Léon Tremblay - Academia.edu (original) (raw)
Papers by Léon Tremblay
The basal ganglia are widely known to play a role in appetitive rewarding behavior. Imaging and p... more The basal ganglia are widely known to play a role in appetitive rewarding behavior. Imaging and psychiatric clinical studies have provided evidence that the basal ganglia, especially the limbic territory, also play a role in aversive information processing. Inappropriate aversive information processing could induce an anxious state, which is widely observed in a variety of psychiatric diseases. Here, we describe how the ventral striatum and the ventral pallidum, two parts of the limbic circuit in the basal ganglia, are involved in negative motivational behavior, which can be linked with the control of approach/avoidance behavior in a normal context and with the expression of anxiety-related disorders. The disturbance of this pathway would induce not only psychiatric symptoms, but also abnormal value-based decision-making.
PubMed, 2002
Parkinson's disease is a neurodegenerative condition who is related to a large loss of nigral dop... more Parkinson's disease is a neurodegenerative condition who is related to a large loss of nigral dopaminergic neurons leading to a depletion of dopamine in the striatum. Experimental research is required in order to increase our knowledge on the cellular mechanism and functional consequences of this degenerative process. These models allow investigations of new therapeutics in order to improve the treatment of patients or to test new drugs able to protect any remaining dopaminergic neurons. It is relatively easy to obtain animal models of this disease since the target structure and the neuronal population are clearly defined. Two neurotoxic compounds are available for inducing animal models of Parkinson's disease, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A new one, rotenone, requires further investigations. Each of the neurotoxic compounds requires a specific protocol which can be used either with rodents or non-human primates. Progressive lesioning, using MPTP on green african monkeys (Cercopithecus aethiops sabaeus) provides the most reliable model of the idiopathic disease.
Bulletin De L Academie Nationale De Medecine, Oct 1, 2010
Considerable progress has been made in the pathophysiology of Parkinson's disease in the last... more Considerable progress has been made in the pathophysiology of Parkinson's disease in the last 25 years. To better understand the nature and diversity of the symptoms of Parkinson's disease it is necessary to integrate clinical knowledge on 1) the role of dopamine, 2) the anatomical and functional organization of the basal ganglia, and 3) the dysfunctions observed in MPTP-treated monkeys. This article reviews the principal discoveries in these three research fields and their contribution to our understanding of the pathophysiology of Parkinson's disease.
Neuropsychopharmacology, Mar 10, 2021
INTRODUCTION: Delayed gastric emptying (DGE) causes substantial morbidity after pancreaticoduoden... more INTRODUCTION: Delayed gastric emptying (DGE) causes substantial morbidity after pancreaticoduodenectomy (PD). The objective of this study was to develop a DGE risk calculator using preoperatively and intraoperatively known variables to identify high-risk patients at the time of the index pancreatic resection. METHODS: The 2015 NSQIP Targeted Pancreatectomy Dataset was used to identify 2,357 patients who underwent PD. An adjusted logistic regression analysis was performed to identify preoperative and intraoperative variables independently associated with DGE. A DGE risk calculator was constructed using these variables as well as a priori-selected characteristics that have been reported to be associated with DGE. External validation was performed using the 2016 NSQIP data set of 2,754 patients. Discrimination and calibration were assessed by receiver operating characteristic curves, the Hosmer-Lemeshow test, and calibration plots).
Elsevier eBooks, 2009
In case of many decisions based on sensory information, the sensory stimulus or its neural repres... more In case of many decisions based on sensory information, the sensory stimulus or its neural representation are noisy. This chapter reviews theories proposing that the brain implements statistically optimal strategies for decision making on the basis of noisy information. These strategies maximize the accuracy and speed of decisions, as well as the rate of receiving rewards for correct choices. The chapter first reviews computational models of cortical decision circuits that can optimally perform choices between two alternatives. Then, it describes a model of cortico-basal-ganglia circuit that implements the optimal strategy for choice between multiple alternatives. Finally, it shows how the basal ganglia may modulate decision processes in the cortex, allowing cortical neurons to represent the probabilities of alternative choices being correct. For each set of theories their predictions are compared with existing experimental data.
Annales pharmaceutiques françaises, Sep 1, 2009
Abnormal movements and behavioral disorders are characteristic manifestations observed in certain... more Abnormal movements and behavioral disorders are characteristic manifestations observed in certain neuropsychiatric diseases such as Tourette's syndrome or Huntington Disease. Together with brain imaging findings, the clinical data could suggest a relationship with basal ganglia dysfunction. In the first part of this review, we recall the anatomic relationships existing, via segregated cortico-cortical circuits, between these structures and the cortical areas having motor and cognitive or motivational-emotional attributes. This structure suggests that in pathologies like Parkinson's or Huntington disease cognitive and motivational-emotional disorders as well motor disturbances could be related to lesions or dysfunctions involving individual or combined zones of the basal ganglia. The second part of the paper focuses on a description of the various methodologies used to explore these relationships: behavioral, anatomic and brain imaging methods are used in non-human primate models in order to reproduce motor and behavioral disturbances and to determine the neuronal circuits involved. Microinjection of bicucullin into the external globus pallidus has been found to induce localized and reversible neuronal activation. Abnormal movements can be obtained from the motor territory of the external globus pallidus whereas hyperactivity with attentional deficit or stereotypies have been obtained from the associative or limbic territory of the same structure. In the striatum, the same pharmacological activation can induce either abnormal movements from motor and associative functional territories or behavioural changes with hyperactivity or, on the contrary, hypoactivity from associative functional territory with stereotyped behavior and sexual manifestations when the microinjections were done in the limbic striatum. Anatomic studies as well as brain imaging using PET confirm the involvement of segregated anatomic pathways through the basal ganglia in behavioral as well as motor disorders.
Neuroscience Research, 2010
s / Neuroscience Research 68S (2010) e223–e334 e265 P2-g16 Comparison of movement-related neurona... more s / Neuroscience Research 68S (2010) e223–e334 e265 P2-g16 Comparison of movement-related neuronal activity recorded from six different areas in the frontal cortex of macaques Yoshihisa Nakayama , Tomoko Yamagata, Nariko Arimura, Jun Tanji, Eiji Hoshi Brain Sci Inst, Tamagawa Univ, Tokyo A hallmark of the frontal cortex (FC) is the existence of marked changes in activity in and around the execution of arm movements. The activity has been called the movement-related activity, and has been considered to play a crucial role in executing coordinated voluntary motor acts. However, it still remains unclear what aspects are common and what aspects are different among the movement-related activity widely found in each area of the FC. This study investigated this issue by directly comparing neuronal activity recorded from multiple areas in FC of monkeys (Macaca fuscata) while they performed reaching movements. We recorded neuronal activity from six different cortical motor areas; the primary motor area (MI), rostral and caudal parts of the dorsal premotor area in area F2 (PMdr and PMdc, respectively), the pre-dorsal premotor area (pre-PMd) in area F7, the ventral premotor area (PMv), and caudal part of the cingulate motor area (CMAc). We found that many neurons (40–70%) in the six areas exhibited the movement-related activity. However, the proportion of neurons exhibiting reach-direction selectivity was less frequent in pre-PMd and CMAc (< 20% of the movement-related neurons) than that (> 30%) in PMdr, PMdc, PMv, and MI. The time of the peak in population activity was reached earlier in pre-PMd and PMdc than in PMdr, PMv, and MI, while that of CMAc was intermediate between the two groups. These results suggest that during the execution of reaching movements, pre-PMd plays a central role in the initiation of movements in general, whereas PMdc, PMdr, PMv, and MI are involved in specifying movement parameters, such as the direction of movements or the selective use of muscles. On the other hand, the nonselective movement-related activity found in CMAc was reminiscent of the activity found in the rostral cingulate motor area (CMAr; Hoshi et al., 2005), suggesting that CMAc is involved in representing general intention to execute movements. Hoshi et al., J. Neurophysiol, 2005 doi:10.1016/j.neures.2010.07.1175 P2-g17 Involvement of the dorsal premotor area (PMd) and the primary motor area (MI) of macaques in the motor selection based on the virtual action plan formed in a voluntary fashion Masashi Hashimoto 1 , Yosuke Saga 1, Leon Tremblay 2, Jun Tanji 1, Eiji Hoshi 1 1 Tamagawa University Brain Science Institute 2 CNRS, Lyon, France Our previous studies have found that the PMd plays a central role in retrieving an action plan at an abstract level from visual instruction signals, and in transforming the virtual action plan into a neural coding reflecting the actual direction of a reaching movement (the motor plan) (Nakayama et al., 2008; Yamagata et al., 2009). In these reports, the retrieval of the virtual action plan, selecting the right or left of reach targets at an abstract level, was based on the presentation of a visual object. In the current study, we aimed at extending these previous findings to explore a further aspect of volitional decision, in which the virtual action plan is formed in a voluntary fashion. We trained two monkeys to perform a task that required them to form a virtual action plan based on a reward amount delivered after making a correct reaching movement. On the appearance of the choice cue consisting of two potential targets, the monkeys also had to specify a forthcoming movement based on the virtual action plan. By analyzing cellular activity recorded from PMd and MI, we obtained three major findings. (1) Around the time when the choice cue was presented, neurons whose activity reflected the action plan and/or the motor plan were found mainly in the rostral PMd. (2) Toward the execution of reaching movements, activity reflecting the motor plan developed in the caudal PMd, whereas the motor-plan specifying activity progressively waned in the rostral PMd. (3) MI was mainly involved in representing the motor plan during the execution of reaching movements. These results suggest that the rostral PMd plays an important role in selecting an action plan based on the outcome of performed action and in specifying an actual motor plan. In contrast, the caudal PMd and MI are more involved in preparing and executing the specified movement. doi:10.1016/j.neures.2010.07.1176 P2-g18 Involvement of the basal ganglia and the frontal cortex in action planning as mediated by the abstract representation of action Nariko Arimura , Yoshihisa Nakayama, Tomoko Yamagata, Yosuke Saga, Jun Tanji, Eiji Hoshi Brain Science Institute, Tamagawa University Although the basal ganglia (BG) and frontal cortex (FC) form an interconnected circuit, the specific functional role played by the BG and FC continues to remain unclear.…
Journal of Neural Transmission, Feb 7, 2017
Thanks to the non-human primate (NHP), we have shown that the pharmacological disturbance of the ... more Thanks to the non-human primate (NHP), we have shown that the pharmacological disturbance of the anterior striatum or of external globus pallidus triggers a set of motivation and movement disorders, depending on the functional subterritory involved. One can, therefore, assume that the aberrant activity of the different subterritories of basal ganglia (BG) could lead to different behavioral disorders in neuropsychiatric disorders as Tourette's syndrome and Parkinson's disease. We are now addressing in the NHP the impact of modulating dopamine or serotonin within the BG on behavioral disorders. Indeed, we have shown a prominent role of serotonergic degeneration within the ventral striatum and caudate nucleus in neuropsychiatric symptoms in de novo PD patients. Of note, the serotonergic modulation of these BG regions in the NHP plays also a critical role in the induction or treatment of behavioral disorders. Given that both dopamine and serotonin are targeted to treat neuropsychiatric disorders, we are studying the effects of modulating dopamine and serotonin transporters in the different territories of the striatum, and more particularly within the ventral striatum on decision-making processing at both behavioral and neuronal levels. Finally, we evidence the need to extend the pharmacological approach to the receptors of these two neuromodulator systems as the use of substances targeting receptor subtypes preferentially localized in the associative and limbic territories of BG could be very effective to specifically improve the behavioral disorders in Parkinson's disease, Gilles de la Tourette syndrome but also in several psychiatric disorders such as depression, anxiety, anorexia, or impulse control disorders.
Discovering how the brain makes decisions is one of the most exciting challenges of neurosciences... more Discovering how the brain makes decisions is one of the most exciting challenges of neurosciences that has emerged in recent years. The evolution of the field of decision neuroscience has benefited from the advance of novel technological capabilities in neurosciences, and the pace at which these capabilities have been developed has accelerated dramatically in the past decade.
Pain, 2019
'Asymbolia for pain' (AP) has shown the potentiality of diseased insular networks to diss... more 'Asymbolia for pain' (AP) has shown the potentiality of diseased insular networks to dissociate sensory from affective-behavioral dimensions of pain, resulting in the lack of appropriate motor and affective responses despite preserved sensory aspect of pain. Here we describe 4 patients with an inverse phenomenon of AP, namely an isolated 'symbolism for pain' (SP) triggered by epileptic seizures, characterized by pain behavior without declarative pain sensation despite fully-preserved contact and vigilance. Stereo-electroencephalography demonstrated in each case focal seizure discharges within the posterior insulo-opercular cortex, with little or no propagation to other cortical structures, especially those thought to drive subjective pain experiences. The pain behavior might reflect seizure propagation from the insula to brain networks serving for behavioral responses associated with pain, including the cingulate motor region and possibly also the basal ganglia. We propose that the isolated SP is a novel epileptic syndrome of dissociation between pain perception and behaviors associated with the insular nociceptive-related networks.
European Neuropsychopharmacology, 2019
Regulatory Peptides, Jul 1, 1993
Using a sensitive in vitro microperfuslon method, the effects of selective and potent agils of NK... more Using a sensitive in vitro microperfuslon method, the effects of selective and potent agils of NK1, NK2, and NK3 tachykinin receptors {[ProSP, [Lys5,MeLeue, NklJNKA-(4-10), and [Pro7]NKB, respectively} on the presynaptic control of doine relase were investgted in striosomal-enriched (area rich in [3Hnlxone bi mg sites) and matrix-enriched areas of the rat riatum. Marked differ
The Journal of Neuroscience, 2002
The subthalamic nucleus (STN) plays a crucial role in basal ganglia functions and has been shown ... more The subthalamic nucleus (STN) plays a crucial role in basal ganglia functions and has been shown to be hyperactive in parkinsonian syndromes. The zona incerta (ZI), located dorsally to the STN, is also reported to be overactive after nigrostriatal denervation. In this study, we examined the behavioral consequences of an increased activity of the STN or the ZI in awake, freely moving rats. Unilateral microinjections of a GABA A receptor antagonist (bicuculline; 25, 50, and 100 g/l) were performed in the STN or in the ZI of rats, and locomotor activity, spontaneous behaviors, and the occurrence of abnormal movements were quantified. Microinjection of bicuculline (50 and 100 g/l) into the STN did not modify spontaneous locomotor activity, whereas it induced an increase in locomotion when injected into the ZI. Furthermore, when injected into the STN or ZI, these same doses of bicuculline produced changes in spontaneous behaviors (sniffing and grooming decreased whereas chewing and rearing increased) and the appearance of abnormal movements directed contralaterally to the injection side. Application of a lower dose of bicuculline (25 ng/l) in the STN or ZI did not modify behavior. This study suggests that the subthalamic region including the ZI, and not the STN per se, might be involved in the induction of abnormal movements. In addition, these data suggest that the hyperactivity of neurons in this region may have different consequences in the normal state and in the pathological state.
Brain : a journal of neurology, Sep 1, 2016
SEE SCHRAG AND POLITIS DOI101093/AWW190 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Apathy, whic... more SEE SCHRAG AND POLITIS DOI101093/AWW190 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Apathy, which can occur separately or in combination with depression and anxiety, is one of the most frequently encountered neuropsychiatric symptoms in Parkinson's disease. Pathophysiological evidence suggests that parkinsonian apathy is primarily due to a mesolimbic dopaminergic denervation, but the role of the serotonergic alteration has never been examined, despite its well-known involvement in the pathogenesis of depression and anxiety. To fill this gap, we address here the pure model of de novo Parkinson's disease, without the confounding effects of antiparkinsonian treatment. Fifteen apathetic (Lille Apathy Rating Scale scores ≥ -21) and 15 non-apathetic (-36 ≤ Lille Apathy Rating Scale scores ≤ -22) drug-naïve de novo parkinsonian patients were enrolled in the present study and underwent detailed clinical assessment and positron emission tomography imaging, using both dopaminergic [(...
Progress in brain research, 2000
An impressive array of neural processing appears to be dedicated to the extraction of reward-rela... more An impressive array of neural processing appears to be dedicated to the extraction of reward-related information from environmental stimuli and use of this information in the generation of goal-directed behaviors. While other structures are certainly involved in these processes, the characteristics of activations seen in mesencephalic dopamine neurons, striatal neurons and neurons of the orbitofrontal cortex provide distinct examples of the different ways in which reward-related information is processed. In addition, the differences in activations seen in these three regions demonstrate the different roles they may play in goal-directed behavior. A principal role played by dopamine neurons is that of a detector of an error in reward prediction. The homogeneity of responsiveness across the population of dopamine neurons indicates that this error signal is widely broadcast to dopamine terminal regions where it could provide a teaching signal for synaptic modifications underlying the l...
Revue neurologique, 2000
L-DOPA-induced dyskinesias are one of the main problems encountered in treating patients with Par... more L-DOPA-induced dyskinesias are one of the main problems encountered in treating patients with Parkinson's disease (PD). They are induced by the antiparkinsonian medications and primarily related to the degree of dopaminergic depletion, as shown by the fact that they tend to appear several years after the onset of the disease. Do the initial therapeutic decisions taken in treating a PD patient influence the point at which dyskinesias first occur? This question is raised in view of the apparent priming phenomenon that occurs in first exposure to L-DOPA. L-DOPA administrated to an MPTP intoxicated monkey rapidly corrects the animals' motor symptoms but generate dyskinesias. In contrast, the administration of dopaminergic agonists with a long half-life has a similar therapeutic effect but without inducing dyskinesias. However, a parkinsonian monkey that had received L-DOPA and developed dyskinesias, which were subsequently abolished when the treatment was withdrawn for several m...
Advances in neurology, 1993
The basal ganglia are widely known to play a role in appetitive rewarding behavior. Imaging and p... more The basal ganglia are widely known to play a role in appetitive rewarding behavior. Imaging and psychiatric clinical studies have provided evidence that the basal ganglia, especially the limbic territory, also play a role in aversive information processing. Inappropriate aversive information processing could induce an anxious state, which is widely observed in a variety of psychiatric diseases. Here, we describe how the ventral striatum and the ventral pallidum, two parts of the limbic circuit in the basal ganglia, are involved in negative motivational behavior, which can be linked with the control of approach/avoidance behavior in a normal context and with the expression of anxiety-related disorders. The disturbance of this pathway would induce not only psychiatric symptoms, but also abnormal value-based decision-making.
PubMed, 2002
Parkinson's disease is a neurodegenerative condition who is related to a large loss of nigral dop... more Parkinson's disease is a neurodegenerative condition who is related to a large loss of nigral dopaminergic neurons leading to a depletion of dopamine in the striatum. Experimental research is required in order to increase our knowledge on the cellular mechanism and functional consequences of this degenerative process. These models allow investigations of new therapeutics in order to improve the treatment of patients or to test new drugs able to protect any remaining dopaminergic neurons. It is relatively easy to obtain animal models of this disease since the target structure and the neuronal population are clearly defined. Two neurotoxic compounds are available for inducing animal models of Parkinson's disease, 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A new one, rotenone, requires further investigations. Each of the neurotoxic compounds requires a specific protocol which can be used either with rodents or non-human primates. Progressive lesioning, using MPTP on green african monkeys (Cercopithecus aethiops sabaeus) provides the most reliable model of the idiopathic disease.
Bulletin De L Academie Nationale De Medecine, Oct 1, 2010
Considerable progress has been made in the pathophysiology of Parkinson's disease in the last... more Considerable progress has been made in the pathophysiology of Parkinson's disease in the last 25 years. To better understand the nature and diversity of the symptoms of Parkinson's disease it is necessary to integrate clinical knowledge on 1) the role of dopamine, 2) the anatomical and functional organization of the basal ganglia, and 3) the dysfunctions observed in MPTP-treated monkeys. This article reviews the principal discoveries in these three research fields and their contribution to our understanding of the pathophysiology of Parkinson's disease.
Neuropsychopharmacology, Mar 10, 2021
INTRODUCTION: Delayed gastric emptying (DGE) causes substantial morbidity after pancreaticoduoden... more INTRODUCTION: Delayed gastric emptying (DGE) causes substantial morbidity after pancreaticoduodenectomy (PD). The objective of this study was to develop a DGE risk calculator using preoperatively and intraoperatively known variables to identify high-risk patients at the time of the index pancreatic resection. METHODS: The 2015 NSQIP Targeted Pancreatectomy Dataset was used to identify 2,357 patients who underwent PD. An adjusted logistic regression analysis was performed to identify preoperative and intraoperative variables independently associated with DGE. A DGE risk calculator was constructed using these variables as well as a priori-selected characteristics that have been reported to be associated with DGE. External validation was performed using the 2016 NSQIP data set of 2,754 patients. Discrimination and calibration were assessed by receiver operating characteristic curves, the Hosmer-Lemeshow test, and calibration plots).
Elsevier eBooks, 2009
In case of many decisions based on sensory information, the sensory stimulus or its neural repres... more In case of many decisions based on sensory information, the sensory stimulus or its neural representation are noisy. This chapter reviews theories proposing that the brain implements statistically optimal strategies for decision making on the basis of noisy information. These strategies maximize the accuracy and speed of decisions, as well as the rate of receiving rewards for correct choices. The chapter first reviews computational models of cortical decision circuits that can optimally perform choices between two alternatives. Then, it describes a model of cortico-basal-ganglia circuit that implements the optimal strategy for choice between multiple alternatives. Finally, it shows how the basal ganglia may modulate decision processes in the cortex, allowing cortical neurons to represent the probabilities of alternative choices being correct. For each set of theories their predictions are compared with existing experimental data.
Annales pharmaceutiques françaises, Sep 1, 2009
Abnormal movements and behavioral disorders are characteristic manifestations observed in certain... more Abnormal movements and behavioral disorders are characteristic manifestations observed in certain neuropsychiatric diseases such as Tourette&amp;#39;s syndrome or Huntington Disease. Together with brain imaging findings, the clinical data could suggest a relationship with basal ganglia dysfunction. In the first part of this review, we recall the anatomic relationships existing, via segregated cortico-cortical circuits, between these structures and the cortical areas having motor and cognitive or motivational-emotional attributes. This structure suggests that in pathologies like Parkinson&amp;#39;s or Huntington disease cognitive and motivational-emotional disorders as well motor disturbances could be related to lesions or dysfunctions involving individual or combined zones of the basal ganglia. The second part of the paper focuses on a description of the various methodologies used to explore these relationships: behavioral, anatomic and brain imaging methods are used in non-human primate models in order to reproduce motor and behavioral disturbances and to determine the neuronal circuits involved. Microinjection of bicucullin into the external globus pallidus has been found to induce localized and reversible neuronal activation. Abnormal movements can be obtained from the motor territory of the external globus pallidus whereas hyperactivity with attentional deficit or stereotypies have been obtained from the associative or limbic territory of the same structure. In the striatum, the same pharmacological activation can induce either abnormal movements from motor and associative functional territories or behavioural changes with hyperactivity or, on the contrary, hypoactivity from associative functional territory with stereotyped behavior and sexual manifestations when the microinjections were done in the limbic striatum. Anatomic studies as well as brain imaging using PET confirm the involvement of segregated anatomic pathways through the basal ganglia in behavioral as well as motor disorders.
Neuroscience Research, 2010
s / Neuroscience Research 68S (2010) e223–e334 e265 P2-g16 Comparison of movement-related neurona... more s / Neuroscience Research 68S (2010) e223–e334 e265 P2-g16 Comparison of movement-related neuronal activity recorded from six different areas in the frontal cortex of macaques Yoshihisa Nakayama , Tomoko Yamagata, Nariko Arimura, Jun Tanji, Eiji Hoshi Brain Sci Inst, Tamagawa Univ, Tokyo A hallmark of the frontal cortex (FC) is the existence of marked changes in activity in and around the execution of arm movements. The activity has been called the movement-related activity, and has been considered to play a crucial role in executing coordinated voluntary motor acts. However, it still remains unclear what aspects are common and what aspects are different among the movement-related activity widely found in each area of the FC. This study investigated this issue by directly comparing neuronal activity recorded from multiple areas in FC of monkeys (Macaca fuscata) while they performed reaching movements. We recorded neuronal activity from six different cortical motor areas; the primary motor area (MI), rostral and caudal parts of the dorsal premotor area in area F2 (PMdr and PMdc, respectively), the pre-dorsal premotor area (pre-PMd) in area F7, the ventral premotor area (PMv), and caudal part of the cingulate motor area (CMAc). We found that many neurons (40–70%) in the six areas exhibited the movement-related activity. However, the proportion of neurons exhibiting reach-direction selectivity was less frequent in pre-PMd and CMAc (< 20% of the movement-related neurons) than that (> 30%) in PMdr, PMdc, PMv, and MI. The time of the peak in population activity was reached earlier in pre-PMd and PMdc than in PMdr, PMv, and MI, while that of CMAc was intermediate between the two groups. These results suggest that during the execution of reaching movements, pre-PMd plays a central role in the initiation of movements in general, whereas PMdc, PMdr, PMv, and MI are involved in specifying movement parameters, such as the direction of movements or the selective use of muscles. On the other hand, the nonselective movement-related activity found in CMAc was reminiscent of the activity found in the rostral cingulate motor area (CMAr; Hoshi et al., 2005), suggesting that CMAc is involved in representing general intention to execute movements. Hoshi et al., J. Neurophysiol, 2005 doi:10.1016/j.neures.2010.07.1175 P2-g17 Involvement of the dorsal premotor area (PMd) and the primary motor area (MI) of macaques in the motor selection based on the virtual action plan formed in a voluntary fashion Masashi Hashimoto 1 , Yosuke Saga 1, Leon Tremblay 2, Jun Tanji 1, Eiji Hoshi 1 1 Tamagawa University Brain Science Institute 2 CNRS, Lyon, France Our previous studies have found that the PMd plays a central role in retrieving an action plan at an abstract level from visual instruction signals, and in transforming the virtual action plan into a neural coding reflecting the actual direction of a reaching movement (the motor plan) (Nakayama et al., 2008; Yamagata et al., 2009). In these reports, the retrieval of the virtual action plan, selecting the right or left of reach targets at an abstract level, was based on the presentation of a visual object. In the current study, we aimed at extending these previous findings to explore a further aspect of volitional decision, in which the virtual action plan is formed in a voluntary fashion. We trained two monkeys to perform a task that required them to form a virtual action plan based on a reward amount delivered after making a correct reaching movement. On the appearance of the choice cue consisting of two potential targets, the monkeys also had to specify a forthcoming movement based on the virtual action plan. By analyzing cellular activity recorded from PMd and MI, we obtained three major findings. (1) Around the time when the choice cue was presented, neurons whose activity reflected the action plan and/or the motor plan were found mainly in the rostral PMd. (2) Toward the execution of reaching movements, activity reflecting the motor plan developed in the caudal PMd, whereas the motor-plan specifying activity progressively waned in the rostral PMd. (3) MI was mainly involved in representing the motor plan during the execution of reaching movements. These results suggest that the rostral PMd plays an important role in selecting an action plan based on the outcome of performed action and in specifying an actual motor plan. In contrast, the caudal PMd and MI are more involved in preparing and executing the specified movement. doi:10.1016/j.neures.2010.07.1176 P2-g18 Involvement of the basal ganglia and the frontal cortex in action planning as mediated by the abstract representation of action Nariko Arimura , Yoshihisa Nakayama, Tomoko Yamagata, Yosuke Saga, Jun Tanji, Eiji Hoshi Brain Science Institute, Tamagawa University Although the basal ganglia (BG) and frontal cortex (FC) form an interconnected circuit, the specific functional role played by the BG and FC continues to remain unclear.…
Journal of Neural Transmission, Feb 7, 2017
Thanks to the non-human primate (NHP), we have shown that the pharmacological disturbance of the ... more Thanks to the non-human primate (NHP), we have shown that the pharmacological disturbance of the anterior striatum or of external globus pallidus triggers a set of motivation and movement disorders, depending on the functional subterritory involved. One can, therefore, assume that the aberrant activity of the different subterritories of basal ganglia (BG) could lead to different behavioral disorders in neuropsychiatric disorders as Tourette's syndrome and Parkinson's disease. We are now addressing in the NHP the impact of modulating dopamine or serotonin within the BG on behavioral disorders. Indeed, we have shown a prominent role of serotonergic degeneration within the ventral striatum and caudate nucleus in neuropsychiatric symptoms in de novo PD patients. Of note, the serotonergic modulation of these BG regions in the NHP plays also a critical role in the induction or treatment of behavioral disorders. Given that both dopamine and serotonin are targeted to treat neuropsychiatric disorders, we are studying the effects of modulating dopamine and serotonin transporters in the different territories of the striatum, and more particularly within the ventral striatum on decision-making processing at both behavioral and neuronal levels. Finally, we evidence the need to extend the pharmacological approach to the receptors of these two neuromodulator systems as the use of substances targeting receptor subtypes preferentially localized in the associative and limbic territories of BG could be very effective to specifically improve the behavioral disorders in Parkinson's disease, Gilles de la Tourette syndrome but also in several psychiatric disorders such as depression, anxiety, anorexia, or impulse control disorders.
Discovering how the brain makes decisions is one of the most exciting challenges of neurosciences... more Discovering how the brain makes decisions is one of the most exciting challenges of neurosciences that has emerged in recent years. The evolution of the field of decision neuroscience has benefited from the advance of novel technological capabilities in neurosciences, and the pace at which these capabilities have been developed has accelerated dramatically in the past decade.
Pain, 2019
'Asymbolia for pain' (AP) has shown the potentiality of diseased insular networks to diss... more 'Asymbolia for pain' (AP) has shown the potentiality of diseased insular networks to dissociate sensory from affective-behavioral dimensions of pain, resulting in the lack of appropriate motor and affective responses despite preserved sensory aspect of pain. Here we describe 4 patients with an inverse phenomenon of AP, namely an isolated 'symbolism for pain' (SP) triggered by epileptic seizures, characterized by pain behavior without declarative pain sensation despite fully-preserved contact and vigilance. Stereo-electroencephalography demonstrated in each case focal seizure discharges within the posterior insulo-opercular cortex, with little or no propagation to other cortical structures, especially those thought to drive subjective pain experiences. The pain behavior might reflect seizure propagation from the insula to brain networks serving for behavioral responses associated with pain, including the cingulate motor region and possibly also the basal ganglia. We propose that the isolated SP is a novel epileptic syndrome of dissociation between pain perception and behaviors associated with the insular nociceptive-related networks.
European Neuropsychopharmacology, 2019
Regulatory Peptides, Jul 1, 1993
Using a sensitive in vitro microperfuslon method, the effects of selective and potent agils of NK... more Using a sensitive in vitro microperfuslon method, the effects of selective and potent agils of NK1, NK2, and NK3 tachykinin receptors {[ProSP, [Lys5,MeLeue, NklJNKA-(4-10), and [Pro7]NKB, respectively} on the presynaptic control of doine relase were investgted in striosomal-enriched (area rich in [3Hnlxone bi mg sites) and matrix-enriched areas of the rat riatum. Marked differ
The Journal of Neuroscience, 2002
The subthalamic nucleus (STN) plays a crucial role in basal ganglia functions and has been shown ... more The subthalamic nucleus (STN) plays a crucial role in basal ganglia functions and has been shown to be hyperactive in parkinsonian syndromes. The zona incerta (ZI), located dorsally to the STN, is also reported to be overactive after nigrostriatal denervation. In this study, we examined the behavioral consequences of an increased activity of the STN or the ZI in awake, freely moving rats. Unilateral microinjections of a GABA A receptor antagonist (bicuculline; 25, 50, and 100 g/l) were performed in the STN or in the ZI of rats, and locomotor activity, spontaneous behaviors, and the occurrence of abnormal movements were quantified. Microinjection of bicuculline (50 and 100 g/l) into the STN did not modify spontaneous locomotor activity, whereas it induced an increase in locomotion when injected into the ZI. Furthermore, when injected into the STN or ZI, these same doses of bicuculline produced changes in spontaneous behaviors (sniffing and grooming decreased whereas chewing and rearing increased) and the appearance of abnormal movements directed contralaterally to the injection side. Application of a lower dose of bicuculline (25 ng/l) in the STN or ZI did not modify behavior. This study suggests that the subthalamic region including the ZI, and not the STN per se, might be involved in the induction of abnormal movements. In addition, these data suggest that the hyperactivity of neurons in this region may have different consequences in the normal state and in the pathological state.
Brain : a journal of neurology, Sep 1, 2016
SEE SCHRAG AND POLITIS DOI101093/AWW190 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Apathy, whic... more SEE SCHRAG AND POLITIS DOI101093/AWW190 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Apathy, which can occur separately or in combination with depression and anxiety, is one of the most frequently encountered neuropsychiatric symptoms in Parkinson's disease. Pathophysiological evidence suggests that parkinsonian apathy is primarily due to a mesolimbic dopaminergic denervation, but the role of the serotonergic alteration has never been examined, despite its well-known involvement in the pathogenesis of depression and anxiety. To fill this gap, we address here the pure model of de novo Parkinson's disease, without the confounding effects of antiparkinsonian treatment. Fifteen apathetic (Lille Apathy Rating Scale scores ≥ -21) and 15 non-apathetic (-36 ≤ Lille Apathy Rating Scale scores ≤ -22) drug-naïve de novo parkinsonian patients were enrolled in the present study and underwent detailed clinical assessment and positron emission tomography imaging, using both dopaminergic [(...
Progress in brain research, 2000
An impressive array of neural processing appears to be dedicated to the extraction of reward-rela... more An impressive array of neural processing appears to be dedicated to the extraction of reward-related information from environmental stimuli and use of this information in the generation of goal-directed behaviors. While other structures are certainly involved in these processes, the characteristics of activations seen in mesencephalic dopamine neurons, striatal neurons and neurons of the orbitofrontal cortex provide distinct examples of the different ways in which reward-related information is processed. In addition, the differences in activations seen in these three regions demonstrate the different roles they may play in goal-directed behavior. A principal role played by dopamine neurons is that of a detector of an error in reward prediction. The homogeneity of responsiveness across the population of dopamine neurons indicates that this error signal is widely broadcast to dopamine terminal regions where it could provide a teaching signal for synaptic modifications underlying the l...
Revue neurologique, 2000
L-DOPA-induced dyskinesias are one of the main problems encountered in treating patients with Par... more L-DOPA-induced dyskinesias are one of the main problems encountered in treating patients with Parkinson's disease (PD). They are induced by the antiparkinsonian medications and primarily related to the degree of dopaminergic depletion, as shown by the fact that they tend to appear several years after the onset of the disease. Do the initial therapeutic decisions taken in treating a PD patient influence the point at which dyskinesias first occur? This question is raised in view of the apparent priming phenomenon that occurs in first exposure to L-DOPA. L-DOPA administrated to an MPTP intoxicated monkey rapidly corrects the animals' motor symptoms but generate dyskinesias. In contrast, the administration of dopaminergic agonists with a long half-life has a similar therapeutic effect but without inducing dyskinesias. However, a parkinsonian monkey that had received L-DOPA and developed dyskinesias, which were subsequently abolished when the treatment was withdrawn for several m...
Advances in neurology, 1993