Cf - Neuroscience
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- Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder in Older Adults: Systematic Review and Meta-analysisPublication . Valiengo, Leandro; Maia, Ana; Cotovio, Gonçalo; Gordon, Pedro C; Brunoni, André R; Forlenza, Orestes V; Oliveira-Maia, Albino JBackground Major depressive disorder (MDD) in older adults is a serious public health concern. Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological intervention approved for MDD treatment in adults, but its value in older adults remains unknown. This study aims to systematically review and meta-analyze evidence of rTMS efficacy in MDD treatment among older adults. Methods We systematically reviewed the literature for randomized controlled trials (RCTs) and open-label studies assessing rTMS for the treatment of MDD in patients older than 50 years, published until June 2020. Random-effects meta-analyses using standardized mean differences (SMDs) were conducted to assess change in depression severity score (primary outcome), while odds ratios (ORs) were used to assess secondary categorical outcomes (response and remission). Additionally, univariate meta-regression analyses were performed to identify potential predictors of change in depression severity scores. Results Fourteen RCTs were included in meta-analyses and 26 studies (10 RCTs and 16 open-label studies) in meta-regression. Active rTMS was significantly superior to sham treatment for reduction of severity (SMD = 0.36; 95% CI = 0.13–0.60), as well as response (OR = 3.26; 95% CI = 2.11–5.04) and remission (OR = 4.63; 95% CI = 2.24–9.55). Studies were of moderate to high quality, with funnel plots and Egger’s regression test not suggestive of publication bias. In meta-regressions, higher mean age and number of sessions were significantly associated with greater improvement. Conclusions Our results support that rTMS is an effective, safe, and well-tolerated treatment for MDD in older adults and that it should be considered in the treatment of this vulnerable population.
- Reward-related gustatory and psychometric predictors of weight loss following bariatric surgery: a multicenter cohort studyPublication . Ribeiro, Gabriela; Camacho, Marta; Fernandes, Ana B; Cotovio, Gonçalo; Torres, Sandra; Oliveira-Maia, Albino JBackground Reward sensitivity has been proposed as a potential mediator of outcomes for bariatric surgery. Objectives We aimed to determine whether gustatory and psychometric measures of reward-related feeding are predictors of bariatric-induced weight loss. Methods A multicenter longitudinal cohort study was conducted in patients scheduled for bariatric surgery (surgical group), assessed at baseline and 2 follow-up assessments. Predictions of % weight loss from baseline (%WL) according to baseline gustatory measures, including intensity and pleasantness ratings of sweet and other tastants, and psychometric measures of reward-related feeding behavior, including hedonic hunger scores, were assessed with multivariable linear regression. Exploratory analyses were conducted to test for associations between %WL and changes in gustatory and psychophysical measures, as well as for comparisons with data from patients on the surgery waiting list (control group). Results We included 212 patients, of whom 96 in the surgical group and 50 in the control group were prospectively assessed. The groups were similar at baseline and, as expected, bariatric surgery resulted in higher %WL (BTreatment-Time = 2.4; 95% CI: 2.1–2.8; P < 0.0001). While variation in gustatory measures did not differ between groups, in the surgery group baseline sweet intensity predicted %WL at the primary endpoint (11 to 18 months postoperatively; β = 0.2; B = 0.2, 95% CI: 0.02 to 0.3; P = 0.02), as did hedonic hunger scores (β = −0.2; B = −2.0, 95% CI: −3.8 to −0.3; P = 0.02). Furthermore, at this endpoint, postsurgical reduction of sweet taste intensity and acceptance of sweet foods were associated with %WL (β = −0.3; B = −3.5, 95% CI: −5.8 to −1.3; P = 0.003, and β = −0.2; B = −4.7, 95% CI: −8.5 to −0.8; P = 0.02, respectively). The use of sweet intensity as a predictor of weight change was confirmed in another bariatric cohort. Conclusions Sweet intensity ratings and hedonic hunger scores predict %WL after surgery. The variability of sweet intensity ratings is also associated with %WL, further suggesting they may reflect physiological processes that are variably modulated by bariatric surgery, influencing clinical outcomes.
- Sweet taste and obesityPublication . Ribeiro, Gabriela; Oliveira-Maia, Albino J.For more than 50 years, there has been evidence for greater consumption of sweet- foods in overweight humans and animals, relative to those that have a normal weight. Furthermore, it has long been suggested that energy deficit resulting from dieting, while moving the individual from a higher weight set point, would result in heightened susceptibility to palatable tastants, namely to sweet tastants. This was the motivation behind the first studies comparing sweet taste perception between individuals with obesity and those of a normal weight. These studies, using direct measures of taste, have been characterized by significant methodological heterogeneity, contributing towards variability in results and conclusions. Nevertheless, some of these findings have been used to support the theory that patients with obesity have decreased taste perception, particularly for sweet tastants. A similar hypothesis has been proposed regarding evidence for reduced brain dopamine receptors in obesity and, in both cases, it is proposed that increased food consumption, and associated weight gain, result from the need to increase sensory and brain stimulation. However, the available literature is not conclusive on the association between obesity and reduced sweet taste perception, with both negative and contradictory findings in comparisons between individuals with obesity and normal weight control subjects, as well as within-subject comparisons before and after bariatric surgery. Nevertheless, following either Roux-en-Y gastric bypass or sleeve gastrectomy, there is evidence of changes in taste perception, particularly for reward-related measures of sweet tastants, that should be further tested and confirmed in large samples, using consensual methodology.
- Explicit knowledge of task structure is a primary determinant of human model-based actionPublication . Castro-Rodrigues, Pedro; Akam, Thomas; Snorasson, Ivar; Camacho, Marta; Paixão, Vitor; Maia, Ana; Barahona-Corrêa, J. Bernardo; Dayan, Peter; Simpson, H. Blair; Costa, Rui M.; Oliveira-Maia, Albino J.Explicit information obtained through instruction profoundly shapes human choice behaviour. However, this has been studied in computationally simple tasks, and it is unknown how model-based and model-free systems, respectively generating goal-directed and habitual actions, are affected by the absence or presence of instructions. We assessed behaviour in a variant of a computationally more complex decision-making task, before and after providing information about task structure, both in healthy volunteers and in individuals suffering from obsessive-compulsive or other disorders. Initial behaviour was model-free, with rewards directly reinforcing preceding actions. Model-based control, employing predictions of states resulting from each action, emerged with experience in a minority of participants, and less in those with obsessive-compulsive disorder. Providing task structure information strongly increased model-based control, similarly across all groups. Thus, in humans, explicit task structural knowledge is a primary determinant of model-based reinforcement learning and is most readily acquired from instruction rather than experience.
- Metastable attractors explain the variable timing of stable behavioral action sequencesPublication . Recanatesi, S; Pereira-Obilinovic, U; Murakami, M; Mainen, ZF; Mazucatto, L
- An effect of serotonergic stimulation on learning rates for rewards apparent after long intertrial intervalsPublication . Iigaya, Kiyohito; Fonseca, Madalena S.; Murakami, Masayoshi; Mainen, Zachary F.; Dayan, PeterSerotonin has widespread, but computationally obscure, modulatory effects on learning and cognition. Here, we studied the impact of optogenetic stimulation of dorsal raphe serotonin neurons in mice performing a non-stationary, reward-driven decision-making task. Animals showed two distinct choice strategies. Choices after short inter-trial-intervals (ITIs) depended only on the last trial outcome and followed a win-stay-lose-switch pattern. In contrast, choices after long ITIs reflected outcome history over multiple trials, as described by reinforcement learning models. We found that optogenetic stimulation during a trial significantly boosted the rate of learning that occurred due to the outcome of that trial, but these effects were only exhibited on choices after long ITIs. This suggests that serotonin neurons modulate reinforcement learning rates, and that this influence is masked by alternate, unaffected, decision mechanisms. These results provide insight into the role of serotonin in treating psychiatric disorders, particularly its modulation of neural plasticity and learning.
- Postingestive Modulation of Food Seeking Depends on Vagus-Mediated Dopamine Neuron ActivityPublication . Fernandes, Ana B.; Alves da Silva, Joaquim; Almeida, Joana; Cui, Guohong; Gerfen, Charles R.; Costa, Rui M.; Oliveira-Maia, Albino J.Postingestive nutrient sensing can induce food preferences. However, much less is known about the ability of postingestive signals to modulate food-seeking behaviors. Here we report a causal connection between postingestive sucrose sensing and vagus-mediated dopamine neuron activity in the ventral tegmental area (VTA), supporting food seeking. The activity of VTA dopamine neurons increases significantly after administration of intragastric sucrose, and deletion of the NMDA receptor in these neurons, which affects bursting and plasticity, abolishes lever pressing for postingestive sucrose delivery. Furthermore, lesions of the hepatic branch of the vagus nerve significantly impair postingestive-dependent VTA dopamine neuron activity and food seeking, whereas optogenetic stimulation of left vagus nerve neurons significantly increases VTA dopamine neuron activity. These data establish a necessary role of vagus-mediated dopamine neuron activity in postingestive-dependent food seeking, which is independent of taste signaling.
- Optogenetic Recruitment of Dorsal Raphe Serotonergic Neurons Acutely Decreases Mechanosensory Responsivity in Behaving MicePublication . Dugué, Guillaume P.; Lörincz, Magor L.; Lottem, Eran; Audero, Enrica; Matias, Sara; Correia, Patricia A.; Léna, Clément; Mainen, Zachary F.The inhibition of sensory responsivity is considered a core serotonin function, yet this hypothesis lacks direct support due to methodological obstacles. We adapted an optogenetic approach to induce acute, robust and specific firing of dorsal raphe serotonergic neurons. In vitro, the responsiveness of individual dorsal raphe serotonergic neurons to trains of light pulses varied with frequency and intensity as well as between cells, and the photostimulation protocol was therefore adjusted to maximize their overall output rate. In vivo, the photoactivation of dorsal raphe serotonergic neurons gave rise to a prominent light-evoked field response that displayed some sensitivity to a 5-HT1A agonist, consistent with autoreceptor inhibition of raphe neurons. In behaving mice, the photostimulation of dorsal raphe serotonergic neurons produced a rapid and reversible decrease in the animals' responses to plantar stimulation, providing a new level of evidence that serotonin gates sensory-driven responses.
- Orbitofrontal Cortex Is Required for Optimal Waiting Based on Decision ConfidencePublication . Lak, Armin; Costa, Gil M.; Romberg, Erin; Koulakov, Alexei A.; Mainen, Zachary F.; Kepecs, AdamConfidence judgments are a central example of metacognition-knowledge about one's own cognitive processes. According to this metacognitive view, confidence reports are generated by a second-order monitoring process based on the quality of internal representations about beliefs. Although neural correlates of decision confidence have been recently identified in humans and other animals, it is not well understood whether there are brain areas specifically important for confidence monitoring. To address this issue, we designed a postdecision temporal wagering task in which rats expressed choice confidence by the amount of time they were willing to wait for reward. We found that orbitofrontal cortex inactivation disrupts waiting-based confidence reports without affecting decision accuracy. Furthermore, we show that a normative model can quantitatively account for waiting times based on the computation of decision confidence. These results establish an anatomical locus for a metacognitive report, confidence judgment, distinct from the processes required for perceptual decisions.
- Neural antecedents of self-initiated actions in secondary motor cortexPublication . Murakami, Masayoshi; Vicente, M Inês; Costa, Gil M; Mainen, Zachary FThe neural origins of spontaneous or self-initiated actions are not well understood and their interpretation is controversial. To address these issues, we used a task in which rats decide when to abort waiting for a delayed tone. We recorded neurons in the secondary motor cortex (M2) and interpreted our findings in light of an integration-to-bound decision model. A first population of M2 neurons ramped to a constant threshold at rates proportional to waiting time, strongly resembling integrator output. A second population, which we propose provide input to the integrator, fired in sequences and showed trial-to-trial rate fluctuations correlated with waiting times. An integration model fit to these data also quantitatively predicted the observed inter-neuronal correlations. Together, these results reinforce the generality of the integration-to-bound model of decision-making. These models identify the initial intention to act as the moment of threshold crossing while explaining how antecedent subthreshold neural activity can influence an action without implying a decision.