Brian Lau

L'Institut du Cerveau

Objective To characterize how disease progression is associated with mortality in a large cohort of patients with Parkinson disease (PD) with long-term follow-up after subthalamic nucleus deep brain stimulation (STN-DBS). Methods Motor and cognitive disabilities were assessed before and 1, 2, 5, and 10 years after STN-DBS in 143 consecutive patie...

When deciding between options that do or do not lead to future choices, humans often choose to choose. We studied choice seeking by asking subjects to decide between a choice opportunity or performing a computer-selected action. Subjects preferred choice when these options were equally rewarded, even deterministically, and were willing to trade ext...

For over 10 years, electrical stimulation within the limbic cor-ticosubcortical network has been evaluated for treating patients with severe obsessive-compulsive disorder (OCD) (1). High-frequency deep brain stimulation (DBS) of various targets has been tested, including the anteromedial part of the subthalamic nucleus (amSTN), nucleus accumbens (N...

Human decisions are frequently explained as the balancing of potential rewards and punishments, such as food, money, or lost time. However, rational models of decision making based on this idea often fail to accurately predict human behavior. Humans and other animals appear to base decisions on value estimation that is often not clearly linked to e...

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics, which is often associated with psychiatric comorbidities. Dysfunction of basal ganglia pathways might account for the wide spectrum of symptoms in TS patients. Although psychiatric symptoms may be related to limbic networks, the specific contribution of d...

Introduction Subthalamic deep-brain-stimulation (STN-DBS) is an effective means to treat Parkinson's disease (PD) symptoms. Its benefit on gait disorders is variable, with freezing of gait (FOG) worsening in about 30% of cases. Here, we investigate the clinical and anatomical features that could explain post-operative FOG. Methods Gait and balance...

Supplementary information for "Choice seeking is motivated by the intrinsic need for personal control"

Background: Dopa-resistant freezing of gait (FOG) and falls represent the dominant motor disabilities in advanced Parkinson's disease (PD). Objective: We investigate the effects of deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR), comprised of the pedunculopontine (PPN) and cuneiform (CuN) nuclei, for treating gait and ba...

Background Subthalamic nucleus (STN) deep brain stimulation (DBS) alleviates obsessive-compulsive disorder (OCD) symptoms, suggesting that this basal ganglia structure may play a key role in integrating limbic and motor information. We explored the modulation of STN neural activity by visual emotional information under different motor demands. Met...

The human gait program involves many brain areas such as motor cortices, cerebellum, basal ganglia, brainstem, and spinal cord. The mesencephalic locomotor region (MLR), which contains the pedunculopontine (PPN) and cuneiform (CN) nuclei, is thought to be one of the key supraspinal gait generators. In daily life activities, gait primarily occurs in...

In the past decade, the mesencephalic locomotor region (MLR) has emerged as a new surgical target for alleviating dopamine-resistant gait and balance disorders in Parkinson's disease. Part of the reticular formation, the MLR contains nuclei with diffuse and open boundaries, which are currently difficult or impossible to visualize directly using con...

Introduction Le rôle de la région locomotrice mésencéphalique (RLM) dans l’initiation du pas, la marche et le contrôle postural chez l’homme reste mal connu. Chez les patients avec maladie de Parkinson, une perte des neurones cholinergiques dans cette région a été corrélée à la survenue du freezing de la marche et/ou des chutes. Dans ce travail de...

Akinesia is a major manifestation of Parkinson's disease (PD) related to difficulties or failures of willed movement to occur. Akinesia is still poorly understood and is not fully alleviated by standard therapeutic strategies. One reason is that the area of the clinical concept has blurred boundaries referring to confounded motor symptoms. Here, we...

Background Deep brain stimulation of the pedunculopontine nucleus has been performed to treat dopamine-resistant gait and balance disorders in patients with degenerative diseases. The outcomes, however, are variable, which may be the result of the lack of a well-defined anatomical target. Objectives The objectives of this study were to identify th...

Objective: Freezing of gait (FOG) represents a major burden for Parkinson's disease (PD) patients. High-frequency (130-Hz) subthalamic deep-brain-stimulation (STN-DBS) has been reported to aggravate FOG whereas lowering the frequency to 60-80 Hz improves FOG. To further understand the effects of STN-DBS on FOG, we assessed the effects of 80-Hz and...

A major question for deep brain stimulation (DBS) research is understanding how DBS of one target area modulates activity in different parts of the brain. EEG gives privileged access to brain dynamics, but its use with implanted patients is limited since DBS adds significant high-amplitude electrical artifacts that can completely obscure neural act...

Clonidine is an anti‐hypertensive medication which acts as an alpha‐adrenergic receptors agonist. As the noradrenergic system is likely to support cognitive functions including attention and executive control, other clinical uses of clonidine have recently gained popularity for the treatment of neuropsychiatric disorders like attention‐deficit hype...

The same reward can possess different motivational meaning depending upon its magnitude relative to other rewards. To study the neurophysiological mechanisms mediating assignment of motivational meaning, we recorded the activity of neurons in the amygdala and orbitofrontal cortex (OFC) of monkeys during a Pavlovian task in which the relative amount...

The mesencephalic locomotor region (MLR) is a highly preserved brainstem structure in vertebrates. The MLR performs a crucial role in locomotion but also controls various other functions such as sleep, attention, and even emotion. The MLR comprises the pedunculopontine (PPN) and cuneiform nuclei (CuN) but their specific roles are still unknown in p...

Introduction Le freezing de la marche (freezing of gait [FOG]) est caractérisé par une incapacité à initier ou à poursuivre la marche. Il est fréquemment rapporté au cours de la maladie de Parkinson (MPI) et induit une augmentation significative du risque de chute et la morbidité. La stimulation cérébrale profonde du noyau sous-thalamique (SCP-NST)...

Introduction Les noyaux subthalamiques (NST) et pédonculopontin (NPP) appartiennent au réseau neuronal impliqué dans le contrôle de la locomotion et l’équilibre, particulièrement conservé d’un point de vue phylogénétique chez les vertébrés. Chez l’Homme, les données d’imagerie et les enregistrements électrophysiologiques suggèrent que seule l’activ...

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) could treat chorea in Huntington's disease patients. The objectives of this study were to evaluate the efficacy of GPi-DBS to reduce abnormal movements of three patients with Huntington's disease and assess tolerability. Three non-demented patients with severe pharmacoresistant chor...

Introduction Les symptômes axiaux de la maladie de Parkinson (MP), tels que le freezing de la marche et les chutes, représentent une source de handicap majeur. Les effets de la stimulation cérébrale profonde (SCP) du noyau subthalamique (NST) sur ces signes moteurs est variable, avec une aggravation rapportée chez certains patients opérés. Pour mie...

Neural activity in visual area V4 is enhanced when attention is directed into neuronal receptive fields. However, the source of this enhancement is unclear, as most physiological studies have manipulated attention by changing the absolute reward associated with a particular location as well as its value relative to other locations. We trained monke...

The brainstem pedunculopontine nucleus has a likely, although unclear, role in gait control, and is a potential deep brain stimulation target for treating resistant gait disorders. These disorders are a major therapeutic challenge for the ageing population, especially in Parkinson's disease where gait and balance disorders can become resistant to b...

Gait and balance disorders are the major source of motor disabilities in advanced forms of Parkinson's disease (PD). Low-frequency stimulation of the pedunculopontine nucleus area (PPNa-DBS) has been recently proposed to treat these symptoms with variable clinical results. To further understand the effects of PPNa-DBS on resistant gait and balance...

Skilled behavior is thought to rely on the dorsal striatum. A study now reports that skills depend on striatal encoding of movement kinematics, linking learned sequences of movements with temporally distributed striatal activity.

A stimulus predicting reinforcement can trigger emotional responses, such as arousal, and cognitive ones, such as increased attention toward the stimulus. Neuroscientists have long appreciated that the amygdala mediates spatially nonspecific emotional responses, but it remains unclear whether the amygdala links motivational and spatial representati...

Decision-making often involves using sensory cues to predict possible rewarding or punishing reinforcement outcomes before selecting a course of action. Recent work has revealed complexity in how the brain learns to predict rewards and punishments. Analysis of neural signaling during and after learning in the amygdala and orbitofrontal cortex, two...

Gait and balance disorders represent a major therapeutic challenge in Parkinson's disease (PD). These symptoms respond poorly to dopaminergic treatments, except in the early phase of the disease. Currently, no other treatment is particularly efficient and rehabilitation appears to be the most effective approach. Since these gait and balance deficit...

The orbitofrontal cortex (OFC) and amygdala are thought to participate in reversal learning, a process in which cue-outcome associations are switched. However, current theories disagree on whether OFC directs reversal learning in the amygdala. Here, we show that during reversal of cues' associations with rewarding and aversive outcomes, neurons tha...

The majority of cortical neurons in area V1 are complex cells with highly nonlinear response properties. While many properties of these cells have been studied in the past, complete descriptions of their stimulus response functions remain difficult to obtain. Here, we recorded from cat primary visual cortex and obtained second-order Wiener kernels...

Making appropriate choices often requires the ability to learn the value of available options from experience. Parkinson's disease is characterized by a loss of dopamine neurons in the substantia nigra, neurons hypothesized to play a role in reinforcement learning. Although previous studies have shown that Parkinson's patients are impaired in tasks...

Projections from the amygdala to the ventral striatum are important for learning. A study finds that fleeting epochs of coherent gamma oscillations between these brain areas may be important for reinforcement learning.

Directing attention to relevant sensory stimuli is critical for survival because attention can facilitate perception, learning, and action. But what makes a sensory stimulus relevant? One property that clearly contributes is the motivational salience of a stimulus; if a stimulus either predicts a reward or punishment, or if it is reinforcing in and...

Choosing the most valuable course of action requires knowing the outcomes associated with the available alternatives. The striatum may be important for representing the values of actions. We examined this in monkeys performing an oculomotor choice task. The activity of phasically active neurons (PANs) in the striatum covaried with two classes of in...

The basal ganglia appear to have a central role in reinforcement learning. Previous experiments, focusing on activity preceding movement execution, support the idea that dorsal striatal neurons bias action selection according to the expected values of actions. However, many phasically active striatal neurons respond at a time too late to initiate o...

Work in behaving primates indicates that midbrain dopamine neurons encode a prediction error, the difference between an obtained reward and the reward expected. Studies of dopamine action potential timing in the alert and anesthetized rat indicate that dopamine neurons respond in tonic and phasic modes, a distinction that has been less well charact...

We studied the choice behavior of 2 monkeys in a discrete-trial task with reinforcement contingencies similar to those Herrnstein (1961) used when he described the matching law. In each session, the monkeys experienced blocks of discrete trials at different relative-reinforcer frequencies or magnitudes with unsignalled transitions between the block...

Reward-sensitive neurons are present throughout the brain. A report in Science now shows that a subset of thalamic neurons respond selectively to the smaller of two rewards, as opposed to just reflecting reward magnitude, as do neurons in other brain areas.

A wealth of evidence, much of it reviewed in this book, suggests that the superior colliculus (SC) plays a crucial role in the control of orienting eye and head movements. Activity in the superior colliculus, for example, predicts both the metrics and the timing of orienting movements. Electrical microstimulation of the SC, to take another example,...

Variance adaptation processes have recently been examined in cells of the fly visual system and various vertebrate preparations. To better understand the contributions of somatic mechanisms to this kind of adaptation, we recorded intracellularly in vitro from neurons of rat sensorimotor cortex. The cells were stimulated with a noise current whose s...

A crucial step in understanding the function of a neural circuit in visual processing is to know what stimulus features are represented in the spiking activity of the neurons. For neurons with complex, nonlinear response properties, characterization of feature representation requires measurement of their responses to a large ensemble of visual stim...

A crucial step toward understanding visual processing is to obtain a comprehensive description of the relationship between visual stimuli and neuronal responses. Many neurons in the visual cortex exhibit nonlinear responses, making it difficult to characterize their stimulus-response relationships. Here, we recorded the responses of primary visual...

Simultaneous EEG recordings from various cortical areas indicate the presence of common-mode, spatially coherent oscillations. These oscillations are characterized by a common wave form with a spatially distributed pattern of amplitude modulation (AM). We observe highly reproducible AM patterns across spatially separated channels within various are...