In situ fNIRS measurements during cognitive behavioral emotion regulation training in rumination-focused therapy: A randomized-controlled trial.

Repetitive negative thinking (RNT), including rumination, plays a key role in various psychopathologies. Although several psychotherapeutic treatments have been developed to reduce RNT, the neural correlates of those specific treatments and of psychotherapy in general are largely unknown. Functional near-infrared spectroscopy (fNIRS) offers the potential to investigate the neural correlates of psychotherapeutic techniques in situ. Therefore, in this study we investigated the efficacy and neural correlates of a fNIRS adapted Mindfulness-based Emotion Regulation Training (MBERT) for the treatment of depressive rumination in 42 subjects with major depressive disorder (MDD) in a cross-over designed randomized controlled trial. Using psychometric measures, subjective ratings and fNIRS, we analyzed in situ changes in depressive symptom severity, ruminative thoughts and cortical activity in the Cognitive Control Network (CCN). Our results show that MBERT is effective in treating depressive symptoms and rumination. On a neural level, we found consistently higher cortical activation during emotion regulation training compared to control trials in the bilateral inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC). Furthermore, cortical oxygenation decreased from session to session in the bilateral DLPFC. The relevance of the results for the psychotherapeutic treatment of MDD as well as further necessary investigations are discussed.

A randomized-controlled neurofeedback trial in adult attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood onset disorder persisting into adulthood for a large proportion of cases. Neurofeedback (NF) has shown promising results in children with ADHD, but randomized controlled trials in adults with ADHD are scarce. We aimed to compare slow cortical potential (SCP)- and functional near-infrared spectroscopy (fNIRS) NF to a semi-active electromyography biofeedback (EMG-BF) control condition regarding changes in symptoms and the impact of learning success, as well as changes in neurophysiological parameters in an adult ADHD population. Patients were randomly assigned to SCP-NF (n = 26), fNIRS-NF (n = 21) or EMG-BF (n = 20). Outcome parameters were assessed over 30 training sessions (pre, intermediate, post) and at 6-months follow-up (FU) including 3 booster sessions. EEG was recorded during two auditory Go/NoGo paradigms assessing the P300 and contingent negative variation (CNV). fNIRS measurements were conducted during an n-back- as well as a Go/NoGo task. All three groups showed equally significant symptom improvements suggesting placebo- or non-specific effects on the primary outcome measure. Only when differentiating between learners and non-learners, fNIRS learners displayed stronger reduction of ADHD global scores compared to SCP non-learners at FU, and fNIRS learners showed specifically low impulsivity ratings. 30.8% in the SCP-NF and 61.9% of participants in the fNIRS-NF learned to regulate the respective NF target parameter. We conclude that some adults with ADHD learn to regulate SCP amplitudes and especially prefrontal hemodynamic activity during NF. We did not find any significant differences in outcome between groups when looking at the whole sample. When evaluating learners only, they demonstrate superior effects as compared to non-learners, which suggests specific effects in addition to non-specific effects of NF when learning occurs.

Relaxation or Regulation: The Acute Effect of Mind-Body Exercise on Heart Rate Variability and Subjective State in Experienced Qi Gong Practitioners.

Mind-body exercises such as Yoga or Qi Gong have demonstrated a wide range of health benefits and hold great promise for employment in clinical practice. However, the psychophysiological mechanism underlying these effects remains unclear. Theoretical frameworks highlight regulation as a characteristic and specific mechanism of mind-body exercise for which empirical evidence is scarce. To investigate the exact nature of this mechanism, we tracked acute changes in autonomic nervous system (ANS) activity and subjective state over a common form of mind-body exercise (Qi Gong). Heart rate variability (HRV) and subjective state were assessed in 42 Qi Gong practitioners from China and Germany during a standard moving Qi Gong exercise (Baduanjin). Relaxation in supine position prior and after the exercise served as a control condition to Qi Gong and to assess changes before and after the exercise. Following Qi Gong, all practitioners reported significantly increased subjective calmness and perceived body activation, attentional focus, and subjective vitality. On the physiological level, a significant decrease of parasympathetic modulation and increase in heart rate indicated a pattern of moderate general physiological activation during Qi Gong. A significant increase in overall RR-interval modulation and cardiac coherence during Qi Gong were indicative of a mechanism of active regulation. Examination of the RR-interval trajectories revealed a rhythmic pattern of ANS activation and deactivation in sync with activating and relaxing segments of the exercise. Significant changes in subjective state, not on the physiological level, before and after the exercise were observed. Significant associations between Qi-Gong-specific beliefs, age, cultural background, and experiential and physiological measures demonstrated the complexity of mind-body exercises as multicomponent interventions. Overall, this study highlights moderate general physiological activation, exercise-dependent rhythmic ANS modulation, and induction of a characteristic state of eutonic calmness as potential psychophysiological mechanisms underlying the health benefits of mind-body exercise.

Neural correlates of mindful emotion regulation in high and low ruminators.

Depressive rumination is considered a prominent risk factor for the occurrence, severity, and duration of depressive episodes. A variety of treatment options have been developed to treat depressive rumination of which mindfulness based programs are especially promising. In the current study, we investigated the neural underpinnings of a short mindfulness intervention and mindful emotion regulation in high and low trait ruminators in an ecologically valid environment using functional near-infrared spectroscopy (fNIRS). Participants were randomly assigned to a mindfulness instruction (MT) group or an instructed thinking (IT) group. Participants in the MT group were trained to either focus their attention mindfully on their breath or their emotions, while the IT group focused their attention on the past or future. Afterwards, all participants underwent an emotion regulation paradigm in which they either watched negative or neutral movie clips. During both paradigms cortical hemodynamic changes were assessed by means of fNIRS. Participants in the MT group showed lower activity in the cognitive control network (CCN) during the focus on breath condition in comparison to the focus on emotion condition. Additionally, oxygenated hemoglobin in the MT group tended to be lower than in the IT group. Further, self-reports of emotional distress during the instruction paradigm were reduced in the MT group. During the emotion regulation paradigm, we observed reduced emotional reactivity in terms of emotional distress and avoidance in the MT group in comparison to the IT group. Furthermore, on a neural level, we observed higher CCN activity in the MT group in comparison to the IT group. We did not find any effect of rumination, neither on the intervention nor on the emotion regulation task. The results of this pilot study are discussed in light of the present literature on the neural correlates of mindfulness based interventions in rumination and emphasize the use of fNIRS to track neural changes in situ over the course of therapy.

Feasibility of NIRS-based neurofeedback training in social anxiety disorder: behavioral and neural correlates.

Attention biases towards threat signals have been linked to the etiology and symptomatology of social anxiety disorder (SAD). Dysfunction of the dorsolateral prefrontal cortex (dlPFC) may contribute to attention biases in anxious individuals. The aim of this study was to investigate the feasibility of near-infrared spectroscopy (NIRS) neurofeedback (NF) training-targeting the dlPFC-and its effects on threat-related attention biases of individuals with SAD. 12 individuals with SAD participated in the NIRS-NF training lasting 6-8 weeks and including a total of 15 sessions. NF performance increased significantly, while the attention bias towards threat-related stimuli and SAD symptom severity decreased after the training. The individual increase in neurofeedback performance as well as the individual decrease in SAD symptom severity was correlated with decreased responses to social threat signals in the cerebral attention system. Thus, this pilot study does not only demonstrate that NIRS-based NF is feasible in SAD patients, but also may be a promising method to investigate the causal role of the dlPFC in attention biases in SAD. Its effectiveness as a treatment tool might be examined in future studies.

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.

Meditation and the brain - Neuronal correlates of mindfulness as assessed with near-infrared spectroscopy.

Mindfulness meditation as a therapeutic intervention has been shown to have positive effects on psychological problems such as depression, pain or anxiety disorders. In this study, we used functional near-infrared spectroscopy (fNIRS) to detect differences in hemodynamic responses of meditation experts (14 participants) and a control group (16 participants) in a resting and a mindfulness condition. In both conditions, the sound of a meditation bowl was used to find group differences in the auditory system and adjacent cortical areas. Different lateralization patterns of the brain were found in expert meditators while being in a resting state (amplified left hemisphere) or being in mindfulness state (amplified right hemisphere). Compared to the control group, meditation experts had a more widespread pattern of activation in the auditory cortex, while resting. In the mindfulness condition, the control group showed a decrease of activation in higher auditory areas (BA 1, 6 and 40), whereas the meditation experts had a significant increase in those areas. In addition, meditation expert had highly activated brain areas (BA 39, 40, 44 and 45) beyond the meditative task itself, indicating possible long-term changes in the brain and their positive effects on empathy, meta cognitive skills and health.

Near-infrared spectroscopy (NIRS) and vagus somatosensory evoked potentials (VSEP) in the early diagnosis of Alzheimer's disease: rationale, design, methods, and first baseline data of the Vogel study.

Functional near-infrared spectroscopy (fNIRS) and vagus somatosensory evoked potentials (VSEP) show deviant patterns in subjects with Alzheimer's disease (AD) compared to healthy controls. We now aimed at testing the predictive value of these methods in the early diagnosis of AD. The Vogel study is a prospective, observational, long-term follow-up study with three time points of investigation within 6 years. Residents of the city of Würzburg born between 1936 and 1941 were recruited. Every participant underwent physical, psychiatric, and laboratory examinations, and performed an intense neuropsychological testing as well as VSEP and NIRS according to the published procedures. 604 subjects were included. Mean age of the participants was 73.9 ± 1.55 years. The most frequent pathological physical and laboratory examination results were observed for blood pressure (62%), body weight (54%), HbA1c (16%), cholesterol (42%), and homocysteine (69%). Comprehensive analysis of cognitive testing showed mild cognitive impairment (MCI) in 12.3% of the patients. Concurrent major depression was found in 6.6% of the patients. We observed a high rate of MCI and somatic comorbidity in our cohort. The high rate of vascular risk factors and depressive symptoms, all of which are known risk factors of AD, is consistent with the notion that there are multiple options to prevent or postpone the onset of AD in a geriatric population like the one of the Vogel studies.

EMG biofeedback training in adult attention-deficit/hyperactivity disorder: An active (control) training?

OBJECTIVE: The present study aimed at revealing neurophysiological effects induced by electromyography (EMG) based biofeedback, considered as a semi-active control condition in neurofeedback studies, in adult attention-deficit/hyperactivity disorder (ADHD) patients. METHODS: 20 adult ADHD patients trained their muscle activity in the left and right supraspinatus muscle over the course of 30 EMG biofeedback sessions. Changes induced by the EMG feedback were evaluated at a clinical and neurophysiological level; additionally, the relation between changes in EEG activity recorded at the vertex over the training course and changes of symptom severity over the treatment course were assessed in order to investigate the mechanisms underlying clinical effects of EMG biofeedback. RESULTS: Participants showed significant behavioral improvements on a self-rating scale. There was a significant increase in alpha power, but no significant changes in the delta frequency range; changes in the theta and beta frequency range were not significant after adjustment for multiple comparisons. No statistically significant correlation was found between changes in EEG frequency bands and changes in ADHD symptoms. CONCLUSIONS: The current results assessed by means of a single-electrode EEG constitute a starting point regarding a clearer understanding of mechanisms underlying clinical effects of EMG biofeedback. Although we did not reveal systematic effects induced by EMG feedback on brain activity it remains an open question whether EMG biofeedback induces changes in brain regions or parameters we did not gather in the present study (e.g. motor cortex).

Neuronavigated left temporal continuous theta burst stimulation in chronic tinnitus.

PURPOSE: Clinical effects of repetitive transcranial magnetic stimulation (rTMS) in chronic tinnitus are moderate. More precise coil localisation strategies, innovative stimulation protocols, and identification of predictors for treatment response were proposed as promising attempts to enhance treatment efficacy. In this pilot study we investigated neuronavigated continuous theta burst TMS (cTBS). METHODS: Twenty-three patients received neuronavigated cTBS over the left primary auditory cortex in a randomized sham-controlled trial (verum = 12; sham = 11). Treatment response was evaluated with tinnitus questionnaires and numeric rating scales. Immediate change in numeric rating scales during the first session was used as predictor for treatment response. RESULTS: Tinnitus was significantly reduced after treatment, but there were no superior effects between verum vs. sham treatment. Immediate change in the first treatment session predicted the response to treatment only in the verum group. CONCLUSIONS: In our study, verum cTBS was not superior to sham which highlights the persistent need for improving non-invasive brain stimulation techniques for the treatment of tinnitus. Future research should focus on the transfer of positive single session effects to daily treatment trials.

Neurofeedback as a nonpharmacological treatment for adults with attention-deficit/hyperactivity disorder (ADHD): study protocol for a randomized controlled trial.

BACKGROUND: Neurofeedback has been applied effectively in various areas, especially in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). This study protocol is designed to investigate the effect of slow cortical potential (SCP) feedback and a new form of neurofeedback using near-infrared spectroscopy (NIRS) on symptomatology and neurophysiological parameters in an adult ADHD population. A comparison of SCP and NIRS feedback therapy methods has not been previously conducted and may yield valuable findings about alternative treatments for adult ADHD. METHODS/DESIGN: The outcome of both neurofeedback techniques will be assessed over 30 treatment sessions and after a 6-month follow-up period, and then will be compared to a nonspecific biofeedback treatment. Furthermore, to investigate if treatment effects in this proof-of-principle study can be predicted by specific neurophysiological baseline parameters, regression models will be applied. Finally, a comparison with healthy controls will be conducted to evaluate deviant pretraining neurophysiological parameters, stability of assessment measures, and treatment outcome. DISCUSSION: To date, an investigation and comparison of SCP and NIRS feedback training to an active control has not been conducted; therefore, we hope to gain valuable insights in effects and differences of these types of treatment for ADHD in adults. TRIAL REGISTRATION: This study is registered with the German Registry of Clinical Trials: DRKS00006767 , date of registration: 8 October 2014.

Functional near-infrared spectroscopy to probe state- and trait-like conditions in chronic tinnitus: a proof-of-principle study.

OBJECTIVE: Several neuroscience tools showed the involvement of auditory cortex in chronic tinnitus. In this proof-of-principle study we probed the capability of functional near-infrared spectroscopy (fNIRS) for the measurement of brain oxygenation in auditory cortex in dependence from chronic tinnitus and from intervention with transcranial magnetic stimulation. METHODS: Twenty-three patients received continuous theta burst stimulation over the left primary auditory cortex in a randomized sham-controlled neuronavigated trial (verum = 12; placebo = 11). Before and after treatment, sound-evoked brain oxygenation in temporal areas was measured with fNIRS. Brain oxygenation was measured once in healthy controls (n = 12). RESULTS: Sound-evoked activity in right temporal areas was increased in the patients in contrast to healthy controls. Left-sided temporal activity under the stimulated area changed over the course of the trial; high baseline oxygenation was reduced and vice versa. CONCLUSIONS: By demonstrating that rTMS interacts with auditory evoked brain activity, our results confirm earlier electrophysiological findings and indicate the sensitivity of fNIRS for detecting rTMS induced changes in brain activity. Moreover, our findings of trait- and state-related oxygenation changes indicate the potential of fNIRS for the investigation of tinnitus pathophysiology and treatment response.

Can intermittent theta burst stimulation as add-on to psychotherapy improve nicotine abstinence? Results from a pilot study.

Smoking is among the leading causes of mortality worldwide. Discontinuing smoking can increase life expectancy to the presmoking level. Unaided attempts are often ineffective, strengthening the necessity of cognitive-behavioral therapy (CBT), nicotine replacement or pharmacotherapy. Still, relapse rates are high. Recently, a modulation of nicotine craving, which predicts relapse, through transcranial magnetic stimulation to the prefrontal cortex was shown. In a pilot study, we investigated whether 4 sessions of intermittent theta burst stimulation (iTBS) as add-on treatment to CBT reduces nicotine craving and improves long-term abstinence (at 3, 6 and 12 months). Smokers were randomly assigned to a treatment (n = 38) or a sham group (n = 36). Although we did not find reduced craving, we could show higher abstinence rates in the treatment group at 3 months. At 6 and 12 months abstinence rates did not differ significantly. Results at 12 months, however, have to be interpreted cautiously due to significant differences in the dropout rates between the two groups at this time point. We provide first evidence for a beneficial effect of additional iTBS on intermediate nicotine abstinence; however, the low number of iTBS sessions might have prevented longer effects. More lasting effects might be achieved by iTBS maintenance sessions in analogy to the treatment of depression.

Is there a negative interpretation bias in depressed patients? An affective startle modulation study.

BACKGROUND/AIMS: Scientists proposed that patients with depression favour negative interpretations when appraising ambiguity. As self-report measures seem prone to response bias, implicit measures of emotional valence should be additionally used. METHODS: A total of 16 patients with depression and 19 controls underwent an acoustic imagery task comprising neutral and negative words, as well as ambiguous words that could be understood either way. Affective startle modulation and direct interrogation were used to assess implicit and explicit emotional valence, respectively. We expected a negative bias for ambiguous words in the patient group, resulting in augmented startle magnitudes and preference for negative interpretations of the ambiguous words in the interrogation. RESULTS: Surprisingly, both groups preferred neutral interpretations and showed augmented startle magnitudes to ambiguous words. Furthermore, both groups displayed an emotional startle potentiation for negative words. CONCLUSION: In summary, our results do not confirm a negative interpretation bias or a blunted emotional response in patients with major depression. The mismatch between self-report and affective startle reaction to ambiguous targets might reflect defensive mobilization or attention effects.

Low performance in attention testing is associated with reduced grey matter density of the left inferior frontal gyrus in euthyroid patients with Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) can casually co-occur with an encephalopathy associated with autoimmune thyroid disease. Recently we found an increased occurrence of weaknesses in sustained attention and response inhibition in a subgroup of euthyroid patients with HT as obtained by the d2 attention test. Previous studies in healthy subjects and patients with brain lesions demonstrated a pivotal role for the left inferior frontal gyrus (LIFG) in these skills. Therefore, we studied the association between the performance in the d2 test and grey matter (GM) density of the LIFG in 13 euthyroid patients with HT compared to a control group of 12 euthyroid patients with other thyroid diseases. A significant correlation between GM density and d2 test total score was detected for the opercular part of the LIFG in patients with HT (p<0.001), but not in the control group (p=0.94). Regression in patients with HT was significantly stronger than in the control group (p=0.02). Moreover, GM density was significantly reduced when comparing HT patients with control patients that scored in the lower third during d2 attention testing (p<0.05). It can be concluded that in HT performance in the d2 test correlated with GM density of the LIFG. Particularly low achievement was associated with reduced GM density of this brain region suggesting an influence of autoimmune processes on the frontal cortex in this disease. This could be due to not yet known antibodies affecting brain morphology or an influence of thyroid antibodies themselves.

Auditory symptom provocation in dental phobia: a near-infrared spectroscopy study.

The act of drilling a tooth belongs to the most feared situations of patients suffering from dental phobia. We presented 25 female patients and 24 nonphobic women with the sound of a dental drill, pleasant and neutral sounds. Brain activation was recorded via near infrared spectroscopy in fronto-parietal and premotor areas. The groups differed in supplementary motor area (SMA) recruitment. Relative to controls, the phobics displayed increased oxy hemoglobin while presented with the phobia-relevant sound, but showed comparable activation in the other conditions. As the SMA is engaged in the preparation of motor actions, the increased response in patients might mirror the priming of flight behavior during exposure. We found no indication of an emotional modulation of parietal and dorsomedial prefrontal cortex activation.

Far field potentials from brain stem after transcutaneous vagus nerve stimulation: optimization of stimulation and recording parameters.

The method of vagus somatosensory evoked potentials (VSEP) was introduced to easily measure the activity of vagus brain stem nuclei. In Alzheimer's disease, this measure was characterized by longer latencies as compared to controls while amplitudes did not show statistical significant differences at frontal and central recording sites. Therefore, the influence of stimulation and recording parameters on amplitudes of VSEP were systematically examined. In 20 healthy participants, VSEP measurement was done by electrical stimulation of the cutaneous representation of the vagus nerve in the external auditory channel and recording of VSEP over the scalp. The optimum stimulation intensity is 8 mA without perception of pain. There is no effect of stimulation side or gender. Maximum VSEP amplitudes are detected at bipolar recordings comprising the electrode T4 without statistically significant differences of latencies, wave shape and polarity. Thus, recordings of future examinations should be performed at 8 mA including this temporal electrode position. The reason for focussing on brain stem evoked potentials is that recent work has accumulated evidence for this area being involved in early phases of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Improved methodological knowledge may facilitate the assessment of this non-invasive and cost-effective method in the early diagnosis of neurodegenerative disorders.

Age effect on far field potentials from the brain stem after transcutaneous vagus nerve stimulation.

Recently, a new electrophysiological method for the assessment of vagus nerve function in the brainstem has been proposed in healthy participants. Before this procedure may be applied to patients with neurodegenerative diseases, its feasibility in elderly healthy participants and a possible age effect on the measurement have to be investigated. The vagus sensory evoked potentials (VSEP) after transcutaneous electric stimulation of the sensory auricular branch of the vagus nerve have been assessed in healthy younger and elderly participants. VSEP measured as far field potentials probably originating in vagus nuclei in the brainstem were recorded in 20 of 22 younger as well as in 39 of 43 elderly healthy participants. Latencies were significantly longer in the elderly as compared to the younger participants, while no clear age effects on amplitudes were identified. These results indicate that the assessment of VSEP is feasible also in elderly healthy participants. This is a prerequisite for testing this method in elderly patients with neurodegenerative diseases like Alzheimer and Parkinson disease as a noninvasive tool to detect an affection of the brainstem nuclei of the vagus nerve early in their course.

Electrophysiological indication for a link between serotonergic neurotransmission and personality in alcoholism.

The serotonergic neurotransmission seems to be involved in the neuropsychobiology of alcoholism. The intensity dependence of the N1/P2 component of auditory-evoked potentials is discussed as an indicator of the central serotonergic neurotransmission in healthy subjects. The aim of this study was to verify this correlation between intensity dependence and serotonergic neurotransmission, as indicated by the personality trait "harm avoidance" (HA) within the Temperament and Character Inventory (TCI) in alcohol-dependent patients. The intensity dependence was measured in 25 alcohol-dependent patients, 10 and 40 days after detoxification. The personality trait HA was assessed, which is supposed to reflect the serotonergic neurotransmission. The intensity dependence was negatively correlated with the temperament trait HA of the TCI (r = - .55, P<.01) at Day 40, but neither on Day 10 nor with the other personality dimensions. We conclude, that the intensity dependence reflects the serotonergic neurotransmission in withdrawn alcohol-dependent patients.