Facing privacy in neuroimaging: removing facial features degrades performance of image analysis methods.

BACKGROUND: Recent studies have created awareness that facial features can be reconstructed from high-resolution MRI. Therefore, data sharing in neuroimaging requires special attention to protect participants' privacy. Facial features removal (FFR) could alleviate these concerns. We assessed the impact of three FFR methods on subsequent automated image analysis to obtain clinically relevant outcome measurements in three clinical groups. METHODS: FFR was performed using QuickShear, FaceMasking, and Defacing. In 110 subjects of Alzheimer's Disease Neuroimaging Initiative, normalized brain volumes (NBV) were measured by SIENAX. In 70 multiple sclerosis patients of the MAGNIMS Study Group, lesion volumes (WMLV) were measured by lesion prediction algorithm in lesion segmentation toolbox. In 84 glioblastoma patients of the PICTURE Study Group, tumor volumes (GBV) were measured by BraTumIA. Failed analyses on FFR-processed images were recorded. Only cases in which all image analyses completed successfully were analyzed. Differences between outcomes obtained from FFR-processed and full images were assessed, by quantifying the intra-class correlation coefficient (ICC) for absolute agreement and by testing for systematic differences using paired t tests. RESULTS: Automated analysis methods failed in 0-19% of cases in FFR-processed images versus 0-2% of cases in full images. ICC for absolute agreement ranged from 0.312 (GBV after FaceMasking) to 0.998 (WMLV after Defacing). FaceMasking yielded higher NBV (p = 0.003) and WMLV (p ≤ 0.001). GBV was lower after QuickShear and Defacing (both p < 0.001). CONCLUSIONS: All three outcome measures were affected differently by FFR, including failure of analysis methods and both "random" variation and systematic differences. Further study is warranted to ensure high-quality neuroimaging research while protecting participants' privacy. KEY POINTS: • Protecting participants' privacy when sharing MRI data is important. • Impact of three facial features removal methods on subsequent analysis was assessed in three clinical groups. • Removing facial features degrades performance of image analysis methods.

Reproducibility of Deep Gray Matter Atrophy Rate Measurement in a Large Multicenter Dataset.

BACKGROUND AND PURPOSE: Precise in vivo measurement of deep GM volume change is a highly demanded prerequisite for an adequate evaluation of disease progression and new treatments. However, quantitative data on the reproducibility of deep GM structure volumetry are not yet available. In this paper we aim to investigate this reproducibility using a large multicenter dataset. MATERIALS AND METHODS: We have assessed the reproducibility of 2 automated segmentation software packages (FreeSurfer and the FMRIB Integrated Registration and Segmentation Tool) by quantifying the volume changes of deep GM structures by using back-to-back MR imaging scans from the Alzheimer Disease Neuroimaging Initiative's multicenter dataset. Five hundred sixty-two subjects with scans at baseline and 1 year were included. Reproducibility was investigated in the bilateral caudate nucleus, putamen, amygdala, globus pallidus, and thalamus by carrying out descriptives as well as multilevel and variance component analysis. RESULTS: Median absolute back-to-back differences varied between GM structures, ranging from 59.6-156.4 µL for volume change, and 1.26%-8.63% for percentage volume change. FreeSurfer had a better performance for the outcome of longitudinal volume change for the bilateral amygdala, putamen, left caudate nucleus (P < .005), and right thalamus (P < .001). For longitudinal percentage volume change, Freesurfer performed better for the left amygdala, bilateral caudate nucleus, and left putamen (P < .001). Smaller limits of agreement were found for FreeSurfer for both outcomes for all GM structures except the globus pallidus. Our results showed that back-to-back differences in 1-year percentage volume change were approximately 1.5-3.5 times larger than the mean measured 1-year volume change of those structures. CONCLUSIONS: Longitudinal deep GM atrophy measures should be interpreted with caution. Furthermore, deep GM atrophy measurement techniques require substantially improved reproducibility, specifically when aiming for personalized medicine.

Recommendations to improve imaging and analysis of brain lesion load and atrophy in longitudinal studies of multiple sclerosis.

Focal lesions and brain atrophy are the most extensively studied aspects of multiple sclerosis (MS), but the image acquisition and analysis techniques used can be further improved, especially those for studying within-patient changes of lesion load and atrophy longitudinally. Improved accuracy and sensitivity will reduce the numbers of patients required to detect a given treatment effect in a trial, and ultimately, will allow reliable characterization of individual patients for personalized treatment. Based on open issues in the field of MS research, and the current state of the art in magnetic resonance image analysis methods for assessing brain lesion load and atrophy, this paper makes recommendations to improve these measures for longitudinal studies of MS. Briefly, they are (1) images should be acquired using 3D pulse sequences, with near-isotropic spatial resolution and multiple image contrasts to allow more comprehensive analyses of lesion load and atrophy, across timepoints. Image artifacts need special attention given their effects on image analysis results. (2) Automated image segmentation methods integrating the assessment of lesion load and atrophy are desirable. (3) A standard dataset with benchmark results should be set up to facilitate development, calibration, and objective evaluation of image analysis methods for MS.

Static and dynamic loading of mandibular condyles and their positional changes after bilateral sagittal split advancement osteotomies.

This study analysed the effects of change of direction of masseter (MAS) and medial pterygoid muscles (MPM) and changes of moment arms of MAS, MPM and bite force on static and dynamic loading of the condyles after surgical mandibular advancement. Rotations of the condyles were assessed on axial MRIs. 16 adult patients with mandibular hypoplasia were studied. The mandibular plane angle (MPA) was <39° in Group I (n=8) and >39° in Group II (n=8). All mandibles were advanced with a bilateral sagittal split osteotomy (BSSO). In Group II, BSSO was combined with Le Fort I osteotomy. Pre and postoperative moment arms of MAS, MPM and bite force were used in a two-dimensional model to assess static loading of the condyles. Pre and postoperative data on muscle cross-sectional area, volume and direction were introduced in three-dimensional dynamic models of the masticatory system to assess the loading of the condyles during opening and closing. Postsurgically, small increases of static condylar loading were calculated. Dynamic loading decreased slightly. Minor rotations of the condyles were observed. The results do not support the idea that increased postoperative condylar loading is a serious cause for condylar resorption or relapse.

Optimizing parameter choice for FSL-Brain Extraction Tool (BET) on 3D T1 images in multiple sclerosis.

BACKGROUND: Brain atrophy studies often use FSL-BET (Brain Extraction Tool) as the first step of image processing. Default BET does not always give satisfactory results on 3DT1 MR images, which negatively impacts atrophy measurements. Finding the right alternative BET settings can be a difficult and time-consuming task, which can introduce unwanted variability. AIM: To systematically analyze the performance of BET in images of MS patients by varying its parameters and options combinations, and quantitatively comparing its results to a manual gold standard. METHODS: Images from 159 MS patients were selected from different MAGNIMS consortium centers, and 16 different 3DT1 acquisition protocols at 1.5 T or 3T. Before running BET, one of three pre-processing pipelines was applied: (1) no pre-processing, (2) removal of neck slices, or (3) additional N3 inhomogeneity correction. Then BET was applied, systematically varying the fractional intensity threshold (the "f" parameter) and with either one of the main BET options ("B" - bias field correction and neck cleanup, "R" - robust brain center estimation, or "S" - eye and optic nerve cleanup) or none. For comparison, intracranial cavity masks were manually created for all image volumes. FSL-FAST (FMRIB's Automated Segmentation Tool) tissue-type segmentation was run on all BET output images and on the image volumes masked with the manual intracranial cavity masks (thus creating the gold-standard tissue masks). The resulting brain tissue masks were quantitatively compared to the gold standard using Dice overlap coefficient (DOC). Normalized brain volumes (NBV) were calculated with SIENAX. NBV values obtained using for SIENAX other BET settings than default were compared to gold standard NBV with the paired t-test. RESULTS: The parameter/preprocessing/options combinations resulted in 20,988 BET runs. The median DOC for default BET (f=0.5, g=0) was 0.913 (range 0.321-0.977) across all 159 native scans. For all acquisition protocols, brain extraction was substantially improved for lower values of "f" than the default value. Using native images, optimum BET performance was observed for f=0.2 with option "B", giving median DOC=0.979 (range 0.867-0.994). Using neck removal before BET, optimum BET performance was observed for f=0.1 with option "B", giving median DOC 0.983 (range 0.844-0.996). Using the above BET-options for SIENAX instead of default, the NBV values obtained from images after neck removal with f=0.1 and option "B" did not differ statistically from NBV values obtained with gold-standard. CONCLUSION: Although default BET performs reasonably well on most 3DT1 images of MS patients, the performance can be improved substantially. The removal of the neck slices, either externally or within BET, has a marked positive effect on the brain extraction quality. BET option "B" with f=0.1 after removal of the neck slices seems to work best for all acquisition protocols.

Positional changes of the masseter and medial pterygoid muscles after surgical mandibular advancement procedures: an MRI study.

This study evaluated whether surgical mandibular advancement procedures induced a change in the direction and the moment arms of the masseter (MAS) and medial pterygoid (MPM) muscles. Sixteen adults participated in this study. The sample was divided in two groups: Group I (n=8) with a mandibular plane angle (mpa) <39° and Group II (n=8) with an mpa >39°. Group I patients were treated with a bilateral sagittal split osteotomy (BSSO). Those in Group II were treated with a BSSO combined with a Le Fort I osteotomy. Pre- and postoperative direction and moment arms of MAS and MPM were compared in these groups. Postsurgically, MAS and MPM in Group II showed a significantly more vertical direction in the sagittal plane. Changes of direction in the frontal plane and changes of moment arms were insignificant in both groups. This study demonstrated that bimaxillary surgery in patients with an mpa >39° leads to a significant change of direction of MAS and MPM in the sagittal plane.

Computer-aided support improves early and adequate delivery of nutrients in the ICU.

BACKGROUND: In 2007 a national guideline on perioperative nutrition was issued in the Netherlands. As external indicator for adequacy of nutritional therapy, the percentage of malnourished patients who reach at least 1.2 grams of protein on day 4 after admission was chosen by the Netherlands Health Care Inspectorate. METHODS: We developed an algorithm that allows users to ask for advice on which artificial nutritional formula to prescribe and at which rate, assuring provision of adequate amounts of both protein and energy. Feedback on nutritional therapy is given to the users on a daily basis, and to the management per quarter. Both the advice and the feedback have been integrated in our data management system. The advice module is also available on-line. RESULTS: In the baseline situation over the first four quarters (2006) an average of 30.2% of patients who had a full day 4 in our unit reached the protein indicator. In the last six quarters post-implementation, the average percentage reached was 56.5% with values consistently over 50%. Changes were statistically significant at third quarter of 2007 (p<0.05) and thereafter (p<0.001). Results for day 7 of admission were unaffected, which indicates that targets were reached earlier during hospital stay. CONCLUSION: Our study shows that integration of nutritional advice and automatically generated feedback to users in a data management system consistently improves delivery of (early) nutrition.

Spinal cord grey matter lesions in multiple sclerosis detected by post-mortem high field MR imaging.

BACKGROUND: Post-mortem studies demonstrate extensive grey matter demyelination in MS, both in the brain and in the spinal cord. However the clinical significance of these plaques is unclear, largely because they are grossly underestimated by MR imaging at conventional field strengths. Indeed post-mortem MR studies suggest the great majority of lesions in the cerebral cortex go undetected, even when performed at high field. Similar studies have not been performed using post-mortem spinal cord material. AIM: To assess the sensitivity of high field post-mortem MRI for detecting grey matter lesions in the spinal cord in MS. METHODS: Autopsy material was obtained from 11 MS cases and 2 controls. Proton Density-weighted images of this formalin-fixed material were acquired at 4.7 Tesla before the tissue was sectioned and stained for Myelin Basic Protein. Both the tissue sections and the MR images were scored for grey matter and white matter plaques, with the readers of the MR images being blinded to the histopathology results. RESULTS: Our results indicate that post-mortem imaging at 4.7 Tesla is highly sensitive for cord lesions, detecting 87% of white matter lesions and 73% of grey matter lesions. The MR changes were highly specific for demyelination, with all lesions scored on MRI corresponding to areas of demyelination. CONCLUSION: Our work suggests that spinal cord grey matter lesions may be detected on MRI more readily than GM lesions in the brain, making the cord a promising site to study the functional consequences of grey matter demyelination in MS.

Mini-review on cardiac complications after mediastinal irradiation for Hodgkin lymphoma.

We present a 62-year-old man who over the years developed almost all the possible cardiac complications of radiation therapy after treatment of a Hodgkin's lymphoma. A review of the literature and a summary of treatment options for cardiac complications after irradiation of the mediastinum for Hodgkin's lymphoma are presented.

A comparison of human jaw muscle cross-sectional area and volume in long- and short-face subjects, using MRI.

OBJECTIVE: In humans, the vertical craniofacial dimensions vary significantly with the size of the jaw muscles, which are regarded as important controlling factors of craniofacial growth. The functional relevance of the maximum cross-sectional area (CSA), indicating maximum muscle strength, is questionable since peak forces are generated only a fraction of the day. Alternatively, muscle volume (indicating the generated loads) might be a more meaningful functional variable. Therefore, the aim of this study was to investigate if jaw muscle volume is stronger related with vertical craniofacial dimensions than with jaw muscle CSA. DESIGN: Thirty-one adult healthy subjects with varying vertical craniofacial morphology participated in this study. Axial magnetic resonance imaging (MRI) scans were used for segmentation of the masseter (Mas) and medial pterygoid muscles (MPM). This enabled measurements of the muscle CSA and volume. Cephalometric analysis was performed using lateral radiographs. With factor analysis, the number of cephalometric variables was reduced into two factors that represented the anterior face height and the posterior face height (PFH), respectively. Subsequently, mutual relationships between these factors and muscular variables were assessed using a multiple regression analysis. RESULTS: It was found that vertical craniofacial dimensions were significantly better (up to 12%) related with muscle volume rather than with CSA. Furthermore, it was shown that especially the PFH factor was significantly correlated with the Mas and MPM. CONCLUSION: Vertical craniofacial dimensions are stronger related with jaw muscle volume than with CSA. Tentatively, it can be assumed that the generated muscle loads, rather than maximum forces, influence vertical craniofacial growth.

Spontaneous remission of acute myeloid leukaemia after recovery from sepsis.

Spontaneous remission of acute myeloid leukaemia (AML) is extremely rare and usually of short duration. We report two patients with documented AML who developed spontaneous remission of their leukaemia shortly after an episode of severe sepsis and respiratory failure requiring mechanical ventilation. The underlying mechanisms of spontaneous remission remain unclear but an association with preceding blood transfusions and severe systemic infections has been reported. An overwhelming immune response due to sepsis and leading to raised levels of TNF-alpha, INF-gamma, IL -2 and an increased activity of NK cells, cytotoxic T-cells and macrophages are thought to play an important role. Better insights into the mechanisms of spontaneous remission of AML after recovery from sepsis could help in developing new therapies for AML.

[Measures for patients taking psychotropic drugs who undergo elective surgery]. / Maatregelen bij patiënten die psychofarmaca gebruiken en die een electieve operatie moeten ondergaan.

Psychotropic drugs can increase the risk of perioperative complications when given in combination with anaesthesia. Evidence-based guidelines that address this issue are lacking. Consensus-based recommendations were formed for the perioperative management of these patients based on the available literature and a systematic evaluation of perioperative risks by the medical specialists directly involved. Patients who use lithium, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants or clozapine are at risk of experiencing adverse interactions. The anaesthesiology literature recommends discontinuing irreversible MAOIs and lithium in all cases, and tricyclic antidepressants in patients with systemic disorders. With the exception of lithium, the risks of psychiatric relapse or recurrence associated with discontinuation necessitate intensive integrated psychiatric treatment. Continuation of treatment under strict haemodynamic observation may also be an option in some cases. Patients taking selective serotonin reuptake inhibitors (SSRIs) should be observed carefully for psychological instability and physical abnormalities, and clinicians should be aware of medications that could increase the risk of haemorrhage when used in combination with SSRIs. In these cases, a psychiatrist should be consulted. The same is true for patients taking antipsychotic or other antidepressant medication who develop psychological instability or have a systemic disorder. Given the widespread use ofpsychotropic drugs and the seriousness of the associated risks, it is recommended that the decision whether to continue or discontinue psychotropic medication should become a standard component of preoperative assessment.

[Indications for respiratory complications during the use of oral nifedipine as a tocolytic agent, especially in patients with multiple pregnancies]. / Aanwijzingen voor respiratoire complicaties bij gebruik van oraal nifedipine als tocolyticum, met name bij patiënten met een meerlingzwangerschap.

In 7 women with premature labour pains, severe dyspnoea developed that was possibly related to the use of nifedipine as an 'off-label' tocolytic. 6 of these women had a twin pregnancy. Diuretics and oxygen therapy had little effect, but the patients recovered after the administration of nifedipine was stopped. The efficacy and safety of nifedipine as a tocolytic agent has been investigated in a number of well-designed randomised studies. However, these studies were performed in a selected group of pregnant women and women with multiple pregnancies or prematurely ruptured membranes were mostly excluded. It can be hypothesised that the respiratory complications in these cases are due to unequal ventilation/perfusion of the lungs in the presence of a physiologically elevated diaphragm due to the pregnancy. These changes are more pronounced in multiple pregnancies. After administration ofnifedipine, there is perfusion of atelectatic areas of the lung that are not or not well ventilated, resulting in ventilation-perfusion discrepancy and hence dyspnoea. Although case reports permit only limited extrapolation, these observations warrant caution with regard to the safety ofnifedipine as a tocolytic agent in patients with multiple pregnancies. The use of medication in groups of patients for which the agent has not been investigated, or which were explicitly excluded from the study, should be done with extreme caution. One should in any case be aware of the possible risks.

Improved reliability of hippocampal atrophy rate measurement in mild cognitive impairment using fluid registration.

MRI-derived rates of hippocampal atrophy may serve as surrogate markers of disease progression in mild cognitive impairment (MCI). Manual delineation is the gold standard in hippocampal volumetry; however, this technique is time-consuming and subject to errors. We aimed to compare regional non-linear (fluid) registration measurement of hippocampal atrophy rates against manual delineation in MCI. Hippocampi of 18 subjects were manually outlined twice on MRI scan-pairs (interval+/-SD: 2.01+/-0.11 years), and volumes were subtracted to calculate change over time. Following global affine and local rigid registration, regional fluid registration was performed from which atrophy rates were derived from the Jacobian determinants over the hippocampal region. Atrophy rates as derived by fluid registration were computed using both forward (repeat onto baseline) and backward (baseline onto repeat) registration. Reliability for both methods and agreement between methods was assessed. Mean+/-SD hippocampal atrophy rates (%/year) derived by manual delineation were: left: 2.13+/-1.62; right: 2.36+/-1.78 and for regional fluid registration: forward: left: 2.39+/-1.68; right: 2.49+/-1.52 and backward: left: 2.21+/-1.51; right: 2.42+/-1.49. Mean hippocampal atrophy rates did not differ between both methods. Reliability for manual hippocampal volume measurements (cross-sectional) was high (intraclass correlation coefficient (ICC): baseline and follow-up, left and right, >0.99). However, the resulting ICC for manual measurements of hippocampal volume change (longitudinal) was considerably lower (left: 0.798; right: 0.850) compared with regional fluid registration (forward: left: 0.985; right: 0.988 and backward: left: 0.975; right: 0.989). We conclude that regional fluid registration is more reliable than manual delineation in assessing hippocampal atrophy rates, without sacrificing sensitivity to change. This method may be useful to quantify hippocampal volume change, given the reduction in operator time and improved precision.

Perspective: How to evaluate studies on peri-operative nutrition? Considerations about the definition of optimal nutrition for patients and its key role in the comparison of the results of studies on nutritional intervention.

Different nutritional outcome studies on the same subject can have vast differences in composition of the chosen food without justification, suggesting that the composition of "optimal" nutrition in patients is not known or that optimal nutrition does not exist. The result will be negative studies which reinforces the existing impression that nutritional intervention is of limited value in every day's patient care. This perspective will put arguments forward that optimal nutrition exists and that the definition of optimal nutrition should be the base of future nutrition intervention studies. This perspective aims at providing a definition of optimal nutrition and consequently a basis to critically appraise the literature upon nutritional interventions in disease states.

Oxybutynin: dry days for patients with hyperhidrosis.

We report the case of a 56-year-old postmenopausal woman who was referred to our Endocrinology Outpatient Clinic because of severe hyperhidrosis. She had a four-year history of excessive sweating of her face and upper body. On presentation no sweating could be documented. Physical examination was also unremarkable. It appeared that five days earlier her general practitioner had prescribed oxybutynin for urge incontinence and this accidentally cured her hyperhidrosis. She was diagnosed with idiopathic hyperhidrosis. We advised her to continue the oxybutynin and six months later, she was still symptom-free. Oral anticholinergic drugs are known to be effective for hyperhidrosis, but only anecdotal reports on oxybutynin can be found in the literature. Oxybutynin is not approved for hyperhidrosis, explaining the unfamiliarity with this medicine. This case shows that oxybutynin can be a very effective and simple treatment with only mild side effects. Therefore, oxybutynin merits consideration in patients with idiopathic hyperhidrosis. This report includes a concise review of the causes and treatment options of hyperhidrosis.

Herpes simplex virus type 1 and respiratory disease in critically-ill patients: Real pathogen or innocent bystander?

Herpes simplex virus type 1 (HSV-1) has been associated with pulmonary disease, mostly in severely immunocompromised patients. After reactivation and shedding in the oropharynx, the virus may reach the lower respiratory tract by aspiration or by contiguous spread. HSV-1 can be detected in clinical specimens by virus culture or quantitatively by nucleic acid amplification techniques. With these techniques, HSV-1 is often detected in the respiratory secretions of critically-ill patients. However, a clear diagnosis of HSV-1 pneumonia is difficult to establish because clinical criteria, radiological features and laboratory findings all lack specificity. Lower respiratory tract HSV-1 infections have not been associated with specific risk-factors. There is also an absence of consistent data concerning the effect of antiviral treatment on the outcome of critically-ill patients. Further studies are needed to better define the pathogenic role of HSV-1 in the lower respiratory tract of these patients, to improve the diagnosis, and, especially, to assess the need for antiviral treatment in the individual patient.

Fecal energy losses in enterally fed intensive care patients: an explorative study using bomb calorimetry.

BACKGROUND & AIMS: Early enteral nutrition and tailored supply of nutrients have become standard in most of the intensive care units (ICU). So far little attention has been given to losses of energy in the stools. The purpose of this explorative study was to evaluate the energy losses of patients with loose stools, necessitating the use of a feces-collector device in a tertiary academic ICU. METHODS: In a group of 13 fully enterally fed and mechanically ventilated patients with loose stools, the daily energy loss in feces was determined, using bomb calorimetry. Malabsorption was defined as an absorption capacity of 85% or less. Energy expenditure was determined with indirect calorimetry. RESULTS: Six out of 13 (46%) patients fulfilled the criterion of malabsorption. The mean total energetic absorption capacity was 84.6+/-13.3%. The mean capacity of absorption of fat was 89.7+/-16.3%. The caloric value of energy loss had a mean of 301+/-259 kcal/day. Fecal fat loss proved not to be a good indicator of total fecal energy loss. A total of 4/13 patients (31%) had a net negative energy balance of over 500 kcal/day. A daily feces production of 250 g or more was a good predictor of malabsorption. Energy loss could accurately be predicted by using a factor 4.87 for the combined energetic value of protein and carbohydrates, if dry weight and fecal fat content are known. CONCLUSIONS: In this clinical study on ICU patients with loose stools, malabsorption proved to be a frequently occurring and so far unrecognized problem, contributing strongly to negative energy balances in 1/3 of the patients.

Corpus callosum size correlates with asymmetric performance on a dichotic listening task in healthy aging but not in Alzheimer's disease.

Alzheimer's disease (AD) involves not only gray matter but also white matter pathology, as reflected by atrophy of the corpus callosum (CC). Since decreased CC size may indicate reduced functional interhemispheric connectivity, differences in callosal size may have cognitive consequences that may become specifically apparent in neuropsychological tasks that tap hemispheric laterality. In the present study, we examined callosal functioning with a dichotic listening task in 25 Alzheimer patients, 20 healthy elderly and 20 healthy elderly with subjective memory complaints. We found decreased performance, increased ear asymmetry, and decreased callosal size in the AD group compared to healthy elderly. As expected, in the healthy elderly, we found significant negative correlations between ear asymmetry and callosal size, specifically in the anterior and posterior callosal subareas. While the association with the posterior subareas (isthmus and splenium) points at involvement of temporal areas mediating language processing, the association with the anterior subarea (the rostrum and genu) points at involvement of frontal areas mediating attention and executive functions. Remarkably however, in contrast to the healthy elderly, callosal size was not related to ear asymmetry in the AD group. The absence of an association between callosal atrophy and ear asymmetry implies that other pathological processes, next to reduced callosal functioning, attribute to ear asymmetry in AD. Difficulties to attend specifically to the left ear during dichotic listening in some of the AD patients, points at decreased attention and executive functions and suggests that pathology of specifically the frontal areas is involved.