Claudia Preuschhof

Differential activation of the dorsal striatum by high-calorie visual food stimuli in obese individuals

The neural systems regulating food intake in obese individuals remain poorly understood. Previous studies applied positron emission tomography and manipulated hunger and satiety to investigate differences in appetitive processing between obese and normal-weight individuals. However, it is not known whether manipulation of stimulus value may yield different neural activity in obese as compared to control subjects when intrinsic physiological states are kept constant. We used functional magnetic resonance imaging to investigate 13 obese and 13 normal-weight subjects and manipulated food motivation by presenting visual food stimuli differing in their caloric content and energy density. In contrast to controls, obese women selectively activated the dorsal striatum while viewing high-caloric foods. Moreover, in the high-calorie condition body mass index (BMI) predicted activation in the dorsal striatum, anterior insula, claustrum, posterior cingulate, postcentral and lateral orbitofrontal cortex. The results indicate that in obese individuals simple visual stimulation with food stimuli activates regions related to reward anticipation and habit learning (dorsal striatum). Additionally, high-calorie food images yielded BMI-dependent activations in regions associated with taste information processing (anterior insula and lateral orbitofrontal cortex), motivation (orbitofrontal cortex), emotion as well as memory functions (posterior cingulate). Collectively, the results suggest that the observed activation is independent of the physiological states of hunger and satiation, and thus may contribute to pathological overeating and obesity. Some of the observed activations (dorsal striatum, orbitofrontal cortex) are likely to be dopamine-mediated.

Age-related differences in white matter microstructure: Region-specific patterns of diffusivity

We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of age-related decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.

Performance level modulates adult age differences in brain activation during spatial working memory

Working memory (WM) shows pronounced age-related decline. Functional magnetic resonance imaging (fMRI) studies have revealed age differences in task-related brain activation. Evidence based primarily on episodic memory studies suggests that brain activation patterns can be modulated by task difficulty in both younger and older adults. In most fMRI aging studies on WM, however, performance level has not been considered, so that age differences in activation patterns are confounded with age differences in performance level. Here, we address this issue by comparing younger and older low and high performers in an event-related fMRI study. Thirty younger (20–30 years) and 30 older (60–70 years) healthy adults were tested with a spatial WM task with three load levels. A region-of-interest analysis revealed marked differences in the activation patterns between high and low performers in both age groups. Critically, among the older adults, a more “youth-like” load-dependent modulation of the blood oxygen level-dependent signal was associated with higher levels of spatial WM performance. These findings underscore the need of taking performance level into account when studying changes in functional brain activation patterns from early to late adulthood.

Load modulation of bold response and connectivity predicts working memory performance in younger and older adults

Individual differences in working memory (WM) performance have rarely been related to individual differences in the functional responsivity of the WM brain network. By neglecting person-to-person variation, comparisons of network activity between younger and older adults using functional imaging techniques often confound differences in activity with age trends in WM performance. Using functional magnetic resonance imaging, we investigated the relations among WM performance, neural activity in the WM network, and adult age using a parametric letter n-back task in 30 younger adults (21–31 years) and 30 older adults (60–71 years). Individual differences in the WM networks responsivity to increasing task difficulty were related to WM performance, with a more responsive BOLD signal predicting greater WM proficiency. Furthermore, individuals with higher WM performance showed greater change in connectivity between left dorsolateral prefrontal cortex and left premotor cortex across load. We conclude that a more responsive WM network contributes to higher WM performance, regardless of adult age. Our results support the notion that individual differences in WM performance are important to consider when studying the WM network, particularly in age-comparative studies.

Spatial Attention Related SEP Amplitude Modulations Covary with BOLD Signal in S1—A Simultaneous EEG—fMRI Study

Recent studies investigating the influence of spatial-selective attention on primary somatosensory processing have produced inconsistent results. The aim of this study was to explore the influence of tactile spatial-selective attention on spatiotemporal aspects of evoked neuronal activity in the primary somatosensory cortex (S1). We employed simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) in 14 right-handed subjects during bilateral index finger Braille stimulation to investigate the relationship between attentional effects on somatosensory evoked potential (SEP) components and the blood oxygenation level-dependent (BOLD) signal. The 1st reliable EEG response following left tactile stimulation (P50) was significantly enhanced by spatial-selective attention, which has not been reported before. FMRI analysis revealed increased activity in contralateral S1. Remarkably, the effect of attention on the P50 component as well as long-latency SEP components starting at 190 ms for left stimuli correlated with attentional effects on the BOLD signal in contralateral S1. The implications are 2-fold: First, the correlation between early and long-latency SEP components and the BOLD effect suggest that spatial-selective attention enhances processing in S1 at 2 time points: During an early passage of the signal and during a later passage, probably via re-entrant feedback from higher cortical areas. Second, attentional modulations of the fast electrophysiological signals and the slow hemodynamic response are linearly related in S1.

Neural correlates of vibrotactile working memory in the human brain

Recent neurophysiological studies in macaques identified a network of brain regions related to vibrotactile working memory (WM), including somatosensory, motor, premotor, and prefrontal cortex. In these studies, monkeys decided which of two vibrotactile stimuli that were sequentially applied to their fingertips and separated by a short delay had the higher vibration frequency. Using the same task, the objective of the present study was to identify the neural correlates related to the different task periods (encoding, maintenance, and decision making) of vibrotactile WM in the human brain. For this purpose, we used event-related functional magnetic resonance imaging and contrasted WM trials with a control condition of vibrotactile stimulation that did not require maintenance and decision making. We found that vibrotactile WM has a similar but not identical neural organization in humans and monkeys. Consistent with neurophysiological data in monkeys and behavioral studies in humans, the primary somatosensory and the ventral premotor cortex exhibited increased activity during encoding. Maintenance of a vibrotactile memory trace evoked activity in the premotor and ventrolateral prefrontal cortex. Decision making caused activation in the somatosensory, premotor, and lateral prefrontal cortex. However, human vibrotactile WM recruited additional areas. Decision making activated a broader network than that studied thus far in monkeys. Maintenance and decision making additionally activated the inferior parietal lobe. Although the different task components evoked activity in distinctive neural networks, there was considerable overlap of activity, especially regarding maintenance and decision making, indicating that similar neural mechanisms are required for the subprocesses related to these task components.

Are there gender differences in major depression and its response to antidepressants

BACKGROUND The prevalence of major depression for women is about twice that for men. This gender difference in prevalence rates has led to much research addressing gender differences in the presentation and features of major depression, and, to a lesser extent, research addressing gender differences in treatment response and personality. However, studies differ considerably in the population sampled, and findings vary significantly. In the current retrospective examination of data, we investigated all of these variables in one single sample of outpatients with major depression seen in a tertiary care centre. METHODS A sample of 139 men and 246 women with major depression receiving antidepressant treatment (SSRIs, TCAs, SNRIs, MAOIs, or RIMAs) in an outpatient setting were contrasted with regard to symptoms and severity of depression, course of illness, treatment response, and personality. RESULTS Women were found to experience more vegetative and atypical symptoms, anxiety, and anger than men, and to report higher severity of depression on self-report measures. Regarding personality, women scored higher on conscientiousness, the extraversion facet warmth, the openness facet feelings, and sociotropy. Effect sizes were small to moderate. No differences were found in the course of the illness and treatment response. LIMITATIONS Findings are not generalizable to inpatient or community samples, and some of the gender differences may be accounted for by gender differences in treatment seeking behaviour. CONCLUSIONS While men and women receiving antidepressant treatment show some gender differences in the psychopathology of major depression, these differences do not appear to translate into differences in response to antidepressants. Gender differences in personality appear less profound than in the average population, indicating the potential role of a certain personality type that predisposes individuals to develop clinical depression, independent of gender. CLINICAL RELEVANCE The current examination underscores the role gender plays in the presentation and treatment of major depression.

KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory.

Individual differences in episodic memory are highly heritable. Several studies have linked a polymorphism in the gene encoding the KIBRA protein to episodic memory performance. Results regarding CLSTN2, the gene encoding the synaptic protein calsyntenin 2, have been less consistent, possibly pointing to interactions with other genes. Given that both KIBRA and CLSTN2 are expressed in the medial temporal lobe and have been linked to synaptic plasticity, we investigated whether KIBRA and CLSTN2 interactively modulate episodic memory performance (n=383). We replicated the beneficial effect of the KIBRA T-allele on episodic memory, and discovered that this effect increases with the associative demands of the memory task. Importantly, the memory-enhancing effect of the KIBRA T-allele was boosted by the presence of the CLSTN2 C-allele, which positively affected memory performance in some previous studies. In contrast, the presence of CLSTN2 C-allele led to reduced performance in subjects homozygous for the KIBRA C-allele. Overall, these findings suggest that KIBRA and CLSTN2 interactively modulate episodic memory performance, and underscore the need for delineating the interactive effects of multiple genes on brain and behavior.

A Scaffold for Efficiency in the Human Brain

The comprehensive relations between healthy adult human brain white matter (WM) microstructure and gray matter (GM) function, and their joint relations to cognitive performance, remain poorly understood. We investigated these associations in 27 younger and 28 older healthy adults by linking diffusion tensor imaging (DTI) with functional magnetic resonance imaging (fMRI) data collected during an n-back working memory task. We present a novel application of multivariate Partial Least Squares (PLS) analysis that permitted the simultaneous modeling of relations between WM integrity values from all major WM tracts and patterns of condition-related BOLD signal across all GM regions. Our results indicate that greater microstructural integrity of the major WM tracts was negatively related to condition-related blood oxygenation level-dependent (BOLD) signal in task-positive GM regions. This negative relationship suggests that better quality of structural connections allows for more efficient use of task-related GM processing resources. Individuals with more intact WM further showed greater BOLD signal increases in typical “task-negative” regions during fixation, and notably exhibited a balanced magnitude of BOLD response across task-positive and -negative states. Structure—function relations also predicted task performance, including accuracy and speed of responding. Finally, structure–function–behavior relations reflected individual differences over and above chronological age. Our findings provide evidence for the role of WM microstructure as a scaffold for the context-relevant utilization of GM regions.

Prior information biases stimulus representations during vibrotactile decision making

Neurophysiological data suggest that the integration of prior information and incoming sensory evidence represents the neural basis of the decision-making process. Here, we aimed to identify the brain structures involved in the integration of prior information about the average magnitude of a stimulus set and current sensory evidence. Specifically, we investigated whether prior average information already biases vibrotactile decision making during stimulus perception and maintenance before the comparison process. For this purpose, we used a vibrotactile delayed discrimination task and fMRI. At the behavioral level, participants showed the time-order effect. This psychophysical phenomenon has been shown to result from the influence of prior information on the perception of and the memory for currently presented stimuli. Similarly, the fMRI signal reflected the integration of prior information about the average vibration frequency and the currently presented vibration frequency. During stimulus encoding, the fMRI signal in primary and secondary somatosensory (S2) cortex, thalamus, and ventral premotor cortex mirrored an integration process. During stimulus maintenance, only a region in the intraparietal sulcus showed this modulation by prior average information. Importantly, the fMRI signal in S2 and intraparietal sulcus correlated with individual differences in the degree to which participants integrated prior average information. This strongly suggests that these two regions play a pivotal role in the integration process. Taken together, these results support the notion that the integration of current sensory and prior average information is a major feature of how the human brain perceives, remembers, and judges magnitude stimuli.