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1.
Cerebellum ; 23(2): 802-832, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37428408

RESUMO

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.


Assuntos
Transtorno Depressivo Maior , Adulto , Humanos , Idoso , Estudos Transversais , Consenso , Qualidade de Vida , Cerebelo/patologia , Envelhecimento , Imageamento por Ressonância Magnética/métodos
2.
Cerebellum ; 22(2): 235-239, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35257295

RESUMO

Spatial navigation is an intricate ability, requiring multisensory and motor integration, that is particularly impacted in aging. The age-related decline in navigational capabilities is known to be associated with changes in brain regions such as the frontal, temporal, and cerebellar cortices. Age-related cerebellar differences in spatial navigation have generally been ascribed to motor impairments, omitting the central role of this structure in several cognitive processes. In the present voxel-based morphometric study, we investigated gray matter volume loss in older adults across cognitive and motor subregions of the cerebellum. Specifically, we hypothesized that age-related gray matter differences would occur mainly in cerebellar regions involved in cognitive processing. Our results showed a significant age-related atrophy in the left neocerebellum of healthy older adults that includes Crus I and lobule VI. The latter are important nodes in the network that subtends cognitive abilities such as object recognition and spatial cognition. This exploratory work sets the ground for future research to investigate the extent of the neocerebellum's contribution to spatial navigation deficits in aging.


Assuntos
Envelhecimento Saudável , Navegação Espacial , Imageamento por Ressonância Magnética , Cerebelo , Encéfalo , Substância Cinzenta
3.
Hum Brain Mapp ; 43(17): 5281-5295, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35776524

RESUMO

Orienting in space requires the processing of visual spatial cues. The dominant hypothesis about the brain structures mediating the coding of spatial cues stipulates the existence of a hippocampal-dependent system for the representation of geometry and a striatal-dependent system for the representation of landmarks. However, this dual-system hypothesis is based on paradigms that presented spatial cues conveying either conflicting or ambiguous spatial information and that used the term landmark to refer to both discrete three-dimensional objects and wall features. Here, we test the hypothesis of complex activation patterns in the hippocampus and the striatum during visual coding. We also postulate that object-based and feature-based navigation are not equivalent instances of landmark-based navigation. We examined how the neural networks associated with geometry-, object-, and feature-based spatial navigation compared with a control condition in a two-choice behavioral paradigm using fMRI. We showed that the hippocampus was involved in all three types of cue-based navigation, whereas the striatum was more strongly recruited in the presence of geometric cues than object or feature cues. We also found that unique, specific neural signatures were associated with each spatial cue. Object-based navigation elicited a widespread pattern of activity in temporal and occipital regions relative to feature-based navigation. These findings extend the current view of a dual, juxtaposed hippocampal-striatal system for visual spatial coding in humans. They also provide novel insights into the neural networks mediating object versus feature spatial coding, suggesting a need to distinguish these two types of landmarks in the context of human navigation.


Assuntos
Sinais (Psicologia) , Navegação Espacial , Humanos , Navegação Espacial/fisiologia , Hipocampo/diagnóstico por imagem , Hipocampo/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Corpo Estriado/diagnóstico por imagem , Percepção Espacial/fisiologia
4.
Eur J Neurosci ; 54(12): 8256-8282, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33738880

RESUMO

Coupling behavioral measures and brain imaging in naturalistic, ecological conditions is key to comprehend the neural bases of spatial navigation. This highly integrative function encompasses sensorimotor, cognitive, and executive processes that jointly mediate active exploration and spatial learning. However, most neuroimaging approaches in humans are based on static, motion-constrained paradigms and they do not account for all these processes, in particular multisensory integration. Following the Mobile Brain/Body Imaging approach, we aimed to explore the cortical correlates of landmark-based navigation in actively behaving young adults, solving a Y-maze task in immersive virtual reality. EEG analysis identified a set of brain areas matching state-of-the-art brain imaging literature of landmark-based navigation. Spatial behavior in mobile conditions additionally involved sensorimotor areas related to motor execution and proprioception usually overlooked in static fMRI paradigms. Expectedly, we located a cortical source in or near the posterior cingulate, in line with the engagement of the retrosplenial complex in spatial reorientation. Consistent with its role in visuo-spatial processing and coding, we observed an alpha-power desynchronization while participants gathered visual information. We also hypothesized behavior-dependent modulations of the cortical signal during navigation. Despite finding few differences between the encoding and retrieval phases of the task, we identified transient time-frequency patterns attributed, for instance, to attentional demand, as reflected in the alpha/gamma range, or memory workload in the delta/theta range. We confirmed that combining mobile high-density EEG and biometric measures can help unravel the brain structures and the neural modulations subtending ecological landmark-based navigation.


Assuntos
Ondas Encefálicas , Navegação Espacial , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Neuroimagem , Adulto Jovem
5.
J Neurosci ; 39(13): 2522-2541, 2019 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-30696727

RESUMO

Hippocampal place cells show position-specific activity thought to reflect a self-localization signal. Several reports also point to some form of goal encoding by place cells. We investigated this by asking whether they also encode the value of spatial goals, which is crucial information for optimizing goal-directed navigation. We used a continuous place navigation task in which male rats navigate to one of two (freely chosen) unmarked locations and wait, triggering the release of reward, which is then located and consumed elsewhere. This allows sampling of place fields and dissociates spatial goal from reward consumption. The two goals varied in the amount of reward provided, allowing assessment of whether the rats factored goal value into their navigational choice and of possible neural correlates of this value. Rats successfully learned the task, indicating goal localization, and they preferred higher-value goals, indicating processing of goal value. Replicating previous findings, there was goal-related activity in the out-of-field firing of CA1 place cells, with a ramping-up of firing rate during the waiting period, but no general overrepresentation of goals by place fields, an observation that we extended to CA3 place cells. Importantly, place cells were not modulated by goal value. This suggests that dorsal hippocampal place cells encode space independently of its associated value despite the effect of that value on spatial behavior. Our findings are consistent with a model of place cells in which they provide a spontaneously constructed value-free spatial representation rather than encoding other navigationally relevant but nonspatial information.SIGNIFICANCE STATEMENT We investigated whether hippocampal place cells, which compute a self-localization signal, also encode the relative value of places, which is essential information for optimal navigation. When choosing between two spatial goals of different value, rats preferred the higher-value goal. We saw out-of-field goal firing in place cells, replicating previous observations that the cells are influenced by the goal, but their activity was not modulated by the value of these goals. Our results suggest that place cells do not encode all of the navigationally relevant aspects of a place, but instead form a value-free "map" that links to such aspects in other parts of the brain.


Assuntos
Objetivos , Hipocampo/fisiologia , Células de Lugar/fisiologia , Recompensa , Navegação Espacial/fisiologia , Animais , Comportamento de Escolha/fisiologia , Masculino , Ratos Long-Evans , Ritmo Teta
6.
PLoS Comput Biol ; 15(3): e1006298, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30860991

RESUMO

Cerebellar Purkinje cells mediate accurate eye movement coordination. However, it remains unclear how oculomotor adaptation depends on the interplay between the characteristic Purkinje cell response patterns, namely tonic, bursting, and spike pauses. Here, a spiking cerebellar model assesses the role of Purkinje cell firing patterns in vestibular ocular reflex (VOR) adaptation. The model captures the cerebellar microcircuit properties and it incorporates spike-based synaptic plasticity at multiple cerebellar sites. A detailed Purkinje cell model reproduces the three spike-firing patterns that are shown to regulate the cerebellar output. Our results suggest that pauses following Purkinje complex spikes (bursts) encode transient disinhibition of target medial vestibular nuclei, critically gating the vestibular signals conveyed by mossy fibres. This gating mechanism accounts for early and coarse VOR acquisition, prior to the late reflex consolidation. In addition, properly timed and sized Purkinje cell bursts allow the ratio between long-term depression and potentiation (LTD/LTP) to be finely shaped at mossy fibre-medial vestibular nuclei synapses, which optimises VOR consolidation. Tonic Purkinje cell firing maintains the consolidated VOR through time. Importantly, pauses are crucial to facilitate VOR phase-reversal learning, by reshaping previously learnt synaptic weight distributions. Altogether, these results predict that Purkinje spike burst-pause dynamics are instrumental to VOR learning and reversal adaptation.


Assuntos
Potenciais de Ação , Adaptação Fisiológica , Células de Purkinje/fisiologia , Animais , Movimentos Oculares , Humanos , Aprendizagem , Potenciação de Longa Duração , Reflexo Vestíbulo-Ocular/fisiologia , Sinapses/fisiologia
7.
Ophthalmic Res ; 63(2): 88-96, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31935739

RESUMO

Glaucoma is the leading cause of irreversible blindness worldwide, with an increasing prevalence. The complexity of the disease has been a major challenge in moving the field forward with regard to both pathophysiological insight and treatment. In this context, discussing possible outcome measures in glaucoma trials is of utmost importance and clinical relevance. A recent meeting of the European Vision Institute (EVI) special interest focus group was held on "New Technologies for Outcome Measures in Retina and Glaucoma," addressing both functional and structural outcomes, as well as translational hot topics in glaucoma and retina research. In conjunction with the published literature, this review summarizes the meeting focusing on glaucoma.


Assuntos
Academias e Institutos , Grupos Focais , Glaucoma/fisiopatologia , Nervo Óptico/fisiopatologia , Avaliação de Resultados em Cuidados de Saúde , Visão Ocular/fisiologia , Europa (Continente) , Humanos , Nervo Óptico/patologia , Células Ganglionares da Retina/patologia
8.
Eur J Epidemiol ; 34(2): 141-152, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30610413

RESUMO

To analyze the longitudinal relationships between vision loss and the risk of dementia in the first 2 years, from 2 to 4 years and beyond 4 years after inclusion and to determine the roles of depressive symptomatology and engagement in cognitively stimulating activities in these associations. This study is based on the Three-City (3C) study, a population-based cohort of 7736 initially dementia-free participants aged 65 years and over with 12 years of follow-up. Near visual impairment (VI) was measured and distance visual function (VF) loss was self-reported. Dementia was diagnosed and screened over the 12-year period. At baseline, 8.7% had mild near VI, 4.2% had moderate to severe near VI, and 5.3% had distance VF loss. Among the 882 dementia cases diagnosed over the 12-year follow-up period, 140 cases occurred in the first 2 years, 149 from 2 to 4 years and 593 beyond 4 years after inclusion. In Cox multivariate analysis, moderate to severe near VI was associated with an increased risk of dementia in the first 2 years (HR 2.0, 95% CI 1.2-3.3) and from 2 to 4 years (HR 1.8, 95% CI 1.1-3.1) but the association was not significant beyond 4 years after inclusion even if pointing in similar direction (HR 1.3, 95% CI 0.95-1.9). Mild near VI was associated with an increased risk of dementia only in the first 2 years (HR 1.6, 95% CI 1.1-2.5). Moreover, self-reported distance VF loss was associated with an increased risk beyond 4 years after inclusion (HR 1.5, 95% CI 1.1-2.0) but the association was no longer significant after taking into account baseline cognitive performances. Further adjustment for engagement in cognitively stimulating activities only slightly decreased these associations. However, there was an interaction between vision loss and depressive symptomatology, with vision loss associated with dementia only among participants with depressive symptomatology. These results suggest that poor vision, in particular near vision loss, may represent an indicator of dementia risk at short and middle-term, mostly in depressed elderly people.


Assuntos
Demência/epidemiologia , Transtornos da Visão/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Depressão/epidemiologia , Feminino , França/epidemiologia , Humanos , Masculino , Modelos de Riscos Proporcionais , Fatores de Risco , Autorrelato , Fatores de Tempo
9.
PLoS Biol ; 13(8): e1002222, 2015 08.
Artigo em Inglês | MEDLINE | ID: mdl-26266537

RESUMO

The frontal cortex controls behavioral adaptation in environments governed by complex rules. Many studies have established the relevance of firing rate modulation after informative events signaling whether and how to update the behavioral policy. However, whether the spatiotemporal features of these neuronal activities contribute to encoding imminent behavioral updates remains unclear. We investigated this issue in the dorsal anterior cingulate cortex (dACC) of monkeys while they adapted their behavior based on their memory of feedback from past choices. We analyzed spike trains of both single units and pairs of simultaneously recorded neurons using an algorithm that emulates different biologically plausible decoding circuits. This method permits the assessment of the performance of both spike-count and spike-timing sensitive decoders. In response to the feedback, single neurons emitted stereotypical spike trains whose temporal structure identified informative events with higher accuracy than mere spike count. The optimal decoding time scale was in the range of 70-200 ms, which is significantly shorter than the memory time scale required by the behavioral task. Importantly, the temporal spiking patterns of single units were predictive of the monkeys' behavioral response time. Furthermore, some features of these spiking patterns often varied between jointly recorded neurons. All together, our results suggest that dACC drives behavioral adaptation through complex spatiotemporal spike coding. They also indicate that downstream networks, which decode dACC feedback signals, are unlikely to act as mere neural integrators.


Assuntos
Potenciais de Ação/fisiologia , Adaptação Psicológica/fisiologia , Giro do Cíngulo/fisiologia , Macaca mulatta/fisiologia , Neurônios/fisiologia , Algoritmos , Animais , Retroalimentação Psicológica/fisiologia , Macaca mulatta/psicologia , Masculino , Modelos Neurológicos , Resolução de Problemas/fisiologia , Tempo de Reação/fisiologia , Recompensa , Fatores de Tempo
10.
J Vis ; 18(6): 19, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30029229

RESUMO

Micromovements of the eye during visual fixations provide clues about how our visual system acquires information. The analysis of fixational eye movements can thus serve as a noninvasive means to detect age-related or pathological changes in visual processing, which can in turn reflect associated cognitive or neurological disorders. However, the utility of such diagnostic approaches relies on the quality and usability of detection methods applied for the eye movement analysis. Here, we propose a novel method for (micro)saccade detection that is resistant to high-frequency recording noise, a frequent problem in video-based eye tracking in either aged subjects or subjects suffering from a vision-related pathology. The method is fast, it does not require manual noise removal, and it can work with position, velocity, or acceleration features, or a combination thereof. The detection accuracy of the proposed method is assessed on a new dataset of manually labeled recordings acquired from 14 subjects of advanced age (69-81 years old), performing an ocular fixation task. It is demonstrated that the detection accuracy of the new method compares favorably to that of two frequently used reference methods and that it is comparable to the best of the two algorithms when tested on an existing low-noise eye-tracking dataset.


Assuntos
Fixação Ocular/fisiologia , Ruído , Movimentos Sacádicos/fisiologia , Percepção Visual/fisiologia , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Humanos , Masculino , Vias Visuais/fisiologia
11.
Entropy (Basel) ; 20(7)2018 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-33265616

RESUMO

Categorization is a fundamental information processing phenomenon in the brain. It is critical for animals to compress an abundance of stimulations into groups to react quickly and efficiently. In addition to labels, categories possess an internal structure: the goodness measures how well any element belongs to a category. Interestingly, this categorization leads to an altered perception referred to as categorical perception: for a given physical distance, items within a category are perceived closer than items in two different categories. A subtler effect is the perceptual magnet: discriminability is reduced close to the prototypes of a category and increased near its boundaries. Here, starting from predefined abstract categories, we naturally derive the internal structure of categories and the phenomenon of categorical perception, using an information theoretical framework that involves both probabilities and pairwise similarities between items. Essentially, we suggest that pairwise similarities between items are to be tuned to render some predefined categories as well as possible. However, constraints on these pairwise similarities only produce an approximate matching, which explains concurrently the notion of goodness and the warping of perception. Overall, we demonstrate that similarity-based information theory may offer a global and unified principled understanding of categorization and categorical perception simultaneously.

12.
J Vis ; 17(1): 17, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28114492

RESUMO

The photopic motion sensitivity function of the energy-based motion system is band-pass peaking around 8 Hz. Using an external noise paradigm to factorize the sensitivity into equivalent input noise and calculation efficiency, the present study investigated if the variation in photopic motion sensitivity as a function of the temporal frequency is due to a variation of equivalent input noise (e.g., early temporal filtering) or calculation efficiency (ability to select and integrate motion). For various temporal frequencies, contrast thresholds for a direction discrimination task were measured in presence and absence of noise. Up to 15 Hz, the sensitivity variation was mainly due to a variation of equivalent input noise and little variation in calculation efficiency was observed. The sensitivity fall-off at very high temporal frequencies (from 15 to 30 Hz) was due to a combination of a drop of calculation efficiency and a rise of equivalent input noise. A control experiment in which an artificial temporal integration was applied to the stimulus showed that an early temporal filter (generally assumed to affect equivalent input noise, not calculation efficiency) could impair both the calculation efficiency and equivalent input noise at very high temporal frequencies. We conclude that at the photopic luminance intensity tested, the variation of motion sensitivity as a function of the temporal frequency was mainly due to early temporal filtering, not to the ability to select and integrate motion. More specifically, we conclude that photopic motion sensitivity at high temporal frequencies is limited by internal noise occurring after the transduction process (i.e., neural noise), not by quantal noise resulting from the probabilistic absorption of photons by the photoreceptors as previously suggested.


Assuntos
Visão de Cores/fisiologia , Sensibilidades de Contraste/fisiologia , Percepção de Movimento/fisiologia , Movimento (Física) , Limiar Sensorial/fisiologia , Humanos , Ruído
13.
J Vis ; 17(2): 5, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-28196375

RESUMO

External noise paradigms are widely used to characterize sensitivity by comparing the effect of a variable on contrast threshold when it is limited by internal versus external noise. A basic assumption of external noise paradigms is that the processing properties are the same in low and high noise. However, recent studies (e.g., Allard & Cavanagh, 2011; Allard & Faubert, 2014b) suggest that this assumption could be violated when using spatiotemporally localized noise (i.e., appearing simultaneously and at the same location as the target) but not when using spatiotemporally extended noise (i.e., continuously displayed, full-screen, dynamic noise). These previous findings may have been specific to the crowding and 0D noise paradigms that were used, so the purpose of the current study is to test if this violation of noise-invariant processing also occurs in a standard contrast detection task in white noise. The rationale of the current study is that local external noise triggers the use of recognition rather than detection and that a recognition process should be more affected by uncertainty about the shape of the target than one involving detection. To investigate the contribution of target knowledge on contrast detection, the effect of orientation uncertainty was evaluated for a contrast detection task in the absence of noise and in the presence of spatiotemporally localized or extended noise. A larger orientation uncertainty effect was observed with temporally localized noise than with temporally extended noise or with no external noise, indicating a change in the nature of the processing for temporally localized noise. We conclude that the use of temporally localized noise in external noise paradigms risks triggering a shift in process, invalidating the noise-invariant processing required for the paradigm. If, instead, temporally extended external noise is used to match the properties of internal noise, no such processing change occurs.


Assuntos
Sensibilidades de Contraste/fisiologia , Ruído , Reconhecimento Visual de Modelos/fisiologia , Adulto , Feminino , Humanos , Masculino , Orientação , Psicofísica , Limiar Sensorial/fisiologia , Incerteza , Adulto Jovem
14.
Behav Res Methods ; 49(4): 1278-1290, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27604602

RESUMO

Noise-masking experiments are widely used to investigate visual functions. To be useful, noise generally needs to be strong enough to noticeably impair performance, but under some conditions, noise does not impair performance even when its contrast approaches the maximal displayable limit of 100 %. To extend the usefulness of noise-masking paradigms over a wider range of conditions, the present study developed a noise with great masking strength. There are two typical ways of increasing masking strength without exceeding the limited contrast range: use binary noise instead of Gaussian noise or filter out frequencies that are not relevant to the task (i.e., which can be removed without affecting performance). The present study combined these two approaches to further increase masking strength. We show that binarizing the noise after the filtering process substantially increases the energy at frequencies within the pass-band of the filter given equated total contrast ranges. A validation experiment showed that similar performances were obtained using binarized-filtered noise and filtered noise (given equated noise energy at the frequencies within the pass-band) suggesting that the binarization operation, which substantially reduced the contrast range, had no significant impact on performance. We conclude that binarized-filtered noise (and more generally, truncated-filtered noise) can substantially increase the energy of the noise at frequencies within the pass-band. Thus, given a limited contrast range, binarized-filtered noise can display higher energy levels than Gaussian noise and thereby widen the range of conditions over which noise-masking paradigms can be useful.


Assuntos
Ruído , Mascaramento Perceptivo , Humanos
15.
J Neurosci ; 33(34): 13914-26, 2013 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-23966711

RESUMO

Long-term memory in the prefrontal cortex is a necessary component of adaptive executive control and is strongly modulated by dopamine. However, the functional significance of this dopaminergic modulation remains elusive. In vitro experimental results on dopamine-dependent shaping of prefrontal long-term plasticity often appear inconsistent and, altogether, draw a complicated picture. It is also generally difficult to relate these findings to in vivo observations given strong differences between the two experimental conditions. This study presents a unified view of the functional role of dopamine in the prefrontal cortex by framing it within the Bienenstock-Cooper-Munro theory of cortical plasticity. We investigate dopaminergic modulation of long-term plasticity through a multicompartment Hodgkin-Huxley model of a prefrontal pyramidal neuron. Long-term synaptic plasticity in the model is governed by a calcium- and dopamine-dependent learning rule, in which dopamine exerts its action via D1 and D2 dopamine receptors in a concentration-dependent manner. Our results support a novel function of dopamine in the prefrontal cortex, namely that it controls the synaptic modification threshold between long-term depression and potentiation in pyramidal neurons. The proposed theoretical framework explains a wide range of experimental results and provides a link between in vitro and in vivo studies of dopaminergic plasticity modulation. It also suggests that dopamine may constitute a new player in metaplastic and homeostatic processes in the prefrontal cortex.


Assuntos
Neurônios Dopaminérgicos/fisiologia , Potenciação de Longa Duração/fisiologia , Depressão Sináptica de Longo Prazo/fisiologia , Modelos Neurológicos , Córtex Pré-Frontal/citologia , Animais , Dopamina/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estimulação Elétrica , Agonistas de Aminoácidos Excitatórios/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Depressão Sináptica de Longo Prazo/efeitos dos fármacos , N-Metilaspartato/farmacologia
16.
J Neurosci ; 33(42): 16790-5, 2013 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-24133279

RESUMO

Head direction (HD) neurons fire selectively according to head orientation in the yaw plane relative to environmental landmark cues. Head movements provoke optic field flow signals that enter the vestibular nuclei, indicating head velocity, and hence angular displacements. To test whether optic field flow alone affects the directional firing of HD neurons, rats walked about on a circular platform as a spot array was projected onto the surrounding floor-to-ceiling cylindrical black curtain. Directional responses in the anterodorsal thalamus of four rats remained stable as they moved about with the point field but in the absence of landmark cues. Then, the spherical projector was rotated about its yaw axis at 4.5°/s for ∼90 s. In 27 sessions the mean drift speed of the preferred directions (PDs) was 1.48°/s (SD=0.78°/s; range: 0.15 to 2.88°/s). Thus, optic flow stimulation entrained PDs, albeit at drift speeds slower than the field rotation. This could be due to conflicts with vestibular, motor command, and efferent copy signals. After field rotation ended, 20/27 PDs drifted back to within 45° of the initial values over several minutes, generally following the shortest path to return to the initial value. Poststimulation drifts could change speed and/or direction, with mean speeds of 0.68±0.64°/s (range 0 to 1.36°/s). Since the HD cell pathway (containing anterodorsal thalamus) is the only known projection of head direction information to entorhinal grid cells and hippocampal place cells, yaw plane optic flow signals likely influence representations in this spatial reference coordinate system for orientation and navigation.


Assuntos
Núcleos Anteriores do Tálamo/fisiologia , Movimentos da Cabeça/fisiologia , Neurônios/fisiologia , Fluxo Óptico/fisiologia , Orientação/fisiologia , Animais , Sinais (Psicologia) , Cabeça/fisiologia , Masculino , Estimulação Luminosa , Ratos , Ratos Long-Evans
17.
Invest Ophthalmol Vis Sci ; 65(8): 13, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38975944

RESUMO

Purpose: This study aims at linking subtle changes of fixational eye movements (FEM) in controls and in patients with foveal drusen using adaptive optics retinal imaging in order to find anatomo-functional markers for pre-symptomatic age-related macular degeneration (AMD). Methods: We recruited 7 young controls, 4 older controls, and 16 patients with presymptomatic AMD with foveal drusen from the Silversight Cohort. A high-speed research-grade adaptive optics flood illumination ophthalmoscope (AO-FIO) was used for monocular retinal tracking of fixational eye movements. The system allows for sub-arcminute resolution, and high-speed and distortion-free imaging of the foveal area. Foveal drusen position and size were documented using gaze-dependent imaging on a clinical-grade AO-FIO. Results: FEM were measured with high precision (RMS-S2S = 0.0015 degrees on human eyes) and small foveal drusen (median diameter = 60 µm) were detected with high contrast imaging. Microsaccade amplitude, drift diffusion coefficient, and ISOline area (ISOA) were significantly larger for patients with foveal drusen compared with controls. Among the drusen participants, microsaccade amplitude was correlated to drusen eccentricity from the center of the fovea. Conclusions: A novel high-speed high-precision retinal tracking technique allowed for the characterization of FEM at the microscopic level. Foveal drusen altered fixation stability, resulting in compensatory FEM changes. Particularly, drusen at the foveolar level seemed to have a stronger impact on microsaccade amplitudes and ISOA. The unexpected anatomo-functional link between small foveal drusen and fixation stability opens up a new perspective of detecting oculomotor signatures of eye diseases at the presymptomatic stage.


Assuntos
Fixação Ocular , Fóvea Central , Degeneração Macular , Drusas Retinianas , Humanos , Feminino , Drusas Retinianas/fisiopatologia , Drusas Retinianas/diagnóstico , Masculino , Fixação Ocular/fisiologia , Fóvea Central/diagnóstico por imagem , Fóvea Central/fisiopatologia , Fóvea Central/patologia , Idoso , Pessoa de Meia-Idade , Degeneração Macular/fisiopatologia , Degeneração Macular/diagnóstico , Adulto , Tomografia de Coerência Óptica/métodos , Oftalmoscopia/métodos , Acuidade Visual/fisiologia , Movimentos Sacádicos/fisiologia , Sintomas Prodrômicos
18.
Elife ; 122023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36912888

RESUMO

Human spatial cognition has been mainly characterized in terms of egocentric (body-centered) and allocentric (world-centered) wayfinding bhavior. It was hypothesized that allocentric spatial coding, as a special high-level cognitive ability, develops later and deteriorates earlier than the egocentric one throughout lifetime. We challenged this hypothesis by testing the use of landmarks versus geometric cues in a cohort of 96 deeply phenotyped participants, who physically navigated an equiangular Y maze, surrounded by landmarks or an anisotropic one. The results show that an apparent allocentric deficit in children and aged navigators is caused specifically by difficulties in using landmarks for navigation while introducing a geometric polarization of space made these participants as efficient allocentric navigators as young adults. This finding suggests that allocentric behavior relies on two dissociable sensory processing systems that are differentially affected by human aging. Whereas landmark processing follows an inverted-U dependence on age, spatial geometry processing is conserved, highlighting its potential in improving navigation performance across the lifespan.


Assuntos
Longevidade , Navegação Espacial , Criança , Adulto Jovem , Humanos , Idoso , Envelhecimento , Orientação Espacial , Sinais (Psicologia) , Percepção Espacial
19.
PLoS Comput Biol ; 7(5): e1002045, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21625569

RESUMO

The interplay between hippocampus and prefrontal cortex (PFC) is fundamental to spatial cognition. Complementing hippocampal place coding, prefrontal representations provide more abstract and hierarchically organized memories suitable for decision making. We model a prefrontal network mediating distributed information processing for spatial learning and action planning. Specific connectivity and synaptic adaptation principles shape the recurrent dynamics of the network arranged in cortical minicolumns. We show how the PFC columnar organization is suitable for learning sparse topological-metrical representations from redundant hippocampal inputs. The recurrent nature of the network supports multilevel spatial processing, allowing structural features of the environment to be encoded. An activation diffusion mechanism spreads the neural activity through the column population leading to trajectory planning. The model provides a functional framework for interpreting the activity of PFC neurons recorded during navigation tasks. We illustrate the link from single unit activity to behavioral responses. The results suggest plausible neural mechanisms subserving the cognitive "insight" capability originally attributed to rodents by Tolman & Honzik. Our time course analysis of neural responses shows how the interaction between hippocampus and PFC can yield the encoding of manifold information pertinent to spatial planning, including prospective coding and distance-to-goal correlates.


Assuntos
Cognição/fisiologia , Aprendizagem/fisiologia , Córtex Pré-Frontal/fisiologia , Comportamento Espacial/fisiologia , Animais , Hipocampo/fisiologia , Modelos Neurológicos , Rede Nervosa/fisiologia , Ratos
20.
Psychol Rev ; 129(4): 732-741, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34968134

RESUMO

Early direction-selective neurons in the primary visual cortex are widely considered to be the main neural basis underlying motion perception even though motion perception can also rely on attentively tracking the position of objects. Because of their small receptive fields, early direction-selective neurons suffer from the aperture problem, which is assumed to be overcome by integrating inputs from many early direction-selective neurons. Because the perceived motion of objects sometimes depends on static form information and does not always match the mean direction of local motion signals, the general consensus is that motion integration is form dependent and complex. Based on the fact that early direction-selective neurons respond to motion only within a short temporal window, the present study used stroboscopic motion to test their contribution to motion perception of objects. For conditions under which the perceived motion was impaired by stroboscopic motion, the perceived motion matched the mean direction of local motion signals and was form independent. For classic conditions under which the perceived motion could not be explained by a simple form independent averaging of local motion signals, neutralizing the contribution of early direction-selective neurons using stroboscopic motion had little impact on the perceived motion, which demonstrates that the perceived motion relied on position tracking, not on early direction-selective neurons. When the perceived motion relies on position tracking, assuming that motion perception relies on early direction-selective neurons can lead to erroneously postulate the existence of complex or form-dependent integration of inputs from early direction-selective neurons. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Percepção de Movimento , Córtex Visual , Humanos , Percepção de Movimento/fisiologia , Neurônios/fisiologia , Estimulação Luminosa , Córtex Visual/fisiologia
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