Thomas Boraud

• MD, PhD
• Directeur de Recherche at Neurodegeneratives Diseases Institute

The basal ganglia (BG), a set of subcortical nuclei involved in motor control, sensorimotor integration, and procedural learning, modulate movement through tonic inhibition of thalamo-cortical networks. While essential for sensorimotor integration and learning, the BG are not necessary for executing well-learned movements. During skill learning, th...

Background: Lixisenatide, a glucagon-like peptide-1 receptor agonist used for the treatment of diabetes, has shown neuroprotective properties in a mouse model of Parkinson's disease. Methods: In this phase 2, double-blind, randomized, placebo-controlled trial, we assessed the effect of lixisenatide on the progression of motor disability in perso...

In 2016, the University of Bordeaux ran a competition within the local neuroscience community to find a name for its new neuroscience building. The name of Paul Broca, who was born nearby in 1824, was chosen in honour of his origins and his contributions to neuroscience. Recently, however, a debate has been ignited about the appropriateness of this...

Les observations biomédicales ne deviennent une source de connaissance qu’après un débat entre chercheurs. Au cours de ce débat, la citation des études antérieures tient un rôle majeur, mais les travaux académiques qui en évaluent l’usage sont rares. Ils ont cependant pu révéler deux types de problèmes : les biais de citation et les écarts de sens...

In humans, the attitude toward risk is not neutral and is dissimilar between bets involving gains and bets involving losses. The existence and prevalence of these decision features in non-human primates are unclear. In addition, only a few studies have tried to simulate the evolution of agents based on their attitude toward risk. Therefore, we stil...

Do we have any valid reasons to affirm that non-human primates display economic behaviour in a sufficiently rich and precise sense of the phrase? To address this question, we have to develop a set of criteria to assess the vast array of experimental studies and field observations on individual cognitive and behavioural competences as well as the co...

This chapter explores the flexibility of the neural network described in the previous chapters. It also shows that the anterior part of the brain can be subdivided into five functional loops that underlie different executive functions. These five major loops are the motor loop, the oculomotor loop, the prefrontal loop, the orbitofrontal loop, and t...

This chapter presents an upgrade of the neural network by implementing the reward prediction error. It then compares the final product with the actor-critic model and discusses the similarities and differences. Reinforcement learning algorithms, more specifically actor-critic models, are currently very successful in the field of decision-making. Th...

This chapter explores the pathophysiology of neural conditions related to the neural network of decision-making. If humans are not fully rational, they manage to pretend to be most of the time. Some individuals are distinguished by traits that influence their decision-making, such as impulsiveness, procrastination, and stubbornness. These behaviour...

This chapter describes the neurobiological approach of decision-making. Until the late 1980s, ignoring the work of experimental economists and behaviourists, electrophysiologists restricted themselves to the study of sensory and motor function, believing it to be impossible for them to access cognitive processes. In 1989, William Newsome and Anthon...

Dopamine and striatal dysfunctions play a key role in the pathophysiology of Parkinson's disease (PD) and Dystonia, but our understanding of the changes in the discharge rate and pattern of striatal projection neurons (SPNs) remains limited. Here, we recorded and examined multi-unit signals from the striatum of PD and dystonic patients undergoing d...

Dopamine and striatal dysfunctions play a key role in the pathophysiology of Parkinson’s disease (PD) and Dystonia, but our understanding of the changes in the discharge rate and pattern of striatal projection neurons (SPNs) remains limited. Here, we recorded and examined multi-unit signals from the striatum of PD and dystonic patients undergoing d...

Dopamine and striatal dysfunctions play a key role in the pathophysiology of Parkinson’s disease (PD) and Dystonia, but our understanding of the changes in the discharge rate and pattern of striatal projection neurons (SPNs) remains limited. Here, we recorded and examined multi-unit signals from the striatum of PD and dystonic patients undergoing d...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are widely used in rodents to manipulate neuronal activity and establish causal links between structure and function. Their utilization in non‐human primates (NHPs) is however limited and their efficacy still debated. Here, we recorded and examined the neuronal activity in the hM4...

The dynamical properties of cortico-basal ganglia (CBG) circuits are dramatically altered following the loss of dopamine in Parkinson’s disease (PD). The neural circuit dysfunctions associated with PD include spike-rate alteration concomitant with excessive oscillatory spike-synchronization in the beta frequency range (12–30 Hz). Which neuronal cir...

Dopamine depletion of the striatum plays a key role in the pathophysiology of Parkinson’s disease (PD), but our understanding of the changes in the discharge rate and pattern of the striatal projection neurons (SPNs) remains limited. Here, we recorded multi-unit signals from the striatum of PD (N = 934) and dystonic (N = 718) patients undergoing de...

Scientific results traditionally disseminate to the scientific community via scientific journals. Studies’ importance is assessed through the number of citations in those journals. The medialization concept postulates an increasing orientation of science towards the mass media. Here, taking up this concept, we hypothesized that if science is indeed...

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are widely used in rodents to manipulate neuronal activity and establish causal links between structure and function. Their utilization in non-human primates (NHPs) is however limited and their efficacy still debated. Here, we tested DREADD expression in the NHP external globus pa...

Several micro-founded macroeconomic models with rational expectations address the issue of money emergence, by characterizing it as a coordination game. These models have in common the use of agents who dispose of perfect or near-perfect information on the global state of the economy and who display full-fledged computational abilities. Several exp...

Decision-making in humans is known to be subject to several biases. For instance, when facing bets, humans demonstrate some asymmetry concerning their preference for the riskiest option depending on whether stakes involve potential gains or potential losses. They are indeed risk-averse for bets involving gains but risk seeking for bets involving lo...

Duopolies are situations where two independent sellers compete for capturing market share. Such duopolies exist in the world economy (e.g., Boeing/Airbus, Samsung/Apple, Visa/MasterCard) and have been studied extensively in the literature using theoretical models. Among these models, the spatial model of Hotelling (1929) is certainly the most proli...

Neurobiology of Moral Judgement: New Epistemic Highway or Dead End? Society increasingly challenges neuroscience to provide explanatory paradigms regarding foundations of moral judgements. This naturalization program of morality has led some neuroscientists to draw normative conclusions about the origin and nature of these judgments. Pioneers of th...

We propose a model that includes interactions between the cortex, the basal ganglia (BG), and the thalamus based on a dual competition. We hypothesize that the striatum, the subthalamic nucleus (STN), the internal globus pallidus (GPi), the thalamus, and the cortex are involved in closed feedback loops through the hyperdirect and direct pathways. T...

News value theory rates geographical proximity as an important factor in the process of issue selection by journalists. But does this apply to science journalism? Previous observational studies investigating whether newspapers preferentially cover scientific studies involving national scientists have generated conflicting answers. Here we used a da...

Introduction: There is an unmet need to better control motor complications in Parkinson's disease (PD). Naftazone, which exhibits glutamate release inhibition properties, has shown antiparkinsonian and antidyskinetic activity in preclinical models of PD and in a clinical proof of concept study. Methods: We conducted a double-blind randomized pla...

Front cover: The cover image, by Radwa Khalil et al., is based on the Review Article Social Decision Making in Autism: On the impact of Mirror Neurons, Motor Control and Imitative Behaviors, DOI: https://doi.org/10.1111/cns.13001.

The dorsal pallium (a.k.a. cortex in mammals) makes a loop circuit with the basal ganglia and the thalamus known to control and adapt behavior but the who's who of the functional roles of these structures is still debated. Influenced by the Triune brain theory that was proposed in the early sixties, many current theories propose a hierarchical orga...

The Mirror Neuron System (MNS) plays a crucial role in action perception and imitative behavior, which is suggested to be impaired in Autism Spectrum Disorders (ASDs). In this review, we discuss the plausibility and empirical evidence of a neural interaction between the MNS, action perception, empathy, imitative behavior, and their impact on social...

Newspapers preferentially cover initial biomedical findings although they are often disconfirmed by subsequent studies. We analyzed 426 newspaper articles covering 40 initial biomedical studies associating a risk factor with 12 pathologies and published between 1988 and 2009. Most articles presented the study as initial but only 21% mentioned that...

Action-outcome (A-O) and stimulus-response (S-R) processes that are two forms of instrumental conditioning that are important components of decision making and action selection. The former adapts its response according to the outcome while the latter is insensitive to the outcome. An unsolved question is how these two processes emerge, cooperate an...

Parkinson’s disease and experimentally induced hemiparkinsonism are characterized by increased beta synchronization between cortical and subcortical areas. This change in beta connectivity might reflect either a symmetric increase in interareal influences or asymmetric changes in directed influences among brain areas. We assessed patterns of functi...

Neuropsychopharmacology, the official publication of the American College of Neuropsychopharmacology, publishing the highest quality original research and advancing our understanding of the brain and behavior.

Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classifie...

Studies with low statistical power increase the likelihood that a statistically significant finding represents a false positive result. We conducted a review of meta-analyses of studies investigating the association of biological, environmental or cognitive parameters with neurological, psychiatric and somatic diseases, excluding treatment studies,...

The mechanisms of decision-making and action selection are generally thought to be under the control of parallel cortico-subcortical loops connecting back to distinct areas of cortex through the basal ganglia and processing motor, cognitive and limbic modalities of decision-making. We have used these properties to develop and extend a connectionist...

Affective memories associated with the negative emotional state experienced during opiate withdrawal are central in maintaining drug-taking, seeking and relapse. Nucleus accumbens (NAC) is a key structure both for acute withdrawal and withdrawal memories reactivation, however NAC neuron coding properties underpinning the expression of these memorie...

Abstract: The mechanisms of decision-making are generally thought to be under the control of a set of cortico-subcortical loops involving basal ganglia and thalamic pathways. These structures include several parallel functional loops connecting back to distinct areas of the cortex, processing motor, cognitive and limbic modalities of decision makin...

This paper introduces a new hypothesis concerning the formation of habits in the cortex of primates under the implicit supervision of the basal ganglia. This hypothesis has been formulated using a theoretical model and confirmed experimentally in monkeys. To do so, and prior to learning, we inactivated the internal part of the globus pallidus (GPi,...

CONTEXT:There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. OBJECTIVE:Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognit...

Twelve flow diagrams. (DOCX)

References of the 447 articles describing the 663 largest observations. (DOCX)

Raw data about initial studies, largest studies and meta-analyses for 12 pathologies. (XLSX)

References of the 333 articles describing the 663 meta-analyses. (DOCX)

References of the 485 articles describing the 663 initial observations. (DOCX)

The mechanisms of decision-making are generally thought to be under the control of a set of cortico-subcortical loops involving basal ganglia and thalamic pathways. These structures include several parallel functional loops connecting back to distinct areas of cortex, processing motor, cognitive and limbic modalities of decision making. Due to conv...

Background: There is an apparent contradiction between experimental data showing that the basal ganglia are involved in goal-oriented and routine behaviors and clinical observations. Lesion or disruption by deep brain stimulation of the globus pallidus interna has been used for various therapeutic purposes ranging from the improvement of dystonia...

The suppression of inappropriate actions is critical for flexible behavior. Cortical-basal ganglia networks provide key gating mechanisms for action suppression, yet the specific roles of neuronal subpopulations are poorly understood. Here, we examine Arkypallidal (“Arky”) and Prototypical (“Proto”) globus pallidus neurons during a Stop task, which...

Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons as well as the presence of proteinaceous inclusions named Lewy bodies. α-synuclein (α-syn) is a major constituent of Lewy bodies, and the first disease-causing protein characterized in PD. Several α-syn-based animal...

If basal ganglia are widely accepted to participate in the high-level cognitive function of decision-making, their role is less clear regarding the formation of habits [1,2]. One of the biggest problem is to understand how goal-directed actions are transformed into habitual responses, or, said differently, how an animal can shift from an action-out...

Decision making takes a crucial role in daily life and can be seriously impaired in neurodegenerative diseases. It implies cortical-basal ganglia loops, but the respective roles of each structure are still debated. Urodeles offer a remarkable opportunity to address this question. First, whereas the organization of the basal ganglia in these animals...

If basal ganglia are widely accepted to participate in the high-level cognitive function of decision-making, their role is less clear regarding the formation of habits. One of the biggest problem is to understand how goal-directed actions are transformed into habitual responses, or, said differently, how an animal can shift from an action-outcome (...

The mechanisms of decision making are generally thought to be under the control of a set of cortico-subcortical loops. There are several parallel functional loops through the basal ganglia connecting back to distinct areas of cortex, process- ing different modalities of decision making, including motor, cognitive and limbic. Due to convergence and...

Abstract: The mechanisms of decision making are generally thought to be under the control of a set of cortico-subcortical loops. There are several parallel functional loops through the basal ganglia connecting back to distinct areas of cortex, process- ing different modalities of decision making, including motor, cognitive and limbic. Due to conver...

Decision making takes a crucial role in daily life and can be seriously impaired in neurodegenerative diseases. It implies cortical-basal ganglia loops, but the respective roles of each structure are still debated. Urodeles offer a remarkable opportunity to address this question. First, whereas the organization of the basal ganglia in these animal...

Computational neuroscience is a powerful ally in our quest to understand the brain. Even the most simple model can shed light on the role of this or that structure and propose new hypothesis concerning the overall brain organization. However, any model in Science is doomed to be proved wrong or incomplete and replaced by a more accurate one. In the...

Et si notre faculté à prendre des décisions relevait plus du hasard que d’un processus rationnel ? On a longtemps admis que, chez l’homme, la prise de décision résultait d’un processus cognitif et psychologique : l’esprit décide, le corps obéit. Or, le schéma est inverse : le mécanisme décisionnel est produit par la matière cérébrale. C’est un phén...

Computational neuroscience is a powerful ally in our quest to understand the brain. Even the most simple model can shed light on the role of this or that structure and propose new hypothesis concerning the overall brain organization. However, any model in Science is doomed to be proved wrong or incomplete and replaced by a more accurate one. In the...

Background A systematic search of brain nuclei putatively involved in L-3,4-dihydroxyphenylalanine (L-Dopa)-induced dyskinesia (LID) in Parkinson’s disease (PD) shed light, notably, upon the lateral habenula (LHb), which displayed an overexpression of the ∆FosB, ARC and Zif-268 immediate-early genes only in rats experiencing abnormal involuntary mo...

The neurological bases of spatial navigation are mainly investigated in rodents and seldom in primates. The few studies led on spatial navigation in both human and non-human primates are performed in virtual, not in real environments. This is mostly because of methodological difficulties inherent in conducting research on freely-moving monkeys in r...

Spatial learning has been recognized over the years to be under the control of the hippocampus and related temporal lobe structures. Hippocampal damage often causes severe impairments in the ability to learn and remember a location in space defined by distal visual cues. Such cognitive disabilities are found in Parkinsonian patients. We recently in...

Day-to-day variability in performance is a common experience. We investigated its neural correlate by studying learning behavior of monkeys in a two-alternative forced choice task, the two-armed bandit task. We found substantial session-to-session variability in the monkeys' learning behavior. Recording the activity of single dorsal putamen neurons...

Among current theories of addiction, hedonic homeostasis dysregulation predicts that the brain reward systems, particularly the mesolimbic dopamine system, switch from a physiological state to a new "set point". In opiate addiction, evidence show that the dopamine system principal targets, prefrontal cortex (PFC), nucleus accumbens (NAC) and basola...

In a previous modeling study Leblois et al. (2006) demonstrated an action selection mechanism in cortico-basal ganglia loops based on competition between the positive feedback, direct pathway through the striatum and the negative feedback, hyperdirect pathway through the subthalamic nucleus. The present study investigates how multiple level action...

The basal ganglia (BG) are crucial structures for decision-making processes, i.e. the cognitive processes resulting in the selection of a set of actions among several alternative scenarios. Modelling of BG circuitry has played an important role in our understanding of these mental processes, over the last 20 years. Until now, many developmental cha...

Coordinated reset neuromodulation consists of the application of consecutive brief high-frequency pulse trains through the different contacts of the stimulation electrode. In theoretical studies, by achieving unlearning of abnormal connectivity between neurons, coordinated reset neuromodulation reduces pathological synchronization, a hallmark featu...

CONTEXT: Because positive biomedical observations are more often published than those reporting no effect, initial observations are often refuted or attenuated by subsequent studies. OBJECTIVE: To determine whether newspapers preferentially report on initial findings and whether they also report on subsequent studies. METHODS: We focused on attenti...

PubMed search of meta-analyses related to the “top 10” scientific articles. (PDF)

We investigated the functional role of oscillatory activity in the local field potential (LFP) of the subthalamic nucleus (STN) in the pathophysiology of Parkinson's disease (PD). It has been postulated that beta (15-30 Hz) oscillatory activity in the basal ganglia induces PD motor symptoms. To assess this hypothesis, an LFP showing significant pow...

Although there are numerous 3T MRI research devices all over the world, only a few functional studies at 3T have been done in anesthetized monkeys. In the past, anesthetized preparations were reported to be misleading when exploring cortical brain regions outside the primary sensory areas. Nonetheless, a great improvement has been achieved in the l...

Spatial learning has been recognized over the years to be under the control of the hippocampus and related temporal lobe structures. Hippocampal damage often causes severe impairments in the ability to learn and remember a location in space defined by distal visual cues. Recent experimental evidence in rodents demonstrates, however, that other brai...

Deep brain stimulation (DBS) has been applied in more than 70000 patients worldwide during the last two decades. The main target is the subthalamic nucleus (STN) for the treatment of motor complications in late stage Parkinson's disease (PD). Positive results in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated non-human primates have set...

Decision is a self-generated phenomenon, which is hard to track with standard time averaging methods, such as peri-event time histograms (PETHs), used in behaving animals. Reasons include variability in duration of events within a task and uneven reaction time of animals. We have developed a temporal normalization method where PETHs were juxtaposed...

Modulation of oscillatory activity through basal ganglia-cortical loops in specific frequency bands is thought to reflect specific functional states of neural networks. A specific negative correlation between beta and gamma sub-bands has been demonstrated in human basal ganglia and may be key for normal basal ganglia function. However, these studie...

J. Neurochem. (2011) 116, 449–458. D2-like antagonists potentiate dopamine release. They also inhibit dopamine uptake by a mechanism yet to be clarified. Here, we monitored dopamine uptake in the striatum of anesthetized mice. The dopamine overflow was evoked by brief electrical stimulation of the medial forebrain bundle (four pulses at 100 Hz) and...

Scientific and media articles reporting on the association between alleles of the gene coding for the D4 dopamine receptor and ADHD. (0.14 MB DOC)

Scientific studies performed in mice and related to ADHD and media articles that echoed to the 3 scientific articles given in Table 3. (0.08 MB DOC)

Distribution of the omission rate with the publication year. (0.04 MB DOC)

Lists of media and scientific articles echoing the studies by Volkow et al (2007) and Barbaresi et al (2007) shown in Table 1. (0.08 MB DOC)

There is often a huge gap between neurobiological facts and firm conclusions stated by the media. Data misrepresentation in the conclusions and summaries of neuroscience articles might contribute to this gap. Using the case of attention deficit hyperactivity disorder (ADHD), we identified three types of misrepresentation. The first relies on promin...

The decision making process is a phenomenon which is hard to track using the standard signal averaging methods such as peri-event time histograms (PETHs). Indeed, even if the sequence of the events is controlled during a behavioural task, the inter-event interval duration remains highly variable. We have applied a temporal normalization method such...