It is well established that the mid-dorsolateral prefrontal cortex (dlPFC) plays a critical role in planning. Neuroimaging studies have yielded predominantly bilateral dlPFC activations, but the existence and nature of functionally specific contributions of left and right dlPFC have remained elusive. In recent experiments, 2 independent parameters have been identified which substantially determine planning: 1) the degree of interdependence between consecutive steps (search depth) and 2) the degree to which the configuration of the goal state renders the order of single steps either clearly evident or ambiguous (goal hierarchy). Thus, search depth affects the actual mental generation and evaluation of action sequences, whereas goal hierarchy reflects the extraction of goal information from an encountered problem. Here, both parameters were independently manipulated in an event-related functional magnetic resonance imaging study using the Tower of London task. Results revealed a double dissociation as indicated by a significant crossover interaction of hemisphere and task parameter: in left dlPFC, activations were stronger for higher demands on goal hierarchy than on search depth, whereas the reversed result emerged in right dlPFC. In conclusion, often observed bilateral patterns of dlPFC activation in complex tasks may reflect the concomitant operation of specific cognitive processes that show opposing lateralizations.

Prospective memory performance shows a decline in late adulthood. The present article examines the role of 3 main executive function facets (i.e., shifting, updating, and inhibition) as possible developmental mechanisms associated with these age effects. One hundred seventy-five young and 110 older adults performed a battery of cognitive tests including measures of prospective memory, shifting, updating, inhibition, working memory, and speed. Age effects were confirmed in prospective memory and also obtained in shifting, updating, and inhibition. Yet, facets of executive control differently predicted prospective memory performance: While inhibition and shifting were strong predictors of prospective memory performance and also explained age differences in prospective memory, updating was not related to prospective memory performance across adulthood. Furthermore, considering executive function measures increased the amount of explained variance in prospective remembering and reduced the influence of speed. Working memory was not revealed to serve as a significant predictor of prospective memory performance in the present study. These findings clarify the role of different facets of controlled attention on age effects in prospective memory and bear important conceptual implications: Results suggest that some but not all facets of executive functioning are important developmental mechanisms of prospective memory across adulthood beyond working memory and speed. Specifically, inhibition and shifting appear to be essential aspects of cognitive control involved in age-related prospective memory performance.

Apraxia is a cognitive disorder of skilled movements that characteristically affects the ability to imitate meaningless gestures, or to pantomime the use of tools. Despite substantial research, the neural underpinnings of imitation and pantomime have remained debated. An influential model states that higher motor functions are supported by different processing streams. A dorso-dorsal stream may mediate movements based on physical object properties, like reaching or grasping, whereas skilled tool use or pantomime rely on action representations stored within a ventro-dorsal stream. However, given variable results of past studies, the role of the two streams for imitation of meaningless gestures has remained uncertain, and the importance of the ventro-dorsal stream for pantomime of tool use has been questioned. To clarify the involvement of ventral and dorsal streams in imitation and pantomime, we performed voxel-based lesion-symptom mapping in a sample of 96 consecutive left-hemisphere stroke patients (mean age ± SD, 63.4 ± 14.8 years, 56 male). Patients were examined in the acute phase after ischaemic stroke (after a mean of 5.3, maximum 10 days) to avoid interference of brain reorganization with a reliable lesion-symptom mapping as best as possible. Patients were asked to imitate 20 meaningless hand and finger postures, and to pantomime the use of 14 common tools depicted as line drawings. Following the distinction between movement engrams and action semantics, pantomime errors were characterized as either movement or content errors, respectively. Whereas movement errors referred to incorrect spatio-temporal features of overall recognizable movements, content errors reflected an inability to associate tools with their prototypical actions. Both imitation and pantomime deficits were associated with lesions within the lateral occipitotemporal cortex, posterior inferior parietal lobule, posterior intraparietal sulcus and superior parietal lobule. However, the areas specifically related to the dorso-dorsal stream, i.e. posterior intraparietal sulcus and superior parietal lobule, were more strongly associated with imitation. Conversely, in contrast to imitation, pantomime deficits were associated with ventro-dorsal regions such as the supramarginal gyrus, as well as brain structures counted to the ventral stream, such as the extreme capsule. Ventral stream involvement was especially clear for content errors which were related to anterior temporal damage. However, movement errors were not consistently associated with a specific lesion location. In summary, our results indicate that imitation mainly relies on the dorso-dorsal stream for visuo-motor conversion and on-line movement control. Conversely, pantomime additionally requires ventro-dorsal and ventral streams for access to stored action engrams and retrieval of tool-action relationships.

In the present study, we identified the most probable trajectories of point-to-point segregated connections between functional attentional centers using a combination of functional magnetic resonance imaging and a novel diffusion tensor imaging-based algorithm for pathway extraction. Cortical regions activated by a visuospatial attention task were subsequently used as seeds for probabilistic fiber tracking in 26 healthy subjects. Combining probability maps of frontal and temporoparietal regions yielded a network that consisted of dorsal and ventral connections. The dorsal connections linked temporoparietal cortex with the frontal eye field and area 44 of the inferior frontal gyrus (IFG). Traveling along superior longitudinal and arcuate fascicles, these fibers are well described in relation to spatial attention. However, the ventral connections, which traveled in the white matter between insula (INS) cortex and putamen parallel to the sylvian fissure, were not previously described for visuospatial attention. Linking temporoparietal cortex with anterior INS and area 45 of IFG, these connections may provide an anatomical substrate for crossmodal cortical integration needed for stimulus perception and response in relation to current intention. The newly anatomically described integral network for visuospatial attention might improve the understanding of spatial attention deficits after white matter lesions.

Despite a large body of research, extant findings on the functional role of left inferior frontal gyrus (LIFG) in phonological and semantic fluency are still controversial. Based on cross-study comparisons, a recent meta-analysis of neuroimaging results suggests that posteriordorsal (Brodmann area, BA, 44) and anterior-ventral parts (BA 45) of LIFG contribute differentially to processes of phonologically and semantically cued word retrieval, respectively. In contrast, a subsequent functional magnetic resonance imaging experiment failed to validate the proposed dissociation using a within-subjects design. In particular, no evidence for a specific role of BA 45 in semantic fluency was found. Here, we resolve this apparent controversy by showing that the conflicting findings can be accounted for when considering the influence of task demands and individual ability on resulting functional magnetic resonance imaging activation patterns. By comparing phonological versus semantic fluency, higher activation was robustly observed in BA 44. For the opposite comparison, higher activation was found in dorsal BA 45; however, this was more pronounced in posterior-dorsal parts of BA 45 for low-performing subjects and was only apparent in anterior-dorsal parts of BA 45 under high demands on controlled semantic retrieval. Our results thus disclose important determinants for detecting a functional segregation of LIFG in verbal fluency that also have implications for the controversial findings in previous lesion studies. Moreover, the present parcellation of dorsal BA 45 corresponds well with anatomical evidence suggesting a subdivision into an anterior (45A) and posterior part (45B) and may therefore represent evidence for its functional significance in humans.

The loss and recovery of language functions are still incompletely understood. This longitudinal functional MRI study investigated the neural mechanisms underlying language recovery in patients with post-stroke aphasia putting particular emphasis on the impact of lesion site. To identify patterns of language-related activation, an auditory functional MRI sentence comprehension paradigm was administered to patients with circumscribed lesions of either left frontal (n = 17) or temporo-parietal (n = 17) cortex. Patients were examined repeatedly during the acute (≤1 week, t1), subacute (1–2 weeks, t2) and chronic phase (>6 months, t3) post-stroke; healthy age-matched control subjects (n = 17) were tested once. The separation into two patient groups with circumscribed lesions allowed for a direct comparison of the contributions of distinct lesion-dependent network components to language reorganization between both groups. We hypothesized that activation of left hemisphere spared and perilesional cortex as well as lesion-homologue cortex in the right hemisphere varies between patient groups and across time. In addition, we expected that domain-general networks serving cognitive control independently contribute to language recovery. First, we found a global network disturbance in the acute phase that is characterized by reduced functional MRI language activation including areas distant to the lesion (i.e. diaschisis) and subsequent subacute network reactivation (i.e. resolution of diaschisis). These phenomena were driven by temporo-parietal lesions. Second, we identified a lesion-independent sequential activation pattern with increased activity of perilesional cortex and bilateral domain-general networks in the subacute phase followed by reorganization of left temporal language areas in the chronic phase. Third, we observed involvement of lesion-homologue cortex only in patients with frontal but not temporo-parietal lesions. Fourth, irrespective of lesion location, language reorganization predominantly occurred in pre-existing networks showing comparable activation in healthy controls. Finally, we detected different relationships of performance and activation in language and domain-general networks demonstrating the functional relevance for language recovery. Our findings highlight that the dynamics of language reorganization clearly depend on lesion location and hence open new perspectives for neurobiologically motivated strategies of language rehabilitation, such as individually-tailored targeted application of neuro-stimulation.

Inter-hemispheric asymmetries are a common phenomenon of the human brain. Some evidence suggests that neurodegeneration related to aging and disease may preferentially affect the left-usually language- and motor-dominant-hemisphere. Here, we used activation likelihood estimation meta-analysis to assess gray matter (GM) loss and its lateralization in healthy aging and in neurodegeneration, namely, mild cognitive impairment (MCI), Alzheimer's dementia (AD), Parkinson's disease (PD), and Huntington's disease (HD). This meta-analysis, comprising 159 voxel-based morphometry publications (enrolling 4,469 patients and 4,307 controls), revealed that GM decline appeared to be asymmetric at trend levels but provided no evidence for increased left-hemisphere vulnerability. Regions with asymmetric GM decline were located in areas primarily affected by neurodegeneration. In HD, the left putamen showed converging evidence for more pronounced atrophy, while no consistent pattern was found in PD. In MCI, the right hippocampus was more atrophic than its left counterpart, a pattern that reversed in AD. The stability of these findings was confirmed using permutation tests. However, due to the lenient threshold used in the asymmetry analysis, further work is needed to confirm our results and to provide a better understanding of the functional role of GM asymmetries, for instance in the context of cognitive reserve and compensation. Hum Brain Mapp 38:5890-5904, 2017. © 2017 Wiley Periodicals, Inc.

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