Neurobiological mechanisms of ECT and TMS treatment in depression: study protocol of a multimodal magnetic resonance investigation.

BACKGROUND: Noninvasive neurostimulation treatments are increasingly being used to treat major depression, which is a common cause of disability worldwide. While electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS) are both effective in treating depressive episodes, their mechanisms of action are, however, not completely understood. ECT is given under general anesthesia, where an electrical pulse is administered through electrodes placed on the patient's head to trigger a seizure. ECT is used for the most severe cases of depression and is usually not prescribed before other options have failed. With TMS, brain stimulation is achieved through rapidly changing magnetic fields that induce electric currents underneath a ferromagnetic coil. Its efficacy in depressive episodes has been well documented. This project aims to identify the neurobiological underpinnings of both the effects and side effects of the neurostimulation techniques ECT and TMS. METHODS: The study will utilize a pre-post case control longitudinal design. The sample will consist of 150 subjects: 100 patients (bipolar and major depressive disorder) who are treated with either ECT (N = 50) or TMS (N = 50) and matched healthy controls (N = 50) not receiving any treatment. All participants will undergo multimodal magnetic resonance imaging (MRI) as well as neuropsychological and clinical assessments at multiple time points before, during and after treatment. Arterial spin labeling MRI at baseline will be used to test whether brain perfusion can predict outcomes. Signs of brain disruption, potentiation and rewiring will be explored with resting-state functional MRI, magnetic resonance spectroscopy and multishell diffusion weighted imaging (DWI). Clinical outcome will be measured by clinician assessed and patient reported outcome measures. Memory-related side effects will be investigated, and specific tests of spatial navigation to test hippocampal function will be administered both before and after treatment. Blood samples will be stored in a biobank for future analyses. The observation time is 6 months. Data will be explored in light of the recently proposed disrupt, potentiate and rewire (DPR) hypothesis. DISCUSSION: The study will contribute data and novel analyses important for our understanding of neurostimulation as well as for the development of enhanced and more personalized treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05135897.

Reduced heart rate variability during mania in a repeated naturalistic observational study.

Background: Bipolar disorder (BD) is a chronic recurrent mood disorder associated with autonomic nervous system (ANS) dysfunction, indexed by heart rate variability (HRV). Changes in HRV between mood states are sparsely studied longitudinally. We aimed to compare HRV of hospitalized manic individuals with their own euthymic selves in a naturalistic observational study. Methods: 34 individuals were included, of which 16 were lost to follow-up. Ultimately 15 patients provided reliable heart rate data in both a manic and euthymic state, using photoplethysmography (PPG) sensor wristbands overnight. We calculated HRV measures Root Mean Square of Successive Differences (RMSSD), High-frequency (HF: 0.15-0.40 Hz), Low-frequency (LF: 0.40-0.15 Hz), Very low-frequency (VLF: 0.0033-0.04 Hz), Total power and Sample Entropy in 5-min night-time resting samples. We compared HRV measures by mood state within individuals using paired t-tests and linear regression to control for age and sex. Results: HRV was lower in the manic state when compared to the euthymic state for all HRV metrics (p ≤ 0.02), with large to medium effect sizes (g = 1.24 to 0.65). HRV changes were not significantly affected by age or sex. Conclusion: This longitudinal study provides evidence of lower HRV in manic states compared to euthymia, indicating an association between ANS dysregulation and changes in bipolar mood state. This corroborates previous cross-sectional studies, although the association may be less clear or reversed in hypomanic states. Further investigation in larger longitudinal samples is warranted.

Low heart rate variability is associated with a negativity valence bias in interpreting ambiguous emotional expressions.

Most people tend to overstate positive aspects of their experiences, that is, a positive valence bias. However, some people tend to have attenuated attention for negative aspects of perceived information, that is, negative valence bias. This dispositional tendency in either valence is especially significant for emotion regulation as it influences the intensity of later stages of emotional experiences. Heart rate variability (HRV) is used as an index of emotion regulation and for the effect dispositional valence bias has on social cognition. The aim of the current study was to investigate whether a positivity or negativity bias in processing ambiguous facial expressions would predict high or lower HRV, respectively, in a healthy sample. The Reading the Mind in the Eyes Test was presented to a sample of 128 healthy participants (N = 86 women participants), and resting HRV was acquired. In multiple linear regression analyses, the mean accuracy scores for items with positive, negative, and neutral valences were included as predictors of HRV. As a follow-up analysis, we tested whether a general tendency to interpret negative stimulus as positive, that is, a positivity bias, predicted HRV. Higher accuracy on items with negative emotional valence predicted lower HRV. There was no association between accuracy scores on items of positive or neutral valence and HRV. Higher positivity bias predicted higher HRV. The present findings suggest that a dispositional valence bias relates to levels of HRV and, as such, is influenced by the functioning of the vagal system. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Vagally mediated heart rate variability, stress, and perceived social support: a focus on sex differences.

Higher vagally mediated heart rate variability (vmHRV), reflecting vagal activity as indexed by heart function and lower stress vulnerability, is associated with higher perceived social support. Seeking social support is an adaptive stress response, and evolutionary theories suggest that females use this strategy more than males. The current study investigated the hypothesis that higher vmHRV is related to higher perceived social support under conditions of higher, relative to lower, stress, and that this association is most prominent in females. A healthy student sample (n = 143; 82 males, 61 females; mean age 19.9) completed the short version of the Medical outcomes study social support survey (MOS) and the Perceived stress scale (PSS). Activity in the high frequency band of heart rate variability (HF-HRV), deducted from five-minute resting electrocardiogram (ECG) recordings, indexed vmHRV. A moderation analysis was conducted, with PSS and sex as moderators of the association between vmHRV and MOS. Statistical effects were adjusted for age, education, physical activity, body mass index (BMI), alcohol and drug use, ECG-derived respiration (EDR), and mean heart rate. Higher PSS scores moderated the association between vmHRV and MOS in females but not males. Lower PSS scores did not moderate the relation between vmHRV and MOS. This suggests that higher vmHRV is associated with higher perceived social support under conditions of higher stress in females but not males, consistent with evolution of different stress management strategies in the sexes. The results may have implications for individualized intervention strategies for increasing vmHRV and perceived social support.

Self-Compassion and Its Association With Ruminative Tendencies and Vagally Mediated Heart Rate Variability in Recurrent Major Depression.

Background: Recurrent Major Depressive Disorder (MDD) is one of the most disabling mental disorders in modern society. Prior research has shown that self-compassion protects against ruminative tendencies, a key feature of recurrent MDD. In addition, self-compassion has been found to be positively related to higher psychophysiological flexibility (indexed by a higher vagally mediated heart rate variability; vmHRV) in young, healthy adults. To our knowledge, there is a lack of studies on how self-compassion relates to vmHRV in patients with recurrent MDD. The aim of the current study was to investigate whether higher self-compassion would associate with (1) lower ruminative tendencies and (2) higher vmHRV in a sample of adults with recurrent MDD. Methods: We included a sample of 63 patients (46 females) between 20 and 71 years old (M = 40.24, SD = 12.8) with a history of three or more depressive episodes. They filled out the Self-Compassion Scale (SCS), Beck Depression Inventory (BDI), and Rumination Rating Scale (RRS). ECG (used to derive vmHRV) was acquired while resting and the square root of the mean squared differences of successive RR interval values (RMSSD) was calculated as measure of vmHRV. Results: As hypothesized, self-compassion was associated with lower ruminative tendencies. However, self-compassion was not associated with level of vmHRV. Several confounding variables were controlled for in the statistical analyses, and higher age predicted lower vmHRV across all statistical analyses. Conclusion: The results confirmed our hypothesis that higher self-compassion would be associated with lower ruminative tendencies in recurrent MDD. Contrary to our expectation, we did not find that the tendency to be more self-compassionate was associated with higher vmHRV. As such, higher self-compassion seems to relate with a lower tendency to ruminate about past mistakes and events but does not seem to relate to a flexible autonomic stress response (as indexed by higher vmHRV). Other potential explanatory factors for lower vmHRV in recurrent MDD is suggested as focus for exploration in future studies.

Innovative approaches in investigating inter-beat intervals: Graph theoretical method suggests altered autonomic functioning in adolescents with ADHD.

Cardiac inter-beat intervals (IBIs) are considered to reflect autonomic functioning and self-regulatory abilities and are often investigated by traditional time- and frequency domain analyses. These analyses investigate IBI fluctuations across relatively long time series. The similarity graph algorithm is a nonlinear method that analyzes segments of IBI time series (i.e., time windows)-possibly being more sensitive to transient and spontaneous IBI fluctuations. We hypothesized that the similarity graph algorithm would detect differences between Attention-Deficit/Hyperactivity Disorder (ADHD) and control groups. Resting electrocardiogram (ECG) recordings were collected in 10-18-year-olds with ADHD (n = 37) and controls (n = 36). IBIs were converted to graphs that were subsequently investigated for similarity. We varied the criterion for defining IBIs as similar, assessing which setting best distinguished ADHD and control groups. Using this setting, we applied the similarity graph algorithm to time windows of 2-5, 6-13 and 12-25 s, respectively. We also performed traditional IBI analyses. Independent samples t tests assessed group differences. Results showed that a 1.5% criterion of similarity and a time window of 2-5 s best distinguished adolescents with ADHD and controls. The similarity graph algorithm showed a higher number of edges, maximum edges and cliques, and lower edges10+10/edges2+2 in the ADHD group compared to controls. The results suggested more similar IBIs in the ADHD group compared to the controls, possibly due to altered vagal activity and less effective regulation of heart rate. Traditional analyses did not detect any group differences. Consequently, the similarity graph algorithm might complement traditional IBI analyses as a marker of psychopathology.

Study protocol of the Bergen brain-gut-microbiota-axis study: A prospective case-report characterization and dietary intervention study to evaluate the effects of microbiota alterations on cognition and anatomical and functional brain connectivity in patients with irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS) is a common clinical label for medically unexplained gastrointestinal (GI) symptoms, recently described as a disturbance of the brain-gut-microbiota (BGM) axis. To gain a better understanding of the mechanisms underlying the poorly understood etiology of IBS, we have designed a multifaceted study that aim to stratify the complex interaction and dysfunction between the brain, the gut, and the microbiota in patients with IBS. METHODS: Deep phenotyping data from patients with IBS (n = 100) and healthy age- (between 18 and 65) and gender-matched controls (n = 40) will be collected between May 2019 and December 2021. Psychometric tests, questionnaires, human biological tissue/samples (blood, faeces, saliva, and GI biopsies from antrum, duodenum, and sigmoid colon), assessment of gastric accommodation and emptying using transabdominal ultrasound, vagal activity, and functional and structural magnetic resonance imaging (MRI) of the brain, are included in the investigation of each participant. A subgroup of 60 patients with IBS-D will be further included in a 12-week low FODMAP dietary intervention-study to determine short and long-term effects of diet on GI symptoms, microbiota composition and functions, molecular GI signatures, cognitive, emotional and social functions, and structural and functional brain signatures. Deep machine learning, prediction tools, and big data analyses will be used for multivariate analyses allowing disease stratification and diagnostic biomarker detection. DISCUSSION: To our knowledge, this is the first study to employ unsupervised machine learning techniques and incorporate systems-based interactions between the central and the peripheral components of the brain-gut-microbiota axis at the levels of the multiomics, microbiota profiles, and brain connectome of a cohort of 100 patients with IBS and matched controls; study long-term safety and efficacy of the low-FODMAP diet on changes in nutritional status, gut microbiota composition, and metabolites; and to investigate changes in the brain and gut connectome after 12 weeks strict low-FODMAP-diet in patients with IBS. However, there are also limitations to the study. As a restrictive diet, the low-FODMAP diet carries risks of nutritional inadequacy and may foster disordered eating patterns. Strict FODMAP restriction induces a potentially unfavourable gut microbiota, although the health effects are unknown. TRIAL REGISTRATION NUMBER: NCT04296552 (ClinicalTrials.gov).

The effects of mindfulness-based cognitive therapy on risk and protective factors of depressive relapse - a randomized wait-list controlled trial.

BACKGROUND: The aim of this randomized wait-list controlled trial was to explore the effects of Mindfulness-Based Cognitive Therapy (MBCT) on risk and protective factors for depressive relapse within the domains of cognition, emotion and self-relatedness. METHODS: Sixty-eight individuals with recurrent depressive disorder were randomized to MBCT or a wait-list control condition (WLC). RESULTS: Completers of MBCT (N = 26) improved significantly on measures assessing risk and protective factors of recurrent depression compared to WLC (N = 30) on measures of rumination (d = 0.59, p = .015), emotion regulation (d = 0.50, p = .028), emotional reactivity to stress (d = 0.32, p = .048), self-compassion (d = 1.02, p < .001), mindfulness (d = 0.59, p = .010), and depression (d = 0.40, p = .018). In the Intention To Treat sample, findings were attenuated, but there were still significant results on measures of rumination, self-compassion and depression. CONCLUSIONS: Findings from the present trial contribute to evidence that MBCT can lead to reduction in risk factors of depressive relapse, and strengthening of factors known to be protective of depressive relapse. The largest changes were found in the domain of self-relatedness, in the form of large effects on the participants' ability to be less self-judgmental and more self-compassionate. TRIAL REGISTRATION: ISRCTN, ISRCTN18001392. Registered 29 June 2018.

Lower Cardiac Vagal Activity Predicts Self-Reported Difficulties With Emotion Regulation in Adolescents With ADHD.

OBJECTIVE: To investigate the relation between cardiac vagal activity (CVA), a measure of autonomic nervous system (ANS) flexibility, and self-reported emotion regulation (ER) difficulties in adolescents with attention-deficit/hyperactivity disorder (ADHD) and controls. METHODS: The sample comprised 11-17-year-old adolescents with ADHD (n=34) and controls (n = 33). Multiple linear regression analyses investigated the relation between CVA, as indexed by high frequency heart rate variability (HF-HRV), and ER difficulties as assessed by the Difficulties in Emotion Regulation Scale (DERS). Supplemental analyses were performed in ADHD and control groups separately. Analyses assessed effects of body mass index (BMI), physical activity levels, and HF peak as a surrogate of respiration on CVA. RESULTS: Lower CVA was associated with ER difficulties, and specifically with limited access to effective ER strategies. When investigating the relation between CVA and ER in the ADHD and control groups separately, there was a tendency of lower CVA predicting limited access to effective ER strategies in the ADHD group, and not in the control group. CONCLUSION: The results suggest that lower CVA, i.e., reduced ANS flexibility, in adolescents with ADHD and controls is associated with self-reported ER difficulties, and specifically with limited access to effective ER strategies. There was a tendency for lower CVA to predict limited ER strategies only in the adolescents with ADHD and not controls.

Is Dispositional Self-Compassion Associated With Psychophysiological Flexibility Beyond Mindfulness? An Exploratory Pilot Study.

BACKGROUND: Dispositional mindfulness and self-compassion are shown to associate with less self-reported emotional distress. However, previous studies have indicated that dispositional self-compassion may be an even more important buffer against such distress than dispositional mindfulness. To our knowledge, no study has yet disentangled the relationship between dispositional self-compassion and mindfulness and level of psychophysiological flexibility as measured with vagally mediated heart rate variability (vmHRV). The aim was thus to provide a first exploratory effort to expand previous research relying on self-report measures by including a psychophysiological measure indicative of emotional stress reactivity. METHODS: Fifty-three university students filled out the "Five Facet Mindfulness Questionnaire" (FFMQ) and the "Self-Compassion Scale" (SCS), and their heart rate was measured during a 5 min resting electrocardiogram. Linear hierarchical regression analyses were conducted to examine the common and unique variance explained by the total scores of the FFMQ and the SCS on level of resting vmHRV. RESULTS: Higher SCS total scores associated significantly with higher levels of vmHRV also when controlling for the FFMQ total scores. The SCS uniquely explained 7% of the vmHRV. The FFMQ total scores did not associate with level of vmHRV. CONCLUSION: These results offer preliminary support that dispositional self-compassion associates with better psychophysiological regulation of emotional arousal above and beyond mindfulness.

The Association Between Juvenile Onset of Depression and Emotion Regulation Difficulties.

Juvenile onset of Major Depressive Disorder (MDD) is associated with increased likelihood of recurrent episodes of depression and more detrimental clinical trajectories. The aim of the current study was to investigate the effect of juvenile onset of MDD on emotion regulation as measured by self-report and Heart Rate Variability (HRV). Furthermore, we wanted to assess whether juvenile onset impacted the association between rumination and depressive symptoms. Sixty-four individuals with at least three prior episodes of MDD were recruited and filled out self-report questionnaires measuring rumination and emotion regulation abilities. In addition, electrocardiographic assessments were used to calculate HRV. Based on self-reported age of MDD onset, individuals were divided in two groups: Juvenile onset of MDD (first MDD episode before the age of 18, n = 30) and adult onset of MDD (first MDD episode after the age of 18, n = 34). Results showed that individuals whose first depressive episode occurred in childhood and adolescence reported more rumination and less emotional clarity compared to individuals who had their first episode of MDD in adulthood. Moreover, the tendency to ruminate was strongly associated with depressive symptoms in the juvenile onset of MDD group, whereas no such association was found in the adult onset group. There was no significant group difference for HRV. The findings are discussed in light of existing literature, in addition to suggesting how our findings may inform clinical practice and future research. We conclude that juvenile onset of MDD may lead to difficulties in emotion regulation and that these difficulties may increase depressive symptoms and vulnerability for relapse in this particular subgroup.

Dispositional Mindfulness and Attentional Control: The Specific Association Between the Mindfulness Facets of Non-judgment and Describing With Flexibility of Early Operating Orienting in Conflict Detection.

Background: A state of mindfulness refers to a present-centered attentional awareness without judging. Being mindful seems to increase the ability to be flexible and adaptive in attention focus according to situational contingencies. The way mindfulness affects such attentional control is often measured with three different but interacting attentional networks of alerting (preparedness), orienting (selection of stimulus), and conflict detection (suppression of irrelevant stimuli). In the current study, the aim was to study the effects of dispositional mindfulness on these attention networks, and specifically the effects on the interactions between these attention networks. Methods: Fifty participants between 19 and 29 years old filled out the questionnaire Five Facet Mindfulness Questionnaire (FFMQ) and performed the revised version of the Attention Network Test (ANT-R). The five FFMQ facets of Describing, Non-Judgment, Orienting, Non-Reactivity, and Acting with Awareness were included as predictors in multiple linear regression analyses with the ANT-R scores of alerting, orienting, conflict detection, and the interaction scores of alerting by conflict detection and orienting by conflict detection as outcome variables, respectively. Results: Higher dispositional mindfulness as measured with the five FFMQ facets predicted interaction scores (faster reaction times) of orienting by conflict detection, but none of the other ANT-R scores. It was specifically the FFMQ facets of Describing and non-judgment that predicted this lower interaction score of orienting by conflict detection. Conclusion: Our findings indicate that being mindful is associated with a more flexible and efficient orienting attention. It is associated with a higher ability to disengage from salient stimuli that is irrelevant to pursue goal-directed behavior (conflict detection).

Listening to Rhythmic Music Reduces Connectivity within the Basal Ganglia and the Reward System.

Music can trigger emotional responses in a more direct way than any other stimulus. In particular, music-evoked pleasure involves brain networks that are part of the reward system. Furthermore, rhythmic music stimulates the basal ganglia and may trigger involuntary movements to the beat. In the present study, we created a continuously playing rhythmic, dance floor-like composition where the ambient noise from the MR scanner was incorporated as an additional instrument of rhythm. By treating this continuous stimulation paradigm as a variant of resting-state, the data was analyzed with stochastic dynamic causal modeling (sDCM), which was used for exploring functional dependencies and interactions between core areas of auditory perception, rhythm processing, and reward processing. The sDCM model was a fully connected model with the following areas: auditory cortex, putamen/pallidum, and ventral striatum/nucleus accumbens of both hemispheres. The resulting estimated parameters were compared to ordinary resting-state data, without an additional continuous stimulation. Besides reduced connectivity within the basal ganglia, the results indicated a reduced functional connectivity of the reward system, namely the right ventral striatum/nucleus accumbens from and to the basal ganglia and auditory network while listening to rhythmic music. In addition, the right ventral striatum/nucleus accumbens demonstrated also a change in its hemodynamic parameter, reflecting an increased level of activation. These converging results may indicate that the dopaminergic reward system reduces its functional connectivity and relinquishing its constraints on other areas when we listen to rhythmic music.

The Association between Self-Reported Difficulties in Emotion Regulation and Heart Rate Variability: The Salient Role of Not Accepting Negative Emotions.

Difficulties in emotion regulation are associated with development and maintenance of psychopathology. Typically, features of emotion regulation are assessed with self-report questionnaires. Heart rate variability (HRV) is an objective measure proposed as an index of emotional regulation capacity. A limited number of studies have shown that self-reported difficulties in emotion regulation are associated with HRV. However, results from prior studies are inconclusive, and an ecological validation of the association has not yet been tested. Therefore, further exploration of the relation between self-report questionnaires and psychophysiological measures of emotional regulation is needed. The present study investigated the contribution of self-reported emotion regulation difficulties on HRV in a student sample. We expected higher scores on emotion regulation difficulties to be associated with lower vagus-mediated HRV (vmHRV). Sixty-three participants filled out the Difficulties in Emotion Regulation Scale and their resting HRV was assessed. In addition, a subsample of participants provided ambulatory 24-h HRV data, in order to ecologically validate the resting data. Correlation analyses indicated that self-reported difficulties in emotion regulation was negatively associated with vmHRV in both resting HRV and 24-h HRV. Specifically, when exploring the contribution of the different facets of emotion dysregulation, the inability to accept negative emotions showed the strongest association with HRV. The results are discussed and need for future research is described.

Trait Self-Compassion Reflects Emotional Flexibility Through an Association with High Vagally Mediated Heart Rate Variability.

Converging evidence shows a positive effect of self-compassion on self-reported well-being and mental health. However, few studies have examined the relation between self-compassion and psychophysiological measures. In the present study, we therefore examined the relation between trait self-compassion and vagally mediated heart rate variability (vmHRV) in 53 students (39 female, mean age = 23.63). Trait self-compassion was assessed using the Self-Compassion Scale, and resting vmHRV was measured during a 5-min ECG baseline period. We hypothesized that higher levels of trait self-compassion would predict higher levels of resting vmHRV. Controlling for potential covariates (including age, gender, and BMI), the results confirmed our hypotheses, showing that higher levels of trait self-compassion predicted higher vmHRV. These results were validated with a 24-h measure of vmHRV, acquired from a subsample of the participants (n = 26, 16 female, mean age = 23.85), confirming the positive correlation between high trait self-compassion and higher vmHRV. The relation between trait self-compassion, vmHRV, self-reported trait anxiety (the trait scale of the State-Trait Anxiety Inventory; STAI) and self-reported rumination (the Rumination subscale of the Rumination-Reflection Questionnaire; RRQ-Rum) was also investigated. Higher levels of trait anxiety and rumination were highly correlated with low levels of trait self-compassion. Trait anxiety, but not rumination, correlated marginally significantly with the level of vmHRV. The findings of the present study indicate that trait self-compassion predicts a better ability to physiologically and psychologically adapt emotional responses. Possible implications and limitations of the study are discussed.

Resting states are resting traits--an FMRI study of sex differences and menstrual cycle effects in resting state cognitive control networks.

To what degree resting state fMRI is stable or susceptible to internal mind states of the individual is currently an issue of debate. To address this issue, the present study focuses on sex differences and investigates whether resting state fMRI is stable in men and women or changes within relative short-term periods (i.e., across the menstrual cycle). Due to the fact that we recently reported menstrual cycle effects on cognitive control based on data collected during the same sessions, the current study is particularly interested in fronto-parietal resting state networks. Resting state fMRI was measured in sixteen women during three different cycle phases (menstrual, follicular, and luteal). Fifteen men underwent three sessions in corresponding time intervals. We used independent component analysis to identify four fronto-parietal networks. The results showed sex differences in two of these networks with women exhibiting higher functional connectivity in general, including the prefrontal cortex. Menstrual cycle effects on resting states were non-existent. It is concluded that sex differences in resting state fMRI might reflect sexual dimorphisms in the brain rather than transitory activating effects of sex hormones on the functional connectivity in the resting brain.

Language lateralization and cognitive control across the menstrual cycle assessed with a dichotic-listening paradigm.

Lateralization has been shown to vary across the menstrual cycle, however, the underlying mechanisms are not fully understood, and results are inconsistent. Additionally, it has been suggested that estradiol enhances cognitive control. By modulating attention in a consonant-vowel dichotic listening test, the current study aims to investigate the effects of cycle-related changes on language lateralization (non-forced condition), as well as the effects of estradiol-modulated cognitive control (forced left condition) on the ear advantage. Fifteen women and fifteen men tested three times on the dichotic listening test, women once in menstrual, follicular, and luteal phase (verified by hormone assays). Whereas the results from the non-forced and forced-right condition remained stable, results from the forced left condition changed across the cycle, where women in the follicular phase compared to both menstrual and luteal phases showed a stronger left ear advantage, i.e. better cognitive control performance. The increase in performance from menstrual to follicular phase correlated negatively with increase in estradiol levels, indicating a shift from a stimulus-driven right ear advantage (indicating a left hemispheric asymmetry for language) when estradiol levels were low toward a cognitively controlled left ear advantage when estradiol levels were high. This finding strongly suggests an active role of estradiol on cognitive control. The study further suggests that the degree of cognitive control demands of a given task is important to consider when investigating lateralization across the menstrual cycle.

Stimulus expectancy modulates inferior frontal gyrus and premotor cortex activity in auditory perception.

In studies on auditory speech perception, participants are often asked to perform active tasks, e.g. decide whether the perceived sound is a speech sound or not. However, information about the stimulus, inherent in such tasks, may induce expectations that cause altered activations not only in the auditory cortex, but also in frontal areas such as inferior frontal gyrus (IFG) and motor cortices, even in the absence of an explicit task. To investigate this, we applied spectral mixes of a flute sound and either vowels or specific music instrument sounds (e.g. trumpet) in an fMRI study, in combination with three different instructions. The instructions either revealed no information about stimulus features, or explicit information about either the music instrument or the vowel features. The results demonstrated that, besides an involvement of posterior temporal areas, stimulus expectancy modulated in particular a network comprising IFG and premotor cortices during this passive listening task.

Effective connectivity analysis demonstrates involvement of premotor cortex during speech perception.

Several reports of premotor cortex involvement in speech perception have been put forward. Still, the functional role of premotor cortex is under debate. In order to investigate the functional role of premotor cortex, we presented parametrically varied speech stimuli in both a behavioral and functional magnetic resonance imaging (fMRI) study. White noise was transformed over seven distinct steps into a speech sound and presented to the participants in a randomized order. As control condition served the same transformation from white noise into a music instrument sound. The fMRI data were modelled with Dynamic Causal Modeling (DCM) where the effective connectivity between Heschl's gyrus, planum temporale, superior temporal sulcus and premotor cortex were tested. The fMRI results revealed a graded increase in activation in the left superior temporal sulcus. Premotor cortex activity was only present at an intermediate step when the speech sounds became identifiable but were still distorted but was not present when the speech sounds were clearly perceivable. A Bayesian model selection procedure favored a model that contained significant interconnections between Heschl's gyrus, planum temporal, and superior temporal sulcus when processing speech sounds. In addition, bidirectional connections between premotor cortex and superior temporal sulcus and from planum temporale to premotor cortex were significant. Processing non-speech sounds initiated no significant connections to premotor cortex. Since the highest level of motor activity was observed only when processing identifiable sounds with incomplete phonological information, it is concluded that premotor cortex is not generally necessary for speech perception but may facilitate interpreting a sound as speech when the acoustic input is sparse.

Increased activation in superior temporal gyri as a function of increment in phonetic features.

A common assumption is that phonetic sounds initiate unique processing in the superior temporal gyri and sulci (STG/STS). The anatomical areas subserving these processes are also implicated in the processing of non-phonetic stimuli such as music instrument sounds. The differential processing of phonetic and non-phonetic sounds was investigated in this study by applying a "sound-morphing" paradigm, where the presence of phonetic features were parametrically varied, creating a step-wise transition from a non-phonetic sound into a phonetic sound. The stimuli were presented in an event-related fMRI design. The fMRI-BOLD data were analysed using parametric contrasts. The results showed a higher sensitivity for sounds containing phonetic features compared to non-phonetic sounds in the middle part of STG, and in the anterior part of the planum temporale (PT) bilaterally. Although the same areas were involved in the processing of non-phonetic sounds, a difference in activation was evident in the STG, with an increase in activation related to increment of phonetic features in the sounds. The results indicate a stimulus-driven, bottom-up process that utilizes general auditory resources in the secondary auditory cortex, depending on specific phonetic features in the sounds.