Alexandra Sebastian

A coordinate-based ALE functional MRI meta-analysis of brain activation during verbal fluency tasks in healthy control subjects

BackgroundThe 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.ResultsFor 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.ConclusionsOur 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.

Frontal dysfunctions of impulse control - a systematic review in borderline personality disorder and attention-deficit/hyperactivity disorder.

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.

Emotional modulation of motor response inhibition in women with borderline personality disorder: an fMRI study

BACKGROUND 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. METHODS 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. RESULTS 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. LIMITATIONS 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. CONCLUSION 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.

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.

Women with borderline personality disorder do not show altered BOLD responses during response inhibition

Impulsivity is central to borderline personality disorder (BPD). Response inhibition, addressing the ability to suppress or stop actions, is one aspect of behavioral impulse control which is frequently used to assess impulsivity. BPD patients display deficits in response inhibition under stress condition or negative emotions. We assessed whether response inhibition and its neural underpinnings are impaired in BPD when tested in an emotionally neutral setting and when co-morbid attention-deficit/hyperactivity disorder (ADHD) is excluded. To this end, we studied response inhibition in unmedicated BPD patients and healthy controls (HC) in two independent samples using functional magnetic resonance imaging during Simon-, Go/nogo-, and Stopsignal tasks. BPD patients and HC did not differ significantly in their performance in the Go/nogo and the Stopsignal tasks. Response interference in the Simon task was increased in BPD patients in one sample, but this could not be replicated in the second sample. In both samples, no significant differences in brain activation patterns during any of the tasks were present while the neural impulse control network was robustly activated during the inhibition tasks in both groups. Our results provide evidence that under emotionally neutral conditions response inhibition is not impaired in patients with BPD without co-occurring ADHD.

Data-driven analysis of simultaneous EEG/fMRI reveals neurophysiological phenotypes of impulse control.

Response inhibition is the ability to suppress inadequate but prepotent or ongoing response tendencies. A fronto‐striatal network is involved in these processes. Between‐subject differences in the intra‐individual variability have been suggested to constitute a key to pathological processes underlying impulse control disorders. Single‐trial EEG/fMRI analysis allows to increase sensitivity for inter‐individual differences by incorporating intra‐individual variability. Thirty‐eight healthy subjects performed a visual Go/Nogo task during simultaneous EEG/fMRI. Of 38 healthy subjects, 21 subjects reliably showed Nogo‐related ICs (Nogo‐IC‐positive) while 17 subjects (Nogo‐IC‐negative) did not. Comparing both groups revealed differences on various levels: On trait level, Nogo‐IC‐negative subjects scored higher on questionnaires regarding attention deficit/hyperactivity disorder; on a behavioral level, they displayed slower response times (RT) and higher intra‐individual RT variability while both groups did not differ in their inhibitory performance. On the neurophysiological level, Nogo‐IC‐negative subjects showed a hyperactivation of left inferior frontal cortex/insula and left putamen as well as significantly reduced P3 amplitudes. Thus, a data‐driven approach for IC classification and the resulting presence or absence of early Nogo‐specific ICs as criterion for group selection revealed group differences at behavioral and neurophysiological levels. This may indicate electrophysiological phenotypes characterized by inter‐individual variations of neural and behavioral correlates of impulse control. We demonstrated that the inter‐individual difference in an electrophysiological correlate of response inhibition is correlated with distinct, potentially compensatory neural activity. This may suggest the existence of electrophysiologically dissociable phenotypes of behavioral and neural motor response inhibition with the Nogo‐IC‐positive phenotype possibly providing protection against impulsivity‐related dysfunction. Hum Brain Mapp 37:3114–3136, 2016.

The Mona Lisa effect: Neural correlates of centered and off‐centered gaze

The Mona Lisa effect describes the phenomenon when the eyes of a portrait appear to look at the observer regardless of the observers position. Recently, the metaphor of a cone of gaze has been proposed to describe the range of gaze directions within which a person feels looked at. The width of the gaze cone is about five degrees of visual angle to either side of a given gaze direction. We used functional magnetic resonance imaging to investigate how the brain regions involved in gaze direction discrimination would differ between centered and decentered presentation positions of a portrait exhibiting eye contact. Subjects observed a given portraits eyes. By presenting portraits with varying gaze directions—eye contact (0°), gaze at the edge of the gaze cone (5°), and clearly averted gaze (10°), we revealed that brain response to gaze at the edge of the gaze cone was similar to that produced by eye contact and different from that produced by averted gaze. Right fusiform gyrus and right superior temporal sulcus showed stronger activation when the gaze was averted as compared to eye contact. Gaze sensitive areas, however, were not affected by the portraits presentation location. In sum, although the brain clearly distinguishes averted from centered gaze, a substantial change of vantage point does not alter neural activity, thus providing a possible explanation why the feeling of eye contact is upheld even in decentered stimulus positions. Hum Brain Mapp 36:619–632, 2015.

Symptom-specific amygdala hyperactivity modulates motor control network in conversion disorder

Initial historical accounts as well as recent data suggest that emotion processing is dysfunctional in conversion disorder patients and that this alteration may be the pathomechanistic neurocognitive basis for symptoms in conversion disorder. However, to date evidence of direct interaction of altered negative emotion processing with motor control networks in conversion disorder is still lacking. To specifically study the neural correlates of emotion processing interacting with motor networks we used a task combining emotional and sensorimotor stimuli both separately as well as simultaneously during functional magnetic resonance imaging in a well characterized group of 13 conversion disorder patients with functional hemiparesis and 19 demographically matched healthy controls. We performed voxelwise statistical parametrical mapping for a priori regions of interest within emotion processing and motor control networks. Psychophysiological interaction (PPI) was used to test altered functional connectivity of emotion and motor control networks. Only during simultaneous emotional stimulation and passive movement of the affected hand patients displayed left amygdala hyperactivity. PPI revealed increased functional connectivity in patients between the left amygdala and the (pre-)supplemental motor area and the subthalamic nucleus, key regions within the motor control network. These findings suggest a novel mechanistic direct link between dysregulated emotion processing and motor control circuitry in conversion disorder.

Data-driven analysis of simultaneous EEG/fMRI using an ICA approach.

Due to its millisecond-scale temporal resolution, EEG allows to assess neural correlates with precisely defined temporal relationship relative to a given event. This knowledge is generally lacking in data from functional magnetic resonance imaging (fMRI) which has a temporal resolution on the scale of seconds so that possibilities to combine the two modalities are sought. Previous applications combining event-related potentials (ERPs) with simultaneous fMRI BOLD generally aimed at measuring known ERP components in single trials and correlate the resulting time series with the fMRI BOLD signal. While it is a valuable first step, this procedure cannot guarantee that variability of the chosen ERP component is specific for the targeted neurophysiological process on the group and single subject level. Here we introduce a newly developed data-driven analysis procedure that automatically selects task-specific electrophysiological independent components (ICs). We used single-trial simultaneous EEG/fMRI analysis of a visual Go/Nogo task to assess inhibition-related EEG components, their trial-to-trial amplitude variability, and the relationship between this variability and the fMRI. Single-trial EEG/fMRI analysis within a subgroup of 22 participants revealed positive correlations of fMRI BOLD signal with EEG-derived regressors in fronto-striatal regions which were more pronounced in an early compared to a late phase of task execution. In sum, selecting Nogo-related ICs in an automated, single subject procedure reveals fMRI-BOLD responses correlated to different phases of task execution. Furthermore, to illustrate utility and generalizability of the method beyond detecting the presence or absence of reliable inhibitory components in the EEG, we show that the IC selection can be extended to other events in the same dataset, e.g., the visual responses.

Improving MRT Image Quality in Patients with Movement Disorders

OBJECTIVE In order to improve image quality in a simultaneous fMRI-EEG study with patients suffering from the involuntary movements typical for Huntingtons disease, the aim was to develop a technique for immobilizing the heads of our patients inside an MRI head coil. METHODS We modified a mask technique previously used for reliable repositioning in temporally fractionated radiotherapy. The mask was tested in three patients with Huntingtons disease, acquiring structural and functional MR images with simultaneous EEG with and without the mask. RESULTS Image as well as EEG signal quality were significantly improved in patients wearing the mask. However, the image quality with mask was comparable to acquisitions from patients without movement disorders only in patients with light to moderate dyskinesia. Although image quality was also significantly improved in a patient suffering from severe dyskinesia with quasi-continuous involuntary movements, the quality of both the MR images as well as the EEG signal was lower than what would be expected in a healthy control person. CONCLUSION We have succeeded in developing a mask that fits into the MRI head coil, does not disturb the MRI signal, and significantly improves both fMRI and EEG signal quality.