Listening to music during intranasal (es)ketamine therapy in patients with treatment-resistant depression correlates with better tolerability and reduced anxiety.

Background: Although the effectiveness of (es)ketamine for therapy-resistant depression (TRD) has been established, potential treatment-limiting factors include side effects like dissociation, anxiety, or elevated blood pressure. Music can reduce stress and negative emotions as anxiety. This study aimed to investigate the impact of listening to music during intranasal (es)ketamine administration on both tolerability and efficacy. Methods: Records of 494 sessions (of 37 patients) with intranasal (es)ketamine administration, each containing data of blood pressure measurements, DSS-IV (dissociation symptoms scale-IV), anxiety and euphoria analogue scale, MADRS (Montgomery-Åsberg Depression Rating Scale) and BDI (Beck's Depression Inventory) were evaluated. Results: The between-group analysis, comparing participants who listened to music with those who did not, revealed significant differences in the administered dose (p-value: 0.003, mean: 131.5 mg with music vs. 116.7 mg without music), scores on the DSS Item 1 (p-value: 0.005, mean: 3 points vs. 2.4 points), levels of anxiety (p-value: <0.001, mean: 0.4 points vs. 1.4 points), and measurements of maximal systolic blood pressure after administration (p-value: 0.017, mean: 137.9 mmHg vs. 140.3 mmHg). Listening to music had no impact on the MARDS-change score between the sessions. Limitations: Key limitations include a non-randomized naturalistic design and the non-standardized selection of music, which was based on individual patient preferences. Conclusion: Listening to music during intranasal (es)ketamine therapy appears to be linked to reduced anxiety and lower blood pressure, stable or increased dissociation levels, and improved tolerance for higher doses. These findings could potentially contribute to the optimization of (es)ketamine therapy, both in terms of treatment efficacy and managing side effects.

Electrophysiological correlates of mindfulness in patients with major depressive disorder.

Objectives: Mindfulness-based interventions (MBI) can reduce both stress and depressive symptoms. However, the impact of mindfulness on stress level in depressed subjects remains unclear. This study aims to assess electrophysiological correlates of mindfulness in patients with major depressive disorder (MDD) at baseline, under stress exposure, and in relaxation following stress exposure. Methods: Perceived mindfulness was assessed with the Freiburger Mindfulness Inventory (FMI) in 89 inpatients (mean age 51) with MDD [mean Beck Depression Inventory (BDI) 30]. Electrophysiological parameters [resting heart rate (RHR), heart rate variability (HRV), respiration rate, skin conductance, and skin temperature] were recorded at 5-min baseline, 1-min stress exposure, and 5-min self-induced relaxation. Results: Freiburger Mindfulness Inventory was strongly inversely correlated with symptom severity measured by BDI (r = -0.53, p < 0.001). No correlations between FM score and electrophysiological parameters in any of the three conditions (baseline, stress exposure, relaxed state) could be found. The factor openness was associated with higher VLF (very low frequency of HRV) in the baseline condition. However, this correlation was no more significant after regression analysis when corrected for respiratory rate, age, and sex. Conclusion: Autonomous nervous reactivity in depression was not associated with perceived mindfulness as measured by FMI score and presented electrophysiological parameters, despite the strong inverse correlation between state mindfulness and symptom severity.

Meta-analysis of real-time fMRI neurofeedback studies using individual participant data: How is brain regulation mediated?

An increasing number of studies using real-time fMRI neurofeedback have demonstrated that successful regulation of neural activity is possible in various brain regions. Since these studies focused on the regulated region(s), little is known about the target-independent mechanisms associated with neurofeedback-guided control of brain activation, i.e. the regulating network. While the specificity of the activation during self-regulation is an important factor, no study has effectively determined the network involved in self-regulation in general. In an effort to detect regions that are responsible for the act of brain regulation, we performed a post-hoc analysis of data involving different target regions based on studies from different research groups. We included twelve suitable studies that examined nine different target regions amounting to a total of 175 subjects and 899 neurofeedback runs. Data analysis included a standard first- (single subject, extracting main paradigm) and second-level (single subject, all runs) general linear model (GLM) analysis of all participants taking into account the individual timing. Subsequently, at the third level, a random effects model GLM included all subjects of all studies, resulting in an overall mixed effects model. Since four of the twelve studies had a reduced field of view (FoV), we repeated the same analysis in a subsample of eight studies that had a well-overlapping FoV to obtain a more global picture of self-regulation. The GLM analysis revealed that the anterior insula as well as the basal ganglia, notably the striatum, were consistently active during the regulation of brain activation across the studies. The anterior insula has been implicated in interoceptive awareness of the body and cognitive control. Basal ganglia are involved in procedural learning, visuomotor integration and other higher cognitive processes including motivation. The larger FoV analysis yielded additional activations in the anterior cingulate cortex, the dorsolateral and ventrolateral prefrontal cortex, the temporo-parietal area and the visual association areas including the temporo-occipital junction. In conclusion, we demonstrate that several key regions, such as the anterior insula and the basal ganglia, are consistently activated during self-regulation in real-time fMRI neurofeedback independent of the targeted region-of-interest. Our results imply that if the real-time fMRI neurofeedback studies target regions of this regulation network, such as the anterior insula, care should be given whether activation changes are related to successful regulation, or related to the regulation process per se. Furthermore, future research is needed to determine how activation within this regulation network is related to neurofeedback success.

Reduced neural differentiation between self-referential cognitive and emotional processes in women with borderline personality disorder.

Borderline personality disorder (BPD) is associated with disturbed emotion regulation. Psychotherapeutic interventions using mindfulness elements have shown effectiveness in reducing clinical symptoms, yet little is known about their underlying neurobiology. In this functional magnetic resonance imaging (fMRI) study, 19 female BPD patients and 19 healthy controls were compared during mindful introspection, cognitive self-reflection and a neutral condition. The activation pattern in the right dorsomedial prefrontal cortex (DMPFC) in BPD patients was different from that in healthy subject when directing attention onto their emotions and bodily feelings in contrast to cognitively thinking about themselves. Mindful introspection compared with the neutral condition was associated with higher activations in bilateral motor/pre-motor regions, left inferior frontal gyrus (IFG), and left posterior cingulate cortex (PCC), while cognitive self-reflection activated the right motor and somatosensory cortex, extending into the right supramarginal gyrus (SMG) and superior temporal gyrus (STG) in BPD patients compared with the controls. Results indicate that self-referential cognitive and emotional processes are not clearly differentiated in BPD patients at the neurobiological level. In particular, altered neural mechanism underlying self-referential thinking may be related to some aspects of the typical emotion dysregulation in BPD. Current data support the finding that mindful self-focused attention is effective in regulating amygdala activity in BPD as well as in healthy subjects.

Making sense of real-time functional magnetic resonance imaging (rtfMRI) and rtfMRI neurofeedback.

This review explains the mechanism of functional magnetic resonance imaging in general and specifically introduces real-time functional magnetic resonance imaging as a method for training self-regulation of brain activity. Using real-time functional magnetic resonance imaging neurofeedback, participants can acquire control over their own brain activity. In patients with neuropsychiatric disorders, this control can potentially have therapeutic implications. In this review, the technical requirements are presented and potential applications and limitations are discussed.

Neural circuits of emotion regulation: a comparison of mindfulness-based and cognitive reappraisal strategies.

Dealing with one's emotions is a core skill in everyday life. Effective cognitive control strategies have been shown to be neurobiologically represented in prefrontal structures regulating limbic regions. In addition to cognitive strategies, mindfulness-associated methods are increasingly applied in psychotherapy. We compared the neurobiological mechanisms of these two strategies, i.e. cognitive reappraisal and mindfulness, during both the cued expectation and perception of negative and potentially negative emotional pictures. Fifty-three healthy participants were examined with functional magnetic resonance imaging (47 participants included in analysis). Twenty-four subjects applied mindfulness, 23 used cognitive reappraisal. On the neurofunctional level, both strategies were associated with comparable activity of the medial prefrontal cortex and the amygdala. When expecting negative versus neutral stimuli, the mindfulness group showed stronger activations in ventro- and dorsolateral prefrontal cortex, supramarginal gyrus as well as in the left insula. During the perception of negative versus neutral stimuli, the two groups only differed in an increased activity in the caudate in the cognitive group. Altogether, both strategies recruited overlapping brain regions known to be involved in emotion regulation. This result suggests that common neural circuits are involved in the emotion regulation by mindfulness-based and cognitive reappraisal strategies. Identifying differential activations being associated with the two strategies in this study might be one step towards a better understanding of differential mechanisms of change underlying frequently used psychotherapeutic interventions.

Mindfulness and emotion regulation--an fMRI study.

Mindfulness--an attentive non-judgmental focus on present experiences--is increasingly incorporated in psychotherapeutic treatments as a skill fostering emotion regulation. Neurobiological mechanisms of actively induced emotion regulation are associated with prefrontally mediated down-regulation of, for instance, the amygdala. We were interested in neurobiological correlates of a short mindfulness instruction during emotional arousal. Using functional magnetic resonance imaging, we investigated effects of a short mindfulness intervention during the cued expectation and perception of negative and potentially negative pictures (50% probability) in 24 healthy individuals compared to 22 controls. The mindfulness intervention was associated with increased activations in prefrontal regions during the expectation of negative and potentially negative pictures compared to controls. During the perception of negative stimuli, reduced activation was identified in regions involved in emotion processing (amygdala, parahippocampal gyrus). Prefrontal and right insular activations when expecting negative pictures correlated negatively with trait mindfulness, suggesting that more mindful individuals required less regulatory resources to attenuate emotional arousal. Our findings suggest emotion regulatory effects of a short mindfulness intervention on a neurobiological level.