Christian Gaden Jensen

Mindfulness training affects attention--or is it attentional effort?

Improvements in attentional performance are at the core of proposed mechanisms for stress reduction in mindfulness meditation practices. However, this claim can be questioned because no previous studies have actively manipulated test effort in control groups and controlled for effects of stress reduction per se. In a blinded design, 48 young, healthy meditation novices were randomly assigned to a mindfulness-based stress reduction (MBSR), nonmindfulness stress reduction (NMSR), or inactive control group. At posttest, inactive controls were randomly split into nonincentive and incentive controls, the latter receiving a financial reward to improve attentional performance. Pre- and postintervention, 5 validated attention paradigms were employed along with self-report scales on mindfulness and perceived stress and saliva cortisol samples to measure physiological stress. Attentional effects of MBSR, NMSR, and the financial incentive were comparable or significantly larger in the incentive group on all reaction-time-based measures. However, selective attention in the MBSR group improved significantly more than in any other group. Similarly, only the MBSR intervention improved the threshold for conscious perception and visual working memory capacity. Furthermore, stress-reducing effects of MBSR were supported because those in the MBSR group showed significantly less perceived and physiological stress while increasing their mindfulness levels significantly. We argue that MBSR may contribute uniquely to attentional improvements but that further research focusing on non-reaction-time-based measures and outcomes less confounded by test effort is needed. Critically, our data demonstrate that previously observed improvements of attention after MBSR may be seriously confounded by test effort and nonmindfulness stress reduction.

The balanced mind: the variability of task-unrelated thoughts predicts error-monitoring

Self-generated thoughts unrelated to ongoing activities, also known as “mind-wandering,” make up a substantial portion of our daily lives. Reports of such task-unrelated thoughts (TUTs) predict both poor performance on demanding cognitive tasks and blood-oxygen-level-dependent (BOLD) activity in the default mode network (DMN). However, recent findings suggest that TUTs and the DMN can also facilitate metacognitive abilities and related behaviors. To further understand these relationships, we examined the influence of subjective intensity, ruminative quality, and variability of mind-wandering on response inhibition and monitoring, using the Error Awareness Task (EAT). We expected to replicate links between TUT and reduced inhibition, and explored whether variance in TUT would predict improved error monitoring, reflecting a capacity to balance between internal and external cognition. By analyzing BOLD responses to subjective probes and the EAT, we dissociated contributions of the DMN, executive, and salience networks to task performance. While both response inhibition and online TUT ratings modulated BOLD activity in the medial prefrontal cortex (mPFC) of the DMN, the former recruited a more dorsal area implying functional segregation. We further found that individual differences in mean TUTs strongly predicted EAT stop accuracy, while TUT variability specifically predicted levels of error awareness. Interestingly, we also observed co-activation of salience and default mode regions during error awareness, supporting a link between monitoring and TUTs. Altogether our results suggest that although TUT is detrimental to task performance, fluctuations in attention between self-generated and external task-related thought is a characteristic of individuals with greater metacognitive monitoring capacity. Achieving a balance between internally and externally oriented thought may thus aid individuals in optimizing their task performance.

Central 5-HT4 receptor binding as biomarker of serotonergic tonus in humans: a [11C]SB207145 PET study.

Identification of a biomarker that can inform on extracellular serotonin (5-HT) levels in the brains of living humans would enable greater understanding of the way brain circuits are modulated by serotonergic neurotransmission. Substantial evidence from studies in animals and humans indicates an inverse relationship between central 5-HT tonus and 5-HT type 4 receptor (5-HT4R) density, suggesting that 5-HT4R receptor density may be a biomarker marker for 5-HT tonus. Here, we investigated whether a 3-week administration of a selective serotonin reuptake inhibitor, expected to increase brain 5-HT levels, is associated with a decline in brain 5-HT4R binding. A total of 35 healthy men were studied in a placebo-controlled, randomized, double-blind study. Participants were assigned to receive 3 weeks of oral dosing with placebo or fluoxetine, 40 mg per day. Brain 5-HT4R binding was quantified at baseline and at follow-up with [11C]SB207145 positron emission tomography (PET). Three weeks of intervention with fluoxetine was associated with a 5.2% reduction in brain 5-HT4R binding (P=0.017), whereas placebo intervention did not change 5-HT4R binding (P=0.52). Our findings are consistent with a model, wherein the 5-HT4R density adjusts to changes in the extracellular 5-HT tonus. Our data demonstrate for the first time in humans that the imaging of central 5-HT4R binding may be used as an in vivo biomarker of the central 5-HT tonus.

The 5-HT4 receptor levels in hippocampus correlates inversely with memory test performance in humans.

The cerebral serotonin (5‐HT) system is involved in cognitive functions such as memory and learning and animal studies have repeatedly shown that stimulation of the 5‐HT type 4 receptor (5‐HT4R) facilitates memory and learning and further that the 5‐HT4R modulates cellular memory processes in hippocampus. However, any associations between memory functions and the expression of the 5‐HT4R in the human hippocampus have not been investigated. Using positron emission tomography with the tracer [11C]SB207145 and Reys Auditory Verbal Learning Test we aimed to examine the individual variation of the 5‐HT4R binding in hippocampus in relation to memory acquisition and consolidation in healthy young volunteers. We found significant, negative associations between the immediate recall scores and left and right hippocampal BPND, (p = 0.009 and p = 0.010 respectively) and between the right hippocampal BPND and delayed recall (p = 0.014). These findings provide evidence that the 5‐HT4R is associated with memory functions in the human hippocampus and potentially pharmacological stimulation of the receptor may improve episodic memory. Hum Brain Mapp 34:3066–3074, 2013.

Fluctuations in [11C]SB207145 PET Binding Associated with Change in Threat-Related Amygdala Reactivity in Humans

Serotonin critically affects the neural processing of emotionally salient stimuli, including indices of threat; however, how alterations in serotonin signaling contribute to changes in brain function is not well understood. Recently, we showed in a placebo-controlled study of 32 healthy males that brain serotonin 4 receptor (5-HT4) binding, assessed with [11C]SB207145 PET, was sensitive to a 3-week intervention with the selective serotonin reuptake inhibitor fluoxetine, supporting it as an in vivo model for fluctuations in central serotonin levels. Participants also underwent functional magnetic resonance imaging while performing a gender discrimination task of fearful, angry, and neutral faces. This offered a unique opportunity to evaluate whether individual fluctuations in central serotonin levels, indexed by change in [11C]SB207145 binding, predicted changes in threat-related reactivity (ie, fear and angry vs neutral faces) within a corticolimbic circuit including the amygdala and medial prefrontal and anterior cingulate cortex. We observed a significant association such that decreased brain-wide [11C]SB207145 binding (ie, increased brain serotonin levels) was associated with lower threat-related amygdala reactivity, whereas intervention group status did not predict change in corticolimbic reactivity. This suggests that in the healthy brain, interindividual responses to pharmacologically induced and spontaneously occurring fluctuations in [11C]SB207145 binding, a putative marker of brain serotonin levels, affect amygdala reactivity to threat. Our finding also supports that change in brain [11C]SB207145 binding may be a relevant marker for evaluating neurobiological mechanisms underlying sensitivity to threat and serotonin signaling.

Development and psychometric validation of the verbal affective memory test

ABSTRACT We here present the development and validation of the Verbal Affective Memory Test-24 (VAMT-24). First, we ensured face validity by selecting 24 words reliably perceived as positive, negative or neutral, respectively, according to healthy Danish adults’ valence ratings of 210 common and non-taboo words. Second, we studied the tests psychometric properties in healthy adults. Finally, we investigated whether individuals diagnosed with Seasonal Affective Disorder (SAD) differed from healthy controls on seasonal changes in affective recall. Recall rates were internally consistent and reliable and converged satisfactorily with established non-affective verbal tests. Immediate recall (IMR) for positive words exceeded IMR for negative words in the healthy sample. Relatedly, individuals with SAD showed a significantly larger decrease in positive recall from summer to winter than healthy controls. Furthermore, larger seasonal decreases in positive recall significantly predicted larger increases in depressive symptoms. Retest reliability was satisfactory, rs ≥ .77. In conclusion, VAMT-24 is more thoroughly developed and validated than existing verbal affective memory tests and showed satisfactory psychometric properties. VAMT-24 seems especially sensitive to measuring positive verbal recall bias, perhaps due to the application of common, non-taboo words. Based on the psychometric and clinical results, we recommend VAMT-24 for international translations and studies of affective memory.

State-dependent alterations in inhibitory control and emotional face identification in seasonal affective disorder.

Background: Depressed individuals often exhibit impaired inhibition to negative input and identification of positive stimuli, but it is unclear whether this is a state or trait feature. We here exploited a naturalistic model, namely individuals with seasonal affective disorder (SAD), to study this feature longitudinally. Aim: The goal of this study was to examine seasonal changes in inhibitory control and identification of emotional faces in individuals with SAD. Method: Twenty-nine individuals diagnosed with winter-SAD and 30 demographically matched controls with no seasonality symptoms completed an emotional Go/NoGo task, requiring inhibition of prepotent responses to emotional facial expressions and an emotional face identification task twice, in winter and summer. Results: In winter, individuals with SAD showed impaired ability to inhibit responses to angry (p = .0006) and sad faces (p = .011), and decreased identification of happy faces (p = .032) compared with controls. In summer, individuals with SAD and controls performed similarly on these tasks (ps > .24). Conclusion: We provide novel evidence that inhibition of angry and sad faces and identification of happy faces are impaired in SAD in the symptomatic phase, but not in the remitted phase. The affective biases in cognitive processing constitute state-dependent features of SAD. Our data show that reinstatement of a normal affective cognition should be possible and would constitute a major goal in psychiatric treatment to improve the quality of life for these patients.

Does Harm Avoidance mediate effects of recollected parental bonding on mental distress in adulthood

BACKGROUND Adverse early life conditions such as perceived low quality of parental bonding increase vulnerability to stress and psychopathology in adulthood. However, the mechanisms by which perceptions of parental bonding translate into vulnerability are unclear and remain sparsely investigated in healthy populations. We proposed a model, in which the personality trait Harm Avoidance would mediate effects of recollected parental bonding during the first sixteen years of life on measures of perceived stress and mental distress severity in adulthood. METHOD Five-hundred-eighteen adults (65.1 % women), aged 18-53years, completed questionnaires of parental bonding, perceived stress, trait Harm Avoidance, and severity of mental distress. Direct and indirect effects mediated through trait Harm Avoidance were examined in a structural equation model. RESULTS Under the causal assumptions of our proposed model, indirect effects of trait Harm Avoidance mediated the relationship between parental overprotection and severity of mental distress, while significantly attenuating the direct effects of parental care on severity of mental distress. Moreover, indirect effects of trait Harm Avoidance significantly attenuated the direct effects of parental overprotection and care on perceived stress. CONCLUSION In this large sample of mentally healthy adults, recollected parental bonding was significantly associated with levels of perceived stress and severity of mental distress. The results from our proposed model further suggest that trait Harm Avoidance may be a developmental link, by which the quality of recollected parental bonding in childhood translates into adult vulnerability to stress and mental distress.