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"Sebastian, Alexandra"
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Right inferior frontal gyrus implements motor inhibitory control via beta-band oscillations in humans
Motor inhibitory control implemented as response inhibition is an essential cognitive function required to dynamically adapt to rapidly changing environments. Despite over a decade of research on the neural mechanisms of response inhibition, it remains unclear, how exactly response inhibition is initiated and implemented. Using a multimodal MEG/fMRI approach in 59 subjects, our results reliably reveal that response inhibition is initiated by the right inferior frontal gyrus (rIFG) as a form of attention-independent top-down control that involves the modulation of beta-band activity. Furthermore, stopping performance was predicted by beta-band power, and beta-band connectivity was directed from rIFG to pre-supplementary motor area (pre-SMA), indicating rIFG’s dominance over pre-SMA. Thus, these results strongly support the hypothesis that rIFG initiates stopping, implemented by beta-band oscillations with potential to open up new ways of spatially localized oscillation-based interventions.
Journal Article
A coordinate-based ALE functional MRI meta-analysis of brain activation during verbal fluency tasks in healthy control subjects
Background
The processing of verbal fluency tasks relies on the coordinated activity of a number of brain areas, particularly in the frontal and temporal lobes of the left hemisphere. Recent studies using functional magnetic resonance imaging (fMRI) to study the neural networks subserving verbal fluency functions have yielded divergent results especially with respect to a parcellation of the inferior frontal gyrus for phonemic and semantic verbal fluency. We conducted a coordinate-based activation likelihood estimation (ALE) meta-analysis on brain activation during the processing of phonemic and semantic verbal fluency tasks involving 28 individual studies with 490 healthy volunteers.
Results
For phonemic as well as for semantic verbal fluency, the most prominent clusters of brain activation were found in the left inferior/middle frontal gyrus (LIFG/MIFG) and the anterior cingulate gyrus. BA 44 was only involved in the processing of phonemic verbal fluency tasks, BA 45 and 47 in the processing of phonemic and semantic fluency tasks.
Conclusions
Our comparison of brain activation during the execution of either phonemic or semantic verbal fluency tasks revealed evidence for spatially different activation in BA 44, but not other regions of the LIFG/LMFG (BA 9, 45, 47) during phonemic and semantic verbal fluency processing.
Journal Article
Dissociable attentional and inhibitory networks of dorsal and ventral areas of the right inferior frontal cortex: a combined task-specific and coordinate-based meta-analytic fMRI study
The right inferior frontal cortex (rIFC) is frequently activated during executive control tasks. Whereas the function of the dorsal portion of rIFC, more precisely the inferior frontal junction (rIFJ), is convergingly assigned to the attention system, the functional key role of the ventral portion, i.e., the inferior frontal gyrus (rIFG), is hitherto controversially debated. Here, we used a two-step methodical approach to clarify the differential function of rIFJ and rIFG. First, we used event-related functional magnetic resonance imaging (fMRI) during a modified stop signal task with an attentional capture condition (acSST) to delineate attentional from inhibitory motor processes (step 1). Then, we applied coordinate-based meta-analytic connectivity modeling (MACM) to assess functional connectivity profiles of rIFJ and rIFG across various paradigm classes (step 2). As hypothesized, rIFJ activity was associated with the detection of salient stimuli, and was functionally connected to areas of the ventral and dorsal attention network. RIFG was activated during successful response inhibition even when controlling for attentional capture and revealed the highest functional connectivity with core motor areas. Thereby, rIFJ and rIFG delineated largely independent brain networks for attention and motor control. MACM results attributed a more specific attentional function to rIFJ, suggesting an integrative role between stimulus-driven ventral and goal-directed dorsal attention processes. In contrast, rIFG was disclosed as a region of the motor control but not attention system, being essential for response inhibition. The current study provides decisive evidence regarding a more precise functional characterization of rIFC subregions in attention and inhibition.
Journal Article
Replication of fMRI group activations in the neuroimaging battery for the Mainz Resilience Project (MARP)
Motivated by the recent replicability crisis we tested replicability of functional magnetic resonance imaging (fMRI) group activations in two independent samples. An identical behavioral and fMRI test battery for the longitudinal investigation of stress resilience mechanisms was developed for the Mainz Resilience Project (MARP) and conducted in a discovery (N = 54) and a replication sample (N = 103). The test battery consisted of a stress reactivity task, a reward sensitivity task, a fear conditioning and extinction paradigm, two volitional reappraisal tasks and an emotional interference inhibition task. Replicability of group activations was tested with the Jaccard index and the Intra Class Correlation (ICC). Overall, we observed good to excellent replicability of activations at the whole brain level. Only a minority of contrasts showed unsatisfactory replicability. Replicability at the level of individual regions of interest (ROIs) was generally lower. Tasks with stronger activation in the discovery sample showed better replicability.
•Replicability of group activations was good to excellent for the majority of tasks.•Replicability at the level of individual regions of interest (ROIs) was lower.•Tasks with stronger activation in the discovery sample showed better replicability.
Journal Article
Positive appraisal style predicts long-term stress resilience and mediates the effect of a pro-resilience intervention
Stress resilience is the maintenance of mental health despite adversity. Identifying factors that predict and promote good long-term mental health outcomes in stressor-exposed individuals is a first step towards developing more effective prevention programs. In two independent observational samples (
N
= 132,
N
= 1034), we find that a tendency to evaluate stressors in a realistic to slightly unrealistically positive fashion (positive appraisal style, PAS) is prospectively associated with resilient outcomes over several years. We also find that PAS is an integrative, proximal resilience factor that mediates the pro-resilience effects of other protective factors (e.g., social support). In an analysis of pre-specified exploratory outcomes of a randomized controlled trial comparing a behavioral intervention targeting a broad set of resilience factors against usual care in a sample of distressed healthcare workers (
N
= 232; trial registry: NCT04980326), we find that PAS is modifiable, with improvements in PAS mediating intervention-induced improvements in resilience. These results establish PAS as a proximal, plastic, and potentially causal resilience factor.
Stress resilience is the maintenance of mental health despite adversity. Here, the authors show that how we typically evaluate adverse events is a key resilience factor and that improving it goes along with improved resilience.
Journal Article
Individualizing deep dynamic models for psychological resilience data
Deep learning approaches can uncover complex patterns in data. In particular, variational autoencoders achieve this by a non-linear mapping of data into a low-dimensional latent space. Motivated by an application to psychological resilience in the Mainz Resilience Project, which features intermittent longitudinal measurements of stressors and mental health, we propose an approach for individualized, dynamic modeling in this latent space. Specifically, we utilize ordinary differential equations (ODEs) and develop a novel technique for obtaining person-specific ODE parameters even in settings with a rather small number of individuals and observations, incomplete data, and a differing number of observations per individual. This technique allows us to subsequently investigate individual reactions to stimuli, such as the mental health impact of stressors. A potentially large number of baseline characteristics can then be linked to this individual response by regularized regression, e.g., for identifying resilience factors. Thus, our new method provides a way of connecting different kinds of complex longitudinal and baseline measures via individualized, dynamic models. The promising results obtained in the exemplary resilience application indicate that our proposal for dynamic deep learning might also be more generally useful for other application domains.
Journal Article
Cognitive training gain transfer in cognitively healthy aging: per protocol results of the German AgeGain study
Cognitive decline is part of the normal aging process, but also a major risk factor for dementia. Cognitive training interventions aim to attenuate cognitive decline, but training gains need to be transferable to untrained cognitive abilities to influence everyday function. Furthermore, the neurobiological basis of cognitive training gain transfer remains elusive. A possible candidate is increased bilateral hemisphere usage enabled by efficient structural connectivity, especially of prefrontal regions. Therefore, the present multicentric study used a cognitive training intervention to demonstrate training transfer and identify neurobiological modulators of successful transfer.
In total 235 subjects were enrolled in AgeGain; 180 underwent a broad 4-week cognitive training intervention at three study sites. Pre- and post-training neuropsychological testing was conducted and successful transferers were identified according to preregistered definitions. Pre-training, subjects underwent diffusion and functional MRI to assess interhemispheric connectivity, measured as microstructural integrity of the corpus callosum and lateralization of functional activation patterns during a cognitive control task. Logistic regression models were estimated to predict successful transfer based on structural connectivity and bilateralization of activation patterns.
Out of 180 subjects, 74 showed short-term training gain transfer that was maintained over 3 months in 19 subjects. Neither microstructural integrity of the corpus callosum, nor bilateralized activation predicted training gain transfer alone. However, their interaction was associated with long-term transfer over 3 months: subjects with higher mean diffusivity of the corpus callosum and more bilateral functional activity or conversely with lower diffusivity of the corpus callosum and more lateral functional activity were more likely successful long-term transferers.
We demonstrated successful training gain transfer in 41.1% of subjects, among whom 25.7% maintained the transfer over 3 months. Successful long-term transfer of training gains may depend on divergent mechanisms of structural and functional connectivity, which may explain previous heterogeneous results in the literature.
German Clinical Trials Register (DRKS), ID: DRKS00013077. Registered on November 19th 2017.
Journal Article
Emotional modulation of motor response inhibition in women with borderline personality disorder: an fMRI study
Both emotion regulation and impulsivity are core aspects of borderline personality disorder (BPD) pathology. Although both problems may be combined specifically in BPD, few studies to date have investigated the emotional modulation of impulsivity in BPD.
Women with BPD and matched healthy controls performed go/no-go tasks after induction of anger, joy or a neutral mood by vocally presented short stories. Dependent variables were the behavioural results and functional magnetic resonance imaging data.
We included 17 women with BPD and 18 controls in our study. No behavioural group differences were found. However, patients with BPD showed stronger activation of the left amygdala and weaker activation of the subgenual anterior cingulate during anger induction than controls. Inhibition in the go/no-go task after anger induction increased activity in the left inferior frontal cortex in controls, but not in women with BPD, who, in turn, showed increased activation in the subthalamic nucleus.
Findings cannot be generalized to men, and 4 patients were taking antidepressant medication (selective serotonin reuptake inhibitors). In addition, no patient control group was investigated, thus we do not know whether findings are specific to BPD compared with other disorders.
Our findings are consistent with the view that a disturbed amygdala–prefrontal network in patients with BPD is compensated by a subcortical loop involving the subthalamic nucleus, leading to normal behavioural inhibition in these patients.
Journal Article
Impulsivity and Cluster B Personality Disorders
Purpose of Review
Impulsivity is a multifaceted construct and an important personality trait in various mental health conditions. Among personality disorders (PDs), especially cluster B PDs are affected. The aims of this review are to summarize the relevant findings of the past 3 years concerning impulsivity in cluster B PDs and to identify those subcomponents of self-reported impulsivity and experimentally measured impulse control that are most affected in these disorders.
Recent Findings
All studies referred to antisocial (ASPD) or borderline PD (BPD), and none were found for narcissistic or histrionic PD. In ASPD as well as BPD, self-report scales primarily revealed heightened impulsivity compared to healthy controls. In experimental tasks, ASPD patients showed impairments in response inhibition, while fewer deficits were found in delay discounting. BPD patients showed specific impairments in delay discounting and proactive interference, while response inhibition was less affected. However, after inducing high levels of stress, deficits in response inhibition could also be observed in BPD patients. Furthermore, negative affect led to altered brain activation patterns in BPD patients during impulse control tasks, but no behavioral impairments were found.
Summary
As proposed by the DSM-5 alternative model for personality disorders, heightened impulsivity is a core personality trait in BPD and ASPD, which is in line with current research findings. However, different components of experimentally measured impulse control are affected in BPD and ASPD, and impulsivity occurring in negative emotional states or increased distress seems to be specific for BPD. Future research could be focused on measures that assess impulsive behaviors on a momentary basis as this is a promising approach especially for further ecological validation and transfer into clinical practice.
Journal Article