Jutta Ernst

Increased self‐focus in major depressive disorder is related to neural abnormalities in subcortical‐cortical midline structures

Patients with major depressive disorder (MDD) often show a tendency to strongly introspect and reflect upon their self, which has been described as increased self‐focus. Although subcortical‐cortical midline structures have been associated with reflection and introspection of oneself in healthy subjects, the neural correlates of the abnormally increased attribution of negative emotions to oneself, i.e. negative self‐attribution, as hallmark of the increased self‐focus in MDD remain unclear. The aim of the study was, therefore, to investigate the neural correlates during judgment of self‐relatedness of positive and negative emotional stimuli thereby testing for emotional self‐attribution. Using fMRI, we investigated 27 acute MDD patients and compared them with 25 healthy subjects employing a paradigm that focused on judgment of self‐relatedness when compared with mere perception of the very same emotional stimuli. Behaviourally, patients with MDD showed significantly higher degrees of self‐relatedness of specifically negative emotional stimuli when compared with healthy subjects. Neurally, patients with MDD showed significantly lower signal intensities in various subcortical and cortical midline regions like the dorsomedial prefrontal cortex (DMPFC), supragenual anterior cingulate cortex, precuneus, ventral striatum (VS), and the dorsomedial thalamus (DMT). Signal changes in the DMPFC correlated with depression severity and hopelessness whereas those in the VS and the DMT were related to judgment of self‐relatedness of negative emotional stimuli. In conclusion, we present first evidence that the abnormally increased negative self‐attribution as hallmark of the increased self‐focus in MDD might be mediated by altered neural activity in subcortical‐cortical midline structures. Hum Brain Mapp, 2009.

Reduced negative BOLD responses in the default-mode network and increased self-focus in depression

Abstract Objectives. Functional imaging studies in major depressive disorder (MDD) indicate abnormal resting state neural activity and negative blood oxygenation level-dependent (BOLD) responses (NBRs) in regions of the default-mode network (DMN). Methods. Since activity in DMN regions has been associated with self-relatedness, we investigated neural activity in these regions during self-related emotional judgement and passive picture viewing in 25 patients with MDD and 25 healthy controls in an event-related fMRI design. Results. Behaviourally, MDD subjects showed significantly higher ratings of self-relatedness that also correlated with depression symptoms such as hopelessness. Neuroimaging results in MDD patients showed significantly lower negative BOLD responses (NBRs) in anterior medial cortical regions during judgement of self-relatedness while posterior medial regions showed increased NBRs. Unlike in healthy subjects, the anterior medial cortical NBRs were no longer parametrically modulated by the degree of self-relatedness in MDD patients. Conclusions. Our findings suggest that reduced NBRs in the anterior regions of the default-mode network may signify decoupling from self-relatedness in MDD patients with the consecutive abnormal increase of self-focus.

The association of interoceptive awareness and alexithymia with neurotransmitter concentrations in insula and anterior cingulate

Alexithymia and increased interoceptive awareness have been associated with affective disorders as well as with altered insula and anterior cingulate cortex (ACC) function. Brain imaging studies have demonstrated an association between neurotransmitter function and affective disorders as well as personality traits. Here, we first examined the relationship between alexithymic facets as assessed with the Toronto Alexithymia Scale (TAS-20) and interoceptive awareness (assessed with the Body Perception Questionnaire) in 18 healthy subjects. Second, we investigated their association with glutamate and gamma-aminobutyric acid (GABA) concentrations in the left insula and the ACC using 3-Tesla proton magnetic resonance spectroscopy. Behaviorally, we found a close association between alexithymia and interoceptive awareness. Furthermore, glutamate levels in the left insula were positively associated with both alexithymia and awareness of autonomic nervous system reactivity, while GABA concentrations in ACC were selectively associated with alexithymia. Although preliminary, our results suggest that increased glutamate-mediated excitatory transmission-related to enhanced insula activity-reflects increased interoceptive awareness in alexithymia. Suppression of the unspecific emotional arousal evoked by increased awareness of bodily responses in alexithymics might thus be reflected in decreased neuronal activity mediated by increased GABA concentration in ACC.

Interoceptive awareness enhances neural activity during empathy

Empathy is a multicomponent function that includes sensorimotor, affective, and cognitive components. Although especially the affective component may implicate interoception and interoceptive awareness, the impact of interoception on empathy has never been evaluated behaviorally or neurophysiologically. Here, we tested how a preceding period of interoceptive awareness impacts and modulates neural activity during subsequent empathy. We used functional magnetic resonance imaging (fMRI) and measured the sequential interaction between interoception and empathy using fMRI in 18 healthy subjects. We found that the preceding interoceptive awareness period significantly enhanced neural activity during empathy in bilateral anterior insula and various cortical midline regions. The enhancement of neural activity during empathy in both interoceptive and empathy networks by preceding interoceptive awareness suggests a close relationship between interoception and empathy; thereby, interoception seems to be implicated to yielding empathy. Hum Brain Mapp, 2013.

Prefrontal Thinning Affects Functional Connectivity and Regional Homogeneity of the Anterior Cingulate Cortex in Depression

Major depressive disorder (MDD) is associated with structural and functional alterations in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Enhanced ACC activity at rest (measured using various imaging methodologies) is found in treatment-responsive patients and is hypothesized to bolster treatment response by fostering adaptive rumination. However, whether structural changes influence functional coupling between fronto-cingulate regions and ACC regional homogeneity (ReHo) and whether these functional changes are related to levels of adaptive rumination and treatment response is still unclear. Cortical thickness and ReHo maps were calculated in 21 unmedicated depressed patients and 35 healthy controls. Regions with reduced cortical thickness defined the seeds for the subsequent functional connectivity (FC) analyses. Patients completed the Response Style Questionnaire, which provided a measure of adaptive rumination associated with better response to psychotherapy. Compared with controls, depressed patients showed thinning of the right anterior PFC, increased prefrontal connectivity with the supragenual ACC (suACC), and higher ReHo in the suACC. The suACC clusters of increased ReHo and FC spatially overlapped. In depressed patients, suACC ReHo scores positively correlated with PFC thickness and with FC strength. Moreover, stronger fronto-cingulate connectivity was related to higher levels of adaptive rumination. Greater suACC ReHo and connectivity with the right anterior PFC seem to foster adaptive forms of self-referential processing associated with better response to psychotherapy, whereas prefrontal thinning impairs the ability of depressed patients to engage the suACC during a major depressive episode. Bolstering the function of the suACC may represent a potential target for treatment.

Essentials of psychoanalytic process and change: how can we investigate the neural effects of psychodynamic psychotherapy in individualized neuro-imaging?

The paper focuses on the essentials of psychoanalytic process and change and the question of how the neural correlates and mechanisms of psychodynamic psychotherapy can be investigated. The psychoanalytic approach aims at enabling the patient to “remember, repeat, and work through” concerning explicit memory. Moreover, the relationship between analyst and patient establishes a new affective configuration which enables a reconstruction of the implicit memory. If psychic change can be achieved it corresponds to neuronal transformation. Individualized neuro-imaging requires controlling and measuring of variables that must be defined. Two main methodological problems can be distinguished: the design problem addresses the issue of how to account for functionally related variables in an experimentally independent way. The translation problem raises the question of how to bridge the gaps between different levels of the concepts presupposed in individualized neuro-imaging (e.g., the personal level of the therapist and the client, the neural level of the brain). An overview of individualized paradigms, which have been used until now is given, including Operationalized Psychodynamic Diagnosis (OPD-2) and the Maladaptive Interpersonal Patterns Q-Start (MIPQS). The development of a new paradigm that will be used in fMRI experiments, the “Interpersonal Relationship Picture Set” (IRPS), is described. Further perspectives and limitations of this new approach concerning the design and the translation problem are discussed.

Current relevance of hypoxia in head and neck cancer

Head and Neck cancer (HNC) is a complex mix of cancers and one of the more common cancers with a relatively poor prognosis. One of the factors that may assist us in predicting survival and allow us to adjust our treatment strategies is the presence of tumor hypoxia. In this overview we aim to evaluate the current evidence and potential clinical relevance of tumor hypoxia in head and neck cancer according to an extensive search of current literature. An abundance of evidence and often contradictory evidence is found in the literature. Even the contradictory evidence and comparisons are difficult to judge as criteria and methodologies differ greatly, furthermore few prospective observational studies exist for verification of the pre-clinical studies. Despite these discrepancies there is clear evidence of associations between prognosis and poor tumor oxygenation biomarkers such as HIF-1α, GLUT-1 and lactate, though these associations are not exclusive. The use of genetic markers is expanding and will probably lead to significantly more and complex evidence. The lack of oxygenation in head and neck tumors is of paramount importance for the prediction of treatment outcomes and prognosis. Despite the wide array of conflicting evidence, the drive towards non-invasive prediction of tumor hypoxia should continue.

One look is worth a thousand words: New picture stimuli of interpersonal situations

ABSTRACT This paper introduces a picture system that can be used in functional imaging experiments exploring interpersonal relations. This is important for psychotherapy research to understand the neural basis of psychological treatment effects. Pictures have many advantages for the design of functional imaging experiments, but no picture system illustrating interpersonal behavior patterns is, to date, available. We therefore developed, on the basis of a validated card-sorting test, the Interpersonal Relations Picture System. In summary, 43 pictures with 2 or more stick figures in different social situations and 9 control pictures were composed. To test the relation between each picture and the appropriate description, two successive online surveys, including 1058 and 675 individuals respectively, were conducted. Using two question types, the grade expressiveness of each picture was assessed. In total, 24 pictures and 6 control pictures met our criteria for sufficient strength and consistency with the appropriate description. Both measures are correlated with each other in all pictures illustrating interpersonal behavior, but not in the control pictures. Relations to other stimulus types and the applicability of the new picture system in functional neuroimaging methods are discussed. It is concluded that the new system will be helpful in studying the profound effect of relational change in psychotherapy.

Thinking about the past to shape the present: neural activation during the recall of relationship episodes

Abstract Reflecting on oneself and others in relationships is an ability that is central to our social existence. Specifically, considering formative autobiographical experiences in relationships may contribute to more flexibility in perceiving, as well as in shaping present relationships. Reflecting on such experiences mobilizes different social cognitive and affective processes. We aim to explore the neural basis of these processes. With a newly developed functional magnetic imaging (fMRI) task, we investigated brain activation in 35 healthy individuals during recall of relationship episodes involving themselves or others. We found that recalling formative episodes involving themselves modulated brain activity in the right parahippocampus, left precuneus, bilateral fusiform gyrus, bilateral insula, and left presupplementary motor area. These areas are involved in memory processes, self‐generated thought, and affective experience. The recall of relationship episodes involving others led to similar activation patterns. Our results underscore the close link between self‐reflection, understanding others, and memory processes and emphasize the role of affective dimensions for self‐relevant experiences. They contribute to a growing body of research on neural mechanisms involved in complex social cognitive processes decisive for our capacity to navigate our social environment.

Expression of CK19 is an independent predictor of negative outcome for patients with squamous cell carcinoma of the tongue

Objectives To explore the prognostic role of CK19 expression in squamous cell carcinomas within a well-defined cohort of oral tongue cancer patients. Methods In our retrospective study, we investigated 129 patients with tongue cancer that had suitable material for inclusion in a tissue microarray (TMA). Where possible, samples were taken from central and peripheral regions of the tumor to generate a representative sample of the tumor. The expression level of CK19 was assessed by immunohistochemical staining. Results Expression of CK19 in squamous cell carcinoma of the tongue was identified as a negative predictor for overall survival (OS; p<0.000) and disease specific survival (DSS; p=0.001). No significant difference could be shown for disease free survival (DFS) between patients with positive and negative CK19 staining (p=.094). Conclusion This is the first description of the highly significant role of CK19 in a selective, organ specific head and neck cancer cohort. Our results are of special importance against the background that CK19 positive carcinomas revealed a significantly poorer prognosis and therefore emphasize its prognostic and possible diagnostic role in tongue cancer.