Stefanie Brassen

Lower Ventral Striatal Activation During Reward Anticipation in Adolescent Smokers

OBJECTIVE Adolescents are particularly vulnerable to addiction, and in the case of smoking, this often leads to long-lasting nicotine dependence. The authors investigated a possible neural mechanism underlying this vulnerability. METHOD Functional MRI was performed during reward anticipation in 43 adolescent smokers and 43 subjects matched on age, gender, and IQ. The authors also assessed group differences in novelty seeking, impulsivity, and reward delay discounting. RESULTS In relation to the comparison subjects, the adolescent smokers showed greater reward delay discounting and higher scores for novelty seeking. Neural responses in the ventral striatum during reward anticipation were significantly lower in the smokers than in the comparison subjects, and in the smokers this response was correlated with smoking frequency. Notably, the lower response to reward anticipation in the ventral striatum was also observed in smokers (N=14) who had smoked on fewer than 10 occasions. CONCLUSIONS The present findings suggest that a lower response to reward anticipation in the ventral striatum may be a vulnerability factor for the development of early nicotine use.

Risk Taking and the Adolescent Reward System: A Potential Common Link to Substance Abuse

OBJECTIVE Increased risk-taking behavior has been associated with addiction, a disorder also linked to abnormalities in reward processing. Specifically, an attenuated response of reward-related areas (e.g., the ventral striatum) to nondrug reward cues has been reported in addiction. One unanswered question is whether risk-taking preference is associated with striatal reward processing in the absence of substance abuse. METHOD Functional and structural MRI was performed in 266 healthy young adolescents and in 31 adolescents reporting potentially problematic substance use. Activation during reward anticipation (using the monetary incentive delay task) and to gray matter density were measured. Risk-taking bias was assessed by the Cambridge Gamble Task. RESULTS With increasing risk-taking bias, the ventral striatum showed decreased activation bilaterally during reward anticipation. Voxel-based morphometry showed that greater risk-taking bias was also associated with and partially mediated by lower gray matter density in the same structure. The decreased activation was also observed when participants with virtually any substance use were excluded. The group with potentially problematic substance use showed greater risk taking as well as lower striatal activation relative to matched comparison subjects from the main sample. CONCLUSIONS Risk taking and functional and structural properties of the reward system in adolescents are strongly linked prior to a possible onset of substance abuse, emphasizing their potential role in the predisposition to drug abuse.

Boys do it the right way: sex-dependent amygdala lateralization during face processing in adolescents.

Previous studies have observed a sex-dependent lateralization of amygdala activation related to emotional memory. Specifically, it was shown that the activity of the right amygdala correlates significantly stronger with memory for images judged as arousing in men than in women, and that there is a significantly stronger relationship in women than in men between activity of the left amygdala and memory for arousing images. Using a large sample of 235 male adolescents and 235 females matched for age and handedness, we investigated the sex-specific lateralization of amygdala activation during an emotional face perception fMRI task. Performing a formal sex by hemisphere analysis, we observed in males a significantly stronger right amygdala activation as compared to females. Our results indicate that adolescents display a sex-dependent lateralization of amygdala activation that is also present in basic processes of emotional perception. This finding suggests a sex-dependent development of human emotion processing and may further implicate possible etiological pathways for mental disorders most frequent in adolescent males (i.e., conduct disorder).

Don’t Look Back in Anger! Responsiveness to Missed Chances in Successful and Nonsuccessful Aging

Emotionally healthy older adults show a reduced responsiveness to regret when performing a sequential decision task. No Regrets As people grow older, the possibility to think about “missed chances” increases. When we are young, thinking about missed opportunities may help to optimize future behavior. However, the older we get the probability of “second chances” decreases and thus the benefit of ruminating upon them disappears. Brassen et al. (p. 612, published online 19 April) studied the behavioral and neural response to missed chances in young adults, the healthy elderly subjects and late-life depressed volunteers. Compared with young and depressed subjects, the healthy elderly subjects showed a reduced sensitivity to missed opportunities. The findings suggest a potential mechanism for preserved emotional health in older age. Life-span theories explain successful aging with an adaptive management of emotional experiences like regret. As opportunities to undo regrettable situations decline with age, a reduced engagement into these situations represents a potentially protective strategy to maintain well-being in older age. Yet, little is known about the underlying neurobiological mechanisms supporting this claim. We used a multimodal psychophysiological approach in combination with a sequential risk-taking task that induces the feeling of regret and investigated young as well as emotionally successfully and unsuccessfully (i.e., late-life depressed) aged participants. Responsiveness to regret was specifically reduced in successful aging paralleled by autonomic and frontostriatal characteristics indicating adaptive shifts in emotion regulation. Our results suggest that disengagement from regret reflects a critical resilience factor for emotional health in older age.

Short-Term Rivastigmine Treatment Reduces EEG Slow-Wave Power in Alzheimer Patients

The effects of a 5-day treatment with rivastigmine on the resting EEG power spectrum were studied in 15 mildly to moderately ill Alzheimer patients. In these patients, beta power was positively correlated with cognitive performance and negatively correlated with functional impairment. Rivastigmine produced a decrease in delta and theta power with no effect of hemisphere and electrode position. Delta power decrease reflects the cerebral cholinergic action of rivastigmine and may thus allow a quantitative assessment of its CNS effects.

Anterior Cingulate Activation Is Related to a Positivity Bias and Emotional Stability in Successful Aging

BACKGROUND Behavioral studies consistently reported an increased preference for positive experiences in older adults. The socio-emotional selectivity theory explains this positivity effect with a motivated goal shift in emotion regulation, which probably depends on available cognitive resources. The present study investigates the neurobiological mechanism underlying this hypothesis. METHODS Functional magnetic resonance imaging data were acquired in 21 older and 22 young subjects while performing a spatial-cueing paradigm that manipulates attentional load on emotional face distracters. We focused our analyses on the anterior cingulate cortex as a key structure of cognitive control of emotion. RESULTS Elderly subjects showed a specifically increased distractibility by happy faces when more attentional resources were available for face processing. This effect was paralleled by an increased engagement of the rostral anterior cingulate cortex, and this frontal engagement was significantly correlated with emotional stability. CONCLUSIONS The current study highlights how the brain might mediate the tendency to preferentially engage in positive information processing in healthy aging. The finding of a resource-dependency of this positivity effect suggests demanding self-regulating processes that are related to emotional well-being. These findings are of particular relevance regarding implications for the understanding, treatment, and prevention of nonsuccessful aging like highly prevalent late-life depression.

Late-Onset Depression with Mild Cognitive Deficits: Electrophysiological Evidences for a Preclinical Dementia Syndrome

Mild cognitive impairment (MCI) is present in up to 60% of patients with late-onset depression and constitutes a major diagnostic problem in geriatric psychiatry. Searching for sensitive markers for the detection of early brain changes suggestive of dementia, we compared this depressive risk population with mildly to moderately demented patients and cognitively unimpaired depressed patients using EEG power and coherence. We found a considerable similarity between Alzheimer’s disease patients and cognitively impaired depressed patients regarding the cognitive profile and EEG pattern. Changes in EEG power and coherence at frontotemporal leads in depressive patients with MCI thereby allowed discrimination from cognitively unimpaired patients with a sensitivity of 88% and a specifity of 81%.

Structure–function interactions of correct retrieval in healthy elderly women

Recent studies have indicated that there are complex interactions between activation changes and structural alterations in aging. To investigate this issue, we combined functional with structural MRI in healthy old and young women. When contrasting correct with incorrect recognition of words, we found decreased right prefrontal as well as increased middle temporal gyrus (MTG) activation in the older adults. Performance was correlated with prefrontal activation in younger and with MTG activation in older subjects, respectively. Furthermore, frontal decrease and MTG increase were associated with reduced gray matter density of the prefrontal cortex (PFC) and the medial temporal lobe (MTL) across young and old subjects. Within older adults, however, left MTG activation and structural integrity were positively correlated. Thus, our data indicates a two-step structure-function interaction of correct retrieval in healthy aging. First, age-related reduced gray matter density is associated with diminished frontal activation, as well as with compensatory activation in the MTG. Second, compensatory utilization of additional resources is dependent upon a certain degree of structural integrity in the PFC and the MTL.

Haloperidol challenge in healthy male humans: a functional magnetic resonance imaging study

Functional magnetic resonance imaging (fMRI) was used to determine the acute blood oxygen level dependent effect (BOLD) of neuroleptic drugs in healthy male subjects. Using a robust simultaneous visuo-acoustic stimulation paradigm fMRI measurements were obtained prior to as well as 1 h and 24 h after intravenous infusion of 5 mg haloperidol to six healthy young men. After the administration, subjects showed significantly reduced BOLD contrast in the middle occipital gyrus while BOLD contrast was increased in the lingual gyrus. This pattern normalised within 24 h. Our results emphasise the necessity to control for interactions through acute medication and confirm fMRI as a non-invasive method for studying cerebral psychopharmacological effects.

Structural Brain Changes Related to Disease Duration in Patients with Asthma

Dyspnea is the impairing, cardinal symptom patients with asthma repeatedly experience over the course of the disease. However, its accurate perception is also crucial for timely initiation of treatment. Reduced perception of dyspnea is associated with negative treatment outcome, but the underlying brain mechanisms of perceived dyspnea in patients with asthma remain poorly understood. We examined whether increasing disease duration in fourteen patients with mild-to-moderate asthma is related to structural brain changes in the insular cortex and brainstem periaqueductal grey (PAG). In addition, the association between structural brain changes and perceived dyspnea were studied. By using magnetic resonance imaging in combination with voxel-based morphometry, gray matter volumes of the insular cortex and the PAG were analysed and correlated with asthma duration and perceived affective unpleasantness of resistive load induced dyspnea. Whereas no associations were observed for the insular cortex, longer duration of asthma was associated with increased gray matter volume in the PAG. Moreover, increased PAG gray matter volume was related to reduced ratings of dyspnea unpleasantness. Our results demonstrate that increasing disease duration is associated with increased gray matter volume in the brainstem PAG in patients with mild-to-moderate asthma. This structural brain change might contribute to the reduced perception of dyspnea in some patients with asthma and negatively impact the treatment outcome.