Carsten Diener

A meta-analysis of neurofunctional imaging studies of emotion and cognition in major depression

Major depressive disorder (MDD) is characterized by altered emotional and cognitive functioning. We performed a voxel-based whole-brain meta-analysis of functional neuroimaging data on altered emotion and cognition in MDD. Forty peer-reviewed studies in English-language published between 1998 and 2010 were included, which used functional neuroimaging during cognitive-emotional challenge in adult individuals with MDD and healthy controls. All studies reported between-groups differences for whole-brain analyses in standardized neuroanatomical space and were subjected to Activation Likelihood Estimation (ALE) of brain cluster showing altered responsivity in MDD. ALE resulted in thresholded and false discovery rate corrected hypo- and hyperactive brain regions. Against the background of a complex neural activation pattern, studies converged in predominantly hypoactive cluster in the anterior insular and rostral anterior cingulate cortex linked to affectively biased information processing and poor cognitive control. Frontal areas showed not only similar under- but also over-activation during cognitive-emotional challenge. On the subcortical level, we identified activation alterations in the thalamus and striatum which were involved in biased valence processing of emotional stimuli in MDD. These results for active conditions extend findings from ALE meta-analyses of resting state and antidepressant treatment studies and emphasize the key role of the anterior insular and rostral anterior cingulate cortex for altered emotion and cognition in MDD.

Neuroimaging-based markers of bipolar disorder: Evidence from two meta-analyses

BACKGROUND Bipolar disorder (BD) is often misdiagnosed or tardily detected, leading to inadequate treatment and devastating consequences. The identification of objective biomarkers, such as functional and structural brain abnormalities of BD might improve diagnosis and help elucidate its pathophysiology. METHODS To identify neurobiological markers of BD, two meta-analyses, one of functional neuroimaging studies related to emotional processing and a second of structural whole-brain neuroimaging studies in BD were conducted in the present study. Conducting a literature search on studies published up to September 2009 we identified 28 studies that were eligible for the meta-analyses: 13 functional magnetic resonance imaging studies, related to emotional processing and 15 structural imaging studies using whole-brain voxel-based morphometry. Only studies comparing patients with bipolar disorder to healthy controls were considered. Data were extracted or converted to a single anatomical reference (Talairach space). The activation likelihood estimation technique was used to assess the voxel-wise correspondence of results between studies. RESULTS In patients with BD, decreased activation and diminution of gray matter were identified in a cortical-cognitive brain network that has been associated with the regulation of emotions. By contrast, patients with BD exhibited increased activation in ventral limbic brain regions that mediate the experience of emotions and generation of emotional responses. The present study provides evidence for functional and anatomical alterations in BD in brain networks associated with the experience and regulation of emotions. CONCLUSIONS These alterations support previously proposed neurobiological models of BD and might represent valid neurobiological markers of the disorder. The specificity of these results to unipolar depression remains to be explored.

Simultaneous EEG and fMRI Reveals a Causally Connected Subcortical-Cortical Network during Reward Anticipation

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) have been used to study the neural correlates of reward anticipation, but the interrelation of EEG and fMRI measures remains unknown. The goal of the present study was to investigate this relationship in response to a well established reward anticipation paradigm using simultaneous EEG-fMRI recording in healthy human subjects. Analysis of causal interactions between the thalamus (THAL), ventral-striatum (VS), and supplementary motor area (SMA), using both mediator analysis and dynamic causal modeling, revealed that (1) THAL fMRI blood oxygenation level-dependent (BOLD) activity is mediating intermodal correlations between the EEG contingent negative variation (CNV) signal and the fMRI BOLD signal in SMA and VS, (2) the underlying causal connectivity network consists of top-down regulation from SMA to VS and SMA to THAL along with an excitatory information flow through a THAL→VS→SMA route during reward anticipation, and (3) the EEG CNV signal is best predicted by a combination of THAL fMRI BOLD response and strength of top-down regulation from SMA to VS and SMA to THAL. Collectively, these findings represent a likely neurobiological mechanism mapping a primarily subcortical process, i.e., reward anticipation, onto a cortical signature.

Altered neural reward and loss processing and prediction error signalling in depression

Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression.

Measuring depression with a well-being index: further evidence for the validity of the WHO Well-Being Index (WHO-5) as a measure of the severity of depression.

BACKGROUND In recent years, the WHO Wellbeing Index (WHO-5) has been used as a screening measure for depression. Nevertheless, research on the validity of this measure in the context of clinical depression is sparse. QUESTIONS The aim of the present study was to investigate the measurement invariance of the WHO-5 across depressed and non-depressed individuals, as well as the shape and specificity of its relationship to measures of depression severity. METHOD Of the 414 subjects who completed the WHO-5 and the Beck Depression Inventory-II (BDI-II), 207 had a diagnosis of a major depressive episode (MDE). A subsample also completed the Beck Anxiety Inventory (BAI) and was assessed by clinicians using the Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). RESULTS The WHO-5 demonstrated strong measurement invariance regarding the presence or absence of a current MDE. The WHO-5 showed a very high negative association with self- and observer-rated measures of depressive symptoms, especially in the range of mild to moderate symptoms. These associations were still substantial after controlling for measures of anxiety symptoms. LIMITATIONS In addition to a diagnostic interview, only one measure for self- and observer-rated symptoms of depression was used. Furthermore, the observer-rated measure was only assessed in one subsample that exhibited a somewhat restricted range of depression severity. CONCLUSION Although this index was originally designed as a measure of well-being, the results support the use of the WHO-5 in the context of depression research.

Effects of stressor controllability on psychophysiological, cognitive and behavioural responses in patients with major depression and dysthymia.

Background The experience of uncontrollability and helplessness in the face of stressful life events is regarded as an important determinant in the development and maintenance of depression. The inability to successfully deal with stressors might be linked to dysfunctional prefrontal functioning. We assessed cognitive, behavioural and physiological effects of stressor uncontrollability in depressed and healthy individuals. In addition, relationships between altered cortical processing and cognitive vulnerability traits of depression were analysed. Method A total of 26 unmedicated depressed patients and 24 matched healthy controls were tested in an expanded forewarned reaction (S1–S2) paradigm. In a factorial design, stressor controllability varied across three consecutive conditions: (a) control, (b) loss of control and (c) restitution of control. Throughout the experiment, error rates, ratings of controllability, arousal, emotional valence and helplessness were assessed together with the post-imperative negative variation (PINV) of the electroencephalogram. Results Depressed participants showed an enhanced frontal PINV as an electrophysiological index of altered information processing during both loss of control and restitution of control. They also felt more helpless than controls. Furthermore, frontal PINV magnitudes were associated with habitual rumination in the depressed subsample. Conclusions These findings indicate that depressed patients are more susceptible to stressor uncontrollability than healthy subjects. Moreover, the experience of uncontrollability seems to bias subsequent information processing in a situation where control is objectively re-established. Alterations in prefrontal functioning appear to contribute to this vulnerability and are also linked to trait markers of depression.

The startle reflex in alcohol-dependent patients: Changes after cognitive-behavioral therapy and predictive validity for drinking behavior : A pilot study

Background: Previous studies demonstrated an attenuation of the affect-modulated startle reflex when alcohol-dependent patients were viewing alcohol-associated pictures. This indicates an appetitive valence of these stimuli. We used the affect-modulated startle reflex to assess the effects of behavioral treatment on the emotional processing of alcohol-associated stimuli. Further, we examined whether the affect-modulated startle reflex is a predictor of treatment success. Methods: Forty-three alcohol-dependent patients (21 females, mean age 45.67 years, SD 9.45) were recruited consecutively from an inpatient alcohol detoxification facility where patients attended a 3-week detoxification program including cognitive-behavioral treatment to successfully handle high-risk situations. The eye blink component of the affect-modulated startle response, self-reported cue-induced craving and skin conductance responses to alcohol-associated and control slides were assessed before and after treatment. Changes were analyzed using repeated measures analysis of variance. Drinking behavior was assessed in the 6 months following treatment, and a regression analysis was performed to evaluate the predictive validity of the affect-modulated startle response for drinking behavior. Results: Drinking behavior as well as craving and skin conductance responses decreased significantly over time. The pattern of the affective modulation of the startle reflex was not altered over time. However, startle modulation and relapse were related, and within the group of relapsers, startle modulation was a significant predictor of drinking behavior. Conclusions: Our results suggest that the modulation of the startle reflex may reflect more enduring and permanent processes of emotional responding to alcohol-related cues than autonomic arousal and self-reported craving, and that startle modulation by alcohol-associated cues may be a better predictor of drinking behavior for relapsers than other measures. Further studies including a control condition are necessary to validate these findings.

The role of context in the processing of alcohol-relevant cues

In line with learning theories of drug addiction, drug‐related cues may be viewed as important motivators of continued drug use. They may be differentially effective depending on the context and motivational significance. The present study aimed to test the significance of different contexts in modulating alcohol‐related cue reactivity. Pictures depicting alcohol intake or its paraphernalia and pictures without any relation to alcohol intake were varied to depict physical and social contexts or different consumptive contexts associated with full/half‐full/empty alcohol beverage containers. We obtained ratings of craving, valence and arousal of the cues as well as skin conductance responses (SCRs) and startle reflex modulation measures from 21 abstinent alcohol‐dependent patients, recruited from an addiction treatment center, and 21 matched healthy controls. Social scenes and full glasses or bottles were rated as more pleasant and arousing compared with neutral drinking situations and empty glasses or bottles in patients. Furthermore, we found a decreased startle reflex magnitude to social compared with neutral drinking situations, and both higher SCRs and decreased startle reflex magnitude to full compared with empty glasses or bottles in patients versus controls. These results show that both physical and social and consumptive contexts differentially influence cue reactivity in abstinent alcohol‐dependent patients with both social and pub‐related physical contexts, and the initial consumptive context eliciting the most appetitive and arousing responses. These data have not only important implications for our understanding of the role of learning in drug dependence but also for treatment, which needs to take these factors into account.

Health anxiety and hypochondriasis in the light of DSM-5

Background: In the DSM-5, the diagnosis of hypochondriasis was replaced by two new diagnositic entities: somatic symptom disorder (SSD) and illness anxiety disorder (IAD). Both diagnoses share high health anxiety as a common criterion, but additonal somatic symptoms are only required for SSD but not IAD. Design: Our aim was to provide empirical evidence for the validity of these new diagnoses using data from a case–control study of highly health-anxious (n = 96), depressed (n = 52), and healthy (n = 52) individuals. Results: The individuals originally diagnosed as DSM-IV hypochondriasis predominantly met criteria for SSD (74%) and rarely for IAD (26%). Individuals with SSD were more impaired, had more often comorbid panic and generalized anxiety disorders, and had more medical consultations as those with IAD. Yet, no significant differences were found between SSD and IAD with regard to levels of health anxiety, other hypochondriacial characteristics, illness behavior, somatic symptom attributions, and physical concerns, whereas both groups differed significantly from clinical and healthy controls in all of these variables. Conclusion: These results do not support the proposed splitting of health anxiety/hypochondriasis into two diagnoses. Further validation studies with larger samples and additional control groups are warranted to prove the validity of the new diagnoses.

Simultaneous EEG–fMRI reveals brain networks underlying recognition memory ERP old/new effects

The mapping of event-related potentials (ERP) on functional magnetic resonance imaging (fMRI) data remains difficult as scalp electroencephalography (EEG) is assumed to be largely insensitive to deep brain structures. Simultaneous recordings of EEG and fMRI might be helpful in reconciling surface ERPs with hemodynamic activations in medial temporal lobe structures related to recognition memory. EEG and imaging studies provide evidence for two independent processes underlying recognition memory, namely recollection and familiarity. Recollection reflects the conscious retrieval of contextual information about a specific episode, while familiarity refers to an acontextual feeling of knowing. Both processes were related to two spatiotemporally different ERP effects, namely the early mid-frontal old/new effect (familiarity) and the late parietal old new effect (recollection). We conducted an exploratory simultaneous EEG-fMRI study using a recognition memory paradigm to investigate which brain activations are modulated in relation to the ERP old/new effects. To this end we examined 17 participants in a yes/no recognition task with word stimuli. Single-trial amplitudes of ERP old/new effects were related to the hemodynamic signal in an EEG-informed fMRI analysis for a subset of 12 subjects. FMRI activation in the right dorsolateral prefrontal cortex and the right intraparietal sulcus was associated with the amplitude of the early frontal old/new effect (350-550ms), and activation in the right posterior hippocampus, parahippocampal cortex and retrosplenial cortex was associated with the amplitude of the late parietal old new effect (580-750ms). These results provide the first direct link between electrophysiological and hemodynamic correlates of familiarity and recollection. Moreover, these findings in healthy subjects complement data from intracranial ERP recordings in epilepsy patients and lesion studies in hypoxia patients.