David Rosenbaum

Aberrant functional connectivity in depression as an index of state and trait rumination

Depression has been shown to be related to a variety of aberrant brain functions and structures. Particularly the investigation of alterations in functional connectivity (FC) in major depressive disorder (MDD) has been a promising endeavor, since a better understanding of pathological brain networks may foster our understanding of the disease. However, the underling mechanisms of aberrant FC in MDD are largely unclear. Using functional near-infrared spectroscopy (fNIRS) we investigated FC in the cortical parts of the default mode network (DMN) during resting-state in patients with current MDD. Additionally, we used qualitative and quantitative measures of psychological processes (e.g., state/trait rumination, mind-wandering) to investigate their contribution to differences in FC between depressed and non-depressed subjects. Our results indicate that 40% of the patients report spontaneous rumination during resting-state. Depressed subjects showed reduced FC in parts of the DMN compared to healthy controls. This finding was linked to the process of state/trait rumination. While rumination was negatively correlated with FC in the cortical parts of the DMN, mind-wandering showed positive associations.

Functional co-activation within the prefrontal cortex supports the maintenance of behavioural performance in fear-relevant situations before an iTBS modulated virtual reality challenge in participants with spider phobia

A number of studies/meta-analyses reported moderate antidepressant effects of activating repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC). Regarding the treatment of anxiety, study outcomes are inconsistent, probably because of the heterogenity of anxiety disorders/study designs. To specifically evaluate the impact of rTMS on emotion regulation in fear-relevant situations we applied a sham-controlled activating protocol (intermittent Theta Burst Stimulation/iTBS) over the left PFC (F3) succeeded by a virtual reality (VR) challenge in n=41 participants with spider phobia and n=42 controls. Prior to/after iTBS and following VR prefrontal activation was assessed by functional near-infrared spectroscopy during an emotional Stroop paradigm. Performance (reaction times/error rates) was evaluated. Stimuli were rated regarding valence/arousal at both measurements. We found diminished activation in the left inferior frontal gyrus (IFG) of participants with spider phobia compared to controls, particularly elicited by emotionally-irrelevant words. Simultaneously, a functional connectivity analysis showed increased co-activation between the left IFG and the contra-lateral hemisphere. Behavioural performance was unimpaired. After iTBS/VR no significant differences in cortical activation between the phobic and control group remained. However, verum-iTBS did not cause an additional augmentation. We interpreted our results in terms of a prefrontal network which gets activated by emotionally-relevant stimuli and supports the maintenance of adequate behavioural reactions. The missing add-on effects of iTBS might be due to a ceiling effect of VR, thereby supporting its potential during exposure therapy. Concurrently, it implies that the efficient application of iTBS in the context of emotion regulation still needs to be studied further.

Stress-related dysfunction of the right inferior frontal cortex in high ruminators: An fNIRS study

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. Methods 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. Results 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. Conclusions 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.

Functionally disconnected: A look at how study design influences neurofeedback data and mechanisms in attention-deficit/hyperactivity disorder

Neurofeedback (NF) is a form of behavioral therapy used to treat e.g. attention-deficit/hyperactivity disorder (ADHD). Briefly, subjects are fed-back a putatively dysfunctional parameter of their brain activity in real time and must learn to control it in a suggested direction. NF protocols for ADHD have been used in practice for decades, though no clear standards on NF design have been implemented. Furthermore, studies often present only data from the general outcome of the NF treatment and do not look at how exactly the NF paradigm affects brain functionality, or what exactly the NF is training. The current study is two-fold: firstly, we look at how the functional connectivity (FC) patterns within key networks associated with ADHD differ between rests, feedback trials, success and failure in a complete functional near-infrared spectroscopy-based NF experiment on adults with ADHD. Secondly, due to methodological concerns discovered during the analysis of our data, we address important considerations in the design of NF that are often ignored in protocols being used widely in therapy and research today. In particular, we examine the common average reference and its impact on network activity as well as the importance of balancing the randomization in a design. Finally, we discuss how these methodological considerations may have influenced our FC results.

Neurophysiological correlates of the attention training technique: A component study

In the current study, we investigate the neuronal correlates of the Attention Training Technique (ATT), a psychotherapeutic intervention used in metacognitive therapy to enhance flexible cognitive control and ameliorate rumination. We adapted the ATT in a neuroscientific attention paradigm in order to investigate the effects of its components: selective attention, attention switching and divided attention in comparison to a control task. Functional near-infrared spectroscopy was used to measure changes in blood oxygenation of fronto-lateral and parietal cortical areas. Furthermore, subjects rated their task performance, effort and attention drifts in each task condition. We observed increased blood oxygenation in the right inferior frontal gyrus, right dorsolateral prefrontal cortex and superior parietal lobule during the ATT conditions in comparison to the control condition. Additionally, subjective effort was associated with blood oxygenation in the right inferior prefrontal cortex. Our results are consistent with the theoretical underpinnings of the ATT suggesting that the ATTs mechanism of change lies in the training of areas of the cognitive control network and dorsal attention network. Aberrant functioning of both networks has been shown to be related to depression and rumination.

Cortical hemodynamic changes during the Trier Social Stress Test: An fNIRS study

&NA; The study of the stress response has been of great interest in the last decades due to its relationship to physical and mental health. Along with the technological progress in the neurosciences, different methods of stress induction have been developed for the special requirements regarding the acquisition of neuroimaging data. However, these paradigms often differ from ecologically valid stress inductions such as the Trier Social Stress Test (TSST) in substantial ways. In the study at hand, we used the rather robust optical imaging method of functional Near‐infrared Spectroscopy (fNIRS) to assess brain activation during the TSST and two non‐stressful control conditions. Additionally, we measured other stress parameters including the cortisol response and subjective stress ratings. As expected we found significant increases in subjective and physiological stress measures during the TSST in comparison to the baseline and control conditions. We found higher activation in parts of the cognitive control network (CCN) and dorsal attention network (DAN) – comprising the dorsolateral prefrontal cortex, the inferior frontal gyrus and superior parietal cortex – during the performance of the TSST in comparison to the control conditions. Further, calculation errors during the TSST as well as subjective and physiological stress parameters correlated significantly with the activation in the CCN. Our study confirms the validity of previous neuroimaging data obtained from adapted stress procedures by providing cortical activation data during a classical stress induction paradigm (i.e., the TSST) for the first time. HighlightsCortical hemodynamic reactions to social stress were assessed in the ecological valid environment of the Trier Social Stress Test (TSST).During the TSST increases in oxygenated blood were observed in parts of the cognitive control network and dorsal attention network.Cortical activation correlated with performance during the TSST and stress indices.Our study confirms the validity of previous neuroimaging data obtained from adapted stress procedures.

Forgiveness and cognitive control – Provoking revenge via theta-burst-stimulation of the DLPFC

&NA; In order to act in a socially acceptable way, the ability to forgive is indispensable. It has been suggested that forgiveness relies on cognitive control, more specifically inhibition. In this study, we combined an ultimatum game (UG) and a dictator game (DG) with inhibitory, continuous theta‐burst stimulation (cTBS; verum vs. placebo, within‐subjects design) of the right dorsolateral prefrontal cortex (DLPFC) to investigate the effect of reduced cognitive control on forgiveness. To this end, participants played an UG against fair and unfair opponents, where they had to accept or reject (fair and unfair) monetary offers, and then received a cTBS prior to playing a DG against the same opponents with reversed roles. The participants now had the possibility to forgive the unfair opponents (allocation of a fair amount of money) or to take revenge whereby the cTBS effects were assessed with functional near‐infrared spectroscopy. Following verum cTBS, participants allocated significantly less money to their unfair opponents than in the placebo cTBS condition. Also, reaction times (RTs) differed significantly between verum and placebo cTBS for unfair opponents (higher RTs following verum stimulation) but not for fair opponents. These results strongly indicate that cognitive control is a fundamental requirement for overcoming unwanted emotional responses.