related to increased mood lability showed increased connectivity during COC treatment, while connections that were related to decreased mood lability showed decreased connectivity during COC treatment. Among these, the connections with the highest effect size could also predict the participants' treatment group above chance.

Blinding integrity of dorsomedial prefrontal intermittent theta burst stimulation in depression.

Background: The antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) is partly placebo, making blinding integrity important. Blinding of high-frequency rTMS and intermittent theta burst stimulation (iTBS) has been reported as successful at study end. However, blinding integrity at study start is rarely reported. The aim of this study was to investigate blinding integrity during a treatment course of iTBS over the dorsomedial prefrontal cortex (DMPFC) in depression. Methods: Forty-nine patients with depression from a double-blind-designed randomized controlled trial (NCT02905604) were included. Patients received either active or sham iTBS over the DMPFC with a placebo coil. The sham group received iTBS-synchronized transcutaneous electrical nerve stimulation. Results: After one session, 74% of participants were able to correctly guess their treatment allocation. This was above chance level (p = 0.001). The percentage dropped to 64% and 56% after the fifth and last sessions. Belonging to the active group influenced the choice to guess "active" (odds ratio: 11.7, 95% CI 2.5-53.7). A higher treatment intensity of the sham treatment increased the probability to guess "active", but pain did not influence the choice. Conclusions: Blinding integrity in iTBS trials must be investigated at study start to avoid uncontrolled confounding. Better sham methods are needed.

Dorsal anterior cingulate cortex activity during cognitive challenge in social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) is associated with aberrant emotional information processing while little is known about non-emotional cognitive processing biases. The dorsal anterior cingulate cortex (dACC) has been implicated in SAD neuropathology and is activated both by emotional and non-affective cognitive challenges like the Multisource Interference Task (MSIT). METHODS: Here, we used fMRI to compare dACC activity and test performance during MSIT in 69 SAD patients and 38 healthy controls. In addition to patient-control comparisons, we examined whether neural activity in the dACC correlated with social anxiety, trait anxiety or depression levels. RESULTS: The MSIT activated the dACC as expected but with no differences in task performance or neural reactivity between SAD patients and controls. There were no significant correlations between dACC activity and social or trait anxiety symptom severity. In patients, there was a significant negative correlation between dACC activity and depressive symptoms. CONCLUSIONS: In absence of affective challenge, we found no disorder-related cognitive profile in SAD patients since neither MSIT task performance nor dACC neural activity deviated in patients relative to controls.

Pupil dilation during negative prediction errors is related to brain choline concentration and depressive symptoms in adolescents.

Depressive symptoms are associated with altered pupillary responses during learning and reward prediction as well as with changes in neurometabolite levels, including brain concentrations of choline, glutamate and gamma-aminobutyric acid (GABA). However, the full link between depressive symptoms, reward-learning-related pupillary responses and neurometabolites is yet to be established as these constructs have not been assessed in the same individuals. The present pilot study, investigated these relations in a sample of 24 adolescents aged 13 years. Participants completed the Revised Child Anxiety and Depression Scale (RCADS) and underwent a reward learning task while measuring pupil dilation and a single voxel dorsal anterior cingulate cortex (dACC) MEGA-PRESS magnetic resonance spectroscopy scan assessing choline, glutamate and GABA concentrations. Pupil dilation was related to prediction errors (PE) during learning, which was captured by a prediction error-weighted pupil dilation response index (PE-PDR) for each individual. Higher PE-PDR scores, indicating larger pupil dilations to negative prediction errors, were related to lower depressive symptoms and lower dACC choline concentrations. Dorsal ACC choline was positively associated with depressive symptoms, whereas glutamate and GABA were not related to PE-PDR or depressive symptoms. The findings support notions of cholinergic involvement in depressive symptoms and cholinergic influence on reward-related pupillary response, suggesting that pupillary responses to negative prediction errors may hold promise as a biomarker of depressive states.

Intercorrelation of physiological seizure parameters and hormonal changes in electroconvulsive therapy.

OBJECTIVE: Physiological parameters that predict electroconvulsive therapy (ECT) effectiveness may reflect propagation of the induced epileptic seizure. As an indication of seizure propagation to the diencephalon, we here examined the correlation between prolactin increase after ECT and clinical seizure evaluation parameters, focusing on peak heart rate. As a proxy for peripheral endocrine stress response, we examined the correlation to postictal cortisol increase. METHODS: Participants were consecutively recruited from clinical ECT patients (n = 131, age 18-85 years). The first ECT session in a series was examined. For each participant, blood serum concentrations of prolactin and cortisol were measured immediately before and within 30 min after the seizure. Physiological parameters were extracted from clinical records: peak heart rate (HR) during seizure, electroencephalography (EEG) seizure duration, and motor seizure duration. Correlations were calculated using non-parametric tests. RESULTS: Serum prolactin increased after ECT and correlated with peak HR, EEG seizure duration, and motor seizure duration. Peak HR during seizure also correlated positively with both EEG seizure duration and motor seizure duration. Correlations were unaffected by age, sex, baseline prolactin levels, antipsychotics, or beta-blocking agents. Serum cortisol increased after ECT but did not correlate with the seizure evaluation parameters, nor with prolactin concentrations. CONCLUSIONS: Our findings of a positive correlation between peak HR and prolactin that was independent from the peripheral endocrine stress response might be in line with the idea that tachycardia during ECT seizures reflects seizure propagation to the diencephalon. This supports the practice of monitoring cardiovascular response for ECT seizure evaluation.

Serotonin and dopamine transporter availability in social anxiety disorder after combined treatment with escitalopram and cognitive-behavioral therapy.

Selective serotonin reuptake inhibitors (SSRIs) and internet-based cognitive behavioral therapy (ICBT) are recommended treatments of social anxiety disorder (SAD), and often combined, but their effects on monoaminergic signaling are not well understood. In this multi-tracer positron emission tomography (PET) study, 24 patients with SAD were randomized to treatment with escitalopram+ICBT or placebo+ICBT under double-blind conditions. Before and after 9 weeks of treatment, patients were examined with positron emission tomography and the radioligands [11C]DASB and [11C]PE2I, probing the serotonin (SERT) and dopamine (DAT) transporter proteins respectively. Both treatment combinations resulted in significant improvement as measured by the Liebowitz Social Anxiety Scale (LSAS). At baseline, SERT-DAT co-expression was high and, in the putamen and thalamus, co-expression showed positive associations with symptom severity. SERT-DAT co-expression was also predictive of treatment success, but predictor-outcome associations differed in direction between the treatments. After treatment, average SERT occupancy in the SSRI + ICBT group was >80%, with positive associations between symptom improvement and occupancy in the nucleus accumbens, putamen and anterior cingulate cortex. Following placebo+ICBT, SERT binding increased in the raphe nuclei. DAT binding increased in both groups in limbic and striatal areas, but relations with symptom improvement differed, being negative for SSRI + ICBT and positive for placebo + ICBT. Thus, serotonin-dopamine transporter co-expression exerts influence on symptom severity and remission rate in the treatment of social anxiety disorder. However, the monoamine transporters are modulated in dissimilar ways when cognitive-behavioral treatment is given concomitantly with either SSRI-medication or pill placebo.

Modulation of dorsolateral prefrontal cortex functional connectivity after intermittent theta-burst stimulation in depression: Combining findings from fNIRS and fMRI.

BACKGROUND: Resting-state functional magnetic resonance imaging (fMRI) can assess modulation of functional connectivity networks following repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. Functional near-infrared spectroscopy (fNIRS) is well suited for the concurrent application during rTMS treatment sessions to capture immediate blood oxygenation (oxy-Hb) effects, however limited in spatial resolution. OBJECTIVE: To understand the network effects behind such a prefrontal fNIRS response during rTMS, and to test whether the fNIRS signal may be predictive of treatment response, we linked data from fNIRS and fMRI within a clinical intervention study. METHODS: 42 patients with ongoing depression were recruited and randomized to receive active or sham intermittent theta-burst stimulation (iTBS) over the dorsomedial prefrontal cortex (dmPFC) twice daily for ten days at target intensity. Oxy-Hb was recorded with fNIRS during the first, fifth, and final day of iTBS, with the probe holders located laterally to the TMS coil over regions corresponding to the left and right dorsolateral prefrontal cortex (dlPFC). Resting-state fMRI scanning was performed before and after the whole iTBS treatment course. Functional connectivity analyses were then performed using dlPFC seeds from parcels of a brain atlas showing most overlap with the fNIRS probe locations during treatment. RESULTS: After active iTBS, left dlPFC-connectivity to the right insula/operculum was reduced compared to sham. The left insula showed a connectivity reduction to the left dlPFC that correlated with an improvement in symptoms. In addition, the posterior parietal cortex showed a connectivity reduction to the left dlPFC that correlated with the fNIRS signal following active iTBS. Finally, the fNIRS oxy-Hb signal from the left dlPFC-seed during the first treatment day was predictive of dlPFC-connectivity change to precentral and temporal cortex regions. CONCLUSION: By linking findings from these two different methods, this study suggests that changes within both the salience network and the central executive network affect the fNIRS response to iTBS.

An fMRI-study of leading and following using rhythmic tapping.

Leading and following is about synchronizing and joining actions in accordance with the differences that the leader and follower roles provide. The neural reactivity representing these roles was measured in an explorative fMRI-study, where two persons lead and followed each other in finger tapping using simple, individual, pre-learnt rhythms. All participants acted both as leader and follower. Neural reactivity for both lead and follow related to social awareness and adaptation distributed over the lateral STG, STS and TPJ. Reactivity for follow contrasted with lead mostly reflected sensorimotor and rhythmic processing in cerebellum IV, V, somatosensory cortex and SMA. During leading, as opposed to following, neural reactivity was observed in the insula and bilaterally in the superior temporal gyrus, pointing toward empathy, sharing of feelings, temporal coding and social engagement. Areas for continuous adaptation, in the posterior cerebellum and Rolandic operculum, were activated during both leading and following. This study indicated mutual adaptation of leader and follower during tapping and that the roles gave rise to largely similar neuronal reactivity. The differences between the roles indicated that leading was more socially focused and following had more motoric- and temporally related neural reactivity.

Postpartum Gray Matter Changes in the Auditory Cortex.

After giving birth, a mother's brain undergoes functional adaptations fostering the ability to properly respond to the needs of her newborn. Tuning into and understanding her baby's crying is among the top skills required and executed in the early stages of motherhood. However, surprisingly little is known about potential changes in the anatomy of the maternal auditory cortex. Therefore, in this longitudinal study, we compared the brains of 14 healthy women between immediate postpartum (within 1-2 days of childbirth) and late postpartum (at 4-6 weeks after childbirth), focusing on areas of the primary, secondary, and higher auditory cortex. We observed significant volume increases within all auditory regions and subregions examined, which might reflect rapid adaptations of the mother's brain in relation to reliably interpreting her newborn's cries. There was also a trend for a larger postpartum increase within right-hemispheric regions compared to left-hemispheric regions that might be specifically linked to the ability to discern the pitch, sound, and volume of a baby's crying. Follow-up research is warranted to replicate these findings and evaluate their current interpretation.

Expectancy effects on serotonin and dopamine transporters during SSRI treatment of social anxiety disorder: a randomized clinical trial.

It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [11C]DASB and [11C]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response.

Unchanged Cognitive Performance and Concurrent Prefrontal Blood Oxygenation After Accelerated Intermittent Theta-Burst Stimulation in Depression: A Sham-Controlled Study.

Aim: Intermittent theta-burst stimulation (iTBS) delivered over the dorsomedial prefrontal cortex (DMPFC) has shown promise as a treatment for anhedonia and amotivation in patients with depression. Here, we investigated whether this protocol modulates cognitive performance and concurrent prefrontal blood oxygenation. We also examined whether depressed patients exhibit cognitive dysfunction and prefrontal hypoactivity at baseline compared to healthy controls. Methods: This sham-controlled study comprises 52 patients randomized to either active or sham accelerated iTBS over the DMPFC (applied twice daily) for 10 consecutive treatment days, and 55 healthy controls. Cognitive performance was assessed at baseline and once again 4 weeks later using a cognitive test battery targeting attention, inhibitory control, and numerical, verbal, and visual working memory. Concurrent prefrontal oxygenated hemoglobin (oxy-Hb) was captured with functional near-infrared spectroscopy. Results: Active iTBS over DMPFC did not affect cognitive performance or concurrent oxy-Hb change compared to sham iTBS in patients with depression. Compared to controls, patients at baseline showed impaired performance in the Trail Making Test, the Rey Auditory Verbal Learning Test, the Animal Naming Test, and the Digit Symbol Substitution Test, however no difference in prefrontal oxy-Hb was observed. Conclusion: Patients with treatment-resistant depression displayed cognitive deficits, however without prefrontal hypoactivity, compared to healthy controls at baseline. iTBS treatment did not alter cognitive performance, nor concurrent prefrontal blood oxygenation, in patients. Taken together, iTBS can likely be considered a cognitively safe treatment option in this sample of patients.

Inhibitory and excitatory neurotransmitter systems in depressed and healthy: A positron emission tomography and magnetic resonance spectroscopy study.

The Gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems are implicated in depression. While previous studies found reduced GABA levels, and a tendency towards reduced Glu, using proton (1H) magnetic resonance spectroscopy (1H-MRS), little is known about GABAA receptor availability in depression. Here, the aim was to characterize GABA and Glu-levels in dorsal anterior cingulate cortex (dACC), whole-brain GABAA availability, and their relationship in patients with depression compared to healthy controls. Forty-two patients and 45 controls underwent 1H-MRS using a MEGA-PRESS sequence to quantify dACC GABA+ and Glu (contrasted against creatine [Cr]). Immediately preceding the 1H-MRS, a subsample of 28 patients and 15 controls underwent positron emission tomography (PET) with [11C]Flumazenil to assess whole-brain GABAA receptor availability. There were no differences in dACC GABA+/Cr or Glu/Cr ratios between patients and controls. The same was true for whole-brain GABAA receptor availability. However, there was a significant negative relationship between GABA+/Cr ratio and receptor availability in ACC, in a whole-brain voxel-wise analysis across patients and controls, controlling for group or depressive symptoms. This relatively large study did not support the GABA-deficit hypothesis in depression, but shed light on GABA-system functioning, suggesting a balance between neurotransmitter concentration and receptor availability in dACC.

Significant increases of the amygdala between immediate and late postpartum: Pronounced effects within the superficial subregion.

Research exploring the underlying neuroanatomical correlates of early motherhood seems to suggest that the period after giving birth is marked by tissue increases in the mother's brain. While some studies point to the amygdala as one of the areas undergoing postpartum changes, existing analyses did not discriminate between the different subregions of this functionally heterogeneous structure. Thus, to further extend this understudied field of research and to better understand the potential role of the amygdala when transitioning to motherhood, we applied an advanced region-of-interest technique that enabled us to analyze the amygdala as a whole as well as its different subareas, specifically the left and right centromedian (CM), laterobasal (LB), and superficial (SF) regions. Comparing the brains of 14 healthy women between immediate postpartum (within 1-2 days of childbirth) and late postpartum (at 4-6 weeks after childbirth), we revealed increases of the amygdala. However, effects manifested differentially across subareas, with particularly strong effects for the SF region, moderate effects for the CM region, and no effects for the LB region. These findings might reflect region-specific adaptations of the mother's brain tuning into the distinct and ever-changing needs of a newborn, either as a cause for it or as a consequence thereof.

Gray matter increases within subregions of the hippocampal complex after pregnancy.

Neuroimaging findings - although still relatively sparse in the realm of postpartum research - suggest significant tissue increases within the hippocampus or its vicinity after giving birth. Given that the hippocampus is not a homogenous structure, effects may manifest differently across the hippocampal complex. Thus, the goal of this study was to determine the presence, magnitude, and direction of postpartum gray matter changes within five hippocampal subregions, specifically the dentate gyrus, the subiculum, and the subfields of the cornu ammonis (CA1, CA2 and CA3). For this purpose, we analyzed brain images of 14 healthy women acquired at immediate postpartum (within 1-2 days of childbirth) and at late postpartum (at 4-6 weeks after childbirth). Changes in hippocampal gray matter between both time points were calculated for all subregions as well as the hippocampal complex as a whole by integrating imaging-based intensity information with microscopically defined cytoarchitectonic probabilities. Hippocampal gray matter increased significantly within the right subiculum, right CA2, and right CA3. These findings may suggest that brain tissue lost during pregnancy is being restored after giving birth, perhaps even expanded compared to before pregnancy. Possible events on the microanatomical level include dendritic branching as well as the generation of new synapses, glia cells, and blood vessels. Altogether, the outcomes of our study confirm that hippocampal gray matter increases in the female human brain after giving birth, with differential effects across the hippocampal complex.

Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia.

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by 18F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

Modulation of the prefrontal blood oxygenation response to intermittent theta-burst stimulation in depression: A sham-controlled study with functional near-infrared spectroscopy.

OBJECTIVE: To better understand the neural mechanisms behind the effect of intermittent theta-burst stimulation (iTBS), we investigated how the prefrontal blood oxygenation response measured by changes in oxygenated haemoglobin (oxy-Hb) was modulated during a sham-controlled iTBS treatment course, and whether this was related to depressive symptom change. METHODS: In this randomised, double-blind study, patients with ongoing treatment-resistant depression received either active (n = 18) or sham (n = 21) iTBS over the dorsomedial prefrontal cortex for ten to fifteen days with two sessions daily. Event-related functional near-infrared spectroscopy (fNIRS) was measured during each iTBS train, and resting-state oxy-Hb was compared before and after each iTBS session at the first, fifth, and last treatment day. RESULTS: Patients receiving active iTBS had an increase of the event-related oxy-Hb response compared to the sham group on the fifth (bilateral prefrontal cortices p < .001) and last (left prefrontal p = .007, right prefrontal p = .025) treatment day. Resting-state analysis showed suppressed oxy-Hb change in active iTBS compared to sham iTBS on the last treatment day (p = .024). Oxy-Hb change was unrelated to depressive symptom change (p = .474). CONCLUSIONS: This study describes a modulation of the blood oxygenation response over the prefrontal cortex that was built up during the course of active iTBS treatment in depression.