RESUMO
Male sexual behavior is innate and rewarding. Despite its centrality to reproduction, a molecularly specified neural circuit governing innate male sexual behavior and reward remains to be characterized. We have discovered a developmentally wired neural circuit necessary and sufficient for male mating. This circuit connects chemosensory input to BNSTprTac1 neurons, which innervate POATacr1 neurons that project to centers regulating motor output and reward. Epistasis studies demonstrate that BNSTprTac1 neurons are upstream of POATacr1 neurons, and BNSTprTac1-released substance P following mate recognition potentiates activation of POATacr1 neurons through Tacr1 to initiate mating. Experimental activation of POATacr1 neurons triggers mating, even in sexually satiated males, and it is rewarding, eliciting dopamine release and self-stimulation of these cells. Together, we have uncovered a neural circuit that governs the key aspects of innate male sexual behavior: motor displays, drive, and reward.
Assuntos
Vias Neurais , Comportamento Sexual Animal , Animais , Masculino , Neurônios/fisiologia , Recompensa , Comportamento Sexual Animal/fisiologia , CamundongosRESUMO
Computational analysis of cellular activity has developed largely independently of modern transcriptomic cell typology, but integrating these approaches may be essential for full insight into cellular-level mechanisms underlying brain function and dysfunction. Applying this approach to the habenula (a structure with diverse, intermingled molecular, anatomical, and computational features), we identified encoding of reward-predictive cues and reward outcomes in distinct genetically defined neural populations, including TH+ cells and Tac1+ cells. Data from genetically targeted recordings were used to train an optimized nonlinear dynamical systems model and revealed activity dynamics consistent with a line attractor. High-density, cell-type-specific electrophysiological recordings and optogenetic perturbation provided supporting evidence for this model. Reverse-engineering predicted how Tac1+ cells might integrate reward history, which was complemented by in vivo experimentation. This integrated approach describes a process by which data-driven computational models of population activity can generate and frame actionable hypotheses for cell-type-specific investigation in biological systems.
Assuntos
Habenula , Recompensa , Dinâmica PopulacionalRESUMO
The anterior insular cortex (aIC) plays a critical role in cognitive and motivational control of behavior, but the underlying neural mechanism remains elusive. Here, we show that aIC neurons expressing Fezf2 (aICFezf2), which are the pyramidal tract neurons, signal motivational vigor and invigorate need-seeking behavior through projections to the brainstem nucleus tractus solitarii (NTS). aICFezf2 neurons and their postsynaptic NTS neurons acquire anticipatory activity through learning, which encodes the perceived value and the vigor of actions to pursue homeostatic needs. Correspondingly, aIC â NTS circuit activity controls vigor, effort, and striatal dopamine release but only if the action is learned and the outcome is needed. Notably, aICFezf2 neurons do not represent taste or valence. Moreover, aIC â NTS activity neither drives reinforcement nor influences total consumption. These results pinpoint specific functions of aIC â NTS circuit for selectively controlling motivational vigor and suggest that motivation is subserved, in part, by aIC's top-down regulation of dopamine signaling.
Assuntos
Tronco Encefálico/fisiologia , Córtex Insular/fisiologia , Motivação , Vias Neurais/fisiologia , Animais , Comportamento Animal , Dopamina/metabolismo , Feminino , Aprendizagem , Masculino , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Núcleo Accumbens/metabolismo , Fatores de TempoRESUMO
Learning valence-based responses to favorable and unfavorable options requires judgments of the relative value of the options, a process necessary for species survival. We found, using engineered mice, that circuit connectivity and function of the striosome compartment of the striatum are critical for this type of learning. Calcium imaging during valence-based learning exhibited a selective correlation between learning and striosomal but not matrix signals. This striosomal activity encoded discrimination learning and was correlated with task engagement, which, in turn, could be regulated by chemogenetic excitation and inhibition. Striosomal function during discrimination learning was disturbed with aging and severely so in a mouse model of Huntington's disease. Anatomical and functional connectivity of parvalbumin-positive, putative fast-spiking interneurons (FSIs) to striatal projection neurons was enhanced in striosomes compared with matrix in mice that learned. Computational modeling of these findings suggests that FSIs can modulate the striosomal signal-to-noise ratio, crucial for discrimination and learning.
Assuntos
Envelhecimento/patologia , Corpo Estriado/patologia , Doença de Huntington/patologia , Aprendizagem , Potenciais de Ação , Animais , Comportamento Animal , Biomarcadores/metabolismo , Corpo Estriado/fisiopatologia , Aprendizagem por Discriminação , Modelos Animais de Doenças , Doença de Huntington/fisiopatologia , Interneurônios/patologia , Camundongos Transgênicos , Modelos Neurológicos , Rede Nervosa/fisiopatologia , Parvalbuminas/metabolismo , Fotometria , Recompensa , Análise e Desempenho de TarefasRESUMO
The striosome compartment within the dorsal striatum has been implicated in reinforcement learning and regulation of motivation, but how striosomal neurons contribute to these functions remains elusive. Here, we show that a genetically identified striosomal population, which expresses the Teashirt family zinc finger 1 (Tshz1) and belongs to the direct pathway, drives negative reinforcement and is essential for aversive learning in mice. Contrasting a "conventional" striosomal direct pathway, the Tshz1 neurons cause aversion, movement suppression, and negative reinforcement once activated, and they receive a distinct set of synaptic inputs. These neurons are predominantly excited by punishment rather than reward and represent the anticipation of punishment or the motivation for avoidance. Furthermore, inhibiting these neurons impairs punishment-based learning without affecting reward learning or movement. These results establish a major role of striosomal neurons in behaviors reinforced by punishment and moreover uncover functions of the direct pathway unaccounted for in classic models.
Assuntos
Aprendizagem da Esquiva/fisiologia , Corpo Estriado/fisiologia , Proteínas de Homeodomínio/genética , Proteínas Repressoras/genética , Animais , Gânglios da Base , Feminino , Proteínas de Homeodomínio/metabolismo , Aprendizagem/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Motivação , Neurônios/fisiologia , Punição , Reforço Psicológico , Proteínas Repressoras/metabolismoRESUMO
Nociceptin and its receptor are widely distributed throughout the brain in regions associated with reward behavior, yet how and when they act is unknown. Here, we dissected the role of a nociceptin peptide circuit in reward seeking. We generated a prepronociceptin (Pnoc)-Cre mouse line that revealed a unique subpopulation of paranigral ventral tegmental area (pnVTA) neurons enriched in prepronociceptin. Fiber photometry recordings during progressive ratio operant behavior revealed pnVTAPnoc neurons become most active when mice stop seeking natural rewards. Selective pnVTAPnoc neuron ablation, inhibition, and conditional VTA nociceptin receptor (NOPR) deletion increased operant responding, revealing that the pnVTAPnoc nucleus and VTA NOPR signaling are necessary for regulating reward motivation. Additionally, optogenetic and chemogenetic activation of this pnVTAPnoc nucleus caused avoidance and decreased motivation for rewards. These findings provide insight into neuromodulatory circuits that regulate motivated behaviors through identification of a previously unknown neuropeptide-containing pnVTA nucleus that limits motivation for rewards.
Assuntos
Motivação/efeitos dos fármacos , Peptídeos Opioides/farmacologia , Recompensa , Área Tegmentar Ventral/metabolismo , Potenciais de Ação , Animais , Comportamento Animal/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/fisiologia , Técnicas de Patch-Clamp , Precursores de Proteínas/genética , Receptores Opioides/agonistas , Receptores Opioides/deficiência , Receptores Opioides/genética , Receptor de Nociceptina , NociceptinaRESUMO
Myriad experiences produce transient memory, yet, contingent on the internal state of the organism and the saliency of the experience, only some memories persist over time. How experience and internal state influence the duration of memory at the molecular level remains unknown. A self-assembled aggregated state of Drosophila Orb2A protein is required specifically for long-lasting memory. We report that in the adult fly brain the mRNA encoding Orb2A protein exists in an unspliced non-protein-coding form. The convergence of experience and internal drive transiently increases the spliced protein-coding Orb2A mRNA. A screen identified pasilla, the fly ortholog of mammalian Nova-1/2, as a mediator of Orb2A mRNA processing. A single-nucleotide substitution in the intronic region that reduces Pasilla binding and intron removal selectively impairs long-term memory. We posit that pasilla-mediated processing of unspliced Orb2A mRNA integrates experience and internal state to control Orb2A protein abundance and long-term memory formation.
Assuntos
Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Íntrons , Memória de Longo Prazo , Ribonucleoproteínas/metabolismo , Fatores de Transcrição/genética , Fatores de Poliadenilação e Clivagem de mRNA/genética , Animais , Sequência de Bases , Comportamento Animal , Encéfalo/metabolismo , Condicionamento Psicológico , Proteínas de Drosophila/química , Drosophila melanogaster/genética , Aprendizagem , Modelos Animais , Motivação , Mutação , Isoformas de Proteínas/metabolismo , Splicing de RNA , Fatores de Transcrição/química , Fatores de Transcrição/metabolismo , Fatores de Poliadenilação e Clivagem de mRNA/química , Fatores de Poliadenilação e Clivagem de mRNA/metabolismoRESUMO
Ventral tegmental area (VTA) dopamine (DA) neurons are often thought to uniformly encode reward prediction errors. Conversely, DA release in the nucleus accumbens (NAc), the prominent projection target of these neurons, has been implicated in reinforcement learning, motivation, aversion, and incentive salience. This contrast between heterogeneous functions of DA release versus a homogeneous role for DA neuron activity raises numerous questions regarding how VTA DA activity translates into NAc DA release. Further complicating this issue is increasing evidence that distinct VTA DA projections into defined NAc subregions mediate diverse behavioral functions. Here, we evaluate evidence for heterogeneity within the mesoaccumbal DA system and argue that frameworks of DA function must incorporate the precise topographic organization of VTA DA neurons to clarify their contribution to health and disease.
Assuntos
Dopamina , Área Tegmentar Ventral , Neurônios Dopaminérgicos , Motivação , Núcleo Accumbens/fisiologia , Recompensa , Área Tegmentar Ventral/fisiologiaRESUMO
Neural network computations are usually assumed to emerge from patterns of fast electrical activity. Challenging this view, we show that a male fly's decision to persist in mating hinges on a biochemical computation that enables processing over minutes to hours. Each neuron in a recurrent network contains slightly different internal molecular estimates of mating progress. Protein kinase A (PKA) activity contrasts this internal measurement with input from the other neurons to represent accumulated evidence that the goal of the network has been achieved. When consensus is reached, PKA pushes the network toward a large-scale and synchronized burst of calcium influx that we call an eruption. Eruptions transform continuous deliberation within the network into an all-or-nothing output, after which the male will no longer sacrifice his life to continue mating. Here, biochemical activity, invisible to most large-scale recording techniques, is the key computational currency directing behavior and motivational state.
Assuntos
Sinalização do Cálcio , Cálcio/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas de Drosophila/metabolismo , Rede Nervosa/metabolismo , Neurônios/metabolismo , Animais , Proteínas Quinases Dependentes de AMP Cíclico/genética , Proteínas de Drosophila/genética , Drosophila melanogasterRESUMO
The brain serotonin systems participate in numerous aspects of reward processing, although it remains elusive how exactly serotonin signals regulate neural computation and reward-related behavior. The application of optogenetics and imaging techniques during the last decade has provided many insights. Here, we review recent progress on the organization and physiology of the dorsal raphe serotonin neurons and the relationships between their activity and behavioral functions in the context of reward processing. We also discuss several interesting theories on serotonin's function and how these theories may be reconciled by the possibility that serotonin, acting in synergy with coreleased glutamate, tracks and calculates the so-called beneficialness of the current state to guide an animal's behavior in dynamic environments.
Assuntos
Encéfalo/fisiologia , Neurônios/fisiologia , Recompensa , Serotonina/metabolismo , Animais , Núcleo Dorsal da Rafe/fisiologia , Humanos , Aprendizagem/fisiologiaRESUMO
Apathy is a disabling syndrome associated with poor functional outcomes that is common across a broad range of neurological and psychiatric conditions. Currently, there are no established therapies specifically for the condition, and safe and effective treatments are urgently needed. Advances in the understanding of motivation and goal-directed behavior in humans and animals have shed light on the cognitive and neurobiological mechanisms contributing to apathy, providing an important foundation for the development of new treatments. Here, we review the cognitive components, neural circuitry, and pharmacology of apathy and motivation, highlighting converging evidence of shared transdiagnostic mechanisms. Though no pharmacological treatments have yet been licensed, we summarize trials of existing and novel compounds to date, identifying several promising candidates for clinical use and avenues of future drug development.
Assuntos
Apatia , Transtornos Mentais , Animais , Humanos , Desenvolvimento de MedicamentosRESUMO
Choosing whether to exert effort to obtain rewards is fundamental to human motivated behavior. However, the neural dynamics underlying the evaluation of reward and effort in humans is poorly understood. Here, we report an exploratory investigation into this with chronic intracranial recordings from the prefrontal cortex (PFC) and basal ganglia (BG; subthalamic nuclei and globus pallidus) in people with Parkinson's disease performing a decision-making task with offers that varied in levels of reward and physical effort required. This revealed dissociable neural signatures of reward and effort, with BG beta (12 to 20 Hz) oscillations tracking effort on a single-trial basis and PFC theta (4 to 7 Hz) signaling previous trial reward, with no effects of net subjective value. Stimulation of PFC increased overall acceptance of offers and sensitivity to reward while decreasing the impact of effort on choices. This work uncovers oscillatory mechanisms that guide fundamental decisions to exert effort for reward across BG and PFC, supports a causal role of PFC for such choices, and seeds hypotheses for future studies.
Assuntos
Gânglios da Base , Tomada de Decisões , Doença de Parkinson , Córtex Pré-Frontal , Recompensa , Ritmo Teta , Humanos , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/fisiopatologia , Tomada de Decisões/fisiologia , Gânglios da Base/fisiologia , Gânglios da Base/fisiopatologia , Masculino , Ritmo Teta/fisiologia , Feminino , Doença de Parkinson/fisiopatologia , Pessoa de Meia-Idade , Ritmo beta/fisiologia , IdosoRESUMO
Survival requires the integration of external information and interoceptive cues to effectively guide advantageous behaviors, particularly foraging and other behaviors that promote energy acquisition and consumption. The vagus nerve acts as a critical relay between the abdominal viscera and the brain to convey metabolic signals. This review synthesizes recent findings from rodent models and humans revealing the impact of vagus nerve signaling from the gut on the control of higher-order neurocognitive domains, including anxiety, depression, reward motivation, and learning and memory. We propose a framework where meal consumption engages gastrointestinal tract-originating vagal afferent signaling that functions to alleviate anxiety and depressive-like states, while also promoting motivational and memory functions. These concurrent processes serve to favor the encoding of meal-relevant information into memory storage, thus facilitating future foraging behaviors. Modulation of these neurocognitive domains by vagal tone is also discussed in the context of pathological conditions, including the use of transcutaneous vagus nerve stimulation for the treatment of anxiety disorders, major depressive disorder, and dementia-associated memory impairments. Collectively, these findings highlight the contributions of gastrointestinal vagus nerve signaling to the regulation of neurocognitive processes that shape various adaptive behavioral responses.
Assuntos
Transtorno Depressivo Maior , Humanos , Eixo Encéfalo-Intestino , Encéfalo/fisiologia , Nervo Vago/fisiologia , CogniçãoRESUMO
Payments for ecosystem services (PES) are increasingly being implemented worldwide as conservation instruments that provide conditional economic incentives to landowners for a prespecified duration. However, in the psychological and economic literature, critics have raised concerns that PES can undermine the recipient's intrinsic motivation to engage in pro-environmental behavior. Such "crowding out" may reduce the effectiveness of PES and may even worsen conservation outcomes once programs are terminated. In this study, we harnessed a randomized controlled trial that provided PES to land users in Western Uganda and evaluated whether these incentives had a persistent effect on pro-environmental behavior and its underlying behavioral drivers 6 y after the last payments were made. We elicited pro-environmental behavior with an incentivized, experimental measure that consisted of a choice for respondents between more and less environmentally friendly tree seedlings. In addition to this main outcome, survey-based measures for underlying behavioral drivers captured self-efficacy beliefs, intrinsic motivation, and perceived forest benefits. Overall, we found no indications that PES led to the crowding out of pro-environmental behavior. That is, respondents from the treatment villages were as likely as respondents from the control villages to choose environmentally friendly tree seedlings. We also found no systematic differences between these two groups in their underlying behavioral drivers, and nor did we find evidence for crowding effects when focusing on self-reported tree planting behavior as an alternative outcome measure.
Assuntos
Conservação dos Recursos Naturais , Ecossistema , Humanos , Uganda , Florestas , Árvores , MotivaçãoRESUMO
Motivation influences goals, decisions, and memory formation. Imperative motivation links urgent goals to actions, narrowing the focus of attention and memory. Conversely, interrogative motivation integrates goals over time and space, supporting rich memory encoding for flexible future use. We manipulated motivational states via cover stories for a reinforcement learning task: The imperative group imagined executing a museum heist, whereas the interrogative group imagined planning a future heist. Participants repeatedly chose among four doors, representing different museum rooms, to sample trial-unique paintings with variable rewards (later converted to bonus payments). The next day, participants performed a surprise memory test. Crucially, only the cover stories differed between the imperative and interrogative groups; the reinforcement learning task was identical, and all participants had the same expectations about how and when bonus payments would be awarded. In an initial sample and a preregistered replication, we demonstrated that imperative motivation increased exploitation during reinforcement learning. Conversely, interrogative motivation increased directed (but not random) exploration, despite the cost to participants' earnings. At test, the interrogative group was more accurate at recognizing paintings and recalling associated values. In the interrogative group, higher value paintings were more likely to be remembered; imperative motivation disrupted this effect of reward modulating memory. Overall, we demonstrate that a prelearning motivational manipulation can bias learning and memory, bearing implications for education, behavior change, clinical interventions, and communication.
Assuntos
Motivação , Reforço Psicológico , Humanos , Aprendizagem , Recompensa , Rememoração MentalRESUMO
Effort-based decisions, in which people weigh potential future rewards against effort costs required to achieve those rewards involve both cognitive and physical effort, though the mechanistic relationship between them is not yet understood. Here, we use an individual differences approach to isolate and measure the computational processes underlying effort-based decisions and test the association between cognitive and physical domains. Patch foraging is an ecologically valid reward rate maximization problem with well-developed theoretical tools. We developed the Effort Foraging Task, which embedded cognitive or physical effort into patch foraging, to quantify the cost of both cognitive and physical effort indirectly, by their effects on foraging choices. Participants chose between harvesting a depleting patch, or traveling to a new patch that was costly in time and effort. Participants' exit thresholds (reflecting the reward they expected to receive by harvesting when they chose to travel to a new patch) were sensitive to cognitive and physical effort demands, allowing us to quantify the perceived effort cost in monetary terms. The indirect sequential choice style revealed effort-seeking behavior in a minority of participants (preferring high over low effort) that has apparently been missed by many previous approaches. Individual differences in cognitive and physical effort costs were positively correlated, suggesting that these are perceived and processed in common. We used canonical correlation analysis to probe the relationship of task measures to self-reported affect and motivation, and found correlations of cognitive effort with anxiety, cognitive function, behavioral activation, and self-efficacy, but no similar correlations with physical effort.
Assuntos
Tomada de Decisões , Esforço Físico , Humanos , Tomada de Decisões/fisiologia , Esforço Físico/fisiologia , Individualidade , Cognição/fisiologia , Recompensa , MotivaçãoRESUMO
Representing the probability and uncertainty of outcomes facilitates adaptive behavior by allowing organisms to prepare in advance and devote attention to relevant events. Probability and uncertainty are often studied only for valenced (appetitive or aversive) outcomes, raising the question of whether the identified neural machinery also processes the probability and uncertainty of motivationally neutral outcomes. Here, we aimed to dissociate valenced from valence-independent (i.e., generic) probability (p; maximum at pâ =â 1) and uncertainty (maximum at p = 0.5) signals using human neuroimaging. In a Pavlovian task (n = 41; 19 females), different cues predicted appetitive, aversive, or neutral liquids with different probabilities (p = 0, p = 0.5, p = 1). Cue-elicited motor responses accelerated, and pupil sizes increased primarily for cues that predicted valenced liquids with higher probability. For neutral liquids, uncertainty rather than probability tended to accelerate cue-induced responding and decrease pupil size. At the neural level, generic uncertainty signals were limited to the occipital cortex, while generic probability also activated the anterior ventromedial prefrontal cortex. These generic probability and uncertainty signals contrasted with cue-induced responses that only encoded the probability and uncertainty of valenced liquids in medial prefrontal, insular, and occipital cortices. Our findings show a behavioral and neural dissociation of generic and valenced signals. Thus, some parts of the brain keep track of motivational charge while others do not, highlighting the need and usefulness of characterizing the exact nature of learned representations.
Assuntos
Sinais (Psicologia) , Humanos , Feminino , Masculino , Incerteza , Adulto , Adulto Jovem , Probabilidade , Imageamento por Ressonância Magnética , Pupila/fisiologia , Condicionamento Clássico/fisiologia , Motivação/fisiologia , Mapeamento Encefálico , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/diagnóstico por imagemRESUMO
Reinforcement learning is a theoretical framework that describes how agents learn to select options that maximize rewards and minimize punishments over time. We often make choices, however, to obtain symbolic reinforcers (e.g., money, points) that are later exchanged for primary reinforcers (e.g., food, drink). Although symbolic reinforcers are ubiquitous in our daily lives, widely used in laboratory tasks because they can be motivating, mechanisms by which they become motivating are less understood. In the present study, we examined how monkeys learn to make choices that maximize fluid rewards through reinforcement with tokens. The question addressed here is how the value of a state, which is a function of multiple task features (e.g., the current number of accumulated tokens, choice options, task epoch, trials since the last delivery of primary reinforcer, etc.), drives value and affects motivation. We constructed a Markov decision process model that computes the value of task states given task features to then correlate with the motivational state of the animal. Fixation times, choice reaction times, and abort frequency were all significantly related to values of task states during the tokens task (n = 5 monkeys, three males and two females). Furthermore, the model makes predictions for how neural responses could change on a moment-by-moment basis relative to changes in the state value. Together, this task and model allow us to capture learning and behavior related to symbolic reinforcement.
Assuntos
Comportamento de Escolha , Macaca mulatta , Motivação , Reforço Psicológico , Recompensa , Animais , Motivação/fisiologia , Masculino , Comportamento de Escolha/fisiologia , Tempo de Reação/fisiologia , Cadeias de Markov , FemininoRESUMO
In spite of its familiar phenomenology, the mechanistic basis for mental effort remains poorly understood. Although most researchers agree that mental effort is aversive and stems from limitations in our capacity to exercise cognitive control, it is unclear what gives rise to those limitations and why they result in an experience of control as costly. The presence of these control costs also raises further questions regarding how best to allocate mental effort to minimize those costs and maximize the attendant benefits. This review explores recent advances in computational modeling and empirical research aimed at addressing these questions at the level of psychological process and neural mechanism, examining both the limitations to mental effort exertion and how we manage those limited cognitive resources. We conclude by identifying remaining challenges for theoretical accounts of mental effort as well as possible applications of the available findings to understanding the causes of and potential solutions for apparent failures to exert the mental effort required of us.
Assuntos
Cognição/fisiologia , Tomada de Decisões/fisiologia , Função Executiva/fisiologia , Motivação/fisiologia , Córtex Pré-Frontal/fisiologia , Humanos , RecompensaRESUMO
Postoperative apathy is a frequent symptom in Parkinson's disease patients who have undergone bilateral deep brain stimulation of the subthalamic nucleus. Two main hypotheses for postoperative apathy have been suggested: (i) dopaminergic withdrawal syndrome relative to postoperative dopaminergic drug tapering; and (ii) direct effect of chronic stimulation of the subthalamic nucleus. The primary objective of our study was to describe preoperative and 1-year postoperative apathy in Parkinson's disease patients who underwent chronic bilateral deep brain stimulation of the subthalamic nucleus. We also aimed to identify factors associated with 1-year postoperative apathy considering: (i) preoperative clinical phenotype; (ii) dopaminergic drug management; and (iii) volume of tissue activated within the subthalamic nucleus and the surrounding structures. We investigated a prospective clinical cohort of 367 patients before and 1â year after chronic bilateral deep brain stimulation of the subthalamic nucleus. We assessed apathy using the Lille Apathy Rating Scale and carried out a systematic evaluation of motor, cognitive and behavioural signs. We modelled the volume of tissue activated in 161 patients using the Lead-DBS toolbox and analysed overlaps within motor, cognitive and limbic parts of the subthalamic nucleus. Of the 367 patients, 94 (25.6%) exhibited 1-year postoperative apathy: 67 (18.2%) with 'de novo apathy' and 27 (7.4%) with 'sustained apathy'. We observed disappearance of preoperative apathy in 22 (6.0%) patients, who were classified as having 'reversed apathy'. Lastly, 251 (68.4%) patients had neither preoperative nor postoperative apathy and were classified as having 'no apathy'. We identified preoperative apathy score [odds ratio (OR) 1.16; 95% confidence interval (CI) 1.10, 1.22; P < 0.001], preoperative episodic memory free recall score (OR 0.93; 95% CI 0.88, 0.97; P = 0.003) and 1-year postoperative motor responsiveness (OR 0.98; 95% CI 0.96, 0.99; P = 0.009) as the main factors associated with postoperative apathy. We showed that neither dopaminergic dose reduction nor subthalamic stimulation were associated with postoperative apathy. Patients with 'sustained apathy' had poorer preoperative fronto-striatal cognitive status and a higher preoperative action initiation apathy subscore. In these patients, apathy score and cognitive status worsened postoperatively despite significantly lower reduction in dopamine agonists (P = 0.023), suggesting cognitive dopa-resistant apathy. Patients with 'reversed apathy' benefited from the psychostimulant effect of chronic stimulation of the limbic part of the left subthalamic nucleus (P = 0.043), suggesting motivational apathy. Our results highlight the need for careful preoperative assessment of motivational and cognitive components of apathy as well as executive functions in order to better prevent or manage postoperative apathy.