Benchmarking therapeutic drug monitoring software: A review of available computer tools

Therapeutic drug monitoring (TDM) aims to optimize treatments by individualizing dosage regimens based on the measurement of blood concentrations. Dosage individualization to maintain concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculations currently represent the gold standard TDM approach but require computation assistance. In recent decades computer programs have been developed to assist clinicians in this assignment. The aim of this survey was to assess and compare computer tools designed to support TDM clinical activities. The literature and the Internet were searched to identify software. All programs were tested on personal computers. Each program was scored against a standardized grid covering pharmacokinetic relevance, user friendliness, computing aspects, interfacing and storage. A weighting factor was applied to each criterion of the grid to account for its relative importance. To assess the robustness of the software, six representative clinical vignettes were processed through each of them. Altogether, 12 software tools were identified, tested and ranked, representing a comprehensive review of the available software. Numbers of drugs handled by the software vary widely (from two to 180), and eight programs offer users the possibility of adding new drug models based on population pharmacokinetic analyses. Bayesian computation to predict dosage adaptation from blood concentration (a posteriori adjustment) is performed by ten tools, while nine are also able to propose a priori dosage regimens, based only on individual patient covariates such as age, sex and bodyweight. Among those applying Bayesian calculation, MM-USC*PACK© uses the non-parametric approach. The top two programs emerging from this benchmark were MwPharm© and TCIWorks. Most other programs evaluated had good potential while being less sophisticated or less user friendly. Programs vary in complexity and might not fit all healthcare settings. Each software tool must therefore be regarded with respect to the individual needs of hospitals or clinicians. Programs should be easy and fast for routine activities, including for non-experienced users. Computer-assisted TDM is gaining growing interest and should further improve, especially in terms of information system interfacing, user friendliness, data storage capability and report generation.

Prevalence of the metabolic syndrome in the Seychelles according to different definitions, contribution of components, and agreement between different definitions

Background: The metabolic syndrome (MS) represents a cluster of metabolic disorders that predicts diabetes and cardiovascular disease. Several definitions exist and further descriptive and prospective data are needed to compare these definitions and their significance in different populations. Objective: We examined, in a country of the African region, i) the prevalence of MS according to three major definitions (ATP, IDF, WHO); ii) the contribution of individual MS components; and iii) the agreement between the three considered definitions. We also examined the prevalence among diabetics and non-diabetics. Methods: We conducted an examination survey in a sample representative of the general population aged 25-64 of the Seychelles (Indian Ocean, African region), attended by 1255 persons (participation rate of 80.2%). Results: The prevalence of MS was similar with either definition of MS in men (24%--25%) but differed in women (WHO: 25%, ATP: 32%; IDF: 35%). Upon exclusion of diabetic persons, the prevalence was 5-10% lower for all three MS definitions: most diabetic persons had MS although a substantial proportion of diabetic men aged 45--64 did not have MS. The following components were found most often among persons with MS: 90% had high blood pressure (HBP) and 78% had obesity (ATP); 95% had obesity and 84% had HBP (WHO), and 89% had HBP and 75% had impaired glucose regulation (IDF) - not considering impaired glucose regulation and obesity that are compulsory components of the WHO and IDF definitions, respectively. Among persons with MS based on either of the three definitions (37% of total population), less than 80% met both ATP and IDF criteria, 67% both WHO and IDF criteria, 54% both WHO and ATP criteria and only 37% met all three definitions. Conclusion: We found a fairly high prevalence of MS in an African population. However, because there was only poor agreement between the 3 MS definitions, the fairly similar proportions of MS based on ATP, IDF or WHO definitions identified, to a substantial extent, different subjects as having MS.

Migraineurs without aura show microstructural abnormalities in the cerebellum and frontal lobe.

The involvement of the cerebellum in migraine pathophysiology is not well understood. We used a biparametric approach at high-field MRI (3 T) to assess the structural integrity of the cerebellum in 15 migraineurs with aura (MWA), 23 migraineurs without aura (MWoA), and 20 healthy controls (HC). High-resolution T1 relaxation maps were acquired together with magnetization transfer images in order to probe microstructural and myelin integrity. Clusterwise analysis was performed on T1 and magnetization transfer ratio (MTR) maps of the cerebellum of MWA, MWoA, and HC using an ANOVA and a non-parametric clusterwise permutation F test, with age and gender as covariates and correction for familywise error rate. In addition, mean MTR and T1 in frontal regions known to be highly connected to the cerebellum were computed. Clusterwise comparison among groups showed a cluster of lower MTR in the right Crus I of MWoA patients vs. HC and MWA subjects (p = 0.04). Univariate and bivariate analysis on T1 and MTR contrasts showed that MWoA patients had longer T1 and lower MTR in the right and left pars orbitalis compared to MWA (p < 0.01 and 0.05, respectively), but no differences were found with HC. Lower MTR and longer T1 point at a loss of macromolecules and/or micro-edema in Crus I and pars orbitalis in MWoA patients vs. HC and vs. MWA. The pathophysiological implications of these findings are discussed in light of recent literature.

Prevalence of the metabolic syndrome in the Seychelles according to different definitions, contribution of components, and agreement between different definitions

Background: The metabolic syndrome (MS) represents a cluster of metabolic disorders that predicts diabetes and cardiovascular disease. Several definitions exist and further descriptive and prospective data are needed to compare these definitions and their significance in different populations. Objective: We examined, in a country of the African region, i) the prevalence of MS according to three major definitions (ATP, IDF, WHO); ii) the contribution of individual MS components; and iii) the agreement between the three considered definitions. We also examined the prevalence among diabetics and non-diabetics. Methods: We conducted an examination survey in a sample representative of the general population aged 25-64 of the Seychelles (Indian Ocean, African region), attended by 1255 persons (participation rate of 80.2%). Results: The prevalence of MS was similar with either definition of MS in men (24%-25%) but differed in women (WHO: 25%, ATP: 32%; IDF: 35%). Upon exclusion of diabetic persons, the prevalence was 5-10% lower for all three MS definitions: most diabetic persons had MS although a substantial proportion of diabetic men aged 45-64 did not have MS. The following components were found most often among persons with MS: 90% had high blood pressure (HBP) and 78% had obesity (ATP); 95% had obesity and 84% had HBP (WHO), and 89% had HBP and 75% had impaired glucose regulation (IDF) -not considering impaired glucose regulation and obesity that are compulsory components of the WHO and IDF definitions, respectively. Among persons with MS based on either of the three definitions (37% of total population), less than 80% met both ATP and IDF criteria, 67% both WHO and IDF criteria, 54% both WHO and ATP criteria and only 37% met all three definitions. Conclusions. We found a fairly high prevalence of MS in an African population. However, because there was only poor agreement between the 3 MS definitions, the fairly similar proportions of MS based on ATP, IDF or WHO definitions identified, to a substantial extent, different subjects as having MS.

Nutritional status using the Mini Nutritional Assessment questionnaire and its relationship with bone quality in a population of institutionalized elderly women.

Malnutrition, a risk factor for osteoporotic fractures, is frequent in elderly people and, is underdiagnosed and undertreated. There are only few studies on the nutritional status of elderly people in Europe. The Mini Nutritional Assessment (MNA) is a non invasive and validated questionnaire to evaluate nutritional status in elderly people, classified in three groups: 1 degree score < 17: malnourished, 2 degrees score >17 and < 24: at risk of malnutrition, 3 degrees score >24: well-nourished, with a maximum of 30 points. Quantitative ultrasound of bone (QUS) is a method for assessing quality of bone which can be easily performed in nursing homes. Therefore, these two tests allowed to study the relationships between nutritional status and ultrasonic parameters of bone in 78 institutionalized women aged 86 +/- 6 years, living in 11 nursing homes around Lausanne (Switzerland). All were assessed by the MNA, had a measurement of the tricipital skin fold and of the grip strength. Functional status was evaluated by the scale "Activity of Daily Living" (ADL), and serum albumin level was measured when permitted. All had QUS of the calcaneus (with an Achilles, GE Lunar). The measured parameters are the Broadband Ultrasound Attenuation (BUA), attenuation of a band of ultrasonic frequencies through the medium, expressed in dB/MHz, and the Speed of Sound (SOS), speed of the ultrasounds through the medium, expressed in m/s. A third parameter, the stiffness index (SI), expressed as a percentage of the values obtained by the manufacturer in a young population and derived from BUA and SOS, was calculated automatically : SI = (0.67xBUA) + (0.28xSOS) - 420, expressed in percent compared to a young adult population (%YA). Fifteen percent of the women were undernourished and 58% were at risk of malnutrition. As expected, compared with the well-nourished minority, undernourished subjects had significant lower body mass index (BMI), tricipital skin fold (TSF), ADL score and albumin level (p < 0,01). The subjects "at risk of malnutrition" had significant lower BMI, ADL score (p < 0.01), tricipital skin fold and serum albumin (p < 0.05). Ultrasound parameters were low independently of the nutritional status. MNA score correlated significantly with tricipital skin fold (r = 0.508, p < 0.01), ADL (r = 0.538, p < 0.01) and albumin serum level (r = 0.409, p = 0.01). There was a trend for a correlation between the MNA and the ultrasound parameter BUA (r = 0.207, p = 0.07), whereas no correlation was found with SOS and SI. A multivariate analysis showed that tricipital skin fold and ADL explained 61% of the variance of the MNA. In conclusion, using simple and non invasive methods, this study showed that malnutrition and osteoporosis are frequent in institutionalized elderly persons in our country, and the ultrasound parameters are influenced by many others factors in addition to nutrition, especially at this age and in elderly residents of nursing homes.

Tibio-talar arthrodesis with long anterograde nail after complex open fracture-dislocation of the ankle : P17

Introduction: Posttraumatic painful osteoarthritis of the ankle joint after fracture-dislocation often has to be treated with arthrodesis. In the presence of major soft tissue lesions and important bone loss the technique to achieve arthrodesis has to be well chosen in order to prevent hardware failure, infection of bulky implants or non-union. Methods: We present the case of a 53 year-old biker suffering of a fracture-dislocation of the ankle associated with a mayor degloving injury of the heel. After initial immobilization of the lesion by external fixation in Spain the patient was transferred to our hospital for further treatment. The degloving injury of the heel with MRSA infection was initially treated by repeated débridement, changing of the configuration of the Ex Fix and antibiotic therapy with favourable outcome. Because of the bony lesions reconstruction of the ankle-joint was juged not to be an option and arthrodesis was planned. Due to bad soft-tissue situation standard open fixtion with plate and/or screws was not wanted but an option for intramedullary nailing was taken. However the use of a standard retrograde arthrodesis nail comes with two problems: 1) Risk of infection of the heel-part of the calaneus/nail in an unstable soft tissue situation with protruding nail. And 2) talo-calcaneal arthrodesis of an initially healthy subtalar joint. Given the situation of an unstable plantar/heel flap it was decided to perform anklearthrodesis by means of an anterograde nail with static fixation in the talus and in the proximal tibia. Results:This operation was performed with minimal opening at the ankle-site in order to remove the remaining cartilage and improve direct bone to bone contact. Arthrodesis was achieved by means of an anterograde T2 Stryker tibial nail.One year after the anterograde nailing the patient walks without pain for up to 4 hours with a heel of good quality and arthrodesis is achieved. Conclusion: Tibiotalar arthrodesis in the presence of mayor soft tissue lesions and bone loss can be successfully achieved with antegrade nailing.

Immunoscintigraphy with antigranulocyte monoclonal antibodies for the diagnosis of septic loosening of hip prostheses.

To determine the value of immunoscintigraphy (IS) with antigranulocyte monoclonal antibodies (Mab) in the diagnosis of subacute or chronic infection of hip prostheses, we prospectively studied 57 patients (23 women and 34 men; age 29-92 years, mean 72.7 years) sent to our institution in the past 6 years for clinical suspicion of septic loosening of a hip prosthesis. Nineteen patients had bilateral prostheses and one of them was studied twice. A total of 78 prostheses were examined. All patients had three-phase bone scans followed by IS with technetium-99m antigranulocyte Mab BW 250/183. Intervals between bone scans and IS varied from 2 days to 4 weeks. Final diagnosis was assessed by culture in 48 cases (articular puncture or intraoperative sampling) and by clinical follow-up of at least 8 months in 30 cases. Twelve prostheses were considered septic and 66 non-septic. The overall sensitivity and specificity were 92% and 64% respectively for bone scans, 67% and 75% for IS and 67% and 84% for both modalities together. In three cases, IS was doubtful and the final clinical diagnosis was negative for infection. False-positive results were observed in the presence of massive loosening of the prosthesis or in association with metaplastic peri-articular bone formation. In three of the four false-negative results, infection was proven only after enrichment of the culture, and the bacterium was Staphylococcus epidermidis. In 12/33 (36%) positive bone scans IS allowed the diagnosis of infection to be excluded. Overall accuracy of both modalities together was 81% and the negative predictive value was 93%, which compares favourably with the results reported for other non-invasive methods.

Detection of Optimal Models in Parameter Space with Support Vector Machines

The paper proposes an approach aimed at detecting optimal model parameter combinations to achieve the most representative description of uncertainty in the model performance. A classification problem is posed to find the regions of good fitting models according to the values of a cost function. Support Vector Machine (SVM) classification in the parameter space is applied to decide if a forward model simulation is to be computed for a particular generated model. SVM is particularly designed to tackle classification problems in high-dimensional space in a non-parametric and non-linear way. SVM decision boundaries determine the regions that are subject to the largest uncertainty in the cost function classification, and, therefore, provide guidelines for further iterative exploration of the model space. The proposed approach is illustrated by a synthetic example of fluid flow through porous media, which features highly variable response due to the parameter values' combination.

Efficacy of brief motivational intervention at army conscription to address alcohol use and related problems: a randomized controlled trial

Objectives: The aim of this study was to evaluate the efficacy of brief motivational intervention (BMI) in reducing alcohol use and related problems among binge drinkers randomly selected from a census of 20 year-old French speaking Swiss men and to test the hypothesis that BMI contributes to maintain low-risk drinking among non-bingers. Methods: Randomized controlled trial comparing the impact of BMI on weekly alcohol use, frequency of binge drinking and occurrence of alcohol-related problems. Setting: Army recruitment center. Participants: A random sample of 622 men were asked to participate, 178 either refused, or missed appointment, or had to follow military assessment procedures instead, resulting in 418 men randomized into BMI or control conditions, 88.7% completing the 6-month follow-up assessment. Intervention: A single face-to-face BMI session exploring alcohol use and related problems in order to stimulate behaviour change perspective in a non-judgmental, empathic manner based on the principles of motivational interviewing (MI). Main outcome measures: Weekly alcohol use, binge drinking frequency and the occurrence of 12 alcohol-related consequences. Results: Among binge drinkers, we observed a 20% change in drinking induced by BMI, with a reduction in weekly drinking of 1.5 drink in the BMI group, compared to an increase of 0.8 drink per week in the control group (incidence rate ratio 0.8, 95% confidence interval 0,66 to 0,98, p = 0.03). BMI did not influence the frequency of binge drinking and the occurrence of 12 possible alcohol-related consequences. However, BMI induced a reduction in the alcohol use of participants who, after drinking over the past 12 months, experienced alcohol-related consequences, i.e., hangover (-20%), missed a class (-53%), got behind at school (-54%), argued with friends (-38%), engaged in unplanned sex (-45%) or did not use protection when having sex (-64%). BMI did not reduce weekly drinking in those who experienced the six other problems screened. Among non-bingers, BMI did not contribute to maintain low-risk drinking. Conclusions: At army conscription, BMI reduced alcohol use in binge drinkers, particularly in those who recently experienced alcohol-related adverse consequences. No preventive effect of BMI was observed among non-bingers. BMI is an interesting preventive option in young binge drinkers, particularly in countries with mandatory army recruitment.

A high proportion of users of low-threshold facilities with needle exchange programmes in Switzerland are currently on methadone treatment: implications for new approaches in harm reduction and care.

BACKGROUND: Increasingly, patients receiving methadone treatment are found in low threshold facilities (LTF), which provide needle exchange programmes in Switzerland. This paper identifies the characteristics of LTF attendees receiving methadone treatment (MT) compared with other LTF attendees (non-MT). METHODS: A national cross-sectional survey was conducted in 2006 over five consecutive days in all LTF (n=25). Attendees were given an anonymous questionnaire, collecting information on socio-demographic indicators, drug consumption, injection, methadone treatment, and self-reported HIV and HCV status. Univariate analysis and logistic regression were performed to compare MT to non-MT. The response rate was 66% (n=1128). RESULTS: MT comprised 57.6% of the sample. In multivariate analysis, factors associated with being on MT were older age (OR: 1.38), being female (OR: 1.60), having one's own accommodation (OR: 1.56), receiving public assistance (OR: 2.29), lifetime injecting (OR: 2.26), HIV-positive status (OR: 2.00), and having consumed cocaine during the past month (OR: 1.37); MT were less likely to have consumed heroin in the past month (OR: 0.76, not significant) and visited LTF less often on a daily basis (OR: 0.59). The number of injections during the past week was not associated with MT. CONCLUSIONS: More LTF attendees were in the MT group, bringing to light an underappreciated LTF clientele with specific needs. The MT group consumption profile may reflect therapeutic failure or deficits in treatment quality and it is necessary to acknowledge this and to strengthen the awareness of LTF personnel about potential needs of MT attendees to meet their therapeutic goals.

Efficacy of brief motivational intervention in reducing binge drinking in young men: A randomized controlled trial.

Background: Brief motivational intervention (BMI) is one of the few effective strategies targeting alcohol consumption, but has not been tested in young men in the community. We evaluated the efficacy of BMI in reducing alcohol use and related problems among binge drinkers and in maintaining low-risk drinking among non-bingers. Methods: A random sample of a census of men included during army conscription (which is mandatory for 20-year-old males in Switzerland) was randomized to receive a single face-to-face BMI session (N = 199) or no intervention (N = 219). A six-month follow-up rate was obtained for 88.7% of the subjects. Results: Among binge drinkers, there was 20% less drinking in the BMI group versus the control group (incidence rate ratio = 0.80, confidence interval 0.66-0.98, p = 0.03): the BMI group showed a weekly reduction of 1.5 drinks compared to an increase of 0.8 drinks weekly in the control group. Among subjects who experienced one or more alcohol-related consequences over the last 12 months, there was 19% less drinking in the BMI group compared to the control group (incidence rate ratio = 0.81; confidence interval 0.67-0.97, p = 0.04). Among non-bingers, BMI did not contribute to the maintenance of low-risk drinking. Conclusion: BMI reduced the alcohol use of binge drinkers, particularly among those who experienced certain alcohol-related adverse consequences. No preventive effect of BMI was observed among non-bingers. BMI is a plausible secondary preventive option for young binge drinkers. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

The Dyadic and Triadic Therapeutic Alliance in Cross-cultural Health Care: The case of Hispanic American Patients

This research project conducted in the Psychology Department of the University of Lausanne (Switzerland) evaluated the therapeutic alliance with Hispanic American Patients. From the patient's perspective, the therapeutic alliance was explored in two types of frameworks: the dyadic and the triadic setting. The dyadic setting is the encounter between a therapist (health professional) and a patient who ideally share the same language. The triadic setting is the encounter of a therapist and a patient who speak different languages, but are able to interact using the help of an interpreter. My specific interest focuses on studying the therapeutic alliance in a cross- cultural setting through a mixed methodology. As part of the quantitative phase, non- parametric tests were used to analyze 55 questionnaires of the Therapeutic Alliance for Migrants - Health Professionals' version (QALM-PS). For the qualitative phase, a thematic analysis was used to analyze 20 transcript interviews. While no differences were found concerning the strength of the therapeutic alliance between the triadic and dyadic settings, results showed that the factors that enrich the therapeutic alliance with migrant patients depend more on an emotional alliance (bond) than on a rational alliance (agreements). Indeed, the positive relationship with the interpreter, and especially with the therapist, relies considerably on human qualities and moral values, bringing the conception of humanity as an important need when meeting foreign patients in health care settings. In addition, the quality of communication, which could be attributed to the type of interpreter in the triadic setting, plays an important role in the establishment of a positive therapeutic relationship. Ce projet de recherche mené au Département de psychologie de l'Université de Lausanne (Suisse) a évalué l'alliance thérapeutique avec les patients hispano-américains. Du point de vue du patient, l'alliance thérapeutique a été étudiée dans deux types de dispositifs: le cadre dyadique et triadique. Le cadre dyadique est la rencontre d'un thérapeute (professionnel de la santé) et d'un patient qui, idéalement, partagent la même langue. Le cadre triadique est la rencontre d'un thérapeute et d'un patient qui parlent différentes langues, mais sont capables d'interagir grâce à l'aide d'un interprète. Mon intérêt porte en particulier sur l'étude de l'alliance thérapeutique dans un cadre interculturel au travers d'une méthodologie mixte. Dans la phase quantitative, des tests non paramétriques ont été utilisés pour les analyses des 55 questionnaires de l'alliance thérapeutique pour les migrants, version - professionnels de la santé (QALM-PS). Pour la phase qualitative, une analyse thématique a été utilisée pour l'analyse des 20 entretiens transcrits. Bien qu'aucune différence n'a été constatée en ce qui concerne la force de l'alliance thérapeutique entre les cadres dyadiques et triadiques, les résultats montrent que les facteurs qui enrichissent l'alliance thérapeutique avec les patients migrants dépendent plus de l'alliance émotionnelle (lien) que sur une alliance rationnelle (accords). En effet, la relation positive avec l'interprète, et en particulier avec le thérapeute, repose en grande partie sur des qualités humaines et des valeurs morales, ce qui porte la conception de l'humanité comme un besoin important lors de la rencontre des patients étrangers dans un cadre de santé. En outre, la qualité de la communication, qui pourrait être attribuée au type d'interprète dans le cadre triadique, joue un rôle important dans l'établissement d'une relation thérapeutique positive.

Benchmarking therapeutic drug monitoring software: A systematic evaluation of available computer tools

Introduction: Therapeutic drug monitoring (TDM) aims at optimizing treatment by individualizing dosage regimen based on measurement of blood concentrations. Maintaining concentrations within a target range requires pharmacokinetic and clinical capabilities. Bayesian calculation represents a gold standard in TDM approach but requires computing assistance. In the last decades computer programs have been developed to assist clinicians in this assignment. The aim of this benchmarking was to assess and compare computer tools designed to support TDM clinical activities.¦Method: Literature and Internet search was performed to identify software. All programs were tested on common personal computer. Each program was scored against a standardized grid covering pharmacokinetic relevance, user-friendliness, computing aspects, interfacing, and storage. A weighting factor was applied to each criterion of the grid to consider its relative importance. To assess the robustness of the software, six representative clinical vignettes were also processed through all of them.¦Results: 12 software tools were identified, tested and ranked. It represents a comprehensive review of the available software's characteristics. Numbers of drugs handled vary widely and 8 programs offer the ability to the user to add its own drug model. 10 computer programs are able to compute Bayesian dosage adaptation based on a blood concentration (a posteriori adjustment) while 9 are also able to suggest a priori dosage regimen (prior to any blood concentration measurement), based on individual patient covariates, such as age, gender, weight. Among those applying Bayesian analysis, one uses the non-parametric approach. The top 2 software emerging from this benchmark are MwPharm and TCIWorks. Other programs evaluated have also a good potential but are less sophisticated (e.g. in terms of storage or report generation) or less user-friendly.¦Conclusion: Whereas 2 integrated programs are at the top of the ranked listed, such complex tools would possibly not fit all institutions, and each software tool must be regarded with respect to individual needs of hospitals or clinicians. Interest in computing tool to support therapeutic monitoring is still growing. Although developers put efforts into it the last years, there is still room for improvement, especially in terms of institutional information system interfacing, user-friendliness, capacity of data storage and report generation.

Learning wind fields with multiple kernels

This paper presents multiple kernel learning (MKL) regression as an exploratory spatial data analysis and modelling tool. The MKL approach is introduced as an extension of support vector regression, where MKL uses dedicated kernels to divide a given task into sub-problems and to treat them separately in an effective way. It provides better interpretability to non-linear robust kernel regression at the cost of a more complex numerical optimization. In particular, we investigate the use of MKL as a tool that allows us to avoid using ad-hoc topographic indices as covariables in statistical models in complex terrains. Instead, MKL learns these relationships from the data in a non-parametric fashion. A study on data simulated from real terrain features confirms the ability of MKL to enhance the interpretability of data-driven models and to aid feature selection without degrading predictive performances. Here we examine the stability of the MKL algorithm with respect to the number of training data samples and to the presence of noise. The results of a real case study are also presented, where MKL is able to exploit a large set of terrain features computed at multiple spatial scales, when predicting mean wind speed in an Alpine region.

How single-trial electrical neuroimaging contributes to multisensory research.

This study details a method to statistically determine, on a millisecond scale and for individual subjects, those brain areas whose activity differs between experimental conditions, using single-trial scalp-recorded EEG data. To do this, we non-invasively estimated local field potentials (LFPs) using the ELECTRA distributed inverse solution and applied non-parametric statistical tests at each brain voxel and for each time point. This yields a spatio-temporal activation pattern of differential brain responses. The method is illustrated here in the analysis of auditory-somatosensory (AS) multisensory interactions in four subjects. Differential multisensory responses were temporally and spatially consistent across individuals, with onset at approximately 50 ms and superposition within areas of the posterior superior temporal cortex that have traditionally been considered auditory in their function. The close agreement of these results with previous investigations of AS multisensory interactions suggests that the present approach constitutes a reliable method for studying multisensory processing with the temporal and spatial resolution required to elucidate several existing questions in this field. In particular, the present analyses permit a more direct comparison between human and animal studies of multisensory interactions and can be extended to examine correlation between electrophysiological phenomena and behavior.