Publications by authors named "Nathalie Gosselin"

47 Publications

Influence of Background Musical Emotions on Attention in Congenital Amusia.

Front Hum Neurosci 2020 25;14:566841. Epub 2021 Jan 25.

International Laboratory for Brain, Music and Sound Research, University of Montreal, Montreal, QC, Canada.

Congenital amusia in its most common form is a disorder characterized by a musical pitch processing deficit. Although pitch is involved in conveying emotion in music, the implications for pitch deficits on musical emotion judgements is still under debate. Relatedly, both limited and spared musical emotion recognition was reported in amusia in conditions where emotion cues were not determined by musical mode or dissonance. Additionally, assumed links between musical abilities and visuo-spatial attention processes need further investigation in congenital amusics. Hence, we here test to what extent musical emotions can influence attentional performance. Fifteen congenital amusic adults and fifteen healthy controls matched for age and education were assessed in three attentional conditions: executive control (distractor inhibition), alerting, and orienting (spatial shift) while music expressing either joy, tenderness, sadness, or tension was presented. Visual target detection was in the normal range for both accuracy and response times in the amusic relative to the control participants. Moreover, in both groups, music exposure produced facilitating effects on selective attention that appeared to be driven by the arousal dimension of musical emotional content, with faster correct target detection during joyful compared to sad music. These findings corroborate the idea that pitch processing deficits related to congenital amusia do not impede other cognitive domains, particularly visual attention. Furthermore, our study uncovers an intact influence of music and its emotional content on the attentional abilities of amusic individuals. The results highlight the domain-selectivity of the pitch disorder in congenital amusia, which largely spares the development of visual attention and affective systems.
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http://dx.doi.org/10.3389/fnhum.2020.566841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868440PMC
January 2021

Effect of Background Music on Attentional Control in Older and Young Adults.

Front Psychol 2020 20;11:557225. Epub 2020 Oct 20.

International Laboratory for Brain, Music and Sound Research (BRAMS), Center for Research on Brain, Language and Music (CRBLM) and Laboratory for Music, Emotions and Cognition Research (MUSEC), Department of Psychology, University of Montreal, Montreal, QC, Canada.

Healthy aging may be accompanied by cognitive decline that includes diminished attentional control, an executive function that allows us to focus our attention while inhibiting distractors. Previous studies have demonstrated that background music can enhance some executive functions in both young and older adults. According to the , the beneficial influence of background music on cognitive performance would be related to its ability to increase the arousal level of the listeners and to improve their mood. Consequently, stimulating and pleasant music might enhance attentional control. Therefore, the aims of this study were (1) to determine if the influence of background music, and more specifically its arousal level, might improve attentional control in older adults and (2) whether this effect is similar across older and young adults. Older and young adults performed a visuo-spatial flanker task during three auditory conditions: stimulating music, relaxing music, and silence. Participants had to indicate as fast and as accurately as possible the direction of a central arrow, which was flanked by congruent or incongruent arrows. As expected, reaction times were slower for the incongruent compared to congruent trials. Interestingly, this difference was significantly greater under the relaxing music condition compared to other auditory conditions. This effect was the same across both age groups. In conclusion, relaxing music seems to interfere with visuo-spatial attentional control compared to stimulating music and silence, regardless of age.
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http://dx.doi.org/10.3389/fpsyg.2020.557225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606979PMC
October 2020

Impact of Music on Working Memory in Rwanda.

Front Psychol 2020 28;11:774. Epub 2020 Apr 28.

Groupe de Recherche CogNAC, Département de Psychologie, Université du Québec à Trois-Rivières, Trois-Rivières, Québec, QC, Canada.

Previous research shows that listening to pleasant, stimulating and familiar music is likely to improve working memory performance. The benefits of music on cognition have been widely studied in Western populations, but not in other cultures. The purpose of this study was to explore the impact of music on working memory in a non-Western sociocultural context: Rwanda. One hundred and nineteen participants were randomly assigned to a control group (short story) or one of four different musical conditions varying on two dimensions: arousal (relaxing, stimulating) and cultural origin (Western, Rwandan). Working memory was measured using a behavioral task, the n-back paradigm, before and after listening to music (or the short story in the control condition). Unlike in previous studies with Western samples, our results with this Rwandan sample did not show any positive effect of familiar, pleasant and stimulating music on working memory. Performance on the n-back task generally improved from pre to post, in all conditions, but this improvement was less important in participants who listened to familiar Rwandan music compared to those who listened to unfamiliar Western music or to a short story. The study highlights the importance of considering the sociocultural context in research examining the impact of music on cognition. Although different aspects of music are considered universal, there may be cultural differences that limit the generalization of certain effects of music on cognition or that modulate the characteristics that favor its beneficial impact.
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http://dx.doi.org/10.3389/fpsyg.2020.00774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198829PMC
April 2020

Population Pharmacokinetic-Pharmacodynamic Model of Serum Transthyretin Following Patisiran Administration.

Nucleic Acid Ther 2020 06 12;30(3):143-152. Epub 2020 Mar 12.

Alnylam Pharmaceuticals, Cambridge, Massachusetts, USA.

Hereditary transthyretin-mediated amyloidosis is an inherited, rapidly progressive, life-threatening disease caused by mutated transthyretin (TTR) protein. Patisiran is a small interfering RNA (siRNA) formulated in a lipid nanoparticle that inhibits hepatic TTR protein synthesis by RNA interference. We have developed an indirect-response pharmacokinetic-pharmacodynamic model relating plasma siRNA (ALN-18328) levels to serum TTR reduction across five clinical studies. A sigmoidal function described this relationship, with estimated Hill coefficient of 0.548, and half maximal inhibitory concentration (IC), IC, and IC values of 9.45, 118.5, and 520.5 ng/mL, respectively. Following patisiran 0.3 mg/kg every 3 weeks (q3w), steady-state plasma ALN-18328 exposures were between IC and IC, yielding average serum TTR reductions of 80%-90% from baseline. Covariate analysis indicated similar TTR reduction across evaluated intrinsic and extrinsic factors, obviating the need for dose adjustment. Modeling results support the recommended patisiran dosing schedule of 0.3 mg/kg q3w, with a maximum dose of 30 mg for patients weighing ≥100 kg.
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http://dx.doi.org/10.1089/nat.2019.0841DOI Listing
June 2020

Neuropsychology supervision: A survey of practices in Quebec and a cross-cultural comparison.

Clin Neuropsychol 2020 Mar 3:1-26. Epub 2020 Mar 3.

Department of Psychology, University of Montreal, Montreal, Canada.

Supervisors in neuropsychology have an ethical responsibility to continuously improve their ability to supervise. Despite a growing interest in the field, there exist little data on the actual practice and few guidelines to help the practitioner through the process of neuropsychology supervision. This study aims to characterize neuropsychology supervisors and their practices in Quebec, Canada and compare these with supervisory practices of supervisors in the United States, with the ultimate aim of offering recommendations to supervisors. Seventy-nine neuropsychology supervisors responded to the 20-question online survey of supervisory experience, education, practices, and familiarity with and use of supervision models that was inspired by Shultz and colleagues. Experience in clinical supervision ranged from 0.12 to 35 years and from having supervised 1-150 supervisees. About half of respondents reported having received continuing education in supervision and about two thirds were familiar with at least one type of supervision model. Some supervisory practices were associated with experience, but not with familiarity and utilization of supervision models. Supervisors from Quebec and the U.S. reported a similar frequency of addressing most of the various supervisory competencies with their supervisees. Based on the competency-based approach we offer a portrait of neuropsychology supervision in Quebec while highlighting some cultural differences with the U.S. Recommendations include focusing more on certain foundational (e.g. reflective practice) and functional competencies (supervision most notably). Neuropsychology supervisors are also encouraged to devote more time to continuing education opportunities in supervision in order to ensure supervisee development and quality care.
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http://dx.doi.org/10.1080/13854046.2020.1732467DOI Listing
March 2020

A randomized, double-blind, placebo-controlled, pharmacokinetic and pharmacodynamic study of a fixed-dose combination of phentermine/topiramate in adolescents with obesity.

Diabetes Obes Metab 2020 04 18;22(4):480-491. Epub 2019 Dec 18.

Cincinnati Children's Hospital/University of Cincinnati, Cincinnati, Ohio, United States.

Aims: To assess the pharmacokinetic (PK) and pharmacodynamic characteristics of VI-0521, a fixed-dose combination of immediate-release phentermine (PHEN) and extended-release topiramate (TPM) in adolescents aged 12 to 17 years with obesity, and to report weight loss and adverse events using this drug combination.

Materials And Methods: This was a multicentre, randomized, double-blind, parallel-design, placebo-controlled study in adolescents with obesity. A total of 42 adolescents were randomly assigned in a 1:1:1 ratio to placebo, or to a mid-dose (PHEN/TPM 7.5 mg/46 mg), or a top-dose (PHEN/TPM 15 mg/92 mg) of VI-0521. A total of 26 adolescents were included in the PK analysis (14 from the mid-dose group and 12 from the top-dose group).

Results: On day 56, arithmetic means of terminal elimination half-life, apparent clearance (CL/F) and apparent central volume of distribution (Vc/F) were consistent across dose levels for both PHEN and TPM. Arithmetic means of CL/F and Vc/F for PHEN and TPM administered as a combination in adolescents with obesity were within 10% to 30% of those previously assessed in adults with obesity enrolled in phase II and III studies. A higher proportion of adolescents in both the mid- and top-dose groups (13.3% and 50.0%, respectively) compared with placebo (0.0%) reached ≥5% weight loss at day 56. The least squares (LS) mean change in systolic blood pressure from baseline to day 56 was -5.2 mmHg for the placebo group, -2.5 mmHg for the mid-dose group, and - 5.5 mmHg for the top-dose group. The LS mean change in diastolic blood pressure from baseline to day 56 was -2.4 mmHg for the placebo group, +3.8 mmHg for the mid-dose group, and + 2.0 mmHg for the top-dose group. Participants in the top-dose group had increases in heart rate from baseline of 4.1 bpm, while participants in the mid-dose group experienced a mean decrease in heart rate of 4.5 bpm at day 56. Both PHEN/TPM dose combinations were safe and well tolerated.

Conclusions: Treatment of adolescents with obesity using a fixed-dose combination of PHEN/TPM for 8 weeks resulted in exposure to PHEN and TPM that was comparable to that observed in adults, statistically significant weight loss, and a tolerable safety profile. These data indicate that both mid- and top-dose levels are appropriate for longer-term safety and efficacy studies in adolescents.
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http://dx.doi.org/10.1111/dom.13910DOI Listing
April 2020

Randomized Population Pharmacokinetic Analysis and Safety of Intravenous Acetaminophen for Acute Postoperative Pain in Neonates and Infants.

J Clin Pharmacol 2020 01 25;60(1):16-27. Epub 2019 Aug 25.

Mallinckrodt Pharmaceuticals, Bedminster, New Jersey, USA.

Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be contraindicated in particular clinical settings. This randomized, placebo-controlled study of intravenous acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant patients with acute postoperative pain assessed pharmacokinetics (PK) and safety, in addition to efficacy and pharmacodynamics of repeated doses administered over 24 hours. Neonate and infant patients (<2 years of age) who were undergoing surgery or had experienced a traumatic injury and were expected to need pain management for at least 24 hours were enrolled. Subjects were randomly assigned to receive intravenous acetaminophen low dose, intravenous acetaminophen high dose, or placebo. A population PK model of intravenous acetaminophen was updated by combining 581 samples from the current study of 158 neonate and infant subjects with results from a previously developed model. The individual predicted-versus-observed concentrations plots showed that the structural PK model fit the blood and plasma acetaminophen concentration-versus-time profiles in the active and placebo groups. Terminal elimination half-life was prolonged in neonates and younger infants and in intermediate and older infants similar to values in adults. When compared with placebo, total rescue opioid consumption was similar and significantly fewer intravenous acetaminophen patients prematurely discontinued because of treatment-emergent adverse events (P < .01). For intravenous acetaminophen, neonates receiving 12.5 mg/kg every 6 hours had PK profiles similar to younger, intermediate, and older infants, adolescents, and adults weighing <50 kg receiving 15 mg/kg every 6 hours and adults ≥ 50 kg receiving 1000 mg every 6 hours.
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http://dx.doi.org/10.1002/jcph.1508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6973014PMC
January 2020

Electrophysiological Responses to Emotional Facial Expressions Following a Mild Traumatic Brain Injury.

Brain Sci 2019 Jun 18;9(6). Epub 2019 Jun 18.

Centre for Interdisciplinary Research in Rehabilitation (CRIR), IURDPM, CIUSSS du Centre-Sud-de-l'Île-de-Montréal, Montreal, QC H3S 2J4, Canada.

The present study aimed to measure neural information processing underlying emotional recognition from facial expressions in adults having sustained a mild traumatic brain injury (mTBI) as compared to healthy individuals. We thus measured early (N1, N170) and later (N2) event-related potential (ERP) components during presentation of fearful, neutral, and happy facial expressions in 10 adults with mTBI and 11 control participants. Findings indicated significant differences between groups, irrespective of emotional expression, in the early attentional stage (N1), which was altered in mTBI. The two groups showed similar perceptual integration of facial features (N170), with greater amplitude for fearful facial expressions in the right hemisphere. At a higher-level emotional discrimination stage (N2), both groups demonstrated preferential processing for fear as compared to happiness and neutrality. These findings suggest a reduced early selective attentional processing following mTBI, but no impact on the perceptual and higher-level cognitive processes stages. This study contributes to further improving our comprehension of attentional versus emotional recognition following a mild TBI.
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http://dx.doi.org/10.3390/brainsci9060142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627801PMC
June 2019

Emotional recognition from dynamic facial, vocal and musical expressions following traumatic brain injury.

Brain Inj 2017 24;31(2):221-229. Epub 2016 Oct 24.

a Centre de recherche interdisciplinaire en réadaptation (CRIR) - Centre de réadaptation Lucie-Bruneau (CRLB).

Objectives: To assess emotion recognition from dynamic facial, vocal and musical expressions in sub-groups of adults with traumatic brain injuries (TBI) of different severities and identify possible common underlying mechanisms across domains.

Methods: Forty-one adults participated in this study: 10 with moderate-severe TBI, nine with complicated mild TBI, 11 with uncomplicated mild TBI and 11 healthy controls, who were administered experimental (emotional recognition, valence-arousal) and control tasks (emotional and structural discrimination) for each domain.

Results: Recognition of fearful faces was significantly impaired in moderate-severe and in complicated mild TBI sub-groups, as compared to those with uncomplicated mild TBI and controls. Effect sizes were medium-large. Participants with lower GCS scores performed more poorly when recognizing fearful dynamic facial expressions. Emotion recognition from auditory domains was preserved following TBI, irrespective of severity. All groups performed equally on control tasks, indicating no perceptual disorders. Although emotional recognition from vocal and musical expressions was preserved, no correlation was found across auditory domains.

Conclusions: This preliminary study may contribute to improving comprehension of emotional recognition following TBI. Future studies of larger samples could usefully include measures of functional impacts of recognition deficits for fearful facial expressions. These could help refine interventions for emotional recognition following a brain injury.
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http://dx.doi.org/10.1080/02699052.2016.1208846DOI Listing
January 2018

Population pharmacokinetics of bevacizumab in cancer patients with external validation.

Cancer Chemother Pharmacol 2016 Aug 21;78(2):341-51. Epub 2016 Jun 21.

Clinical Pharmacology, Genentech Inc, 1 DNA Way, South San Francisco, CA, 94080, USA.

Background: Bevacizumab is approved for various cancers. This analysis aimed to comprehensively evaluate bevacizumab pharmacokinetics and the influence of patient variables on bevacizumab pharmacokinetics.

Methods: Rich and sparse bevacizumab serum concentrations were collected from Phase I through IV studies in early and metastatic cancers. Bevacizumab was given intravenously as single agent or in combination with chemotherapy for single- and multiple-dose schedules.

Results: Model-building used 8943 bevacizumab concentrations from 1792 patients with colon/colorectal, non-small cell lung, kidney, pancreatic, breast, prostate and brain cancer. Bevacizumab doses ranged from 1 to 20 mg/kg given once every 1, 2 or 3 weeks. A two-compartment model best described the data. The population estimates of clearance (CL), central volume of distribution (V1) and half-life for a typical 70-kg patient were 9.01 mL/h, 2.88 L and 19.6 days. CL and V1 increased with body weight and were higher in males than females by 14 and 18 %, respectively. CL decreased with increasing albumin and decreasing alkaline phosphatase. The final model was externally validated using 1670 concentrations from 146 Japanese patients that were not used for model-building. Mean prediction errors were -2.1, 3.1 and 1.0 % for concentrations, CL and V1, respectively, confirming adequate predictive performance.

Conclusions: A robust bevacizumab pharmacokinetic model was developed and externally validated, which may be used to simulate bevacizumab exposure to optimize dosing strategies. Asian and non-Asian patients exhibited similar bevacizumab pharmacokinetics. Given the similarity in pharmacokinetics among monoclonal antibodies, this may inform pharmacokinetic studies in different ethnic groups for other therapeutic antibodies.
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http://dx.doi.org/10.1007/s00280-016-3079-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965493PMC
August 2016

Population pharmacokinetic modeling of motesanib and its active metabolite, M4, in cancer patients.

Clin Pharmacol Drug Dev 2015 11 23;4(6):463-72. Epub 2015 Jul 23.

PKDM, Amgen Inc., Thousand Oaks, CA, USA.

Motesanib is a small molecule and potent multikinase inhibitor with antiangiogenic and antitumor activity. Population pharmacokinetic (POPPK) modeling of motesanib and M4, an active metabolite, was performed to assess sources of variability in cancer patients. The analysis included data collected from 451 patients from 8 clinical trials with oral doses of motesanib ranging from 25 to 175 mg, either once daily or twice daily. The POPPK analyses were performed using nonlinear mixed-effect models with a sequential approach. Covariate effects of demographics and other baseline characteristics were assessed with stepwise covariate modeling. A 2-compartment model with food effect on absorption parameters fitted the PK data of motesanib well. The effects albumin and sex on apparent clearance (CL/F) of motesanib were statistically significant. The albumin effect was more important but remained below a 25% difference. A 1-compartment model fitted PK data of M4 well. Effects of race (Asian vs non-Asian) and dosing frequency were identified as statistically significant covariates on the CL/F of M4. The maximum effect of albumin would result in less than 25% change in motesanib CL/F and as such would not warrant any dosing adjustment. However, faster elimination of M4 in Asian patients requires further investigation.
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http://dx.doi.org/10.1002/cpdd.196DOI Listing
November 2015

Bevacizumab dosing strategy in paediatric cancer patients based on population pharmacokinetic analysis with external validation.

Br J Clin Pharmacol 2016 Jan 10;81(1):148-60. Epub 2015 Dec 10.

Clinical Pharmacology, Genentech Inc., South San Francisco, CA, USA.

Aim: The aim of the present study was to evaluate the pharmacokinetics of bevacizumab and various dosing strategies for this agent in paediatric patients.

Methods: Data were collected from 232 paediatric patients (1971 concentrations) in five studies, with a wide range of age (0.5-21 years), body weight (BWT; 5.9-125 kg), and regimens (5-15 mg kg(-1) biweekly or triweekly). Data from 152 patients (1427 concentrations) and 80 patients (544 concentrations) were used for model building and external validation, respectively. Steady-state exposure was simulated under BWT-based, body surface area (BSA)-based, ideal body weight (IBW)-based, and tier-based doses. NONMEM and R were used for analyses.

Results: Typical estimates of clearance, central volume of distribution (V1), and median half-life were 9.04 ml h(-1) , 2851 ml, and 19.6 days, respectively. Clearance decreased with increasing albumin. Clearance and V1 increased with BWT and were higher in male patients. Clearance and V1 were lower in children with primary central nervous system (CNS) tumours than in children with sarcomas, resulting in 49% higher trough (C min) and 29% higher peak (Cmax) concentrations. BWT-adjusted clearance and V1 remained unchanged across ages. Paediatric C min was similar to adult C min under all dosing strategies. Paediatric Cmax exceeded adult Cmax under tier-based doses.

Conclusions: BWT-adjusted pharmacokinetic parameter estimates in paediatric patients were similar to those in adults, and similar across ages. Bevacizumab exposure was higher in children with primary CNS tumours than in children with sarcomas. BSA-based, IBW-based, and tier-based doses offered no substantial advantage over the BWT-based dose currently used in adults for bevacizumab. Given the similarity in pharmacokinetics among many monoclonal antibodies, this may help to develop practical paediatric dosing guidelines for other therapeutic antibodies.
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http://dx.doi.org/10.1111/bcp.12778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4693565PMC
January 2016

Population pharmacokinetic and pharmacodynamic analyses from a 4-month intradose escalation and its subsequent 12-month dose titration studies for a human monoclonal anti-FGF23 antibody (KRN23) in adults with X-linked hypophosphatemia.

J Clin Pharmacol 2016 Apr 26;56(4):429-38. Epub 2015 Oct 26.

Yale Center for X-Linked Hypophosphatemia, Yale University School of Medicine, New Haven, CT, USA.

X-linked hypophosphatemia (XLH) is an inherited metabolic bone disease with abnormally elevated serum FGF23 resulting in low renal maximum threshold for phosphate reabsorption, low serum phosphate (Pi) and 1,25-dihydroxyvitamin D levels with subsequent development of short stature and skeletal deformities. KRN23 is a novel human anti-FGF23 antibody for the treatment of XLH. The pharmacokinetics (PK) and pharmacodynamics (PD) models of KRN23 were assessed following subcutaneous dosing every 28 days over an initial 4-month dose escalation (0.05-0.6 mg/kg) and a subsequent 12-month titration period (0.1-1.0 mg/kg) in XLH adults. The PK of KRN23 was described by a 1-compartmental model with first-order absorption and elimination at doses ≥0.1 mg/kg. The elimination half-life was 17.8 days. Covariates did not affect KRN23 PK. Mean peak serum Pi was attained 7-10 days after dosing and progressively increased following each of the initial 4 doses with comparable peak values attained following the sixth through tenth doses with a slight decrease thereafter. A PK-PD model with a maximum effect (Emax ) and a time-varying effective concentration to reach 50% of Emax (EC50,t ) described data adequately. Typical Emax was 1.5 mg/dL. Typical EC50,t was 1780 ng/mL and 5999 ng/mL after first and last dose, respectively.
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http://dx.doi.org/10.1002/jcph.611DOI Listing
April 2016

Sensitivity to musical emotions in congenital amusia.

Cortex 2015 Oct 6;71:171-82. Epub 2015 Jul 6.

International Laboratory for Brain, Music and Sound Research (BRAMS), Center for Research on Brain, Language and Music (CRBLM), Montreal, Quebec, Canada; Department of Psychology, University of Montreal, Montreal, Quebec, Canada. Electronic address:

The emotional experience elicited by music is largely dependent on structural characteristics such as pitch, rhythm, and dynamics. We examine here to what extent amusic adults, who have experienced pitch perception difficulties all their lives, still maintain some ability to perceive emotions from music. Amusic and control participants judged the emotions expressed by unfamiliar musical clips intended to convey happiness, sadness, fear and peacefulness (Experiment 1A). Surprisingly, most amusic individuals showed normal recognition of the four emotions tested here. This preserved ability was not due to some peculiarities of the music, since the amusic individuals showed a typical deficit in perceiving pitch violations intentionally inserted in the same clips (Experiment 1B). In Experiment 2, we tested the use of two major structural determinants of musical emotions: tempo and mode. Neutralization of tempo had the same effect on both amusics' and controls' emotional ratings. In contrast, amusics did not respond to a change of mode as markedly as controls did. Moreover, unlike the control participants, amusics' judgments were not influenced by subtle differences in pitch, such as the number of semitones changed by the mode manipulation. Instead, amusics showed normal sensitivity to fluctuations in energy, to pulse clarity, and to timbre differences, such as roughness. Amusics even showed sensitivity to key clarity and to large mean pitch differences in distinguishing happy from sad music. Thus, the pitch perception deficit experienced by amusic adults had only mild consequences on emotional judgments. In sum, emotional responses to music may be possible in this condition.
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http://dx.doi.org/10.1016/j.cortex.2015.06.022DOI Listing
October 2015

Cochlear implant users move in time to the beat of drum music.

Hear Res 2015 Mar 6;321:25-34. Epub 2015 Jan 6.

International Laboratory for Brain, Music and Sound Research (BRAMS), Pavillon 1420 boul. Mont Royal, University of Montreal, Case Postale 6128, Station Centre-Ville, Montreal Québec H3C 3J7, Canada; Department of Psychology, University of Montreal, C.P. 6128, Succursale Centre-Ville, Montréal, Québec H3C 3J7, Canada. Electronic address:

Cochlear implant users show a profile of residual, yet poorly understood, musical abilities. An ability that has received little to no attention in this population is entrainment to a musical beat. We show for the first time that a heterogeneous group of cochlear implant users is able to find the beat and move their bodies in time to Latin Merengue music, especially when the music is presented in unpitched drum tones. These findings not only reveal a hidden capacity for feeling musical rhythm through the body in the deaf and hearing impaired population, but illuminate promising avenues for designing early childhood musical training that can engage implanted children in social musical activities with benefits potentially extending to non-musical domains.
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http://dx.doi.org/10.1016/j.heares.2014.12.007DOI Listing
March 2015

Population pharmacokinetic analysis of dutogliptin, a selective dipeptidyl peptidase-4 inhibitor.

Clin Pharmacol Drug Dev 2014 07 10;3(4):297-304. Epub 2014 Feb 10.

Phenomix Corporation, San Diego, CA, USA.

Dutogliptin is a selective dipeptidyl peptidase-4 inhibitor shown to be efficacious and safe in patients with type 2 diabetes mellitus (T2DM). Population pharmacokinetic (PK) analysis of dutogliptin was performed based on data collected in 561 healthy subjects and patients with T2DM enrolled in Phase I and II studies to assess sources of variability and support dosing rationale. The effect of extrinsic (formulations, fed/fasting conditions, potential drug-drug interaction with metformin) and intrinsic (baseline characteristics, markers of renal function, renal impairment category, and disease status) covariates was evaluated using non-linear mixed effect modeling. Plasma concentrations of dutogliptin were best fitted with a two-compartment model with a first-order rate constant of absorption (Ka) and a lag time. No differences were observed between healthy subjects and patients with T2DM. Apparent clearance (CL/F) and terminal elimination half-life of dutogliptin were 176 L/h and 12.2 hours, respectively. Typical CL/F values in patients with mild and moderate renal impairment were 121 and 79 L/h, respectively. No drug-drug interaction was observed with metformin. These results suggest that a reduction in dosing from 400 to 200 mg daily is warranted in T2DM patients with moderate renal impairment. No dose adjustments were deemed necessary for other evaluated patient characteristics and coadministration with metformin.
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http://dx.doi.org/10.1002/cpdd.87DOI Listing
July 2014

Amusic does not mean unmusical: beat perception and synchronization ability despite pitch deafness.

Cogn Neuropsychol 2013 ;30(5):311-31

a International Laboratory for Brain , Music and Sound Research (BRAMS), University of Montreal , Montreal , QC , Canada.

Pitch deafness, the most commonly known form of congenital amusia, refers to a severe deficit in musical pitch processing (i.e., melody discrimination and recognition) that can leave time processing--including rhythm, metre, and "feeling the beat"--preserved. In Experiment 1, we show that by presenting musical excerpts in nonpitched drum timbres, rather than pitched piano tones, amusics show normal metre recognition. Experiment 2 reveals that body movement influences amusics' interpretation of the beat of an ambiguous drum rhythm. Experiment 3 and a subsequent exploratory study show an ability to synchronize movement to the beat of popular dance music and potential for improvement when given a modest amount of practice. Together the present results are consistent with the idea that rhythm and beat processing are spared in pitch deafness--that is, being pitch-deaf does not mean one is beat-deaf. In the context of drum music especially, amusics can be musical.
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http://dx.doi.org/10.1080/02643294.2013.863183DOI Listing
April 2014

Differential Pharmacokinetics of Ganitumab in Patients With Metastatic Pancreatic Cancer Versus Other Advanced Solid Cancers.

Clin Pharmacol Drug Dev 2013 Oct 26;2(4):367-78. Epub 2013 Aug 26.

Amgen Inc., Thousand Oaks, CA, USA.

Ganitumab is an investigational, fully human monoclonal antibody antagonist of the insulin-like growth factor-1 receptor (IGF1R) that has shown trends towards improved progression-free survival and overall survival in a phase 2 pancreatic cancer clinical trial. To characterize ganitumab pharmacokinetics (PK) and identify factors affecting PK, ganitumab serum concentration data from three clinical trials were analyzed. The PK of ganitumab as monotherapy and in combination with gemcitabine in patients with pancreatic or non-pancreatic cancer were assessed with a non-linear mixed-effect model. We found that ganitumab exhibited linear and time-invariant kinetics. A two-compartment model adequately described data over a dose range of 1-20 mg/kg with good predictive capability. Typical clearance and central volume of distribution values were 1.7- and 1.3-fold higher, respectively, in patients with pancreatic cancer than in patients with other advanced solid cancers, resulting in lower ganitumab exposure. Covariate analysis was used to evaluate effects of cancer type, gemcitabine coadministration, clinical study, demographics, and laboratory values on ganitumab PK. Pancreatic cancer type was the most significant covariate on clearance along with weight, albumin, and serum creatinine. Gemcitabine coadministration did not affect ganitumab clearance. Thus, disease state can significantly affect PK and should be considered when selecting the clinically effective dose.
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http://dx.doi.org/10.1002/cpdd.48DOI Listing
October 2013

A novel tool for evaluating children's musical abilities across age and culture.

Front Syst Neurosci 2013 10;7:30. Epub 2013 Jul 10.

Department of Psychology, International Laboratory of Brain, Music, and Sound Research, University of Montreal Montreal, QC, Canada.

THE PRESENT STUDY INTRODUCES A NOVEL TOOL FOR ASSESSING MUSICAL ABILITIES IN CHILDREN: The Montreal Battery of Evaluation of Musical Abilities (MBEMA). The battery, which comprises tests of memory, scale, contour, interval, and rhythm, was administered to 245 children in Montreal and 91 in Beijing (Experiment 1), and an abbreviated version was administered to an additional 85 children in Montreal (in less than 20 min; Experiment 2). All children were 6-8 years of age. Their performance indicated that both versions of the MBEMA are sensitive to individual differences and to musical training. The sensitivity of the tests extends to Mandarin-speaking children despite the fact that they show enhanced performance relative to French-speaking children. Because this Chinese advantage is not limited to musical pitch but extends to rhythm and memory, it is unlikely that it results from early exposure to a tonal language. In both cultures and versions of the tests, amount of musical practice predicts performance. Thus, the MBEMA can serve as an objective, short and up-to-date test of musical abilities in a variety of situations, from the identification of children with musical difficulties to the assessment of the effects of musical training in typically developing children of different cultures.
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http://dx.doi.org/10.3389/fnsys.2013.00030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707384PMC
July 2013

Pharmacokinetic and pharmacodynamic modeling to determine the dose of ST-246 to protect against smallpox in humans.

Antimicrob Agents Chemother 2013 Mar 17;57(3):1136-43. Epub 2012 Dec 17.

SIGA Technologies, Corvallis, OR, USA.

Although smallpox has been eradicated, the United States government considers it a "material threat" and has funded the discovery and development of potential therapeutic compounds. As reported here, the human efficacious dose for one of these compounds, ST-246, was determined using efficacy studies in nonhuman primates (NHPs), together with pharmacokinetic and pharmacodynamic analysis that predicted the appropriate dose and exposure levels to provide therapeutic benefit in humans. The efficacy analysis combined the data from studies conducted at three separate facilities that evaluated treatment following infection with a closely related virus, monkeypox virus (MPXV), in a total of 96 NHPs. The effect of infection on ST-246 pharmacokinetics in NHPs was applied to humans using population pharmacokinetic models. Exposure at the selected human dose of 600 mg is more than 4-fold higher than the lowest efficacious dose in NHPs and is predicted to provide protection to more than 95% of the population.
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http://dx.doi.org/10.1128/AAC.00959-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591874PMC
March 2013

Relationship between prenatal exposure to polychlorinated biphenyls and birth weight: a systematic analysis of published epidemiological studies through a standardization of biomonitoring data.

Regul Toxicol Pharmacol 2012 Oct 23;64(1):161-76. Epub 2012 Jun 23.

Département de santé environnementale et santé au travail, Chaire d'analyse et de gestion des risques toxicologiques and Institut de recherche en santé publique de l'Université de Montréal (IRSPUM), Faculté de Médecine, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.

Impact of prenatal PCB exposure on birth weight was investigated in various children cohorts and findings of published studies show inconsistencies. Because a direct comparison of results obtained from different studies remains difficult, the "biological concentration-birth weight" relationship is not clearly established. The objective of this research was to perform a systematic analysis of published epidemiological data to reassess relationship between prenatal PCB exposure and low birth weight, using toxicokinetic considerations and a novel standardization procedure of biological concentration data across studies. A systematic analysis of 20 epidemiological studies published up to 2011 on this topic was conducted. This was achieved through a standardization of reported exposure data in terms of total PCBs per kg of lipids in maternal plasma. Systematic analysis of the "standardized biological concentration-birth weight" relationship across studies was then conducted through the application of Hill criteria. Combining results of all 20 reviewed studies did not allow to establish an association between prenatal exposure to PCBs at the described levels and abnormal birth weight (<2500g). Our approach provides a framework for the use of published data to establish "PCB biological concentration-response" relationships.
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http://dx.doi.org/10.1016/j.yrtph.2012.06.007DOI Listing
October 2012

Statistical learning of speech, not music, in congenital amusia.

Ann N Y Acad Sci 2012 Apr;1252:361-7

International Laboratory of Brain, Music and Sound Research, Department of Psychology, University of Montreal, Montreal, Quebec, Canada.

The acquisition of both speech and music uses general principles: learners extract statistical regularities present in the environment. Yet, individuals who suffer from congenital amusia (commonly called tone-deafness) have experienced lifelong difficulties in acquiring basic musical skills, while their language abilities appear essentially intact. One possible account for this dissociation between music and speech is that amusics lack normal experience with music. If given appropriate exposure, amusics might be able to acquire basic musical abilities. To test this possibility, a group of 11 adults with congenital amusia, and their matched controls, were exposed to a continuous stream of syllables or tones for 21-minute. Their task was to try to identify three-syllable nonsense words or three-tone motifs having an identical statistical structure. The results of five experiments show that amusics can learn novel words as easily as controls, whereas they systematically fail on musical materials. Thus, inappropriate musical exposure cannot fully account for the musical disorder. Implications of the results for the domain specificity of statistical learning are discussed.
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http://dx.doi.org/10.1111/j.1749-6632.2011.06429.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644481PMC
April 2012

Priming paradigm reveals harmonic structure processing in congenital amusia.

Cortex 2012 Sep 13;48(8):1073-8. Epub 2012 Jan 13.

CNRS, UMR5292, INSERM, U1028, Lyon Neuroscience Research Center, Auditory Cognition and Psychoacoustics Team, France.

Deficits for pitch structure processing in congenital amusia has been mostly reported for melodic stimuli and explicit judgments. The present study investigated congenital amusia with harmonic stimuli and a priming task. Amusic and control participants performed a speeded phoneme discrimination task on sung chord sequences. The target phoneme was sung either on a functionally important chord (tonic chord, referred to as "related target") or a less important one (subdominant chord, referred to as "less-related target"). Correct response times were faster when the target phoneme was sung on tonic chords rather than on subdominant chords, and this effect was less pronounced, albeit significant, in amusic participants. These data report for the first time a deficit in congenital amusia for chord processing, but also provide evidence that, despite this deficit, amusic individuals have internalized sophisticated syntactic-like functions of chords in the Western tonal musical system. This finding suggests that thanks to this musical knowledge, amusic individuals could develop expectancies for musical events, and, presumably, follow the tension-relaxation schemas in Western tonal music, which also influence emotional responses to music.
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http://dx.doi.org/10.1016/j.cortex.2012.01.001DOI Listing
September 2012

Congenital Amusia (or Tone-Deafness) Interferes with Pitch Processing in Tone Languages.

Front Psychol 2011 17;2:120. Epub 2011 Jun 17.

CNRS, UMR5292; INSERM, U1028; Lyon Neuroscience Research Center, Auditory Cognition and Psychoacoustics Team Lyon, France.

Congenital amusia is a neurogenetic disorder that affects music processing and that is ascribed to a deficit in pitch processing. We investigated whether this deficit extended to pitch processing in speech, notably the pitch changes used to contrast lexical tones in tonal languages. Congenital amusics and matched controls, all non-tonal language speakers, were tested for lexical tone discrimination in Mandarin Chinese (Experiment 1) and in Thai (Experiment 2). Tones were presented in pairs and participants were required to make same/different judgments. Experiment 2 additionally included musical analogs of Thai tones for comparison. Performance of congenital amusics was inferior to that of controls for all materials, suggesting a domain-general pitch-processing deficit. The pitch deficit of amusia is thus not limited to music, but may compromise the ability to process and learn tonal languages. Combined with acoustic analyses of the tone material, the present findings provide new insights into the nature of the pitch-processing deficit exhibited by amusics.
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http://dx.doi.org/10.3389/fpsyg.2011.00120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3119887PMC
July 2011

Impaired recognition of musical emotions and facial expressions following anteromedial temporal lobe excision.

Cortex 2011 Oct 25;47(9):1116-25. Epub 2011 May 25.

International Laboratory for Brain, Music and Sound Research (BRAMS), University of Montreal, Canada.

We have shown that an anteromedial temporal lobe resection can impair the recognition of scary music in a prior study (Gosselin et al., 2005). In other studies (Adolphs et al., 2001; Anderson et al., 2000), similar results have been obtained with fearful facial expressions. These findings suggest that scary music and fearful faces may be processed by common cerebral structures. To assess this possibility, we tested patients with unilateral anteromedial temporal excision and normal controls in two emotional tasks. In the task of identifying musical emotion, stimuli evoked either fear, peacefulness, happiness or sadness. Participants were asked to rate to what extent each stimulus expressed these four emotions on 10-point scales. The task of facial emotion included morphed stimuli whose expression varied from faint to more pronounced and evoked fear, happiness, sadness, surprise, anger or disgust. Participants were requested to select the appropriate label. Most patients were found to be impaired in the recognition of both scary music and fearful faces. Furthermore, the results in both tasks were correlated, suggesting a multimodal representation of fear within the amygdala. However, inspection of individual results showed that recognition of fearful faces can be preserved whereas recognition of scary music can be impaired. Such a dissociation found in two cases suggests that fear recognition in faces and in music does not necessarily involve exactly the same cerebral networks and this hypothesis is discussed in light of the current literature.
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http://dx.doi.org/10.1016/j.cortex.2011.05.012DOI Listing
October 2011

Born to dance but beat deaf: a new form of congenital amusia.

Neuropsychologia 2011 Apr 21;49(5):961-969. Epub 2011 Feb 21.

International Laboratory for Brain, Music and Sound Research (BRAMS), Pavillon 1420 boul. Mont Royal. Université de Montréal, Case Postale 6128, Station Centre-Ville, Montreal, Québec, Canada H3C 3J7; Department of Psychology, University of Montreal, C.P. 6128, Succursale Centre-Ville, Montréal, Québec, Canada H3C 3J7. Electronic address:

Humans move to the beat of music. Despite the ubiquity and early emergence of this response, some individuals report being unable to feel the beat in music. We report a sample of people without special training, all of whom were proficient at perceiving and producing the musical beat with the exception of one case ("Mathieu"). Motion capture and psychophysical tests revealed that people synchronized full-body motion to music and detected when a model dancer was not in time with the music. In contrast, Mathieu failed to period- and phase-lock his movement to the beat of most music pieces, and failed to detect most asynchronies of the model dancer. Mathieu's near-normal synchronization with a metronome suggests that the deficit concerns beat finding in the context of music. These results point to time as having a distinct neurobiological origin from pitch in music processing.
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http://dx.doi.org/10.1016/j.neuropsychologia.2011.02.002DOI Listing
April 2011

The amusic brain: lost in music, but not in space.

PLoS One 2010 Apr 21;5(4):e10173. Epub 2010 Apr 21.

Université Lyon 1, Lyon, France.

Congenital amusia is a neurogenetic disorder of music processing that is currently ascribed to a deficit in pitch processing. A recent study challenges this view and claims the disorder might arise as a consequence of a general spatial-processing deficit. Here, we assessed spatial processing abilities in two independent samples of individuals with congenital amusia by using line bisection tasks (Experiment 1) and a mental rotation task (Experiment 2). Both amusics and controls showed the classical spatial effects on bisection performance and on mental rotation performance, and amusics and controls did not differ from each other. These results indicate that the neurocognitive impairment of congenital amusia does not affect the processing of space.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0010173PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858073PMC
April 2010

Identification of Changes along a Continuum of Speech Intonation is Impaired in Congenital Amusia.

Front Psychol 2010 27;1:236. Epub 2010 Dec 27.

BRAMS Laboratory, Department of Psychology, University of Montreal Montreal, QC, Canada.

A small number of individuals have severe musical problems that have neuro-genetic underpinnings. This musical disorder is termed "congenital amusia," an umbrella term for lifelong musical disabilities that cannot be attributed to deafness, lack of exposure, or brain damage after birth. Amusics seem to lack the ability to detect fine pitch differences in tone sequences. However, differences between statements and questions, which vary in final pitch, are well perceived by most congenital amusic individuals. We hypothesized that the origin of this apparent domain-specificity of the disorder lies in the range of pitch variations, which are very coarse in speech as compared to music. Here, we tested this hypothesis by using a continuum of gradually increasing final pitch in both speech and tone sequences. To this aim, nine amusic cases and nine matched controls were presented with statements and questions that varied on a pitch continuum from falling to rising in 11 steps. The sentences were either naturally spoken or were tone sequence versions of these. The task was to categorize the sentences as statements or questions and the tone sequences as falling or rising. In each case, the observation of an S-shaped identification function indicates that amusics can accurately identify unambiguous examples of statements and questions but have problems with fine variations between these endpoints. Thus, the results indicate that a deficient pitch perception might compromise music, not because it is specialized for that domain but because music requirements are more fine-grained.
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http://dx.doi.org/10.3389/fpsyg.2010.00236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153840PMC
November 2011

Determination of carboxyhaemoglobin in humans following low-level exposures to carbon monoxide.

Inhal Toxicol 2009 Nov;21(13):1077-91

Pharsight, Montreal, Quebec, Canada.

This study proposes to estimate carboxyhaemoglobin (COHb) levels in the blood of men and women of various ages exposed to common concentrations of carbon monoxide (CO) using a model with only one free parameter while integrating alveoli-blood and blood-tissue CO exchanges. The model retained is essentially that of Coburn et al. (1965) with two important additions: an alveoli compartment for the dynamics of CO exchanges between alveoli and blood, and a compartment for the significant amounts of CO bound to heme proteins in extravascular spaces. The model was validated by comparing its simulations with various published data sets for the COHb time profiles of volunteers exposed to known CO concentrations. Once the model was validated, it was used to simulate various situations of interest for their impact on public health. This approach yields reliable estimations of the time profiles of COHb levels resulting from different levels of CO exposure over various periods of time and under various conditions (resting, exercise, working, and smoking). The non-linear kinetics of CO, observed experimentally, were correctly reproduced by simulations with the model. Simulations were also carried out iteratively to determine the exposure times and CO concentrations in ambient air needed to reach the maximum levels of COHb recommended by Health Canada, the U.S. Environmental Protection Agency (EPA), and the World Health Organisation (WHO) for each age group of the general population. The lowest CO concentrations leading to maximum COHb levels of 1.5, 2, and 2.5% were determined.
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http://dx.doi.org/10.3109/08958370902744848DOI Listing
November 2009