How the brains of young and old human adults cope with increased working memory demands

Working memory tasks are generally more difficult for older adults due to decreasing working memory capacity that is evoked by changes in the ageing brain. To successfully cope with this increased challenge in cognitive demand, elderly adults additionally activate the contralateral counterparts of specific prefrontal brain regions, whereas young adults do engage them unilaterally. At first glance, this strategy seems at odds with the idea of lateralized cognitive functions in cerebral cortex. In this dissertation, I investigated whether bilateral recruitment is a general strategy of the human brain to respond to increased working memory demands that is independent of age, task content and cerebral region. To answer these questions, we conducted our main experiment in which a group of young and a group of old adult participants worked on verbal, spatial, and object-based working memory tasks that had been individually tailored to push each subject to her or his capacity limit in each working memory domain. Simultaneously, we used functional magnetic resonance imaging to measure brain activity associated with working memory maintenance and to compare this activity between cross-hemispheric counterparts of the respective brain regions. Our results clearly indicate that language-related regions such as Broca’s area in the left ventrolateral prefrontal cortex, the left supplementary motor area, right lobule VI and crus1 of lobule VII of the cerebellum, and the left ventral premotor cortex maintained their lateralized activation patterns across the two age groups despite our highly challenging working memory tasks. In contrast, dorsolateral prefrontal cortex and anterior prefrontal cortex showed bilateral activation in difficult conditions across all working memory domains and this was true for both age groups. To further confirm that also young adults shift from a unilateral to a bilateral recruitment of these prefrontal brain regions in easy vs. highly demanding working memory tasks, respectively, we conducted an additional control experiment that engaged both the verbal and the spatial working memory domain. The results of this control experiment demonstrated that dorsolateral prefrontal cortex and anterior prefrontal cortex are unilaterally recruited during the easy task variants and – together with the results of the main experiment – they showed that this unilaterality transforms into bilaterality in difficult tasks. The additional activation of contralateral cerebral counterparts seems to be a strategy of the brain to cope with increased cognitive challenges independent of age and working memory task content. This phenomenon mainly emerges in prefrontal cortex – a brain structure that is less specialized and more flexible than other parts of the brain

Neural correlates of verbal working memory: an fMRI meta-analysis

Verbal Working memory (vWM) capacity measures the ability to maintain and manipulate verbal information for a short period of time. The specific neural correlates of this construct are still a matter of debate. The aim of this study was to conduct a coordinate-based meta-analysis of 42 fMRI studies on visual vWM in healthy subjects (n=795, males=459, females=325, unknown=11; age range: 18-75). The studies were obtained after an exhaustive literature search on PubMed, Scopus, Web of Science, and Brainmap database. We analyzed regional activation differences during fMRI tasks with the anisotropic effect-size version of seed-based d mapping software (ES-SDM). The results were further validated by performing jackknife sensitivity analyses and heterogeneity analyses. We investigated the effect of numerous relevant influencing factors by fitting corresponding linear regression models. We isolated consistent activation in a network containing fronto-parietal areas, right cerebellum, and basal ganglia structures. Regarding lateralization, the results pointed towards a bilateral frontal activation, a left-lateralization of parietal regions and a right-lateralization of the cerebellum, indicating that the left-hemisphere concept of vWM should be reconsidered. We also isolated activation in regions important for response inhibition, emphasizing the role of attentional control in vWM. Moreover, we found a significant influence of mean reaction time, load and age on activation associated with vWM. Activation in left medial frontal gyrus, left precentral gyrus and left precentral gyrus turned out to be positively associated with mean reaction time whereas load was associated with activation across the PFC, fusiform gyrus, parietal cortex and parts of the cerebellum. In the latter case activation was mainly detectable in both hemispheres whereas the influence of age became manifest predominantly in the left hemisphere. This led us to conclude that future vWM studies should take these factors into consideration

Remember how to use it: Effector-dependent modulation of spatial working memory activity in posterior parietal cortex

Working memory (WM) is the key process linking perception to action. Several lines of research have, accordingly, highlighted WM's engagement in sensori-motor associations between retrospective stimuli and future behavior. Using human fMRI we investigated whether prior information about the effector used to respond in a WM task would have an impact on the way the same sensory stimulus is maintained in memory despite a behavioral response could not be readily planned. We focused on WM-related activity in posterior parietal cortex during the maintenance of spatial items for a subsequent match-to-sample comparison, which was reported either with a verbal or with a manual response. We expected WM activity to be higher for manual response trials, because of posterior parietal cortex's engagement in both spatial WM and hand movement preparation. Increased fMRI activity for manual response trials in bilateral anterior intraparietal sulcus confirmed our expectations. These results imply that the maintenance of sensory material in WM is optimized for motor context, i.e. for the effector that will be relevant in the upcoming behavioral responses

Disrupted Working Memory Circuitry in Adolescent Psychosis

Individuals with schizophrenia (SZ) consistently show deficits in spatial working memory (WM) and associated atypical patterns of neural activity within key WM regions, including the dorsolateral prefrontal cortex (dlPFC) and parietal cortices. However, little research has focused on adolescent psychosis (AP) and potential age-associated disruptions of WM circuitry that may occur in youth with this severe form of illness. Here we utilized each subject’s individual spatial WM capacity to investigate task-based neural dysfunction in 17 patients with AP (16.58 ± 2.60 years old) as compared to 17 typically developing, demographically comparable adolescents (18.07 ± 3.26 years old). AP patients showed lower behavioral performance at higher WM loads and lower overall WM capacity compared to healthy controls. Whole-brain activation analyses revealed greater bilateral precentral and right postcentral activity in controls relative to AP patients, when controlling for individual WM capacity. Seed-based psychophysiological interaction (PPI) analyses revealed significantly greater co-activation between the left dlPFC and left frontal pole in controls relative to AP patients. Significant group-by-age interactions were observed in both whole-brain and PPI analyses, with AP patients showing atypically greater neural activity and stronger coupling between WM task activated brain regions as a function of increasing age. Additionally, AP patients demonstrated positive relationships between right dlPFC neural activity and task performance, but unlike healthy controls, failed to show associations between neural activity and out-of-scanner neurocognitive performance. Collectively, these findings are consistent with atypical WM-related functioning and disrupted developmental processes in youth with AP