RESUMO
Higher cardiorespiratory fitness has been associated with improved cognitive control in preadolescent children, with various studies highlighting related brain health benefits. This cross-sectional study aimed to provide novel insights into the fitness-cognition relationship by investigating task-related changes in effective connectivity within two brain networks involved in cognitive control: the cingulo-opercular and fronto-parietal networks. Twenty-four higher-fit and twenty-four lower-fit preadolescent children completed a modified flanker task that modulated inhibitory control demand while their EEG and task performance were concurrently recorded. Effective connectivity for correct trials in the theta band was estimated using directed transfer function. The results indicate that children with higher fitness levels demonstrated greater connectivity in specific directions within the cingulo-opercular network (average effect size, d = 0.72). Brain-behavior correlations demonstrated a positive association between the majority of these connections and general task accuracy, which was also higher in higher fit children (average correlation coefficient, ρ = 0.34). The findings further support a positive relationship between fitness and cognitive performance in children. EEG findings offer novel insights into the potential brain mechanisms underlying the fitness-cognition relationship. The study suggests that increased task-related connectivity within the cingulo-opercular network may mediate the cognitive benefits associated with higher fitness levels in preadolescent children.
Assuntos
Aptidão Cardiorrespiratória , Cognição , Eletroencefalografia , Humanos , Criança , Cognição/fisiologia , Masculino , Feminino , Aptidão Cardiorrespiratória/fisiologia , Estudos Transversais , Rede Nervosa/fisiologia , Giro do Cíngulo/fisiologia , Encéfalo/fisiologiaRESUMO
Pain aversion is an avoidance response to painful stimuli. Previous research has indicated that the anterior cingulate cortex (ACC) is involved in pain aversion processing. However, as interneurons, the role of GABAergic neurons in the ACC (GABAACC neurons) in pain aversion is still unclear. Electroacupuncture (EA) has been shown to ameliorate pain aversion, but the mechanism is not clarified. The present study provided evidence that inhibition of GABAACC neurons contributed to pain aversion. EA alleviated pain aversion by activating GABAACC neurons in an intensity-dependent manner. Specifically, 0.3 mA EA stimulation showed better effects on pain aversion than 0.1 mA stimulation, which could be reversed by chemical genetic inhibition of GABAACC neurons. These results provide a novel mechanism by which EA alleviates pain aversion by reversing GABAACC neurons.
Assuntos
Carragenina , Eletroacupuntura , Neurônios GABAérgicos , Giro do Cíngulo , Dor , Eletroacupuntura/métodos , Neurônios GABAérgicos/metabolismo , Animais , Giro do Cíngulo/fisiopatologia , Giro do Cíngulo/fisiologia , Dor/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Aprendizagem da Esquiva/fisiologiaRESUMO
Anorexia nervosa (AN) is associated with food restriction and significantly low body weight, but the neurobiology of food avoidance in AN is unknown. Animal research suggests that food avoidance can be triggered by conditioned fear that engages the anterior cingulate and nucleus accumbens. We hypothesized that the neural activation during food avoidance in AN could be modeled based on aversive goal value processing. Nineteen females with AN and thirty healthy controls matched for age underwent functional magnetic resonance brain imaging while conducting a food avoidance task. During active control free-bid and computer-generated forced-bid trials, participants bid money to avoid eating food items. Brain activation was parametrically modulated with the trial-by-trial placed bids. During free-bid trials, the AN group engaged the caudate nucleus, nucleus accumbens, ventral anterior cingulate, and inferior and medial orbitofrontal cortex more than the control group. High- versus low-bid trials in the AN group were associated with higher caudate nucleus response. Emotion dysregulation and intolerance of uncertainty scores were inversely associated with nucleus accumbens free-bid trial brain response in AN. This study supports the idea that food avoidance behavior in AN involves aversive goal value computation in the nucleus accumbens, caudate nucleus, anterior cingulate, and orbitofrontal cortex.
Assuntos
Anorexia Nervosa , Aprendizagem da Esquiva , Objetivos , Imageamento por Ressonância Magnética , Humanos , Feminino , Anorexia Nervosa/psicologia , Anorexia Nervosa/fisiopatologia , Adulto , Adulto Jovem , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Núcleo Accumbens/fisiologia , Núcleo Accumbens/fisiopatologia , Adolescente , Núcleo Caudado/fisiopatologia , Giro do Cíngulo/fisiopatologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Estudos de Casos e Controles , Mapeamento Encefálico/métodos , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/fisiopatologiaRESUMO
Marked dysregulation of the human prefrontal cortex (PFC) and anterior cingulate cortex (ACC) characterises a variety of anxiety disorders, and its amelioration is a key feature of treatment success. Overall treatment response, however, is highly variable, and about a third of patients are resistant to treatment. In this review we hypothesise that a major contributor to this variation in treatment response are the multiple faces of anxiety induced by distinct forms of frontal cortex dysregulation. Comparison of findings from humans and non-human primates reveals marked similarity in the functional organisation of threat regulation across the frontal lobes. This organisation is discussed in relation to the 'predatory imminence continuum' model of threat and the differential engagement of executive functions at the core of both emotion generation and regulation strategies.
Assuntos
Ansiedade , Lobo Frontal , Humanos , Animais , Lobo Frontal/fisiologia , Ansiedade/fisiopatologia , Córtex Pré-Frontal/fisiologia , Giro do Cíngulo/fisiologiaRESUMO
How cellular adaptations give rise to opioid analgesic tolerance to opioids like morphine is not well understood. For one, pain is a complex phenomenon comprising both sensory and affective components, largely mediated through separate circuits. Glutamatergic projections from the medial thalamus (MThal) to the anterior cingulate cortex (ACC) are implicated in processing of affective pain, a relatively understudied component of the pain experience. The goal of this study was to determine the effects of chronic morphine exposure on mu-opioid receptor (MOR) signaling on MThal-ACC synaptic transmission within the excitatory and feedforward inhibitory pathways. Using whole cell patch-clamp electrophysiology and optogenetics to selectively target these projections, we measured morphine-mediated inhibition of optically evoked postsynaptic currents in ACC layer V pyramidal neurons in drug-naïve and chronically morphine-treated mice. We found that morphine perfusion inhibited the excitatory and feedforward inhibitory pathways similarly in females but caused greater inhibition of the inhibitory pathway in males. Chronic morphine treatment robustly attenuated morphine presynaptic inhibition within the inhibitory pathway in males, but not females, and mildly attenuated presynaptic inhibition within the excitatory pathway in both sexes. These effects were not observed in MOR phosphorylation-deficient mice. This study indicates that chronic morphine treatment induces cellular tolerance to morphine within a thalamo-cortical circuit relevant to pain and opioid analgesia. Furthermore, it suggests this tolerance may be driven by MOR phosphorylation. Overall, these findings improve our understanding of how chronic opioid exposure alters cellular signaling in ways that may contribute to opioid analgesic tolerance.NEW & NOTEWORTHY Opioid signaling within the anterior cingulate cortex (ACC) is important for opioid modulation of affective pain. Glutamatergic medial thalamus (MThal) neurons synapse in the ACC and opioids, acting through mu opioid receptors (MORs), acutely inhibit synaptic transmission from MThal synapses. However, the effect of chronic opioid exposure on MThal-ACC synaptic transmission is not known. Here, we demonstrate that chronic morphine treatment induces cellular tolerance at these synapses in a sex-specific and phosphorylation-dependent manner.
Assuntos
Analgésicos Opioides , Morfina , Receptores Opioides mu , Tálamo , Animais , Receptores Opioides mu/metabolismo , Morfina/farmacologia , Morfina/administração & dosagem , Masculino , Feminino , Camundongos , Analgésicos Opioides/farmacologia , Analgésicos Opioides/administração & dosagem , Tálamo/efeitos dos fármacos , Tálamo/fisiologia , Tálamo/metabolismo , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiologia , Giro do Cíngulo/metabolismo , Sinapses/efeitos dos fármacos , Sinapses/fisiologia , Tolerância a Medicamentos/fisiologia , Camundongos Endogâmicos C57BL , Caracteres Sexuais , Transdução de Sinais/efeitos dos fármacos , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologiaRESUMO
BACKGROUND: Detecting and responding to errors is central to goal-directed behavior and cognitive control and is thought to be supported by a network of structures that includes the anterior cingulate cortex and anterior insula. Sex differences in the maturational timing of cognitive control systems create differential periods of vulnerability for psychiatric conditions, such as substance use disorders. METHODS: We examined sex differences in error-related activation across an array of distributed brain regions during a Go/No-Go task in young adults with problem alcohol use (N=69; 34 females; M=19.4 years). Regions of interest previously linked to error-related activation, including anterior cingulate cortex, insula, and frontoparietal structures, were selected in a term-based meta-analysis. Individual differences in their responses to false alarm (FA) inhibitory errors relative to "go" trials (FA>GO) and correct rejections (FA>CR) were indexed using multivariate summary measures derived from principal components analysis. RESULTS: FA>GO and FA>CR activation both revealed a first component that explained the majority of the variance across error-associated regions and displayed the strongest loadings on salience network structures. Compared to females, males exhibited significantly higher levels of the FA>GO component but not the FA>CR component. CONCLUSIONS: Males exhibit greater salience network activation in response to inhibitory errors, which could be attributed to sex differences in error-monitoring processes or to other functions (e.g., novelty detection). The findings are relevant for the further characterization of sex differences in cognitive control and may have implications for understanding individual differences in those at risk for substance use or other cognitive control disorders.
Assuntos
Imageamento por Ressonância Magnética , Caracteres Sexuais , Humanos , Masculino , Feminino , Adulto Jovem , Alcoolismo/fisiopatologia , Adolescente , Encéfalo/fisiologia , Adulto , Inibição Psicológica , Giro do Cíngulo/fisiologia , Mapeamento EncefálicoRESUMO
Task-switching is a fundamental cognitive ability that allows animals to update their knowledge of current rules or contexts. Detecting discrepancies between predicted and observed events is essential for this process. However, little is known about how the brain computes cognitive prediction-errors and whether neural prediction-error signals are causally related to task-switching behaviours. Here we trained mice to use a prediction-error to switch, in a single trial, between responding to the same stimuli using two distinct rules. Optogenetic silencing and un-silencing, together with widefield and two-photon calcium imaging revealed that the anterior cingulate cortex (ACC) was specifically required for this rapid task-switching, but only when it exhibited neural prediction-error signals. These prediction-error signals were projection-target dependent and were larger preceding successful behavioural transitions. An all-optical approach revealed a disinhibitory interneuron circuit required for successful prediction-error computation. These results reveal a circuit mechanism for computing prediction-errors and transitioning between distinct cognitive states.
Assuntos
Giro do Cíngulo , Optogenética , Animais , Giro do Cíngulo/fisiologia , Camundongos , Masculino , Cognição/fisiologia , Camundongos Endogâmicos C57BL , Comportamento Animal/fisiologia , Interneurônios/fisiologiaRESUMO
Egocentric neural representations of environmental features, such as edges and vertices, are important for constructing a geometrically detailed egocentric cognitive map for goal-directed navigation and episodic memory. While egocentric neural representations of edges like egocentric boundary/border cells exist, those that selectively represent vertices egocentrically are yet unknown. Here we report that granular retrosplenial cortex (RSC) neurons in male mice generate spatial receptive fields exclusively near the vertices of environmental geometries during free exploration, termed vertex cells. Their spatial receptive fields occurred at a specific orientation and distance relative to the heading direction of mice, indicating egocentric vector coding of vertex. Removing physical boundaries defining the environmental geometry abolished the egocentric vector coding of vertex, and goal-directed navigation strengthened the egocentric vector coding at the goal-located vertex. Our findings suggest that egocentric vector coding of vertex by granular RSC neurons helps construct an egocentric cognitive map that guides goal-directed navigation.
Assuntos
Neurônios , Animais , Masculino , Neurônios/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Percepção Espacial/fisiologia , Córtex Cerebral/fisiologia , Córtex Cerebral/citologia , Giro do Cíngulo/fisiologia , Giro do Cíngulo/citologia , Orientação/fisiologia , Navegação Espacial/fisiologiaRESUMO
Cortical neurons store information across different timescales, from seconds to years. Although information stability is variable across regions, it can vary within a region as well. Association areas are known to multiplex behaviorally relevant variables, but the stability of their representations is not well understood. Here, we longitudinally recorded the activity of neuronal populations in the mouse retrosplenial cortex (RSC) during the performance of a context-choice association task. We found that the activity of neurons exhibits different levels of stability across days. Using linear classifiers, we quantified the stability of three task-relevant variables. We find that RSC representations of context and trial outcome display higher stability than motor choice, both at the single cell and population levels. Together, our findings show an important characteristic of association areas, where diverse streams of information are stored with varying levels of stability, which may balance representational reliability and flexibility according to behavioral demands.
Assuntos
Neurônios , Animais , Neurônios/fisiologia , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Comportamento de Escolha/fisiologia , Córtex Cerebral/fisiologia , Córtex Cerebral/citologia , Giro do Cíngulo/fisiologia , Giro do Cíngulo/citologia , Comportamento Animal/fisiologiaRESUMO
Making choices about whether and when to engage cognitive effort are a common feature of everyday experience, with important consequences for academic, career, and health outcomes. Yet, despite their hypothesized importance, very little is understood about the underlying mechanisms that support this form of human cost-benefit decision-making. To investigate these mechanisms, we used the Cognitive Effort Discounting Paradigm (Cog-ED) during fMRI scanning to precisely quantify the neural encoding of varying cognitive effort demands relative to reward outcomes, within two distinct cognitive domains (working memory, speech comprehension). The findings provide strong evidence that the dorsal anterior cingulate cortex (dACC) plays a central and selective role in this decision-making process. Trial-by-trial modulations in dACC activation tracked the relative subjective value of the low-effort, low-reward option, with the strongest activity occurring when this was of greater value than the high-effort, high-reward option. In contrast, dACC activity was not modulated by decision difficulty, though such effects were found in other frontoparietal regions. Critically, dACC activity was also strongly correlated across the two decision-making task domains and further predicted subsequent choice behavior in both. Together, the results suggest that dACC activity modulation reflects a domain-general valuation comparison mechanism, which acts to bias participants away from decisions to engage in cognitive effort, when the perceived subjective costs of such engagement outweigh the reward-related benefits. These findings complement work in other cost domains and species by pointing to a clear role of the dACC in representing subjective value differences between choice options during cost-benefit decision-making.
Assuntos
Cognição , Tomada de Decisões , Giro do Cíngulo , Imageamento por Ressonância Magnética , Recompensa , Humanos , Masculino , Feminino , Giro do Cíngulo/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Adulto , Adulto Jovem , Cognição/fisiologia , Tomada de Decisões/fisiologia , Memória de Curto Prazo/fisiologia , Comportamento de Escolha/fisiologia , Mapeamento EncefálicoRESUMO
The anterior cingulate cortex (ACC) has been implicated across multiple highly specialized cognitive functions-including task engagement, motivation, error detection, attention allocation, value processing, and action selection. Here, we ask if ACC lesions disrupt task performance and firing in dorsomedial striatum (DMS) during the performance of a reward-guided decision-making task that engages many of these cognitive functions. We found that ACC lesions impacted several facets of task performance-including decreasing the initiation and completion of trials, slowing reaction times, and resulting in suboptimal and inaccurate action selection. Reductions in movement times towards the end of behavioral sessions further suggested attenuations in motivation, which paralleled reductions in directional action selection signals in the DMS that were observed later in recording sessions. Surprisingly, however, beyond altered action signals late in sessions-neural correlates in the DMS were largely unaffected, even though behavior was disrupted at multiple levels. We conclude that ACC lesions result in overall deficits in task engagement that impact multiple facets of task performance during our reward-guided decision-making task, which-beyond impacting motivated action signals-arise from dysregulated attentional signals in the ACC and are mediated via downstream targets other than DMS.
Assuntos
Corpo Estriado , Tomada de Decisões , Giro do Cíngulo , Neurônios , Recompensa , Giro do Cíngulo/fisiologia , Giro do Cíngulo/fisiopatologia , Animais , Masculino , Tomada de Decisões/fisiologia , Neurônios/fisiologia , Corpo Estriado/fisiologia , Corpo Estriado/fisiopatologia , Potenciais de Ação/fisiologia , Tempo de Reação/fisiologia , Motivação/fisiologia , Desempenho Psicomotor/fisiologiaRESUMO
The functional organization of the frontal lobe is a source of debate, focusing on broad functional subdivisions, large-scale networks, or local refined specificities. Multiple neurocognitive models have tried to explain how functional interactions between cingulate and lateral frontal regions contribute to decision making and cognitive control, but their neuroanatomical bases remain unclear. We provide a detailed description of the functional connectivity between cingulate and lateral frontal regions using resting-state functional MRI in rhesus macaques. The analysis focuses on the functional connectivity of the rostral part of the cingulate sulcus with the lateral frontal cortex. Data-driven and seed-based analysis revealed three clusters within the cingulate sulcus organized along the rostro-caudal axis: the anterior, mid, and posterior clusters display increased functional connectivity with, respectively, the anterior lateral prefrontal regions, face-eye lateral frontal motor cortical areas, and hand lateral frontal motor cortex. The location of these clusters can be predicted in individual subjects based on morphological landmarks. These results suggest that the anterior cluster corresponds to the anterior cingulate cortex, whereas the posterior clusters correspond to the face-eye and hand cingulate motor areas within the anterior midcingulate cortex. These data provide a comprehensive framework to identify cingulate subregions based on functional connectivity and local organization.
Assuntos
Mapeamento Encefálico , Giro do Cíngulo , Macaca mulatta , Imageamento por Ressonância Magnética , Vias Neurais , Giro do Cíngulo/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Animais , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodos , Masculino , Vias Neurais/fisiologia , Vias Neurais/diagnóstico por imagem , Lobo Frontal/fisiologia , Lobo Frontal/diagnóstico por imagem , FemininoRESUMO
The anterior cingulate cortex gyrus (ACCg) has been implicated in prosocial behaviors and reasoning about social cues. While this indicates that ACCg is involved in social behavior, it remains unclear whether ACCg neurons also encode social information during goal-directed actions without social consequences. To address this, we assessed how social information is processed by ACCg neurons in a reward localization task. Here we show that neurons in the ACCg of female rhesus monkeys differentiate the identities of conspecifics in task images, even when identity was task-irrelevant. This was in contrast to the prearcuate cortex (PAC), which has not been strongly linked to social behavior, where neurons differentiated identities in both social and nonsocial images. Many neurons in the ACCg also categorically distinguished social from nonsocial trials, but this encoding was only slightly more common in ACCg compared to the PAC. Together, our results suggest that ACCg neurons are uniquely sensitive to social information that differentiates individuals, which may underlie its role in complex social reasoning.
Assuntos
Giro do Cíngulo , Macaca mulatta , Neurônios , Comportamento Social , Animais , Giro do Cíngulo/fisiologia , Feminino , Neurônios/fisiologia , Recompensa , Sinais (Psicologia)RESUMO
Adaptive behavior relies on efficient cognitive control. The anterior cingulate cortex (ACC) is a key node within the executive prefrontal network. The reciprocal connectivity between the locus ceruleus (LC) and ACC is thought to support behavioral reorganization triggered by the detection of an unexpected change. We transduced LC neurons with either excitatory or inhibitory chemogenetic receptors in adult male rats and trained rats on a spatial task. Subsequently, we altered LC activity and confronted rats with an unexpected change of reward locations. In a new spatial context, rats with decreased noradrenaline (NA) in the ACC entered unbaited maze arms more persistently which was indicative of perseveration. In contrast, the suppression of the global NA transmission reduced perseveration. Neither chemogenetic manipulation nor inactivation of the ACC by muscimol affected the rate of learning, possibly due to partial virus transduction of the LC neurons and/or the compensatory engagement of other prefrontal regions. Importantly, we observed behavioral deficits in rats with LC damage caused by virus injection. The latter finding highlights the importance of careful histological assessment of virus-transduced brain tissue as inadvertent damage of the targeted cell population due to virus neurotoxicity or other factors might cause unwanted side effects. Although the specific role of ACC in the flexibility of spatial behavior has not been convincingly demonstrated, our results support the beneficial role of noradrenergic transmission for an optimal function of the ACC. Overall, our findings suggest the LC exerts the projection-specific modulation of neural circuits mediating the flexibility of spatial behavior.
Assuntos
Giro do Cíngulo , Locus Cerúleo , Norepinefrina , Comportamento Espacial , Animais , Masculino , Locus Cerúleo/efeitos dos fármacos , Locus Cerúleo/fisiologia , Norepinefrina/metabolismo , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiologia , Comportamento Espacial/fisiologia , Comportamento Espacial/efeitos dos fármacos , Ratos , Muscimol/farmacologia , Aprendizagem em Labirinto/fisiologia , Aprendizagem em Labirinto/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Neurônios Adrenérgicos/efeitos dos fármacos , Neurônios Adrenérgicos/fisiologiaRESUMO
Placebo effects are notable demonstrations of mind-body interactions1,2. During pain perception, in the absence of any treatment, an expectation of pain relief can reduce the experience of pain-a phenomenon known as placebo analgesia3-6. However, despite the strength of placebo effects and their impact on everyday human experience and the failure of clinical trials for new therapeutics7, the neural circuit basis of placebo effects has remained unclear. Here we show that analgesia from the expectation of pain relief is mediated by rostral anterior cingulate cortex (rACC) neurons that project to the pontine nucleus (rACCâPn)-a precerebellar nucleus with no established function in pain. We created a behavioural assay that generates placebo-like anticipatory pain relief in mice. In vivo calcium imaging of neural activity and electrophysiological recordings in brain slices showed that expectations of pain relief boost the activity of rACCâPn neurons and potentiate neurotransmission in this pathway. Transcriptomic studies of Pn neurons revealed an abundance of opioid receptors, further suggesting a role in pain modulation. Inhibition of the rACCâPn pathway disrupted placebo analgesia and decreased pain thresholds, whereas activation elicited analgesia in the absence of placebo conditioning. Finally, Purkinje cells exhibited activity patterns resembling those of rACCâPn neurons during pain-relief expectation, providing cellular-level evidence for a role of the cerebellum in cognitive pain modulation. These findings open the possibility of targeting this prefrontal cortico-ponto-cerebellar pathway with drugs or neurostimulation to treat pain.
Assuntos
Vias Neurais , Percepção da Dor , Dor , Efeito Placebo , Animais , Feminino , Masculino , Camundongos , Analgesia , Antecipação Psicológica/fisiologia , Sinalização do Cálcio , Cerebelo/citologia , Cerebelo/fisiologia , Cognição/fisiologia , Eletrofisiologia , Perfilação da Expressão Gênica , Giro do Cíngulo/citologia , Giro do Cíngulo/fisiologia , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Dor/fisiopatologia , Dor/prevenção & controle , Dor/psicologia , Manejo da Dor/métodos , Manejo da Dor/psicologia , Manejo da Dor/tendências , Percepção da Dor/fisiologia , Limiar da Dor/fisiologia , Limiar da Dor/psicologia , Ponte/citologia , Ponte/fisiologia , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/fisiologia , Células de Purkinje/fisiologia , Receptores Opioides/metabolismo , Transmissão SinápticaRESUMO
The anterior cingulate cortex (ACC) is a key cortical region for pain perception and emotion. Different forms of synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), have been reported in the ACC. Synaptic tagging of LTP plays an important role in hippocampus-related associative memory. In this study, we demonstrate that synaptic tagging of LTD is detected in the ACC of adult male and female mice. This form of tagged LTD requires the activation of metabotropic glutamate receptor subtype 1 (mGluR1). The induction of tagged LTD is time-related with the strongest tagged LTD appearing when the interval between two independent stimuli is 30â min. Inhibitors of mGluR1 blocked the induction of tagged LTD; however, blocking N-methyl-d-aspartate receptors did not affect the induction of tagged LTD. Nimodipine, an inhibitor of L-type voltage-gated calcium channels, also blocked tagged LTD. In an animal model of amputation, we found that tagged LTD was either reduced or completely blocked. Together with our previous report of tagged LTP in the ACC, this study strongly suggests that excitatory synapses in the adult ACC are highly plastic. The biphasic tagging of synaptic transmission provides a new form of heterosynaptic plasticity in the ACC which has functional and pathophysiological significance in phantom pain.
Assuntos
Giro do Cíngulo , Depressão Sináptica de Longo Prazo , Camundongos Endogâmicos C57BL , Animais , Giro do Cíngulo/fisiologia , Giro do Cíngulo/efeitos dos fármacos , Camundongos , Depressão Sináptica de Longo Prazo/fisiologia , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , Masculino , Feminino , Sinapses/fisiologia , Sinapses/efeitos dos fármacos , Receptores de Glutamato Metabotrópico/metabolismo , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacosRESUMO
Animals must simultaneously select and balance multiple action contingencies in ambiguous situations: for instance, evading danger during feeding. This has rarely been examined in the context of information selection; despite corticothalamic pathways that mediate sensory attention being relatively well characterized, neural mechanisms filtering conflicting actions remain unclear. Here, we develop a new loom/feed test to observe conflict between naturally induced fear and feeding and identify a novel anterior cingulate cortex (ACC) output to the ventral anterior and ventral lateral thalamus (VA/VL) that adjusts selectivity between these innate actions. Using micro-endoscopy and fiber photometry, we reveal that activity in corticofugal outputs was lowered during unbalanced/singularly occupied periods, as were the resulting decreased thalamic initiation-related signals for less-favored actions, suggesting that the integration of ACC-thalamic firing may directly regulate the output of behavior choices. Accordingly, the optoinhibition of ACC-VA/VL circuits induced high bias toward feeding at the expense of defense. To identify upstream "commander" cortical cells gating this output, we established dual-order tracing (DOT)-translating ribosome affinity purification (TRAP)-a scheme to label upstream neurons with transcriptome analysis-and found a novel population of neurotensin-positive interneurons (ACCNts). The photoexcitation of ACCNts cells indeed caused similarly hyper-selective behaviors. Collectively, this new "corticofugal action filter" scheme suggests that communication in multi-step cingulate circuits may critically influence the summation of motor signals in thalamic outputs, regulating bias between innate action types.
Assuntos
Giro do Cíngulo , Vias Neurais , Neurotensina , Animais , Giro do Cíngulo/metabolismo , Giro do Cíngulo/fisiologia , Camundongos , Masculino , Vias Neurais/fisiologia , Neurotensina/metabolismo , Tálamo/metabolismo , Tálamo/fisiologia , Camundongos Endogâmicos C57BL , Medo/fisiologia , Comportamento AlimentarRESUMO
Prior studies have reported inconsistent results regarding the relationships between the integrity of the fornix and parahippocampal cingulum and both memory performance and longitudinal change in performance. In the present study, we examined associations in a sample of cognitively healthy older adults between free water-corrected fractional anisotropy (FA) metrics derived from the fornix and cingulum, baseline memory performance, and 3-year memory change. Neither fornix nor cingulum FA correlated with memory performance at baseline. By contrast, FA of each tract was predictive of memory change, such that greater FA was associated with less longitudinal decline. These associations remained significant after controlling for FA of other white matter tracts and for performance in other cognitive domains. Furthermore, fornix and cingulum FA explained unique variance in memory change. These results suggest that free water-corrected measures of fornix and parahippocampal cingulum integrity are reliable predictors of future memory change in cognitively healthy older adults. The findings for the fornix in particular highlight the utility of correcting for free water when estimating diffusion tensor imaging metrics of white matter integrity.
Assuntos
Cognição , Imagem de Tensor de Difusão , Fórnice , Memória , Humanos , Masculino , Fórnice/diagnóstico por imagem , Fórnice/fisiologia , Feminino , Idoso , Anisotropia , Imagem de Tensor de Difusão/métodos , Memória/fisiologia , Cognição/fisiologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiologia , Idoso de 80 Anos ou mais , Água , Giro Para-Hipocampal/diagnóstico por imagem , Giro Para-Hipocampal/fisiologia , Envelhecimento/psicologia , Envelhecimento/fisiologia , Envelhecimento/patologia , Estudos Longitudinais , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiologia , Envelhecimento Saudável/psicologia , Envelhecimento Saudável/fisiologia , Envelhecimento Saudável/patologiaRESUMO
The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for either epilepsy or major depressive disorder. We found that beta (12-30 Hz) oscillations in the ACC predicted both associated reward and the size of the choice bias, and also tracked reward receipt, thereby predicting bias on future trials. We found reduced magnitude of bias in depressed patients, in whom the beta-specific effects were correspondingly reduced. Our findings suggest that ACC beta oscillations may orchestrate the learning of reward information to guide adaptive choice, and, more broadly, suggest a potential biomarker for anhedonia and point to future development of interventions to enhance reward impact for therapeutic benefit.
Assuntos
Transtorno Depressivo Maior , Giro do Cíngulo , Recompensa , Humanos , Giro do Cíngulo/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Masculino , Adulto , Feminino , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Comportamento de Escolha/fisiologia , Pessoa de Meia-Idade , Ritmo beta/fisiologia , Epilepsia/fisiopatologia , Adulto JovemRESUMO
In social interaction, age-related differences in emotional processing may lead to varied social decision making between young and older adults. However, previous studies of social decision making have paid less attention to the interactants' emotions, leaving age differences and underlying neural mechanisms unexplored. To address this gap, the present study combined functional and structural magnetic resonance imaging, employing a modified dictator game task with recipients displaying either neutral or sad facial expressions. Behavioral results indicated that although older adults' overall allocations did not differ significantly from those of young adults, older adults' allocations showing a decrease in emotion-related generosity compared to young adults. Using representational similarity analysis, we found that older adults showed reduced neural representations of recipients' emotions and gray matter volume in the right anterior cingulate gyrus (ACC), right insula, and left dorsomedial prefrontal cortex (DMPFC) compared to young adults. More importantly, mediation analyses indicated that age influenced allocations not only through serial mediation of neural representations of the right insula and left DMPFC, but also through serial mediation of the mean gray matter volume of the right ACC and left DMPFC. This study identifies the potential neural pathways through which age affects emotion-related social decision making, advancing our understanding of older adults' social interaction behavior that they may not be less generous unless confronted with individuals with specific emotions.