RESUMO
Humans often face the challenge of making decisions between ambiguous options. The level of ambiguity in decision-making has been linked to activity in the parietal cortex, but its exact computational role remains elusive. To test the hypothesis that the parietal cortex plays a causal role in computing ambiguous probabilities, we conducted consecutive fMRI and TMS-EEG studies. We found that participants assigned unknown probabilities to objective probabilities, elevating the uncertainty of their decisions. Parietal cortex activity correlated with the objective degree of ambiguity and with a process that underestimates the uncertainty during decision-making. Conversely, the midcingulate cortex (MCC) encodes prediction errors and increases its connectivity with the parietal cortex during outcome processing. Disruption of the parietal activity increased the uncertainty evaluation of the options, decreasing cingulate cortex oscillations during outcome evaluation and lateral frontal oscillations related to value ambiguous probability. These results provide evidence for a causal role of the parietal cortex in computing uncertainty during ambiguous decisions made by humans.
Assuntos
Mapeamento Encefálico , Tomada de Decisões , Humanos , Mapeamento Encefálico/métodos , Assunção de Riscos , Incerteza , Lobo Parietal , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past 10 years, tDCS physiologic mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodologic, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. METHODS: We convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research. MAIN FINDINGS/DISCUSSION: We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (1) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (2) methodologic aspects related to the clinical research of tDCS as divided according to study phase (ie, preclinical, phase I, phase II, and phase III studies); (3) ethical and regulatory concerns; and (4) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS.
Assuntos
Pesquisa Biomédica/tendências , Encefalopatias/fisiopatologia , Encefalopatias/terapia , Encéfalo/fisiopatologia , Previsões , Estimulação Magnética Transcraniana/tendências , Animais , HumanosRESUMO
Social isolation in rodents is the most well characterized animal model for early stressful experiences and their neurobehavioral consequences. The present study analyzed the effects of early social isolation on the expression of the calcium binding protein calbindin-D28k (CAD) and dendritic arborization in the medial prefrontal cortex (mPFC) of the rat. Sprague-Dawley male rats were reared either under isolation or social conditions from 21 to 51 postnatal days. At the end of this period the animals were behaviorally evaluated in the open-field test, sacrificed, and mPFC serial sections were processed either for immunocytochemical labeling against CAD or Golgi-Cox-Sholl staining. Isolated-reared rats exhibited a dramatic decrease in the number of CAD immunoreactive neurons and a significant dendritic atrophy of layer II/III pyramidal cells in association with a reduced exploratory behavior.
Assuntos
Dendritos/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/ultraestrutura , Proteína G de Ligação ao Cálcio S100/metabolismo , Isolamento Social/psicologia , Animais , Animais Recém-Nascidos , Comportamento Animal , Calbindina 1 , Calbindinas , Comportamento Exploratório/fisiologia , Imuno-Histoquímica/métodos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
In the present study we evaluated the effects of early social isolation and re-socialization on dendritic development and the expression of the vasoactive intestinal peptide (VIP) in the medial prefrontal cortex (mPFC) of the rat. Sprague-Dawley male rats were reared either in isolation (IC) or social (SC) conditions from postnatal day 18 to 32. Rats were then behaviorally evaluated in the open field test, and approximately half of the animals were sacrificed. Their brains were processed either for immunocytochemical labeling against VIP or for the Golgi-Cox-Sholl staining. The remaining IC rats were re-socialized during 30 additional days. The results demonstrated that early social isolation impair neuronal dendritic arborization and increase the number of VIP-immunoreactive neurons. Furthermore, animals displayed hyperlocomotion in the open-field test. According to our structural, immunocytochemical and open-field data, the resocialization experience was unable to reverse neuronal and behavioral abnormalities.
Assuntos
Dendritos/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Córtex Pré-Frontal/fisiologia , Isolamento Social , Peptídeo Intestinal Vasoativo/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Comportamento Animal , Peso Corporal/fisiologia , Contagem de Células/métodos , Imuno-Histoquímica/métodos , Masculino , Atividade Motora/fisiologia , Neurônios/citologia , Neurônios/fisiologia , Córtex Pré-Frontal/citologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , SocializaçãoRESUMO
Repetitive Magnetic Stimulation (rTMS) has shown to modify the excitability of targeted cortical regions in animals and humans, thus transiently altering the efficiency of neural projections within extended brain networks. Adequate processing and behavioral output depend on a given state of functional interactions between cortical and subcortical nodes within this network. We applied rTMS trains targeted at the visuoparietal (VP) cortex, which is a crucial cortical node of an extended visuo-spatial neural network, in both, intact (n=2) and injured cats (n=2) with unilateral ablation of the VP region. All four intact cats were intensively trained in a set of visuo-spatial tasks consisting in the detection and localization of moving or static targets. In two of these cats, a 50 mm circular coil was centered on the left VP cortex and Sham or real rTMS was delivered during 20 minutes at 1 Hz. Real but not Sham rTMS significantly increased the number of errors in orienting responses towards static but not moving targets, presented at the contralateral visual hemifield (38±4%; and 48±3% p<0.05 vs. pre rTMS), whereas no increase respect to baseline was observed for ipsilateral targets (5±2%; 2±1%; n.s). Performance went back to baseline error levels 45 minutes after the end of the stimulation (4±2; 6±1%). In 2 other animals, the right or left parietal and primary visual cortex was surgically removed, generating a Daily stimulation with 1 Hz rTMS on the intact VP region resulted in a progressive reduction of detection¬orienting mistakes to moving but not static stimuli (down to 34±5% and 28±4% errors; p<0.05). We conclude that rTMS is able to interact with brain networks in both ways, transiently disrupting visuo-spatial processing in normal animals, and also canceling spatial neglect generated by lesions of the same areas. It constitutes, thus, a non-invasive surgery-less method to manipulate brain activity and promote recovery after injuries.