Eva Bauer

ADHD related behaviors are associated with brain activation in the reward system

Neuroimaging studies on attention-deficit/hyperactivity disorder (ADHD) suggest dysfunctional reward processing, with hypo-responsiveness during reward anticipation in the reward system including the nucleus accumbens (NAcc). In this study, we investigated the association between ADHD related behaviors and the reward system using functional magnetic resonance imaging in a non-clinical sample. Participants were 31 healthy, female undergraduate students with varying levels of self-reported ADHD related behaviors measured by the adult ADHD self-report scale. The anticipation of different types of reward was investigated: monetary reward, punishment avoidance, and verbal feedback. All three reward anticipation conditions were found to be associated with increased brain activation in the reward system, with the highest activation in the monetary reward anticipation condition, followed by the punishment avoidance anticipation condition, and the lowest activation in the verbal feedback anticipation condition. Most interestingly, in all three conditions, NAcc activation was negatively correlated with ADHD related behaviors. In conclusion, our results from a non-clinical sample are in accordance with reported deficits in the reward system in ADHD patients: the higher the number and severity of ADHD related behaviors, the lower the neural responses in the dopaminergic driven reward anticipation task. Thus, our data support current aetiological models of ADHD which assume that deficits in the reward system might be responsible for many of the ADHD related behaviors.

The impact of age on load-related dorsolateral prefrontal cortex activation

Healthy aging is accompanied by working memory-related functional cerebral changes. Depending on performance accuracy and the level of working memory demands, older adults show task-related patterns of either increased or decreased activation compared to younger adults. Controversies remain concerning the interpretation of these changes and whether they already manifest in earlier decades of life. To address these issues, functional magnetic resonance imaging (fMRI) was used to examine brain activation during spatial working memory retrieval in 45 healthy individuals between 20 and 68 years of age. Participants performed a modified version of the Corsi Block-Tapping test (CBT). The CBT requires the storage and subsequent reproduction of spatial target sequences and allows modulating working memory load by a variation of sequence length. Results revealed that activation intensity at the lowest CBT load level increased with increasing age and positively correlated with the number of errors. At higher CBT load levels, activation intensity decreased with increasing age together with a disproportional accuracy decline on the behavioral level. Moreover, results suggests that younger individuals showed higher activation intensity at high CBT load than at low CBT load switching to the opposite pattern at an age of about 40 years. Consistent with the assumptions of the Compensation-Related Utilization of Neural Circuits Hypothesis (CRUNCH), the present results reveal specific age-related alterations in left dorsolateral prefrontal cortex activation in response to increasing task load. Specifically, the results point toward increasing neural inefficiency with age at low task load and a progressive limitation of resources with age at higher task load. The present findings argue for an increasing functional cerebral dysfunction over a time span of 50 years that may partly be compensated on the behavioral level until a resource ceiling is approached.

The significance of caudate volume for age-related associative memory decline

Aging comes along with reduced gray matter (GM) volume in several cerebral areas and with cognitive performance decline in different cognitive domains. Moreover, regional GM volume is linked to specific cognitive sub processes in older adults. However, it remains unclear which regional changes in older individuals are directly associated with decreased cognitive performance. Moreover, most of the studies on this topic focused on hippocampal and prefrontal brain regions and their relation to memory and executive functioning. Interestingly, there are only a few studies that reported an association between striatal brain volume and cognitive performance. This is insofar surprising that striatal structures are (1) highly affected by age and (2) involved in different neural circuits that serve intact cognition. To address these issues, voxel-based morphometry (VBM) was used to analyze GM volume in 18 younger and 18 older adults. Moreover, several neuropsychological tests from different neuropsychological test batteries were applied to assess a broad range of cognitive domains. Older adults showed less GM volume than younger adults within frontal, striatal, and cerebellar brain regions. In the group of older adults, significant correlations were found between striatal GM volume and memory performance and between prefrontal/temporal GM volume and executive functioning. The only direct overlap between brain regions associated with regional atrophy and cognitive performance in older adults was found for the right caudate: older adults showed reduced caudate volume relative to younger adults. Moreover, caudate volume was positively correlated with associative memory accuracy in older adults and older adults showed poorer performances than younger adults in the respective associative memory task. Taken together, the current findings indicate the relevance of the caudate for associative memory decline in the aging brain.

Neuroimaging Evidence for Processes Underlying Repetition of Ignored Stimuli

Prolonged response times are observed with targets having been presented as distractors immediately before, called negative priming effect. Among others, inhibitory and retrieval processes have been suggested underlying this behavioral effect. As those processes would involve different neural activation patterns, a functional magnetic resonance imaging (fMRI) study including 28 subjects was conducted. Two tasks were used to investigate stimulus repetition effects. One task focused on target location, the other on target identity. Both tasks are known to elicit the expected response time effects. However, there is less agreement about the relationship of those tasks with the explanatory accounts under consideration. Based on within-subject comparisons we found clear differences between the experimental repetition conditions and the neutral control condition on neural level for both tasks. Hemodynamic fronto-striatal activation patterns occurred for the location-based task favoring the selective inhibition account. Hippocampal activation found for the identity-based task suggests an assignment to the retrieval account; however, this task lacked a behavioral effect.

Trying to Put the Puzzle Together: Age and Performance Level Modulate the Neural Response to Increasing Task Load within Left Rostral Prefrontal Cortex

Age-related working memory decline is associated with functional cerebral changes within prefrontal cortex (PFC). Kind and meaning of these changes are heavily discussed since they depend on performance level and task load. Hence, we investigated the effects of age, performance level, and load on spatial working memory retrieval-related brain activation in different subregions of the PFC. 19 younger (Y) and 21 older (O) adults who were further subdivided into high performers (HP) and low performers (LP) performed a modified version of the Corsi Block-Tapping test during fMRI. Brain data was analyzed by a 4 (groups: YHP, OHP, YLP, and OLP) × 3 (load levels: loads 4, 5, and 6) ANOVA. Results revealed significant group × load interaction effects within rostral dorsolateral and ventrolateral PFC. YHP showed a flexible neural upregulation with increasing load, whereas YLP reached a resource ceiling at a moderate load level. OHP showed a similar (though less intense) pattern as YHP and may have compensated age-effects at high task load. OLP showed neural inefficiency at low and no upregulation at higher load. Our findings highlight the relevance of age and performance level for load-dependent activation within rostral PFC. Results are discussed in the context of the compensation-related utilization of neural circuits hypothesis (CRUNCH) and functional PFC organization.

Reproducibility of Complex Functional Magnetic Resonance Imaging Effects.

To the Editor: Recent research suggests low reproducibility of experimental psychological studies. Because there is a great variety of paradigms, models, and analytical approaches, this may particularly apply to studies using functional magnetic resonance imaging (fMRI). Consequently, confirmation of previous results using different tasks, designs, or statistical methods is desirable and necessary to verify specific and complex effects. However, replications are rare, probably because reporting similar results reduces the likelihood of a high-impact publication. In the last decade, several working groups have focused on neurocognitive changes associated with normal aging. Different factors such as performance level and task load strongly modulate these changes. As a result, findings are inconsistent depending on which of these factors are considered in study design. Greater prefrontal activation or bilaterality in older adults together with age-related performance decline, for example, argue for neural inefficiency, less regional specificity, or failed compensation, whereas overactivation or greater bilaterality at a steady performance level may be signs of successful compensation. By contrast, less prefrontal activation in older adults associated with lower performance accuracy can be interpreted as neural dysfunction, whereas less prefrontal activation associated with steady or better performance indicates greater efficiency. Moreover, older adults have greater bilateral activation at low task load as a sign of compensation and lower activation at high task load as a sign of exhausted neural resources. One of the few studies that have included both performance and task load in a single analysis revealed activation differences between younger high-performing, younger low-performing, older high-performing, and older low-performing subjects. Most importantly, the results point toward a more-efficient or ‘youthlike’ load-dependent up-regulation of the spatial working memory network in older high-performing subjects. Recent results confirmed these effects, although a different paradigm, a different design, and a different methodological approach were used (e.g., serial vs parallel stimulus presentation; retrieval vs recognition; load levels 4, 5, and 6 vs 1, 3, and 7; different region of interest masks and analysis of variance designs). Nevertheless, particularly for the left dorsolateral prefrontal cortex, activation patterns modulated by performance level and task load are surprisingly similar, which provides further evidence of the validity of these effects (compare left Figure 5A in with bottom Figure 4 in). In addition, it appears that cerebral up-regulation of younger low-performing subjects plateaus at moderate load levels, whereas the neural resources of older low-performing subjects seem to be exhausted already at low task load. A better understanding of these mechanisms is an important prerequisite for interpretation of functional changes in the aging brain, which makes their replication indispensable. The studies described show that even complex fMRI effects are reproducible and provide a good example of the validity of experimental psychological research.

Deficient Symbol Processing in Alzheimer Disease

Symbols and signs have been suggested to improve the orientation of patients suffering from Alzheimer disease (AD). However, there are hardly any studies that confirm whether AD patients benefit from signs or symbols and which symbol characteristics might improve or impede their symbol comprehension. To address these issues, 30 AD patients and 30 matched healthy controls performed a symbol processing task (SPT) with 4 different item categories. A repeated-measures analysis of variance was run to identify impact of different item categories on performance accuracy in both the experimental groups. Moreover, SPT scores were correlated with neuropsychological test scores in a broad range of other cognitive domains. Finally, diagnostic accuracy of the SPT was calculated by a receiver-operating characteristic curve analysis. Results revealed a global symbol processing dysfunction in AD that was associated with semantic memory and executive deficits. Moreover, AD patients showed a disproportional performance decline at SPT items with visual distraction. Finally, the SPT total score showed high sensitivity and specificity in differentiating between AD patients and healthy controls. The present findings suggest that specific symbol features impede symbol processing in AD and argue for a diagnostic benefit of the SPT in neuropsychological assessment.

Altered negative priming in older subjects: first evidence from behavioral and neural level

The impact of aging on the negative priming (NP) effect has been subject of many studies using behavioral measures. Results are inconsistent and corresponding neural data do not exist. We were interested in, whether or not processing of NP is altered in older in comparison to young adults (YA) on behavioral and neural level. Eighteen young and eighteen older healthy adults performed a location-based NP paradigm during fMRI. YA behaviorally showed a NP effect and NP associated fronto-striatal activation, which is in accordance with the inhibitory model of NP. In older subjects no significant behavioral NP effect and no NP-related activation in predefined brain regions could be found. This is discussed in context of the “loss of efficiency” hypothesis. One possible source for the lack of NP-related activation is a reduction of gray matter (GM) volume in older subjects as shown using voxel based morphometry (VBM).

Does Mount Vesuvius Indicate an Outbreak of Alzheimer's Disease?

degree of hemodynamic change in response to CSM is associated with greater WMH volume. Symptoms such as dizziness, presyncope, and syncope are thought to result from low cerebral blood flow. It may be that, in asymptomatic CSH-positive individuals, cerebral autoregulation maintains cerebral blood flow despite large changes in systemic blood pressure, whereas in symptomatic individuals, systemic BP falls below the lower limit of cerebral autoregulation, or cerebral autoregulation fails, causing symptoms and anoxic white matter damage.

Performance Level and Cortical Atrophy Modulate the Neural Response to Increasing Working Memory Load in Younger and Older Adults

There is evidence that the neural response to increasing working memory (WM) load is modulated by age and performance level. For a valid interpretation of these effects, however, it is important to understand, whether and how they are related to gray matter atrophy. In the current work, we therefore used functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM) to examine the association between age, performance level, spatial WM load-related brain activation and gray matter volume in 18 younger high-performers (YHP), 17 younger low-performers (YLP), 17 older high-performers (OHP), and 18 older low-performers (OLP). In multiple sub regions of the prefrontal cortex (PFC), load-related activation followed a linear trend with increasing activation at increasing load in all experimental groups. Results did not reveal differences between the sub groups. Older adults additionally showed a pattern of increasing activation from low to medium load but stable or even decreasing activation from medium to high load in other sub regions of the PFC (quadratic trend). Quadratic trend related brain activation was higher in older than in younger adults and in OLP compared to OHP. In OLP, quadratic trend related brain activation was negatively correlated with both performance accuracy and prefrontal gray matter volume. The results suggest an efficient upregulation of multiple PFC areas as response to increasing WM load in younger and older adults. Older adults and particularly OLP additionally show dysfunctional response patterns (i.e., enhanced quadratic trend related brain activation compared to younger adults and OHP, respectively) in other PFC clusters being associated with gray matter atrophy.