State and trait predictors of cognitive responses to acute stress and uncertainty.

Stress occurs when conditions burden or exceed an individual's adaptive resources. Military personnel are often tasked with maintaining peak performance under such stressful conditions. Importantly, the effects of stress are nuanced and may vary as a function of individual traits and states. Recent interdisciplinary research has sought to model and identify such relationships. In two previously reported efforts, Soldiers first completed a comprehensive battery of trait assessments across four general domains thought to be predictive of performance: cognitive, health, physical, and social-emotional, and then completed the Decision-Making under Uncertainty and Stress (DeMUS) virtual reality task that probed spatial cognition, memory, and decision-making under stress and variable uncertainty. The present analysis explores whether cognitive, health, physical, and social-emotional trait assessments, as well as physiological state measures, predict or modulate DeMUS performance outcomes under stress. Multiple regression analyses examined the effect of each trait predictor and stress responsiveness on quantitative task performance outcomes. Results revealed that one measure of state stress reactivity, salivary cortisol, predicted lower recognition memory sensitivity. Further, trait measures of healthy eating, agility, flexibility, cognitive updating, and positive emotion predicted enhanced spatial orienting and decision-making performance and confidence. Together, the results suggest that select individual states and traits may predict cognition under stress. Future research should expand to ecologically relevant military stressors during training and operations.

From Image to Diagnosis: Characterizing Sources of Error in Histopathologic Interpretation.

An accurate histopathologic diagnosis on surgical biopsy material is necessary for the clinical management of patients and has important implications for research, clinical trial design/enrollment, and public health education. This study used a mixed methods approach to isolate sources of diagnostic error while residents and attending pathologists interpreted digitized breast biopsy slides. Ninety participants, including pathology residents and attending physicians at major United States medical centers reviewed a set of 14 digitized whole-slide images of breast biopsies. Each case had a consensus-defined diagnosis and critical region of interest (cROI) representing the most significant pathology on the slide. Participants were asked to view unmarked digitized slides, draw their participant region of interest (pROI), describe its features, and render a diagnosis. Participants' review behavior was tracked using case viewer software and an eye-tracking device. Diagnostic accuracy was calculated in comparison to the consensus diagnosis. We measured the frequency of errors emerging during 4 interpretive phases: (1) detecting the cROI, (2) recognizing its relevance, (3) using the correct terminology to describe findings in the pROI, and (4) making a diagnostic decision. According to eye-tracking data, trainees and attending pathologists were very likely (∼94% of the time) to find the cROI when inspecting a slide. However, trainees were less likely to consider the cROI relevant to their diagnosis. Pathology trainees (41% of cases) were more likely to use incorrect terminology to describe pROI features than attending pathologists (21% of cases). Failure to accurately describe features was the only factor strongly associated with an incorrect diagnosis. Identifying where errors emerge in the interpretive and/or descriptive process and working on building organ-specific feature recognition and verbal fluency in describing those features are critical steps for achieving competency in diagnostic decision making.

More scanning, but not zooming, is associated with diagnostic accuracy in evaluating digital breast pathology slides.

Diagnoses of medical images can invite strikingly diverse strategies for image navigation and visual search. In computed tomography screening for lung nodules, distinct strategies, termed scanning and drilling, relate to both radiologists' clinical experience and accuracy in lesion detection. Here, we examined associations between search patterns and accuracy for pathologists (N = 92) interpreting a diverse set of breast biopsy images. While changes in depth in volumetric images reveal new structures through movement in the z-plane, in digital pathology changes in depth are associated with increased magnification. Thus, "drilling" in radiology may be more appropriately termed "zooming" in pathology. We monitored eye-movements and navigation through digital pathology slides to derive metrics of how quickly the pathologists moved through XY (scanning) and Z (zooming) space. Prior research on eye-movements in depth has categorized clinicians as either "scanners" or "drillers." In contrast, we found that there was no reliable association between a clinician's tendency to scan or zoom while examining digital pathology slides. Thus, in the current work we treated scanning and zooming as continuous predictors rather than categorizing as either a "scanner" or "zoomer." In contrast to prior work in volumetric chest images, we found significant associations between accuracy and scanning rate but not zooming rate. These findings suggest fundamental differences in the relative value of information types and review behaviors across two image formats. Our data suggest that pathologists gather critical information by scanning on a given plane of depth, whereas radiologists drill through depth to interrogate critical features.

Brief, prior, exposure to red decreases categorical and coordinate spatial task performance.

Location information is processed through two types of spatial processing; categorical and coordinate processing. Categorical spatial relations indicate where an object is relative to another object, without regard to the metric distance between the two objects. Coordinate spatial relations indicate metric distance without regard to relative location. In human behavioral studies, the magnocellular pathway of the lateral geniculate nucleus has been implicated in coordinate spatial processing abilities. Magnocellular pathway cells (type IV) have a center surround organization, such that red light inhibits neuronal firing. In these behavioral studies, red stimuli decreases coordinate spatial processing accuracy. Prior studies also show that there is a lag between the time of visual stimulus presentation and the time of observing a neural response in the magnocellular pathway. We sought to understand whether prior presentation of red stimuli decreases coordinate spatial performance, and also examined its effects on categorical spatial performance. The results indicate that prior presentation of red stimuli decreases accuracy and perceived confidence on both the categorical and coordinate tasks. These results confirm prior findings of the association between magnocellular pathway function and coordinate spatial processing. Implications for categorical task results and associated neural pathways are discussed.

Action compatibility in spatial knowledge developed through virtual navigation.

Action-compatibility effects (ACEs) arise due to incongruity between perceptuo-motor traces stored in memory and the perceptuo-motor demands of a retrieval task. Recent research has suggested that ACEs arising during spatial memory retrieval are additionally modulated by individual differences in how experienced participants are with a college campus environment. However, the extent and nature of experience with a real-world environment is difficult to assess and control, and characteristics of the retrieval task itself might modulate ACEs during spatial memory retrieval. The present study provides a more controlled and in-depth examination of how individual differences and task-based factors interact to shape ACEs when participants retrieve spatial memories. In two experiments, participants with varied video game experience learned a virtual environment and then used the computer mouse to verify spatial relationships from different perspectives. Mouse trajectories demonstrated ACEs, differing by retrieval perspective and video game experience. Videogame experts demonstrated the ACE based on learned spatial relationships during egocentric retrieval only, whereas videogame novices showed the ACE based on semantic processing of directional terms only. Specifically, gaming experts invoke perspective-specific perceptuo-motor associations to retrieve spatial knowledge, whereas non-experts are influenced by semantically based associations specific to the retrieval task. Results are discussed in the context of action-compatibility effects, the intentional weighting hypothesis, and the flexible encoding and retrieval of spatial information.

Cognitive focus affects spatial decisions under conditions of uncertainty.

Finding one's way to a destination is a common, everyday task that often relies on spatial information provided by humans and/or automatic devices. However, the information can be inaccurate. How we decide which route to take will depend on our thoughts about the available route information, including who or what provided it, and how these sources may be associated with differential accuracy and fallibility. In three experiments (previously reported in Brunyé et al. (Q J Exper Psychol 68(3):585-607, 2015)), we found that when route directions conflicted with the perceived environment, people trusted the landmark information other humans provided, but relied on the turn direction information from an automatic device. But what guides these behavioral results? Here we present a systematic linguistic analysis of retrospective reports that sheds some light on how information about the direction source affects cognitive focus. A focus on direction sources in the instruction triggered a cognitive focus on the direction source throughout. Participants who systematically switched strategies focused more on features of the scenario than those who did not. Non-switching strategies were associated with a higher focus on the participants' own reasoning processes, in particular when relying on turn information. These results highlight how cognitive focus is guided by scenario factors and individual preferences, triggering inferences that influence decisions.

Superior categorical and coordinate spatial task performance in inconsistent-handers relative to consistent-right-handers.

Categorical versus coordinate spatial tasks rely differentially on the left versus right hemisphere. Given the neuroanatomical and neurophysiological differences between inconsistent- versus consistent-right-handers (ICH versus CRH, respectively), such that the former demonstrates increased access to right hemisphere processes relative to the latter, it was hypothesized that ICH would outperform CRH on a test of coordinate spatial knowledge. Previous work demonstrating reliance on the right hemisphere for both categorical and coordinate information in non-right-handers using lateralized stimuli of brief duration suggested ICH might also outperform CRH on a categorical task as well. Participants navigated a virtual environment, landmark-to-landmark, within a 3-dimensional first-person point of view with high ecological validity, and then were tested on either their categorical or coordinate spatial knowledge. ICH were superior relative to the CRH on both types of spatial knowledge. Additionally, ICH navigated the environment during learning more quickly, and reported being more confident in their knowledge of the location of landmarks within the environment, compared with CRH. Results are discussed in terms of potential handedness differences in spatial ability generally.

Categorical and coordinate spatial task performance in inconsistent-handers versus consistent-right-handers: part II.

A previous study reported superior categorical and coordinate spatial task performance in inconsistent-versus consistent-right-handers (ICH versus CRH). Propper et al. used a three-dimensional (3D) computer-based task wherein individuals navigated to 21 locations within a realistic cityscape. During testing, participants were queried on their categorical and coordinate spatial knowledge of the map. In that study, the categorical and coordinate tasks may have inadvertently encouraged language coding of learned spatial information, potentially confounding spatial processing with recall ability for language-based information. Also, that study used a between-subjects design, which precludes examination of relationships between spatial knowledge as a function of handedness. The present study duplicated the learning task in Propper et al. using test stimuli that more faithfully represent spatial, and not language-based, information, as well as a within-subjects design. Results did not significantly replicate the previous study. Possible reasons for this finding are discussed.

Verbal long-term memory is enhanced by retrieval practice but impaired by prefrontal direct current stimulation.

Retrieval practice involves repeatedly testing a student during the learning experience, reliably conferring learning advantages relative to repeated study. Transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex (dlPFC) has also been shown to confer learning advantages for verbal memory, though research is equivocal. The present study examined the effects of retrieval versus study practice with or without left dlPFC tDCS on verbal episodic memory. Participants (N = 150) experienced either retrieval practice or study practice, and active anodal, active cathodal, or sham tDCS while encoding word lists, and then returned two days later for a final recall test. Three primary patterns emerged: first, during encoding, tDCS did not influence recall rates in the retrieval practice group. Second, during final recall, participants in the retrieval practice groups recalled more than those in the study practice groups. Finally, during final recall, anodal tDCS decreased recall relative to sham and cathodal stimulation, suggesting that it interfered with developing highly detailed memories that could be relied upon for subsequent recollection. Data support existing research demonstrating the effectiveness of retrieval practice as a learning strategy, but also suggest that anodal dlPFC stimulation can induce long-term negative impacts on verbal episodic memory retrieval.

Characterizing Diagnostic Search Patterns in Digital Breast Pathology: Scanners and Drillers.

Following a baseline demographic survey, 87 pathologists interpreted 240 digital whole slide images of breast biopsy specimens representing a range of diagnostic categories from benign to atypia, ductal carcinoma in situ, and invasive cancer. A web-based viewer recorded pathologists' behaviors while interpreting a subset of 60 randomly selected and randomly ordered slides. To characterize diagnostic search patterns, we used the viewport location, time stamp, and zoom level data to calculate four variables: average zoom level, maximum zoom level, zoom level variance, and scanning percentage. Two distinct search strategies were confirmed: scanning is characterized by panning at a constant zoom level, while drilling involves zooming in and out at various locations. Statistical analysis was applied to examine the associations of different visual interpretive strategies with pathologist characteristics, diagnostic accuracy, and efficiency. We found that females scanned more than males, and age was positively correlated with scanning percentage, while the facility size was negatively correlated. Throughout 60 cases, the scanning percentage and total interpretation time per slide decreased, and these two variables were positively correlated. The scanning percentage was not predictive of diagnostic accuracy. Increasing average zoom level, maximum zoom level, and zoom variance were correlated with over-interpretation.

Habitual exercise is associated with cognitive control and cognitive reappraisal success.

Habitual exercise is associated with enhanced domain-general cognitive control, such as inhibitory control, selective attention, and working memory, all of which rely on the frontal cortex. However, whether regular exercise is associated with more specific aspects of cognitive control, such as the cognitive control of emotion, remains relatively unexplored. The present study employed a correlational design to determine whether level of habitual exercise was related to performance on the Stroop test measuring selective attention and response inhibition, the cognitive reappraisal task measuring cognitive reappraisal success, and associated changes in prefrontal cortex (PFC) oxygenation using functional near-infrared spectroscopy. 74 individuals (24 men, 50 women, age 18-32 years) participated. Higher habitual physical activity was associated with lower Stroop interference (indicating greater inhibitory control) and enhanced cognitive reappraisal success. Higher habitual exercise was also associated with lower oxygenated hemoglobin (O2Hb) in the PFC in response to emotional information. However, NIRS data indicated that exercise was not associated with cognitive control-associated O2Hb in the PFC. Behaviorally, the findings support and extend the previous findings that habitual exercise relates to more successful cognitive control of neutral information and cognitive reappraisal of emotional information. Future research should explore whether habitual exercise exerts causal benefits to cognitive control and PFC oxygenation, as well as isolate specific cognitive control processes sensitive to change through habitual exercise.

Cognitive strategies in the mental rotation task revealed by EEG spectral power.

The classic mental rotation task (MRT; Shepard & Metzler, 1971) is commonly thought to measure mental rotation, a cognitive process involving covert simulation of motor rotation. Yet much research suggests that the MRT recruits both motor simulation and other analytic cognitive strategies that depend on visuospatial representation and visual working memory (WM). In the present study, we investigated cognitive strategies in the MRT using time-frequency analysis of EEG and independent component analysis. We scrutinized sensorimotor mu (µ) power reduction, associated with motor simulation, parietal alpha (pα) power reduction, associated with visuospatial representation, and frontal midline theta (fmθ) power enhancement, associated with WM maintenance and manipulation. µ power increased concomitant with increasing task difficulty, suggesting reduced use of motor simulation, while pα decreased and fmθ power increased, suggesting heightened use of visuospatial representation processing and WM, respectively. These findings suggest that MRT performance involves flexibly trading off between cognitive strategies, namely a motor simulation-based mental rotation strategy and WM-intensive analytic strategies based on task difficulty. Flexible cognitive strategy use may be a domain-general cognitive principle that underlies aptitude and spatial intelligence in a variety of cognitive domains. We close with discussion of the present study's implications as well as future directions.

Non-invasive brain stimulation targeting the right fusiform gyrus selectively increases working memory for faces.

The human extrastriate cortex contains a region critically involved in face detection and memory, the right fusiform gyrus. The present study evaluated whether transcranial direct current stimulation (tDCS) targeting this anatomical region would selectively influence memory for faces versus non-face objects (houses). Anodal tDCS targeted the right fusiform gyrus (Brodmann's Area 37), with the anode at electrode site PO10, and cathode at FP2. Two stimulation conditions were compared in a repeated-measures design: 0.5mA versus 1.5mA intensity; a separate control group received no stimulation. Participants completed a working memory task for face and house stimuli, varying in memory load from 1 to 4 items. Individual differences measures assessed trait-based differences in facial recognition skills. Results showed 1.5mA intensity stimulation (versus 0.5mA and control) increased performance at high memory loads, but only with faces. Lower overall working memory capacity predicted a positive impact of tDCS. Results provide support for the notion of functional specialization of the right fusiform regions for maintaining face (but not non-face object) stimuli in working memory, and further suggest that low intensity electrical stimulation of this region may enhance demanding face working memory performance particularly in those with relatively poor baseline working memory skills.

Accuracy is in the eyes of the pathologist: The visual interpretive process and diagnostic accuracy with digital whole slide images.

Digital whole slide imaging is an increasingly common medium in pathology, with application to education, telemedicine, and rendering second opinions. It has also made it possible to use eye tracking devices to explore the dynamic visual inspection and interpretation of histopathological features of tissue while pathologists review cases. Using whole slide images, the present study examined how a pathologist's diagnosis is influenced by fixed case-level factors, their prior clinical experience, and their patterns of visual inspection. Participating pathologists interpreted one of two test sets, each containing 12 digital whole slide images of breast biopsy specimens. Cases represented four diagnostic categories as determined via expert consensus: benign without atypia, atypia, ductal carcinoma in situ (DCIS), and invasive cancer. Each case included one or more regions of interest (ROIs) previously determined as of critical diagnostic importance. During pathologist interpretation we tracked eye movements, viewer tool behavior (zooming, panning), and interpretation time. Models were built using logistic and linear regression with generalized estimating equations, testing whether variables at the level of the pathologists, cases, and visual interpretive behavior would independently and/or interactively predict diagnostic accuracy and efficiency. Diagnostic accuracy varied as a function of case consensus diagnosis, replicating earlier research. As would be expected, benign cases tended to elicit false positives, and atypia, DCIS, and invasive cases tended to elicit false negatives. Pathologist experience levels, case consensus diagnosis, case difficulty, eye fixation durations, and the extent to which pathologists' eyes fixated within versus outside of diagnostic ROIs, all independently or interactively predicted diagnostic accuracy. Higher zooming behavior predicted a tendency to over-interpret benign and atypia cases, but not DCIS cases. Efficiency was not predicted by pathologist- or visual search-level variables. Results provide new insights into the medical interpretive process and demonstrate the complex interactions between pathologists and cases that guide diagnostic decision-making. Implications for training, clinical practice, and computer-aided decision aids are considered.

Caffeine and theanine exert opposite effects on attention under emotional arousal.

Tea is perceived as more relaxing than coffee, even though both contain caffeine. L-theanine in tea may account for the difference. Consumed together, caffeine and theanine exert similar cognitive effects to that of caffeine alone, but exert opposite effects on arousal, in that caffeine accentuates and theanine mitigates physiological and felt stress responses. We evaluated whether caffeine and theanine influenced cognition under emotional arousal. Using a double-blind, repeated-measures design, 36 participants received 4 treatments (200 mg caffeine + 0 mg theanine, 0 mg caffeine + 200 mg theanine, 200 mg caffeine + 200 mg theanine, 0 mg caffeine + 0 mg theanine) on separate days. Emotional arousal was induced by highly arousing negative film clips and pictures. Mood, salivary cortisol, and visual attention were evaluated. Caffeine accentuated global processing of visual attention on the hierarchical shape task (p < 0.05), theanine accentuated local processing (p < 0.05), and the combination did not differ from placebo. Caffeine reduced flanker conflict difference scores on the Attention Network Test (p < 0.05), theanine increased difference scores (p < 0.05), and the combination did not differ from placebo. Thus, under emotional arousal, caffeine and theanine exert opposite effects on certain attentional processes, but when consumed together, they counteract the effects of each other.

Relationship between sustained unilateral hand clench, emotional state, line bisection performance, and prefrontal cortical activity: A functional near-infrared spectroscopy study.

Sustained unilateral hand clenching alters perceptual processing and affective/motivational state, with these alterations presumed to reflect increased hemispheric activity contralateral to the side of motor movement. However, data from electroencephalographic and imaging studies are contradictory regarding the relationship between sustained hand clenching and brain activity. In order to investigate the relationship between brain activity, sustained unilateral hand clenching, and changes in affect and perceptual processing, frontal hemispheric activity was measured via functional near-infrared spectroscopy (fNIRS), using derived O2Hb prior to, during, and post-sustained unilateral hand clench. Participants' mood and spatial perception were recorded pre- and post-clenching. Sustained unilateral hand clenching altered brain activity and mood, but not spatial perception. Results revealed increased O2Hb bilaterally following sustained unilateral hand clenching, relative to baseline, regardless of hand. In agreement with previous fNIRS studies, sustained unilateral hand clenching resulted in greater ipsilateral, compared with contralateral, O2Hb. An interaction between side of hand clench and change in mood was in the direction predicted by theories of hemispheric lateralization of emotion: Following left-hand clenching, individuals became more affectively negative, and following right-hand clenching, they became more affectively positive.

Region of interest identification and diagnostic agreement in breast pathology.

A pathologist's accurate interpretation relies on identifying relevant histopathological features. Little is known about the precise relationship between feature identification and diagnostic decision making. We hypothesized that greater overlap between a pathologist's selected diagnostic region of interest (ROI) and a consensus derived ROI is associated with higher diagnostic accuracy. We developed breast biopsy test cases that included atypical ductal hyperplasia (n=80); ductal carcinoma in situ (n=78); and invasive breast cancer (n=22). Benign cases were excluded due to the absence of specific abnormalities. Three experienced breast pathologists conducted an independent review of the 180 digital whole slide images, established a reference consensus diagnosis and marked one or more diagnostic ROIs for each case. Forty-four participating pathologists independently diagnosed and marked ROIs on the images. Participant diagnoses and ROI were compared with consensus reference diagnoses and ROI. Regression models tested whether percent overlap between participant ROI and consensus reference ROI predicted diagnostic accuracy. Each of the 44 participants interpreted 39-50 cases for a total of 1972 individual diagnoses. Percent ROI overlap with the expert reference ROI was higher in pathologists who self-reported academic affiliation (69 vs 65%, P=0.002). Percent overlap between participants' ROI and consensus reference ROI was then classified into ordinal categories: 0, 1-33, 34-65, 66-99 and 100% overlap. For each incremental change in the ordinal percent ROI overlap, diagnostic agreement increased by 60% (OR 1.6, 95% CI (1.5-1.7), P<0.001) and the association remained significant even after adjustment for other covariates. The magnitude of the association between ROI overlap and diagnostic agreement increased with increasing diagnostic severity. The findings indicate that pathologists are more likely to converge with an expert reference diagnosis when they identify an overlapping diagnostic image region, suggesting that future computer-aided detection systems that highlight potential diagnostic regions could be a helpful tool to improve accuracy and education.

Pupil diameter changes reflect difficulty and diagnostic accuracy during medical image interpretation.

BACKGROUND: No automated methods exist to objectively monitor and evaluate the diagnostic process while physicians review computerized medical images. The present study tested whether using eye tracking to monitor tonic and phasic pupil dynamics may prove valuable in tracking interpretive difficulty and predicting diagnostic accuracy. METHODS: Pathologists interpreted digitized breast biopsies varying in diagnosis and rated difficulty, while pupil diameter was monitored. Tonic diameter was recorded during the entire duration of interpretation, and phasic diameter was examined when the eyes fixated on a pre-determined diagnostic region during inspection. RESULTS: Tonic pupil diameter was higher with increasing rated difficulty levels of cases. Phasic diameter was interactively influenced by case difficulty and the eventual agreement with consensus diagnosis. More difficult cases produced increases in pupil diameter, but only when the pathologists' diagnoses were ultimately correct. All results were robust after adjusting for the potential impact of screen brightness on pupil diameter. CONCLUSIONS: Results contribute new understandings of the diagnostic process, theoretical positions regarding locus coeruleus-norepinephrine system function, and suggest novel approaches to monitoring, evaluating, and guiding medical image interpretation.

Localization of Diagnostically Relevant Regions of Interest in Whole Slide Images: a Comparative Study.

Whole slide digital imaging technology enables researchers to study pathologists' interpretive behavior as they view digital slides and gain new understanding of the diagnostic medical decision-making process. In this study, we propose a simple yet important analysis to extract diagnostically relevant regions of interest (ROIs) from tracking records using only pathologists' actions as they viewed biopsy specimens in the whole slide digital imaging format (zooming, panning, and fixating). We use these extracted regions in a visual bag-of-words model based on color and texture features to predict diagnostically relevant ROIs on whole slide images. Using a logistic regression classifier in a cross-validation setting on 240 digital breast biopsy slides and viewport tracking logs of three expert pathologists, we produce probability maps that show 74 % overlap with the actual regions at which pathologists looked. We compare different bag-of-words models by changing dictionary size, visual word definition (patches vs. superpixels), and training data (automatically extracted ROIs vs. manually marked ROIs). This study is a first step in understanding the scanning behaviors of pathologists and the underlying reasons for diagnostic errors.

Gardony Map Drawing Analyzer: Software for quantitative analysis of sketch maps.

Sketch maps are effective tools for assessing spatial memory. However, despite their widespread use in cognitive science research, sketch map analysis techniques remain unstandardized and carry limitations. In the present article, we present the Gardony Map Drawing Analyzer (GMDA), an open-source software package for sketch map analysis. GMDA combines novel and established analysis techniques into a graphical user interface that permits rapid computational sketch map analysis. GMDA calculates GMDA-unique measures based on pairwise comparisons between landmarks, as well as bidimensional regression parameters (Friedman & Kohler, 2003), which together reflect sketch map quality at two levels: configural and individual landmark. The configural measures assess the overall landmark configuration and provide a whole-map analysis. Individual landmark measures, introduced in GMDA, assess individual landmark placement and indicate how individual landmarks contribute to the configural scores. Together, these measures provide a more complete psychometric picture of sketch map analysis, allowing for comparisons between sketch maps and between landmarks. The calculated measures reflect specific and cognitively relevant aspects of interlandmark spatial relationships, including distance and angular representation. GMDA supports complex environments (up to 48 landmarks) and two software modes that capture aspects of maps not addressed by existing techniques, such as landmark size and shape variation and interlandmark containment relationships. We describe the software and its operation and present a formal specification of calculation procedures for its unique measures. We then validate the software by demonstrating the capabilities and reliability of its measures using simulation and experimental data. The most recent version of GMDA is available at www.aarongardony.com/tools/map-drawing-analyzer.