A Meta-analysis on the neural basis of planning: Activation likelihood estimation of functional brain imaging results in the Tower of London task.

The ability to mentally design and evaluate series of future actions has often been studied in terms of planning abilities, commonly using well-structured laboratory tasks like the Tower of London (ToL). Despite a wealth of studies, findings on the specific localization of planning processes within prefrontal cortex (PFC) and on the hemispheric lateralization are equivocal. Here, we address this issue by integrating evidence from two different sources of data: First, we provide a systematic overview of the existing lesion data on planning in the ToL (10 studies, 211 patients) which does not indicate any evidence for a general lateralization of planning processes in (pre)frontal cortex. Second, we report a quantitative meta-analysis with activation likelihood estimation based on 31 functional neuroimaging datasets on the ToL. Separate meta-analyses of the activation patterns reported for Overall Planning (537 participants) and for Planning Complexity (182 participants) congruently show bilateral contributions of mid-dorsolateral PFC, frontal eye fields, supplementary motor area, precuneus, caudate, anterior insula, and inferior parietal cortex in addition to a left-lateralized involvement of rostrolateral PFC. In contrast to previous attributions of planning-related brain activity to the entire dorsolateral prefrontal cortex (dlPFC) and either its left or right homolog derived from single studies on the ToL, the present meta-analyses stress the pivotal role specifically of the mid-dorsolateral part of PFC (mid-dlPFC), presumably corresponding to Brodmann Areas 46 and 9/46, and strongly argue for a bilateral rather than lateralized involvement of the dlPFC in planning in the ToL. Hum Brain Mapp 38:396-413, 2017. © 2016 Wiley Periodicals, Inc.

Predicting planning performance from structural connectivity between left and right mid-dorsolateral prefrontal cortex: moderating effects of age during postadolescence and midadulthood.

Complex cognitive abilities such as planning are known to critically rely on activity of bilateral mid-dorsolateral prefrontal cortex (mid-dlPFC). However, the functional relevance of the structural connectivity between left and right mid-dlPFC is yet unknown. Here, we applied global tractography to derive streamline counts as estimates of the structural connectivity between mid-dlPFC homologs and related it to planning performance in the Tower of London task across early to midadulthood, assuming a moderating effect of age. Multiple regression analyses with interaction effects revealed that streamline counts between left and right mid-dlPFC were negatively associated with planning performance specifically in early postadolescence. From the fourth life decade on, there was a trend for a reversed, positive association. These differential findings were corroborated by converging results from fractional anisotropy and white-matter density estimates in the genu of the corpus callosum where fibers connecting mid-dlPFC homologs traversed. Moreover, the results for streamline counts were regionally specific, marking the strength of mid-dlPFC connectivity as critical in predicting interindividual differences in planning performance across different stages of adulthood. Taken together, present findings provide first evidence for nonadditive effects of age on the relation between complex cognitive abilities and the structural connectivity of mid-dlPFC homologs.

Linking planning performance and gray matter density in mid-dorsolateral prefrontal cortex: moderating effects of age and sex.

Planning of behavior relies on the integrity of the mid-dorsolateral prefrontal cortex (mid-dlPFC). Yet, only indirect evidence exists on the association of protracted maturation of dlPFC and continuing gains in planning performance post adolescence. Here, gray matter density of mid-dlPFC in young, healthy adults (18-32 years) was regressed onto performance on the Tower of London planning task while accounting for moderating effects of age and sex on this interrelation. Multiple regression analysis revealed an association of planning performance and mid-dlPFC gray matter density that was especially strong in late adolescence and early twenties. As expected, for males better planning performance was linked to reduced gray matter density of mid-dlPFC, possibly due to maturational processes such as synaptic pruning. Most surprisingly, females showed an inverted, positive interrelation of planning performance and mid-dlPFC gray matter density, indicating that sexually dimorphic development of dlPFC continues during early adulthood. Age and sex are hence important moderators of the link between planning performance and gray matter density in mid-dlPFC. Consequently, the assessment of moderator effects in regression designs can significantly enhance understanding of brain-behavior relationships.

T2* Relaxometry in Patients with Parkinson's Disease : Use of an Automated Atlas-based Approach.

BACKGROUND: Magnetic resonance (MR) relaxometry is of increasing scientific relevance in neurodegenerative disorders but is still not established in clinical routine. Several studies have investigated relaxation time alterations in disease-specific areas in Parkinson's disease (PD), all using manually drawn regions of interest (ROI). Implementing MR relaxometry into the clinical setting involves the reduction of time needed for postprocessing using an investigator-independent and reliable approach. The aim of this study was to evaluate an automated, atlas-based ROI method for evaluating T2* relaxation times in patients with PD. METHOD: Automated atlas-based ROI analysis of quantitative T2* maps were generated from 20 PD patients and 20 controls. To test for the accuracy of the atlas-based ROI segmentation, we evaluated the spatial overlap in comparison with manually segmented ROIs using the Dice similarity coefficient (DSC). Additionally, we tested for group differences using our automated atlas-based ROIs of the putamen, globus pallidus, and substantia nigra. RESULTS: A good spatial overlap accuracy was shown for the automated segmented putamen (mean DSC, 0.64 ± 0.04) and was inferior but still acceptable for the substantia nigra (mean DSC, 0.50 ± 0.17). Based on our automated defined ROI selection, a significant decrease of T2* relaxation time was found in the putamen as well as in the internal and external globus pallidus in PD patients compared with healthy controls. CONCLUSION: Automated digital brain atlas-based approaches are reliable, more objective and time-efficient, and therefore have the potential to replace the time-consuming manual drawing of ROIs.

Assessment of planning ability: Psychometric analyses on the unidimensionality and construct validity of the Tower of London Task (TOL-F).

OBJECTIVE: The Tower of London (TOL) is widely used to assess planning ability as a prototypical executive function in healthy and clinical populations. Despite its popularity, there is still no consensus on (a) whether the TOL measures a psychometrically unidimensional trait, and (b) how differences in problem structure relate to the difficulty of individual items. METHOD: Employing the framework of factor analysis and item response theory we investigated these issues of construct validity in a sample of 798 participants (443 female; 16 to 84 years). Participants worked on the TOL-Freiburg version (TOL-F) comprising a set of 24 4- to 6-move problems, which--based on comprehensive cognitive task analyses-systematically differ with regard to several structural problem parameters (minimum number of moves, search depth, goal hierarchy). RESULTS: Results revealed that TOL-F performance is mainly explained by 1 major factor, while further minor factors additionally account for smaller, but possibly still informative, shares of variance. Individual item difficulties can be predicted by the experimentally varied problem parameters to a high degree (r = .89) and can be considered stable across different levels of age, sex, education, and planning ability. CONCLUSION: These findings demonstrate the TOL-F's construct validity as measuring planning ability in terms of an essentially unidimensional cognitive function while adhering to theory-driven concepts of task difficulty. TOL-F task performance hence represents an accurate, robust, and theoretically grounded estimation of a participant's planning ability. The results further highlight the merit of using established concepts from experimental psychology for improving neuropsychological assessment.

Analyses of Rule Breaks and Errors During Planning in Computerized Tower Tasks: Insights From Neurological Patients.

OBJECTIVE: Planning as a prototypical executive function is frequently compromised in clinical samples. Analyses of rule breaking during performance on tower tasks are highly informative for clinical inferences on planning deficits, but are as yet only available for manual task versions. Therefore, the present study investigated whether valid rule-break information can also be gained using a computerized Tower of London (TOL) version. METHOD: For patients with stroke (N = 60), Parkinson's disease (PD; N = 51), and Mild Cognitive Impairment (MCI; N = 29), rule breaks (e.g., selecting a blocked ball) and online-planning errors (re-considering the next move) on the TOL-Freiburg (TOL-F) were compared to that of matched healthy controls, and diagnostic accuracy for these measures was assessed. RESULTS: Stroke and PD patients committed significantly more rule breaks and online-planning errors than matched controls, with this group difference being significantly greater for rule breaks. For MCI patients, only a trend for elevated numbers of rule breaks emerged. In all patients, rule breaks and errors increased as a function of problem complexity. Diagnostic accuracy was the highest for PD and lowest for MCI patients, with both rule breaks and errors demonstrating moderate sensitivity but higher specificity across all samples. DISCUSSION: Direct attempts to break the TOL-F's task rules are particularly informative of clinical impairments in planning ability. Similar to findings from studies employing manual versions, using a computerized tower task revealed consistent rule break and error patterns across patients. Thus, computerized tower tasks can yield useful clinical information on rule-breaking behavior during planning in clinical populations.

Planning Decrements in Healthy Aging: Mediation Effects of Fluid Reasoning and Working Memory Capacity.

OBJECTIVES: Although age-related differences in planning ability are well known, their cognitive foundations remain a matter of contention. To elucidate the specific processes underlying planning decrements in older age, the relative contributions of fluid reasoning, working memory (WM) capacity, and processing speed to accuracy on the Tower of London (TOL) planning task were investigated. METHOD: Mediation analyses were used to relate overall and search depth-related TOL accuracy from older (N = 106; 60-89 years) and younger adults (N = 69; 18-54 years) to age and measures of fluid reasoning, WM capacity, and speed. RESULTS: For overall planning, fluid abilities mediated the effects of age, WM capacity, and speed in older adults. By contrast, fluid abilities and WM capacity mediated each other in younger adults. For planning accuracy under low demands on the depth of search, WM capacity was specifically important in older age, whereas younger adults recruited both WM capacity and fluid reasoning. Under high search-depth-demands, fluid abilities underlay the cognitive operations critical for resolving move interdependencies in both age groups. DISCUSSION: Fluid abilities and WM capacity undergo significant changes from younger to older age in their unique contribution to planning, which might represent a mechanism whereby planning decrements in older age are brought about.

Assessing Planning Ability Across the Adult Life Span: Population-Representative and Age-Adjusted Reliability Estimates for the Tower of London (TOL-F).

Planning ahead the consequences of future actions is a prototypical executive function. In clinical and experimental neuropsychology, disc-transfer tasks like the Tower of London (TOL) are commonly used for the assessment of planning ability. Previous psychometric evaluations have, however, yielded a poor reliability of measuring planning performance with the TOL. Based on theory-grounded task analyses and a systematic problem selection, the computerized TOL-Freiburg version (TOL-F) was developed to improve the task's psychometric properties for diagnostic applications. Here, we report reliability estimates for the TOL-F from two large samples collected in Mainz, Germany (n = 3,770; 40-80 years) and in Vienna, Austria (n = 830; 16-84 years). Results show that planning accuracy on the TOL-F possesses an adequate internal consistency and split-half reliability (>0.7) that are stable across the adult life span while the TOL-F covers a broad range of graded difficulty even in healthy adults, making it suitable for both research and clinical application.

Category and design fluency in mild cognitive impairment: Performance, strategy use, and neural correlates.

The exploration and retrieval of words during category fluency involves different strategies to improve or maintain performance. Deficits in that task, which are common in patients with amnestic mild cognitive impairment (aMCI), mirror either impaired semantic memory or dysfunctional executive control mechanisms. Relating category fluency to tasks that place greater demands on either semantic knowledge or executive functions might help to determine the underlying cognitive process. The aims of this study were to compare performance and strategy use of 20 patients with aMCI to 30 healthy elderly controls (HC) and to identify the dominant component (either executive or semantic) for better task performance in category fluency. Thus, the relationship between category fluency, design fluency and naming was examined. As fluency tasks have been associated with the superior frontal gyrus (SFG), the inferior frontal gyrus (IFG), and the temporal pole, we further explored the relationship between gray matter volume in these areas and both performance and strategy use. Patients with aMCI showed significantly lower performance and significantly less strategy use during fluency tasks compared to HC. However, both groups equally improved their performance when repeatedly confronted with the same task. In aMCI, performance during category fluency was significantly predicted by design fluency performance, while in HC, it was significantly predicted by naming performance. In HC, volume of the SFG significantly predicted both category and design fluency performance, and strategy use during design fluency. In aMCI, the SFG and the IFG predicted performance during both category and design fluency. The IFG significantly predicted strategy use during category fluency in both groups. The reduced category fluency performance in aMCI seems to be primarily due to dysfunctional executive control mechanisms rather than impaired semantic knowledge. This finding is directly relevant to patients in the different stages of Alzheimer's disease as it links the known semantic fluency deficit in this population to executive functions. Although patients with aMCI are impaired in both performance and strategy use compared to HC, they are able to increase performance over time. However, only HC were able to significantly improve the utilization of fluency strategies in both category and design fluency over time. HC seem to rely more heavily on the SFG during fluency tasks, while in patients with aMCI additional frontal brain areas are involved, possibly reflecting compensational processes.

Contribution of the Cholinergic System to Verbal Memory Performance in Mild Cognitive Impairment.

Acetylcholine is critically involved in modulating learning and memory function, which both decline in neurodegeneration. It remains unclear to what extent structural and functional changes in the cholinergic system contribute to episodic memory dysfunction in mild cognitive impairment (MCI), in addition to hippocampal degeneration. A better understanding is critical, given that the cholinergic system is the main target of current symptomatic treatment in mild to moderate Alzheimer's disease. We simultaneously assessed the structural and functional integrity of the cholinergic system in 20 patients with MCI and 20 matched healthy controls and examined their effect on verbal episodic memory via multivariate regression analyses. Mediating effects of either cholinergic function or hippocampal volume on the relationship between cholinergic structure and episodic memory were computed. In MCI, a less intact structure and function of the cholinergic system was found. A smaller cholinergic structure was significantly correlated with a functionally more active cholinergic system in patients, but not in controls. This association was not modulated by age or disease severity, arguing against compensational processes. Further analyses indicated that neither functional nor structural changes in the cholinergic system influence verbal episodic memory at the MCI stage. In fact, those associations were fully mediated by hippocampal volume. Although the cholinergic system is structurally and functionally altered in MCI, episodic memory dysfunction results primarily from hippocampal neurodegeneration, which may explain the inefficiency of cholinergic treatment at this disease stage.

Test-retest reliability of the Tower of London Planning Task (TOL-F).

Test-retest reliability is difficult to establish for measures of executive functioning that rely on task novelty. Correspondingly, evidence on the test-retest reliability of the commonly used Tower of London (TOL) planning task is, as yet, equivocal and only based on indices of relative consistency, rather than absolute agreement of individual scores. Further, the stability of planning latencies over repeated testing has not been investigated. The present study assessed test-retest reliability of planning performance measures using a structurally balanced problem set implemented in the TOL-Freiburg version (TOL-F). The TOL-F was administered in 2 structurally identical versions to a sample of young, healthy adults over a 1-week interval. For planning accuracy, the Pearson correlation and intraclass correlation coefficient for relative consistency were adequate (r = .739 and .734), with the intraclass correlation coefficient for absolute agreement only slightly decreased (r = .690). For initial thinking and movement execution times, relative consistency and absolute agreement reliability indices were uniformly low (all r between .274 and .519). Given adequate planning accuracy test-retest reliability, the TOL-F can be reliably used to measure planning ability in group-based studies and with individual participants, as is important for clinical testing. Planning latencies, however, should only be used as complementary, but not sole measures of planning ability, particularly for normative evaluations in clinical assessment. In sum, TOL-F planning accuracy possesses adequate absolute and relative test-retest reliability for experimental utility. Future studies should assess whether this indeed translates into clinical utility of the TOL-F for measuring planning ability in patients.

Processing of bilateral versus unilateral conditions: evidence for the functional contribution of the ventral attention network.

Processing of multiple or bilateral conditions presented simultaneously in both hemifields reflects the natural mode of perception in our multi-target environment, but is not yet completely understood. While region-of-interest based studies in healthy subjects reported single cortical areas as the right inferior parietal lobe (IPL) or temporoparietal junction (TPJ) to process bilateral conditions, studies in extinction patients with reduced ability in this regard suggested the right superior temporal cortex to hold a key role. The present fMRI study on healthy subjects aimed at resolving these discrepancies by contrasting bilateral versus unilateral visual conditions in a paradigm similar to the bed-side test for patients with visual extinction on a whole brain level. Additionally, reduced attentional capacity in spatial processing was investigated in normal aging. Processing of bilateral conditions compared to unilateral ones showed to require stronger activation of not one single cortical region but the entire right-lateralized ventral attention network, bilateral parietal and visual association areas. These results might suggest a conceptual difference between unilateral and bilateral spatial processing with the latter depending on additional anatomical and functional brain resources. Reduced attentional capacity in elderly subjects was associated with compensatory recruitment of contralateral functional homologues [left IPL, TPJ, frontal eye field (FEF)]. These data reveal the functional anatomy of our ability to visually process and respond to the entity of the environment and improve our understanding of neglect and extinction. Moreover, the data demonstrate that a restriction of the attentional capacity is based on processing limitations in the network of high-level cortical areas and not due to restriction in the primary sensory ones.

Assessment of planning performance in clinical samples: Reliability and validity of the Tower of London task (TOL-F).

OBJECTIVE: Executive deficits are frequent sequelae of neurological and psychiatric disorders, but their adequate neuropsychological assessment is still a matter of contention, given that executive tasks draw on a multitude of cognitive processes that are often not sufficiently specified. In line with this, results on psychometric properties of the Tower of London, a task measuring planning ability as a prototypical executive function, are equivocal and furthermore lacking completely for adult clinical populations. METHODS: We used a structurally balanced item set implemented in the Tower of London (Freiburg version, TOL-F) that accounts for major determinants of problem difficulty beyond the commonly used minimum number of moves to solution. Split-half reliability, internal consistency, and criterion-related concurrent validity of TOL-F accuracy were assessed in patients with stroke (N = 60), Parkinson syndrome (N = 51), and mild cognitive impairment (N = 29), and healthy adults (N = 155). RESULTS: Across samples, mean split-half and lower-bound indices of reliability of accuracy scores were adequate (r ≥ .7) or higher. Compared to a subset of healthy controls matched for age, sex, and education levels, deficits in planning accuracy emerged for all three clinical samples. CONCLUSIONS: Based on consistently adequate reliability and a good criterion-related validity of accuracy scores, the TOL-F demonstrates its utility for testing planning ability in clinical samples and healthy adults. Using item sets systematically accounting for several determinants of task difficulty can thus significantly enhance the contended reliability of executive tasks and provide an opportunity to resolve the underspecification of cognitive processes contributing to executive functioning in health and disease.

Development of planning abilities in normal aging: differential effects of specific cognitive demands.

In line with the frontal hypothesis of aging, the ability to plan ahead undergoes substantial change during normal aging. Although impairments on the Tower of London planning task were reported earlier, associations between age-related declines and specific cognitive demands on planning have not been studied. Here we investigated the impact of search depth and goal ambiguity on planning, which impose demands on the depth and breadth of look-ahead processes, respectively. Besides an overall age-related decline in planning accuracy of 106 healthy older adults, differential search depth effects were found: Whereas planning accuracy of subjects in the early 60s was not affected by variations in search depth, between the ages of 65 and 76 years, accuracy was significantly decreased for high versus low levels of search depth. For subjects older than 76, different search depth levels did not further impact on accuracy, which was lowest overall. This nonlinear pattern may reflect differential impairments in fluid abilities and working memory capacity across various stages of older age. As no age-related effects of goal ambiguity were found, normal aging seems to be specifically sensitive to planning demands on the depth but not the breadth of anticipatory search processes. Hence, cognitive functions subserved by the prefrontal cortex experience differential development over the course of normal aging.

Differential patterns of planning impairments in Parkinson's disease and sub-clinical signs of dementia? A latent-class model-based approach.

Planning impairments mark a well-documented consequence of neurodegenerative diseases such as Parkinson's disease (PD). Recently, using the Tower of London task we demonstrated that, rather than being generally impaired, PD patients selectively fail when planning requires flexible in-breadth search strategies. For a better understanding of the interindividual patterns underlying specific planning impairments, here we performed an explorative re-analysis of the original data using a latent-class model-based approach. Data-driven classification according to subjects' performance was based on a multinomial processing tree (MPT) model accommodating the impact of increased breadth versus depth of looking ahead during planning. In order to assess interindividual variability in coping with these different task demands, an extension of MPT models was used in which sample-immanent heterogeneity is accounted for by identifying different latent classes of individuals. Two latent classes were identified that differed considerably in performance for problems placing high demands on the depth of anticipatory search processes. In addition, these impairments were independent of PD diagnosis. However, latent-class mediated search depth-related deficits in planning performance were associated with poorer outcomes in dementia screenings, albeit sub-clinical. PD patients exhibited additional deficits related to the breadth of searching ahead. Taken together, results revealed dissociable impairments in specific planning processes within a single task of visuospatial problem solving. Present analyses put forward the hypothesis that cognitive sequelae of PD and sub-clinical signs of dementia may be related to differential patterns of planning impairments.

Reviewing the impact of problem structure on planning: a software tool for analyzing tower tasks.

Cognitive, clinical, and neuroimaging studies on planning abilities most frequently implement the Tower of London task or one of its variants. Yet, cumulating evidence from a series of experiments suggests that the commonly used approximation of problem difficulty in terms of the minimum number of moves for goal attainment is too coarse a measure for the underlying cognitive operations, and in some cases may be even misleading. Rather, problem difficulty can be more specifically characterized by a set of structural task parameters such as the number and nature of optimal and suboptimal solution paths, the required search depths, the patterns of intermediate and goal moves, goal hierarchies and the associated degree of ambiguity in the sequential ordering of goal moves. First applications in developmental and patient studies have proven fruitful in targeting fundamental alterations of planning abilities in healthy and clinical conditions. In addition, recent evidence from neuroimaging shows that manipulations of problem structure relate to separate cognitive and neural processes and are accompanied by dissociable brain activation patterns. Here, we briefly review these structural problem parameters and the concepts behind. As controlling for task parameters and selecting a balanced problem set is a complex and error-prone endeavor, we further present TowerTool, a software solution that allows easy access to in-depth analysis of the problem structure of widely used planning tasks like the Tower of London, the Tower of Hanoi, and their variants. Thereby, we hope to encourage and facilitate the implementation of structurally balanced task sets in future studies on planning and to promote transfer between the cognitive, developmental, and clinical neurosciences.