Max Toepper

Neural correlates of the individual emotional Stroop in borderline personality disorder.

OBJECTIVEnEmotional dysregulation is a key feature of borderline personality disorder (BPD) with altered inhibitory functions having suggested as being crucial. The anterior cingulate cortex and further prefrontal brain regions are crucial for response inhibition. The regulation of emotions is ensured via inhibitory control over the amygdala. The present study aimed to investigate neural correlates of response inhibition in BPD by using an emotional Stroop paradigm extending the task to word stimuli which were related to stressful life events.nnnMETHODSnTwenty BPD patients and 20 healthy controls underwent functional magnetic resonance imaging (fMRI) while performing the individual emotional Stroop task. A block design was used with the following word type conditions: neutral words, general negative words, and individual negative words. The individual negative words were recruited from a prior interview conducted with each participant.nnnRESULTSnWhile BPD patients had overall slower reaction times in the Stroop task compared to healthy controls, there was no increased slowing with emotional interference. Controls exhibited significant fMRI blood oxygenation level-dependent signal increases in the anterior cingulate cortex as well as in frontal cortex contrasting generally negative vs. neutral and individual negative vs. neutral conditions, respectively. BPD patients did not show equivalent signal changes.nnnCONCLUSIONSnThese results provide further evidence for a dysfunctional network of brain areas in BPD, including the ACC and frontal brain regions. These areas are crucial for the regulation of stress and emotions, the core problems of BPD patients.

Functional correlates of distractor suppression during spatial working memory encoding.

Executive working memory operations are related to prefrontal regions in the healthy brain. Moreover, neuroimaging data provide evidence for a functional dissociation of ventrolateral and dorsolateral prefrontal cortex. Most authors either suggest a modality-specific or a function-specific prefrontal cortex organization. In the present study we particularly aimed at the identification of different prefrontal cerebral areas that are involved in executive inhibitory processes during spatial working memory encoding. In an fMRI study (functional magnetic resonance imaging) we examined the neural correlates of spatial working memory processing by varying the amount of executive demands of the task. Twenty healthy volunteers performed the Corsi Block-Tapping test (CBT) during fMRI. The CBT requires the storage and reproduction of spatial target sequences. In a second condition, we presented an adapted version of the Block-Suppression-Test (BST). The BST is based on the original CBT but additionally requires the active suppression of visual distraction within the target sequences. In comparison to the CBT performance, particularly the left dorsolateral prefrontal cortex (BA 9) showed more activity during the BST condition. Our results show that the left dorsolateral prefrontal cortex plays a crucial role for executive controlled inhibition of spatial distraction. Furthermore, our findings are in line with the processing model of a functional dorsolateral-ventrolateral prefrontal cortex organization.

Hippocampal involvement in working memory encoding of changing locations: An fMRI study

Whereas the role of the hippocampus for spatial learning and long-term memory is largely undisputed, there is less evidence for a participation of hippocampal structures in spatial working memory operations. In an fMRI study (functional magnetic resonance imaging), we therefore examined the role of the hippocampus during spatial working memory performance. Nineteen healthy volunteers performed a modified version of the Corsi Block-Tapping test (CBT) during fMRI. The CBT is a neuropsychological instrument that is widely used in clinical settings. It requires the storage and subsequent reproduction of spatial target sequences. Brain activity during CBT performance has rarely been examined in the past, at least not the hemodynamic correlates. In a baseline condition, participants processed a number of subsequently presented targets as in the CBT condition. The only difference was that targets did not change their location. As compared to baseline activity, the right hippocampus showed more activation during the CBT condition. In addition, whole-brain analysis showed working memory related frontal and parietal brain activation. The results indicate that hippocampal structures contribute to serial working memory encoding of spatial locations in the human brain.

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.

The impact of age on prefrontal cortex integrity during spatial working memory retrieval

Healthy aging is accompanied by a decline in spatial working memory that is related to functional cerebral changes within the spatial working memory network. In the last decade, important findings were presented concerning the location (e.g., prefrontal), kind (e.g., underactivation, overactivation), and meaning (e.g., functional deficits, compensation) of these changes. Less is known about how functional connections between specific brain regions are affected by age and how these changes are related to behavioral performance. To address these issues, we used functional magnetic resonance imaging to examine retrieval-related brain activation and functional connectivity in 18 younger individuals and 18 older individuals. We assessed working memory with a modified version of the Corsi Block-Tapping test, which requires the storage and reproduction of spatial target sequences. Analyses of group differences in brain activation and functional connectivity included comparisons between younger individuals, older individuals, older high-performers, and older low-performers. In addition, we conducted a functional connectivity analysis by using a seed region approach. In comparison to younger individuals, older individuals showed lower right-hemispheric dorsolateral prefrontal activation and lower functional connectivity between the right dorsolateral prefrontal cortex and the bilateral orbitofrontal cortex. Older high-performers showed higher right dorsolateral and anterior prefrontal cortex activation than older low-performers, as well as higher functional connectivity between these brain regions. The present results suggest age-related reductions of prefrontal activation during spatial working memory retrieval. Moreover, task-related functional connectivity appears to be lower in older adults. Performance accuracy in older adults is associated with right dorsolateral and anterior prefrontal cortex activation, and with the functional connection between these regions.

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.

Preliminary Validation of a Questionnaire Covering Risk Factors for Impaired Driving Skills in Elderly Patients

Due to rather unspecific statutory regulations in Germany, particularly for patients with neurodegenerative disorders, many seniors still drive despite severe driving-related cognitive deficits. An accurate assessment of driving fitness requires immense financial, personnel and temporal resources which go beyond daily clinical routines. In cooperation with a working group from Switzerland, we therefore developed the questionnaire Safety Advice For Elderly drivers (SAFE), an economic instrument covering different risk factors for driving safety. The main aim of the current work was a first validation of the SAFE. Twenty-two driving seniors performed the Corporal A, a test battery permitted by law to assess driving-related cognitive functions. Based upon the Corporal results and the percentile rank 16 criterion, participants were divided into cognitively impaired and unimpaired drivers. Moreover, participants were assessed using the SAFE and an extensive neuropsychological test battery. The results revealed high sensitivity and specifity scores for the SAFE suggesting that the SAFE may be a valuable and economical instrument to quantify and document individual risk factors for driving safety and to differentiate between impaired and unimpaired drivers. Notably, the results must be replicated in future studies including a larger sample, different clinical subgroups, and a practical driving lesson.

Advice for Elderly Drivers in a German Memory Clinic: A Case Report on Medical, Ethical and Legal Consequences

We report on a 75-year-old female who consulted our Memory Clinic because of subjective memory complaints that she first recognized three months previously. Next to the standard detailed patient history, neuropsychological assessment, psychopathological status, the patient’s driving history played an important role in the diagnostic process. In this case report, we illustrate the diagnostic process starting with the first consultation, including a short neuropsychological examination and communicating its results, reporting on further work-up (detailed neuropsychological assessment, MRI scan and cerebrospinal fluid (CSF) analysis) up to the final consultation, including advice for the patient. We will focus on several medical, ethical and legal difficulties that may occur when consulting elderly drivers with initial cognitive decline.

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.