Dot Counting Research Articles

Decreased fronto-temporal interaction during fixation after memory retrieval.

Previous studies have revealed top-down control during memory retrieval from the prefrontal cortex to the temporal cortex. In the present functional MRI study, we investigated whether the fronto-temporal functional interaction occurs even during fixation periods after memory retrieval trials. During recency judgments, subjects judged the temporal order of two items in a study list. The task used in the present study consisted of memory trials of recency judgments and non-memory trials of counting dots, and post-trial fixation periods. By comparing the brain activity during the fixation periods after the memory trials with that during the fixation periods after the non-memory trials, we detected heightened brain activity in the lateral prefrontal cortex, the lateral temporal cortex and the hippocampus. Functional interactions during the fixation periods after the memory vs. non-memory trials as examined using a psychophysiological interaction revealed a decreased interaction from the lateral prefrontal cortex to the lateral temporal cortex, but not to the hippocampus. The functional interaction between the same frontal and temporal regions was also present during the memory trials. A trial-based functional connectivity analysis further revealed that the fronto-temporal interaction was positive and decreased during the fixation periods after the memory trials, relative to the fixation periods after the non-memory trials. These results suggest that the fronto-temporal interaction existed during the post-trial fixation periods, which had been present during the memory trials and temporally extended into the fixation periods.

Abstract 4568: A new quantitative in-situ IHC method - validation of analytical performance

Abstract Background In routine pathology, in situ quantification of protein in formalin-fixed, paraffin-embedded (FFPE) tissue is limited to immunohistochemistry (IHC) which is semi-quantitative at best. Accurate and robust measurement of protein expression in FFPE samples, without loss of morphological information, is currently not achievable. Quantitative protein assessment of FFPE tissue can be destructive, and/or time consuming with risk of analyzing non-relevant tissue due to heterogeneity. We have developed a new reliable quantitative IHC (qIHC) method based on a novel amplification system that enables quantification of protein directly in FFPE tissue by counting dots using a standard bright field microscope. The qIHC method combines the ease, speed and morphological information gained from classical IHC staining together with quantitative assessment of protein expression in situ. The goal of this study was to assess the analytical performance of qIHC in a HER2 assay analyzing both FFPE cell pellets and breast cancer specimens. Methods Five different cell lines with HER2 expression ranging from undetectable with IHC to strongly positive (IHC 3+) were used as test samples. Flow cytometry, and ELISA were used as reference methods to confirm protein expression levels and stability of the cell lines. The qIHC assay was conducted using an automated Autostainer Link 48 stainer, and quantitative assessment was done by counting dots per cell using an image analysis algorithm. Repeatability, reproducibility, robustness, linearity, sensitivity, and quantification limits were evaluated. In addition, 44 breast cancer specimens were stained to compare standard HER2 IHC with qIHC. Results We validated the quantitative test through testing for accuracy, reproducibility, repeatability, robustness, and precision. Each of the different tests showed statistical significant results (p: <0.0001-0.005). The dynamic range and linearity of the assay were investigated by correlating the qIHC results to an in-house-developed flow cytometry assay as well as an FDA-approved ELISA kit for HER2 measurement. All tests demonstrated statistically significant correlation (p: 0.0002-0.0045). No overlap was seen between the different cell lines and a broad dynamic range could be demonstrated ranging from 1*103 receptors/cell up to 2.5*106 receptors/cell. Furthermore, HER2 was clearly detectable above background in the low expression cell line MDA-MB-468, thus showing the inherent high sensitivity of the qIHC assay. To demonstrate the capability of the qIHC assay in tumor tissue, we tested the qIHC concordance to HER2 IHC in 44 breast cancer specimens. We confirmed a strong correlation between IHC and qIHC (p: <0.0001). Conclusions The results show that qIHC provides a highly sensitive, accurate, quantitative, and reliable assay for protein expression in FFPE tissue, which could provide better and more precise diagnosis and thus improved personalized cancer treatment. Citation Format: Kristian Jensen, Rikke M. Jørgensen, Kenneth H. Petersen, Jesper Lohse, Helene Derand. A new quantitative in-situ IHC method - validation of analytical performance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4568. doi:10.1158/1538-7445.AM2014-4568

Estimating light climate in forest with the convex densiometer: operator effect, geometry and relation to diffuse light

Although light is a key factor in forestry, it is surprisingly seldom measured in day-to-day management of European forests. The spherical convex densiometer is a simple instrument that allows to evaluate the canopy openness (CO) by counting the number of ‘canopy’ dots on a grid lying on a convex mirror reflecting the canopy. In this contribution, we compared the performances of this instrument in mixed oak–beech hardwood forests spanning the lower end of the light gradient [1–17 % above canopy photosynthetically active radiation (PAR)] to two reference techniques: PAR measurements and fish-eye photography, based on a detailed analysis of its functioning. Discrepancies between the densiometer and the fish-eye estimates of CO were due to a combination of differences in dot resolution, dot counting and portion of the hemisphere considered. By contrast, the various effects of operator on densiometer estimates, including the influence of conformation on the angle of view, were found to be relatively minor. Densiometer readings were closely related to the relative light intensity assessed by PAR sensors in overcast conditions, which suggests that the use of this inexpensive tool should be expanded.

Quantifying Human Response: Linking metrological and psychometric characterisations of Man as a Measurement Instrument

A better understanding of how to characterise human response is essential to improved person-centred care and other situations where human factors are crucial. Challenges to introducing classical metrological concepts such as measurement uncertainty and traceability when characterising Man as a Measurement Instrument include the failure of many statistical tools when applied to ordinal measurement scales and a lack of metrological references in, for instance, healthcare. The present work attempts to link metrological and psychometric (Rasch) characterisation of Man as a Measurement Instrument in a study of elementary tasks, such as counting dots, where one knows independently the expected value because the measurement object (collection of dots) is prepared in advance. The analysis is compared and contrasted with recent approaches to this problem by others, for instance using signal error fidelity.

Abstract P3-05-06: Automated analysis of Her2 FISH using combined Immunofluorescence and FISH signals

Abstract Introduction: Qualifying patients for Her2 targeted therapy is currently done by detecting Her2 protein overexpression or gene amplification using immunohistochemistry and/or FISH. We have recently developed a method for detecting both signals on the same tissue section allowing direct correlation of protein expression and gene copy number on a cell by cell basis. Accurate assessment of Her2 gene copy number is critical and can pose a challenge due to tumor heterogeneity. This paper reports the accuracy of a proprietary FISH dot counting algorithm on a cell-by-cell basis, potentially allowing analysis of thousands instead of dozens of tumor cells. Method: Automatic FISH signal counts were compared to manual counts of 888 cells selected from 19 invasive ductal breast carcinoma samples exhibiting varying degrees of Her2 expression collected between June 2011 and March 2012. Tissue sections (4 µm) were mounted on positively charged slides, baked and processed through deparaffinization, rehydration and antigen retrieval, then stained for immunofluorescence (IF) using Cy5 labeled Her2 and Cy3 labeled cytokeratin antibodies, counterstained with DAPI, and imaged using InCell 2000 analyzer with GE-proprietary acquisition and processing software. Images were collected at 10x magnification and digitally stitched to span the entire tissue section. A pathologist then selected separate tumor and adjacent normal epithelium regions for subsequent imaging at 40x magnification. Slides were subsequently processed for FISH by pepsin digestion and then subjected to FISH by using PathVysion kit (Abbott Molecular, Des Plaines, IL). After hybridization and subsequent high stringency washes, samples were DAPI stained and mounted for microscopy. Samples were imaged at 40x at the same regions recorded for 40x IF acquisition, using filtersets appropriate for FISH fluorophores and DAPI. A proprietary automated processing algorithm was used to analyze combined IF and FISH signals and derive case specific Her2 score from the tumor and/or adjacent normal epithelium. Cell-level dot counting accuracy was assessed using two metrics comparing automated counts to manual counts: cell classification agreement, where a normal cell was defined as having 3 or less Her2 and Cep17 dots; and dot-counting match, where a difference of more than 20% in absolute counts was considered an error. Result: Our automatic results gave an overall cell-by-cell classification agreement of 88% (range 71% to 98% by case). Combining classification agreement and counting match, our algorithm gave an overall accuracy of 81% (range 63% to 97% by case). Restricting to tumor tissues (as judged by pathologist review of IF) classification agreement and accuracy were 84% and 72%, respectively. Conclusion: The observed variability in algorithm performance between the different cases was due to the fact that error root causes were case dependent. For instance, the main cause of over-counting errors was image noise and artifacts. On the other hand, the main cause of under-counting was low image contrast, especially in highly amplified cases. These results are an early indication of the promise of automatic dot counting applied to breast cancer slides multiplexed for Her2 IF and FISH. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-05-06.

Breast cancer evaluation by fluorescent dot detection using combined mathematical morphology and multifractal techniques

BackgroundFluorescence in situ hybridization (FISH) is very accurate method for measuring HER2 gene copies, as a sign of potential breast cancer. This method requires small tissue samples, and has a high sensitivity to detect abnormalities from a histological section. By using multiple colors, this method allows the detection of multiple targets simultaneously. The target parts in the cells become visible as colored dots. The HER-2 probes are visible as orange stained spots under a fluorescent microscope while probes for centromere 17 (CEP-17), the chromosome on which the gene HER-2/neu is located, are visible as green spots.MethodsThe conventional analysis involves the scoring of the ratio of HER-2/neu over CEP 17 dots within each cell nucleus and then averaging the scores for a number of 60 cells. A ratio of 2.0 of HER-2/neu to CEP 17 copy number denotes amplification. Several methods have been proposed for the detection and automated evaluation (dot counting) of FISH signals. In this paper the combined method based on the mathematical morphology (MM) and inverse multifractal (IMF) analysis is suggested. Similar method was applied recently in detection of microcalcifications in digital mammograms, and was very successful.ResultsThe combined MM using top-hat and bottom-hat filters, and the IMF method was applied to FISH images from Molecular Biology Lab, Department of Pathology, Wielkoposka Cancer Center, Poznan. Initial results indicate that this method can be applied to FISH images for the evaluation of HER2/neu status.ConclusionsMathematical morphology and multifractal approach are used for colored dot detection and counting in FISH images. Initial results derived on clinical cases are promising. Note that the overlapping of colored dots, particularly red/orange dots, needs additional improvements in post-processing.

Subitizing and counting in typical and atypical development

Enumeration performance in standard dot counting paradigms was investigated for different age groups with typical and atypically poor development of arithmetic skills. Experiment 1 showed a high correspondence between response times and saccadic frequencies for four age groups with typical development. Age differences were more marked for the counting than the subitizing range. In Experiment 2 we found a discontinuity between subitizing and counting for dyscalculic children; however, their subitizing slopes were steeper than those of typically developing control groups, indicating a dysfunctional subitizing mechanism. Across both experiments a number of factors could be identified that affect enumeration in the subitizing and the counting range differentially. These differential patterns further support the assumption of two qualitatively different enumeration processes.

Heterogeneity of visual deficits in posterior cortical atrophy

Posterior cortical atrophy (PCA) is a progressive neurodegenerative condition most commonly associated with the histopathological features of Alzheimer's disease (AD). Individuals with PCA exhibit a progressive decline in higher visual object and space processing and other posterior cortical functions. However the extent to which these visuoperceptual and visuospatial processing problems are underpinned by basic visual processing deficits is unknown because elementary visual processes (e.g. form, colour, motion, location) have not been examined previously. This study investigated visual deficits in 21 patients with a clinical diagnosis of probable Alzheimer's disease (AD) who also met behavioural criteria for PCA. Basic visual processing skills were examined in detail, including assessments of form detection, form discrimination, form coherence, motion coherence, colour discrimination and point localisation. The relationship between these six basic visual processes was assessed, and their association with general cognitive function, episodic memory, dominant parietal function (calculation, spelling), space perception (dot counting, number location) and object perception (canonical and non-canonical view apperception) was investigated. 100% of participants showed impairment in at least one aspect of basic visual processing, but form, colour, motion and location processing were not uniformly affected (see Table). Higher order object and space perception deficits were associated with different patterns of basic visual impairment. However, with relevance to theories of network-based disease progression between non-contiguous brain areas in AD, basic visual processing did not correlate with performance on non-visual tasks (e.g. spelling, calculation) thought to depend upon cortical regions of equivalent proximity. Furthermore, the study revealed continuous rather than discrete differences in neuropsychological profile between three previously-claimed variant PCA syndromes held to reflect predominant dorsal, ventral and caudal tissue loss. The object and space perception problems commonly reported in PCA are underpinned by distinct and identifiable patterns of disruption to more basic visual processes associated with occipital lobe function. These behavioural data also complement neuroimaging findings from the same participants showing largely overlapping patterns of atrophy and cortical thinning, and indicate that different PCA phenotypes represent points within the space of continuous variation within the wider PCA syndrome.

Abstract 3760: Development of automatic FISH probe counting in CTC

Abstract Introduction: Presence of Circulating Tumor Cells (CTC) in blood of patients with metastatic carcinomas has been associated with poor progression free and overall survival. Characterization of CTC can be performed by Fluorescence In Situ Hybridization (FISH), however counting of FISH dots by human reviewers can be tiring and subjective and thus likely produces variable outcomes. We investigated whether automated counting of FISH dots in CTC is comparable to the counts obtained by expert reviewers. Material and Methods: Samples processed on the CellSearchTM system for CTC counting were hybridized with fluorescent DNA probes targeting the HER2/neu gene region and the centromeric region of chromosome 17 or the centromeric regions of chromosome 1,7,8,17. (1) For optimization of the algorithm 492 Z-stacks from leukocytes carried over through the CellSearch procedure were recorded and a maximum intensity profile (MIP) was created. Five reviewers counted FISH dots in the MIP data set to create a ground truth. The automatic counting algorithm was validated in a set of stored images of CTC probed for chromosome 1,7,8,17 from castration resistant prostate cancer patients (CRPC).(1) Results: The data set with carried-over leukocytes was counted reliably by the algorithm: 97.8% of the HER2/neu FISH dots and 97.5% of the centromeric 17 dots were counted equally by the PC and the reviewers, regarding only the subset of images for which all the reviewers agreed. The mean intra-reviewer agreement was 96.5%. In the validation set copy number of chromosome 1 in carried-over leukocytes scored by an expert agreed in 50.8% with the automated count, for chromosome 7 34.4% for chromosome 8 22.8.% and for chromosome 17 55.0%. For CTC in the validation set copy number of chromosome 1 scored by an expert agreed in 71.6% with the automated count, for chromosome 7 56.2% for chromosome 8 64.8% and for chromosome 17 41.0%. For copy numbers larger than 6 both the expert and automated count were recorded as larger than 6. Agreement between the expert count and automated count did not significantly alter with the detected copy number. Over-count in the validation set was largely due to clustering of nuclei that were counted as one cell. Conclusions: Automatic FISH dot counting in CTC images is feasible for images where reviewers agree upon. The intra-reviewer variation of 3.5% shows that reviewers have ambiguous rules and are not reliable. This variation is closely related to the heterogeneity -size and shape- of the FISH dots. The PC has a reproducibility of 100% and is thus a good replacement for human reviewers. 1. Swennenhuis JF, Tibbe AGJ, Levink R, Sipkema RCJ, Terstappen LWMM. Characterization of Circulating Tumor Cells by Fluorescence In-Situ Hybridization. Cytometry Part A 75A: 520-527, 2009. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3760.

Functional compensation of visual field deficits in hemianopic patients under the influence of different task demands

We investigated the task-specific role of eye and head movements as a compensatory strategy in patients with homonymous visual field deficits (HVFDs) and in age-matched normal controls. All participants were tested in two tasks, i.e. a dot counting (DC) task requiring mostly simple visual scanning and a cognitively more demanding comparative visual search (CVS) task. The CVS task involved recognition and memory of geometrical objects and their configuration in two test fields. Based on task performance, patients were assigned to one of two groups, “adequate” (HVFDA) and “inadequate” (HVFDI); the group definitions based on either task turned out to be identical. With respect to the gaze related parameters in the DC task we obtained results in agreement with previous studies: the gaze pattern of HVFDA patients and normal controls did not differ significantly, while HVFDI patients showed increased gaze movement activity. In contrast, for the more complex CVS task we identified a deviating pattern of compensatory strategy use. Adequately performing subjects, who had used the same gaze strategies as normals in the DC task, now changed to increased gaze movement activity that allowed coping with the increasing task demands. Inadequately performing patients switched to a novel pattern of compensatory behavior in the CVS task. Different compensatory strategies are discussed with respect to the task-specific demands (in particular working memory involvement), the specific behavioral deficits of the patients, and the corresponding brain lesions.

Crowding counting

Counting a few objects in one glimpse is easy. The ability to count (estimate number) is perfect in the “subitizing” domain of up to about 4 objects, but beyond that, error increases linearly with the number of target objects (Jevons, 1871; Kaufman et al., 1949). This is usually explained by supposing that a second, independent process provides estimates of many objects. We wondered whether crowding might affect one process more than the other, and thus help to distinguish them. Five observers performed several dot counting tasks. Visual conditions included surrounding the target dots, in a box, by distracter dots outside the box, using peripheral as opposed to central dot presentation, or both. We expected crowding only when the dots were peripheral and surrounded by distracters. Indeed, we find that this condition increases the standard deviation of the observers' counts by about 2 at every number of dots presented. This is trivial at large numbers, but dramatic at small numbers since the standard deviation is normally zero in the subitizing domain. Even so, the consistent increase of SD by +2 at all dot numbers seems difficult to reconcile with the popular two-process model of counting ability.

Visual Perception in Delirium

Delirium is a syndrome characterized by acute change or fluctuating course of mental status, disorganized or incoherent thought, impaired attention, and altered consciousness. Neuropsychological symptoms such as hallucinations are common in delirium, but potential underlying visual disorders have not been documented previously. Now, researchers have measured the integrity of cognitive processes behind visual perception in 17 patients with delirium, 14 patients with Alzheimer disease (AD), and 18 cognitively intact subjects. The participants completed five neuropsychological tests of visual perception (dot counting, position discrimination of dots within a square, shape detection, incomplete letters, and an object-decision task) and …

Attention during active visual tasks: Counting, pointing, or simply looking

Visual attention and saccades are typically studied in artificial situations, with stimuli presented to the steadily fixating eye, or saccades made along specified paths. By contrast, in real-world tasks saccadic patterns are constrained only by the demands of the motivating task. We studied attention during pauses between saccades made to perform three free-viewing tasks: counting dots, pointing to the same dots with a visible cursor, or simply looking at the dots using a freely-chosen path. Attention was assessed by the ability to identify the orientation of a briefly-presented Gabor probe. All primary tasks produced losses in identification performance, with counting producing the largest losses, followed by pointing and then looking-only. Looking-only resulted in a 37% increase in contrast thresholds in the orientation task. Counting produced more severe losses that were not overcome by increasing Gabor contrast. Detection or localization of the Gabor, unlike identification, were largely unaffected by any of the primary tasks. Taken together, these results show that attention is required to control saccades, even with freely-chosen paths, but the attentional demands of saccades are less than those attached to tasks such as counting, which have a significant cognitive load. Counting proved to be a highly demanding task that either exhausted momentary processing capacity (e.g., working memory or executive functions), or, alternatively, encouraged a strategy of filtering out all signals irrelevant to counting itself. The fact that the attentional demands of saccades (as well as those of detection/localization) are relatively modest makes it possible to continually adjust both the spatial and temporal pattern of saccades so as to re-allocate attentional resources as needed to handle the complex and multifaceted demands of real-world environments.

Image enhancement for increased dot‐counting efficiency in FISH

The most commonly used molecular cytogenetic technique is fluorescence in situ hybridization (FISH). It has been widely applied in many areas of diagnosis and research, including pre-natal and post-natal screening of chromosomal aberrations, pre-implantation genetic diagnosis, cancer cytogenetics, gene mapping, molecular pathology and developmental molecular biology. The analysis of FISH images consists of detecting fluorescent dots, after which the number of dots per cell can be counted or their relative positions can be measured. A major impediment in the analysis of FISH specimens is signal (dot) quality, which is influenced by the hybridization efficiency and/or the sensitivity of the camera that records the images. In this paper, we present an approach to improve the efficiency of detecting fluorescent signals in FISH images by recovering the radiance map of the camera. This allows us to generate a high-dynamic-range image wherein an extended range of the sample radiance captured by the camera can be visualized at distinct intensity values. The resulting higher-order numeric complexity of the transformed image is adjusted (or simplified) by examining the intensity distribution in each of the three colour channels (red, green and blue), and remapping the intensity values to generate a high-contrast image with a lower-order (compressed) dynamic range. The remapping is based on a criterion that optimizes the detection of the hybridized signals, allowing attenuation of saturated intensity values while amplifying low-intensity signals. A simple dot-counting algorithm is used to automatically process 2000 FISH images. The images are taken for lymphocytes from cultured blood specimens for cytogenetic testing. Images are manually analyzed by an expert to obtain ground truth for dot counts. A quantitative analysis is performed by comparing results of automated dot detection on images before and after enhancement with the developed algorithms. In addition, common errors in dot counting due to split dots, dust, poor segmentation and overlapping signals are analyzed and the robustness of the developed approach against these errors evaluated. It is observed that dot-detection efficiency is increased by an average of 9% across all colour channels while reducing errors in missed and false dot counts. Our proposed method and results demonstrate that dot-counting specificity and sensitivity can be improved by pre-processing and enhancing the image using the radiance curve of the camera and generating a high-contrast, remapped high-dynamic-range image prior to using any algorithm for dot counting.

What dot clusters and bar graphs reveal: Subitizing is fast counting and subtraction

In two studies, we found that dot enumeration tasks resulted in shallow-sloped response time (RT) functions for displays of 1-4 dots and steep-sloped functions for displays of 5-8 dots, replicating results implicating subitizing and counting processes for low and high ranges of dots, respectively. Extracting number from a specific type of bar graph within the same numerical range produced a shallow-sloped but scallop-shaped RT function. Factor analysis confirmed two independent subranges for dots, but all bar graph values defined a unitary factor. Significantly, factor scores and asymmetries both showed correlations of bar graph recognition to dot subitizing but not to dot counting, strongly suggesting that subitizing was used in both enumeration of low numbers of dots and bar graph recognition. According to these results, subitizing appears to be a nonverbal process operating flexibly in either additive or subtractive fashion on analog quantities having spatial extent, a conclusion consistent with a fast-counting model of subitizing but not with other models of the subitizing process.

Fast binary multiplication by performing dot counting and complement recoding

In this paper, we present a new computation method by combining the dots counting method and the complement recoding method to efficiently evaluate modular multiplication in binary multiplications. The LUT (Look-Up Table) technique can be adopted in our proposed method to efficiently reduce the number of multiplications. And the proposed method can be easily implemented for the hardware. Numerous examples are provided to show the efficient and easy operations of the binary multiplication method. In average case, the worst case for the Hamming weight of the product X∗ Y is uv 4 , where u is the bit-length of multiplicand X, v is the bit-length of multiplier Y. If the proposed method is applied, we could effectively reduce the Hamming weight of the product X∗ Y to 0.25 u.

Counting Complex Dot Patterns in Alzheimer’s Disease

Patients affected by Alzheimer’s disease (DAT) showed considerable difficulties assessing the numerosity of complex dot patterns (up to 30 dots). Patients’ and controls’ performance was found to be modulated by the spatial array of dot patters. Dots presented in curved lines were easier to count than dots in circle arrays or in random arrays. Highly significant between group differences were found in counting dots in circle arrays, but not in counting curved lines. Patients and controls differed in the choice of counting strategies. While controls efficiently adapted their counting strategies to the respective dot patterns, DAT patients were not able to adapt counting strategies to the requirements of the spatial arrays. Analysis of error types further evidenced the particular difficulties of patients. Several recounts in counting circle arrays reflected difficulties to stop counting, while omissions in random patterns suggested deficits in monitoring already counted items. Results of this study suggest that deficits in executive functions prevented patients from selecting and adapting counting strategies in order to keep track of already counted items, to enhance accuracy and to reduce demands on cognitive resources.

Number processing in posterior cortical atrophy—A neuropsycholgical case study

Posterior cortical atrophy (PCA) is an uncommon syndrome of dementia with early onset, characterised by disorders of higher visual function, variable symptoms of Balint's syndrome, visual agnosia, alexia, agraphia, finger agnosia, right-left disorientation and dyscalculia [Benson D. F., Davis R. J., & Snyder B. D. (1988). Posterior cortical atrophy. Archives of Neurology, 45, 789–793]. In a single case study specific numerical deficits were observed which may be predicted by parietal neurodegeneration (more pronounced on the right side; verified by SPECT). Besides impairments in all tasks involving visuo-spatial abilities (e.g., dot counting, analog number scale task), deficits appeared in tasks requiring access to an internal representation of numbers such as mental number bisection, approximation, estimation and semantic facts. In number comparison an increased distance effect was found. In simple arithmetic, a striking dissociation between operations was found—multiplication and addition facts being preserved at a superficial level, subtraction and division being severely impaired. The study confirms the close relation between spatial and numerical processing and highlights the modular organisation of the semantic system (number semantics impaired). Moreover, the study adds evidence about the clinical manifestation of the particular degenerative syndrome.

Calculation impairment in neurodegenerative diseases

We examined oral calculation in patients with corticobasal degeneration (CBD; N=17), frontotemporal dementia (FTD; N=17), and Alzheimer's disease (AD; N=20), as well as 17 healthy seniors matched for age and education. Our calculation model involves at least three components: numerosity, combinatorial processes, and executive resources such as working memory. We assessed addition, subtraction, multiplication, and division involving small numbers (small, single-digit answers) and large numbers (larger, single- and double-digit answers). We also assessed dot counting for small numbers (2–5) and large numbers (6–9), as well as a measure of working memory. All patient groups differed from healthy seniors in oral calculation. CBD (36% correct) and FTD (65% correct) demonstrated a significant overall impairment in oral calculation relative to AD (76% correct). CBD (66% correct) had more difficulty counting dots overall relative to AD (94% correct) and FTD (86% correct), consistent with our hypothesis that the calculation deficit in CBD is due in large part to a numerosity deficit. FTD had more difficulty relative to AD in their performance of reverse digit span, consistent with our hypothesis that FTD patients' executive resource limitation contributes to their pattern of calculation impairment.

Sensitivity and specificity of the Rey Dot Counting Test in patients with suspect effort and various clinical samples

The Rey Dot Counting Test was administered to 100 patients with suspect effort drawn from two separate settings (personal injury/disability, n=86; prison hospital, n=14) and to 251 subjects in nine clinical groups (head injury, learning disability, right and left cerebrovascular accident, schizophrenia, older normals, depressed elderly, and mild and moderate dementia). Sensitivity of cut-offs for individual test scores (mean grouped dot counting time, ratio of mean grouped to ungrouped dot counting time, and number of errors) differed markedly across the two suspect effort groups (e.g., 28–100%), indicating that noncredible patients drawn from different settings employ somewhat differing approaches in their fabrication of cognitive symptoms. Use of a cut-off of ≥17 applied to a combination score (mean ungrouped dot counting time+meangrouped dot counting time+number of errors) resulted in 100% sensitivity in the forensic suspect effort group and 75% sensitivity in the civil litigation/disability suspect effort group, while maintaining specificity of ≥90% for the clinical groups combined (excluding moderate dementia).