Biomedical subjects

Julien Doyon

Publications and source records attributed to Julien Doyon.

At least 19 recordsLinked to original sources

PubMed2006

CORSICA: correction of structured noise in fMRI by automatic identification of ICA components.

When applied to functional magnetic resonance imaging (fMRI) data, spatial independent component analysis (sICA), a data-driven technique that addresses the blind source separation problem, seems able to extract components specifically related to physiological noise and brain movements. These components should be removed from the data to achieve structured noise reduction and improve any subsequent detection and analysis of signal fluctuations related to neural activity. We propose a new automatic method called CORSICA (CORrection of Structured noise using spatial Independent Component Analysis) to identify the components related to physiological noise, using prior information on the spatial localization of the main physiological fluctuations in fMRI data. As opposed to existing spectral priors, which may be subject to aliasing effects for long-TR data sets (typically acquired with TR >1 s), such spatial priors can be applied to fMRI data, regardless of the TR of the acquisitions. By comparing the proposed automatic selection to a manual selection performed visually by a human operator, we first show that CORSICA is able to identify the noise-related components for long-TR data with a high sensitivity and a specificity of 1. On short-TR data sets, we validate that the proposed method of noise reduction allows a substantial improvement of the signal-to-noise ratio evaluated at the cardiac and respiratory frequencies, even in the gray matter, while preserving the main fluctuations related to neural activity.

Biometry↗

PubMed2006

Partial correlation for functional brain interactivity investigation in functional MRI.

Examination of functional interactions through effective connectivity requires the determination of three distinct levels of information: (1) the regions involved in the process and forming the spatial support of the network, (2) the presence or absence of interactions between each pair of regions, and (3) the directionality of the existing interactions. While many methods exist to select regions (Step 1), very little is available to complete Step 2. The two main methods developed so far, structural equation modeling (SEM) and dynamical causal modeling (DCM), usually require precise prior information to be used, while such information is sometimes lacking. Assuming that Step 1 was successfully completed, we here propose a data-driven method to deal with Step 2 and extract functional interactions from fMRI datasets through partial correlations. Partial correlation is more closely related to effective connectivity than marginal correlation and provides a convenient graphical representation for functional interactions. As an instance of brain interactivity investigation, we consider how simple hand movements are processed by the bihemispheric cortical motor network. In the proposed framework, Bayesian analysis makes it possible to estimate and test the partial statistical dependencies between regions without any prior model on the underlying functional interactions. We demonstrate the interest of this approach on real data.

Cerebral Cortex↗

PubMed2006

Functional role of the basal ganglia in the planning and execution of actions.

OBJECTIVE: Recent studies of functional brain imaging have shown the involvement of the basal ganglia in executive processes such as planning and set-shifting. However, the specific contributions of the striatum in those processes remain unknown. This study aimed to test the hypothesis that the caudate nucleus is primarily involved in the preparation of a novel action and not in set-shifting per se. METHODS: In the present event-related functional magnetic resonance imaging (fMRI) study, a new task was developed that permitted, for the first time, to distinguish between shifts in classification when the rule is implicitly given by the task from shifts that require cognitive comparison and planning. RESULTS: Significantly increased activity in the caudate nucleus and the putamen was observed only in conditions in which cognitive planning was required to perform a set-shift, whereas significant activation was seen in the subthalamic nucleus (another region of the basal ganglia) in all shifting conditions whether or not planning was required. INTERPRETATION: We suggest that the caudate nucleus and the putamen are particularly important, respectively, in the planning and the execution of a self-generated novel action, whereas the subthalamic nucleus may be required when a new motor program is solicited independently of the choice of strategy.

Adolescent↗

PubMed2006

Elucidation of the absolute configuration of JNJ-27553292, a CCR2 receptor antagonist, by vibrational circular dichroism analysis of two precursors.

The absolute configurations of two precursors, that is, 1-(3',4'-dichlorophenyl)-propanol and 1-(3',4'-dichlorophenyl)-propanamine, of a potent 2-mercapto-imidazole CCR-2 receptor antagonist, JNJ-27553292, were determined using vibrational circular dichroism. As a consequence, the absolute configuration of the antagonist itself was also determined. The two precursor compounds were subjected to a thorough conformational analysis and rotational strengths were calculated at the B3LYP/cc-pVTZ level of theory. Based on these data, vibrational circular dichroism spectra were simulated, which in turn were compared with experimental spectra. Agreement between the spectra allowed the assignment of the absolute configuration, which is in agreement with the proposed configuration based on stereospecific reactions on similar compounds.

Circular Dichroism↗

PubMed2006

Effects of environmental demands on locomotion after traumatic brain injury.

OBJECTIVE: To determine the effects of increasingly demanding environments related to simultaneous visual tasks and physical obstructions on the locomotor ability of people with traumatic brain injury (TBI). DESIGN: Group comparison study. SETTING: Gait analysis laboratory within a postacute rehabilitation facility. PARTICIPANTS: Volunteer sample of 9 people (8 men, 1 woman; age, 39.3+/-13.0y) with moderate to severe TBI and a comparison group of 9 subjects without neurologic problems matched for age and sex (8 men, 1 woman; age, 39.7+/-12.3y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Reading times for the Stroop bar and Stroop word tasks, walking speeds, stride lengths, and obstacle clearance margin. RESULTS: The TBI group was slower than the control group in performing the Stroop bar task during sitting (P=.002), and while avoiding the narrow obstacle (P=.05), and in performing the Stroop word task while avoiding the wide obstacle (P=.019). Despite their relatively normal gait speeds on level ground, subjects with TBI walked more slowly than control subjects for the narrow (P=.024) and the wide (P=.019) obstacle conditions and for the most complex dual task (P=.042). Greater lead-limb clearance margins were observed for the TBI group than for control subjects for all conditions whereas no differences were found for the trail limb except at the far end of the wide obstacle. CONCLUSIONS: Despite their good recovery of locomotor function, with respect to normal level walking speeds and ability to avoid obstacles, subjects with moderate and severe TBI showed residual deficits in relation to greater difficulties in dealing with environments that challenge their locomotor and attentional abilities. The use of such naturally based dual tasks may help identify some of the environmental obstructions to social participation after TBI.

Adult↗

PubMed2006

Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases.

Rapid-eye-movement (REM) sleep behaviour disorder (RBD) is characterised by loss of muscular atonia and prominent motor behaviours during REM sleep. RBD can cause sleep disruption and severe injuries for the patient or bed partner. The disorder is strongly associated with neurodegenerative diseases, such as multiple-system atrophy, Parkinson's disease, dementia with Lewy bodies, and progressive supranuclear palsy. In many cases, the symptoms of RBD precede other symptoms of these neurodegenerative disorders by several years. Furthermore, several recent studies have shown that RBD is associated with abnormalities of electroencephalographic activity, cerebral blood flow, and cognitive, perceptual, and autonomic functions. RBD might be a stage in the development of neurodegenerative disorders and increased awareness of this could lead to substantial advances in knowledge of mechanisms, diagnosis, and treatment of neurodegenerative disorders.

Brain↗

PubMed2005

Identification of large-scale networks in the brain using fMRI.

Cognition is thought to result from interactions within large-scale networks of brain regions. Here, we propose a method to identify these large-scale networks using functional magnetic resonance imaging (fMRI). Regions belonging to such networks are defined as sets of strongly interacting regions, each of which showing a homogeneous temporal activity. Our method of large-scale network identification (LSNI) proceeds by first detecting functionally homogeneous regions. The networks of functional interconnections are then found by comparing the correlations among these regions against a model of the correlations in the noise. To test the LSNI method, we first evaluated its specificity and sensitivity on synthetic data sets. Then, the method was applied to four real data sets with a block-designed motor task. The LSNI method correctly recovered the regions whose temporal activity was locked to the stimulus. In addition, it detected two other main networks highly reproducible across subjects, whose activity was dominated by slow fluctuations (0-0.1 Hz). One was located in medial and dorsal regions, and mostly overlapped the "default" network of the brain at rest [Greicius, M.D., Krasnow, B., Reiss, A.L., Menon, V., 2003. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences of the U.S.A. 100, 253-258]; the other was composed of lateral frontal and posterior parietal regions. The LSNI method we propose allows to detect in an exploratory and systematic way all the regions and large-scale networks activated in the working brain.

Adult↗

PubMed2005

Distinct basal ganglia territories are engaged in early and advanced motor sequence learning.

In this study, we used functional MRI (fMRI) at high field (3T) to track the time course of activation in the entire basal ganglia circuitry, as well as other motor-related structures, during the explicit learning of a sequence of finger movements over a month of training. Fourteen right-handed healthy volunteers had to practice 15 min daily a sequence of eight moves using the left hand. MRI sessions were performed on days 1, 14 and 28. In both putamen, activation decreased with practice in rostrodorsal (associative) regions. In contrast, there was a significant signal increase in more caudoventral (sensorimotor) regions of the putamen. Subsequent correlation analyses between signal variations and behavioral variables showed that the error rate (movement accuracy) was positively correlated with signal changes in areas activated during early learning, whereas reaction time (movement speed) was negatively correlated with signal changes in areas activated during advanced learning stages, including the sensorimotor putamen and globus pallidus. These results suggest the possibility that motor representations shift from the associative to the sensorimotor territories of the striato-pallidal complex during the explicit learning of motor sequences, suggesting that motor skills are stored in the sensorimotor territory of the basal ganglia that supports a speedy performance.

Adult↗

PubMed2005

2-Mercaptoimidazoles, a new class of potent CCR2 antagonists.

We describe the synthesis and SAR of a new class of CCR2 antagonists based on 2-mercaptoimidazole scaffold. The initial lead 1a was optimized to the 3,4-disubstituted analogues 1p-(S) and 1q-(S), which have IC(50) values in the MCP-1 induced Ca-flux below 0.01 microM.

Calcium Signaling↗

PubMed2005

Reorganization and plasticity in the adult brain during learning of motor skills.

On the basis of brain imaging studies, Doyon and Ungerleider recently proposed a model describing the cerebral plasticity that occurs in both cortico-striatal and cortico-cerebellar systems of the adult brain during learning of new motor skilled behaviors. This theoretical framework makes several testable predictions with regards to the contribution of these neural systems based on the phase (fast, slow, consolidation, automatization, and retention) and nature of the motor learning processes (motor sequence versus motor adaptation) acquired through repeated practice. There has been recent behavioral, lesion and additional neuroimaging studies that have addressed the assumptions made in this theory that will help in the revision of this model.

Adult↗

PubMed2004

Bilateral slowing of mentally simulated actions after stroke.

The ability to mentally simulate motor actions was studied in 25 patients with stroke. The duration of imagined and executed movements of the arm and leg was compared. Both executed and imagined movements took longer with the affected limbs than with the unaffected limbs. For both tasks, the duration of movements with the unaffected limbs was longer in the imagined than in the executed conditions, indicating a lack of temporal congruence on that side. Because the temporal uncoupling was found in the limbs contralateral to the intact hemisphere, we propose that this reflects a general slowing in motor imagery that is an indirect consequence of the lesion, rather than a deficit in movement representation within the unaffected hemisphere per se.

Aged↗

PubMed2004

Neural bases of set-shifting deficits in Parkinson's disease.

Patients with Parkinson's disease (PD) exhibit impairments in several cognitive functions similar to those observed in patients with prefrontal cortex (PFC) lesions. The physiological origins of these cognitive deficits are not well documented. Two mechanisms have been proposed: disruptions in corticostriatal circuits or a deficiency in frontal dopamine. We previously used functional magnetic resonance imaging (fMRI) in young healthy subjects to separate patterns of PFC and striatum activity during distinct phases of performance of the Wisconsin Card Sorting Task, a set-shifting task that reveals deficits in patients with PD. Here, the same fMRI protocol was used in PD patients and matched controls. Decreased activation was observed in the PD group compared with the matched control group in the ventrolateral PFC when receiving negative feedback and the posterior PFC when matching after negative feedback. In controls, these prefrontal regions specifically coactivated with the striatum during those stages of task performance. In contrast, greater activation was found in the PD group compared with the matched control group in prefrontal regions, such as the posterior and the dorsolateral PFC when receiving positive or negative feedback, that were not coactivated with the striatum in controls. These results suggest that both nigrostriatal dopamine depletion and intracortical dopamine deficiency may play a role in cognitive deficits in PD, depending on the involvement of the striatum in the task at hand.

Adult↗

PubMed2004

Working memory and mental practice outcomes after stroke.

OBJECTIVE: To examine the relationship between working memory and motor improvement obtained after a single training session combining mental and physical practice. DESIGN: Before-after trial. SETTING: Laboratory of a university-affiliated research rehabilitation center. PARTICIPANTS: A sample of 12 patients with stroke and 14 age- and gender-matched healthy subjects. INTERVENTION: In a single session, patients were trained with combined mental and physical practice to increase the loading on the affected leg while standing up and sitting down. MAIN OUTCOME MEASURES: Motor improvement as measured by the percentage change in limb loading on the affected limb after training and 24 hours later (follow-up), and the relationship between working memory and percentage motor improvement. RESULTS: The loading on the affected leg was improved after training (P< .01) and at follow-up (P< .05), and working memory scores at follow-up correlated significantly (P< .004 to P< .007) with the level of improvement. The visuospatial domain yielded the strongest correlation (r= .83), followed by the verbal (r= .62) and kinesthetic (r= .59) domains. CONCLUSIONS: These results suggest that the outcome (improved limb loading) of mental rehearsal with motor imagery depends on the ability to maintain and manipulate information in working memory.

Adult↗

PubMed2004

Acquiring a cognitive skill with a new repeating version of the Tower of London task.

A computerized version of the Tower of London task was used to investigate cognitive skill learning. Thirty-six healthy volunteers were assigned to either a random condition (nonrecurring problems), or to a sequence condition in which, unbeknownst to the subjects, a repeating sequence of three problems was presented. Indices of execution, planning, and total time, as well as number of moves performed, were used to measure behavioural change. Subjects' performance improved in both conditions across blocks of practice. A distinct learning effect related to the repeating sequence was also observed. This suggests that a specific skill that reflects procedural learning of the strategies, rules, and procedures pertaining to repeating problems can develop over and above a more general skill at solving cognitive planning problems with practice.

Adolescent↗

PubMed2004

Motor-learning impairment by amantadine in healthy volunteers.

NMDA receptor antagonists impair learning and memory in animal models, presumably by inhibiting long-term potentiation in the motor cortex. Human studies are limited and restricted by the paucity of safe NMDA antagonists. Here, we investigated the contribution of glutamatergic neurotransmission to the capacity of acquiring motor-adaptation learning in humans. In a double-blind design, 200 mg of amantadine (a low-affinity NMDA receptor channel blocker) or a matching placebo were given orally to groups of 14 and 13 human healthy young volunteers, respectively. Blood samples were collected 3 h after treatment to assay plasma concentrations, and the subjects were then tested using a motor-adaptation paradigm consisting of an eight-target-pointing task. To rule out drug-related generalized impairments such sedation, tests measuring motor dexterity and attention were also administered pre- and post-treatment. Comparison of the mean performance levels on the motor-adaptation task revealed that subjects in the amantadine group performed at a lower level than those in the placebo group, but this difference did not reach significance. Interestingly, however, despite plasma amantadine concentrations being relatively low, ranging from 2.09 to 4.74 microM (mean=3.3 microM), they nevertheless correlated negatively with motor learning. Furthermore, when the amantadine group was divided into low-performance and high-performance subgroups, subjects in the former subgroup displayed mean amantadine concentrations 36% higher than the latter subgroup, and performed significantly worser than the placebo group. No change in performance was found on the motor-dexterity and attention tests. Altogether, our results lend support to the hypothesis that normal NMDA receptor function is necessary for the acquisition of motor adaptation.

Adaptation, Psychological↗

PubMed2004

The efficacy of combined physical and mental practice in the learning of a foot-sequence task after stroke: a case report.

OBJECTIVE: To investigate the effect of mental practice on the learning of a sequential task for the lower limb in a patient with a hemiparesis resulting from a stroke. DESIGN: A single-case study. SETTING: Research laboratory of a university-affiliated rehabilitation center. PATIENT: A right-handed 38-year-old man who had suffered a left hemorrhagic subcortical stroke 4 months prior. INTERVENTION: The patient practiced a serial response time task with the lower limb in 3 distinct training phases over a period of 5 weeks: 2 weeks of physical practice, 1 week of combined physical and mental practice, and then 2 weeks of mental practice alone. MAIN OUTCOME MEASURES: Performance on the task measured through errors and response times. Imagery abilities measured through questionnaires. RESULTS: The patient's average response time improved significantly during the 1st 5 days of physical practice (26%) but then failed to show further improvement during the following week of physical practice. The combination of mental and physical practice during the 3rd week yielded additional improvement (10.3%), whereas the following 2 weeks of mental practice resulted in a marginal increase in performance (2.2%). CONCLUSION: The findings show that mental practice, when combined with physical practice, can improve the performance of a sequential motor skill in people who had a stroke, and suggest that mental practice could play a role in the retention of newly acquired abilities.

Adult↗

PubMed2004

Training mobility tasks after stroke with combined mental and physical practice: a feasibility study.

This study examines the potential of using mental practice (MP) to promote the learning of 2 mobility tasks in persons with stroke. Twelve patients were trained with MP to increase the loading of the affected limb while standing up from a chair and sitting down. Vertical forces were recorded using force plates under each foot and the chair. Changes in the loading of the affected limb and in task duration, immediately after 1 training session and 24 h later, served as outcomes. After training, the loading of the affected limb had increased (P < 0.001) during standing up (16.2%) and sitting down (17.9%), and the improvement remained significant 24 h later, indicating a learning effect. In contrast, the duration of the performance did not change with training. The results indicate that, in the early stage of learning with MP, changes in limb-loading strategies are a more sensitive measure of performance than is speed.

Adult↗

PubMed2003

Brain activations during motor imagery of locomotor-related tasks: a PET study.

Positron emission tomography (PET) was used to study the involvement of supraspinal structures in human locomotion. Six right-handed adults were scanned in four conditions while imagining locomotor-related tasks in the first person perspective: Standing (S), Initiating gait (IG), Walking (W) and Walking with obstacles (WO). When these conditions were compared to a rest (control) condition to identify the neural structures involved in the imagination of locomotor-related tasks, the results revealed a common pattern of activations, which included the dorsal premotor cortex and precuneus bilaterally, the left dorsolateral prefrontal cortex, the left inferior parietal lobule, and the right posterior cingulate cortex. Additional areas involving the pre-supplementary motor area (pre-SMA), the precentral gyrus, were activated during conditions that required the imagery of locomotor movements. Further subtractions between the different locomotor conditions were then carried out to determine the cerebral regions associated with the simulation of increasingly complex locomotor functions. These analyses revealed increases in rCBF activity in the left cuneus and left caudate when the W condition was compared to the IG condition, suggesting that the basal ganglia plays a role in locomotor movements that are automatic in nature. Finally, subtraction of the W from the WO condition yielded increases in activity in the precuneus bilaterally, the left SMA, the right parietal inferior cortex and the left parahippocampal gyrus. Altogether, the present findings suggest that higher brain centers become progressively engaged when demands of locomotor tasks require increasing cognitive and sensory information processing.

Adult↗