RESUMO
When making decisions in a cluttered world, humans and other animals often have to hold multiple items in memory at once-such as the different items on a shopping list. Psychophysical experiments in humans and other animals have shown remembered stimuli can sometimes become confused, with participants reporting chimeric stimuli composed of features from different stimuli. In particular, subjects will often make "swap errors" where they misattribute a feature from one object as belonging to another object. While swap errors have been described behaviorally and theoretical explanations have been proposed, their neural mechanisms are unknown. Here, we elucidate these neural mechanisms by analyzing neural population recordings from monkeys performing two multistimulus working memory tasks. In these tasks, monkeys were cued to report the color of an item that either was previously shown at a corresponding location or will be shown at the corresponding location. Animals made swap errors in both tasks. In the neural data, we find evidence that the neural correlates of swap errors emerged when correctly remembered information is selected from working memory. This led to a representation of the distractor color as if it were the target color, underlying the eventual swap error. We did not find consistent evidence that swap errors arose from misinterpretation of the cue or errors during encoding or storage in working memory. These results provide evidence that swap errors emerge during selection of correctly remembered information from working memory, and highlight this selection as a crucial-yet surprisingly brittle-neural process.
Assuntos
Memória de Curto Prazo , Animais , Memória de Curto Prazo/fisiologia , Macaca mulatta , Masculino , Sinais (Psicologia) , Neurônios/fisiologiaRESUMO
Human working memory is a key cognitive process that engages multiple functional anatomical nodes across the brain. Despite a plethora of correlative neuroimaging evidence regarding the working memory architecture, our understanding of critical hubs causally controlling overall performance is incomplete. Causal interpretation requires cognitive testing following safe, temporal, and controllable neuromodulation of specific functional anatomical nodes. Such experiments became available in healthy humans with the advance of transcranial alternating current stimulation (tACS). Here, we synthesize findings of 28 placebo-controlled studies (in total, 1,057 participants) that applied frequency-specific noninvasive stimulation of neural oscillations and examined working memory performance in neurotypical adults. We use a computational meta-modeling method to simulate each intervention in realistic virtual brains and test reported behavioral outcomes against the stimulation-induced electric fields in different brain nodes. Our results show that stimulating anterior frontal and medial temporal theta oscillations and occipitoparietal gamma rhythms leads to significant dose-dependent improvement in working memory task performance. Conversely, prefrontal gamma modulation is detrimental to performance. Moreover, we found distinct spatial expression of theta subbands, where working memory changes followed orbitofrontal high-theta modulation and medial temporal low-theta modulation. Finally, all these results are driven by changes in working memory accuracy rather than processing time measures. These findings provide a fresh view of the working memory mechanisms, complementary to neuroimaging research, and propose hypothesis-driven targets for the clinical treatment of working memory deficits.
Assuntos
Memória de Curto Prazo , Estimulação Transcraniana por Corrente Contínua , Adulto , Humanos , Memória de Curto Prazo/fisiologia , Ritmo Gama/fisiologia , Encéfalo , Cognição/fisiologia , Transtornos da Memória , Estimulação Transcraniana por Corrente Contínua/métodosRESUMO
In order to investigate the involvement of the primary visual cortex (V1) in working memory (WM), parallel, multisite recordings of multi-unit activity were obtained from monkey V1 while the animals performed a delayed match-to-sample (DMS) task. During the delay period, V1 population firing rate vectors maintained a lingering trace of the sample stimulus that could be reactivated by intervening impulse stimuli that enhanced neuronal firing. This fading trace of the sample did not require active engagement of the monkeys in the DMS task and likely reflects the intrinsic dynamics of recurrent cortical networks in lower visual areas. This renders an active, attention-dependent involvement of V1 in the maintenance of WM contents unlikely. By contrast, population responses to the test stimulus depended on the probabilistic contingencies between sample and test stimuli. Responses to tests that matched expectations were reduced which agrees with concepts of predictive coding.
Assuntos
Memória de Curto Prazo , Córtex Visual Primário , Animais , Macaca mulatta , Memória de Curto Prazo/fisiologia , Neurônios/fisiologia , Atenção , Estimulação LuminosaRESUMO
Working memories are thought to be held in attractor networks in the brain. These attractors should keep track of the uncertainty associated with each memory, so as to weigh it properly against conflicting new evidence. However, conventional attractors do not represent uncertainty. Here, we show how uncertainty could be incorporated into an attractor, specifically a ring attractor that encodes head direction. First, we introduce a rigorous normative framework (the circular Kalman filter) for benchmarking the performance of a ring attractor under conditions of uncertainty. Next, we show that the recurrent connections within a conventional ring attractor can be retuned to match this benchmark. This allows the amplitude of network activity to grow in response to confirmatory evidence, while shrinking in response to poor-quality or strongly conflicting evidence. This "Bayesian ring attractor" performs near-optimal angular path integration and evidence accumulation. Indeed, we show that a Bayesian ring attractor is consistently more accurate than a conventional ring attractor. Moreover, near-optimal performance can be achieved without exact tuning of the network connections. Finally, we use large-scale connectome data to show that the network can achieve near-optimal performance even after we incorporate biological constraints. Our work demonstrates how attractors can implement a dynamic Bayesian inference algorithm in a biologically plausible manner, and it makes testable predictions with direct relevance to the head direction system as well as any neural system that tracks direction, orientation, or periodic rhythms.
Assuntos
Encéfalo , Redes Neurais de Computação , Teorema de Bayes , Encéfalo/fisiologia , Memória de Curto Prazo , Cabeça/fisiologia , Modelos NeurológicosRESUMO
Working memory involves the short-term maintenance of information and is critical in many tasks. The neural circuit dynamics underlying working memory remain poorly understood, with different aspects of prefrontal cortical (PFC) responses explained by different putative mechanisms. By mathematical analysis, numerical simulations, and using recordings from monkey PFC, we investigate a critical but hitherto ignored aspect of working memory dynamics: information loading. We find that, contrary to common assumptions, optimal loading of information into working memory involves inputs that are largely orthogonal, rather than similar, to the late delay activities observed during memory maintenance, naturally leading to the widely observed phenomenon of dynamic coding in PFC. Using a theoretically principled metric, we show that PFC exhibits the hallmarks of optimal information loading. We also find that optimal information loading emerges as a general dynamical strategy in task-optimized recurrent neural networks. Our theory unifies previous, seemingly conflicting theories of memory maintenance based on attractor or purely sequential dynamics and reveals a normative principle underlying dynamic coding.
Assuntos
Memória de Curto Prazo , Neurônios , Memória de Curto Prazo/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Redes Neurais de ComputaçãoRESUMO
Learning advances through repetition. A classic paradigm for studying this process is the Hebb repetition effect: Immediate serial recall performance improves for lists presented repeatedly as compared to nonrepeated lists. Learning in the Hebb paradigm has been described as a slow but continuous accumulation of long-term memory traces over repetitions [e.g., Page & Norris, Phil. Trans. R. Soc. B 364, 3737-3753 (2009)]. Furthermore, it has been argued that Hebb repetition learning requires no awareness of the repetition, thereby being an instance of implicit learning [e.g., Guérard et al., Mem. Cogn. 39, 1012-1022 (2011); McKelvie, J. Gen. Psychol. 114, 75-88 (1987)]. While these assumptions match the data from a group-level perspective, another picture emerges when analyzing data on the individual level. We used a Bayesian hierarchical mixture modeling approach to describe individual learning curves. In two preregistered experiments, using a visual and a verbal Hebb repetition task, we demonstrate that 1) individual learning curves show an abrupt onset followed by rapid growth, with a variable time for the onset of learning across individuals, and that 2) learning onset was preceded by, or coincided with, participants becoming aware of the repetition. These results imply that repetition learning is not implicit and that the appearance of a slow and gradual accumulation of knowledge is an artifact of averaging over individual learning curves.
Assuntos
Memória de Curto Prazo , Aprendizagem Seriada , Humanos , Teorema de Bayes , Tempo de Reação , Curva de AprendizadoRESUMO
Cortical neurons exhibit multiple timescales related to dynamics of spontaneous fluctuations (intrinsic timescales) and response to task events (seasonal timescales) in addition to selectivity to task-relevant signals. These timescales increase systematically across the cortical hierarchy, for example, from parietal to prefrontal and cingulate cortex, pointing to their role in cortical computations. It is currently unknown whether these timescales are inherent properties of neurons and/or depend on training in a specific task and if the latter, how their modulations contribute to task performance. To address these questions, we analyzed single-cell recordings within five subregions of the prefrontal cortex (PFC) of male macaques before and after training on a working-memory task. We found fine-grained but opposite gradients of intrinsic and seasonal timescales that mainly appeared after training. Intrinsic timescales decreased whereas seasonal timescales increased from posterior to anterior subregions within both dorsal and ventral PFC. Moreover, training was accompanied by increases in proportions of neurons that exhibited intrinsic and seasonal timescales. These effects were comparable to the emergence of response selectivity due to training. Finally, task selectivity accompanied opposite neural dynamics such that neurons with task-relevant selectivity exhibited longer intrinsic and shorter seasonal timescales. Notably, neurons with longer intrinsic and shorter seasonal timescales exhibited superior population-level coding, but these advantages extended to the delay period mainly after training. Together, our results provide evidence for plastic, fine-grained gradients of timescales within PFC that can influence both single-cell and population coding, pointing to the importance of these timescales in understanding cognition.
Assuntos
Memória de Curto Prazo , Córtex Pré-Frontal , Animais , Masculino , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/fisiologia , Macaca , Neurônios/fisiologia , PrimatasRESUMO
The periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain-body communication, and is often studied for its role in "fight-or-flight" and "freezing" responses to threat. We used ultra-high-field 7â T fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining its in vivo function during a working memory task (N = 87). Both mild and moderate cognitive demands elicited spatially similar patterns of whole-brain blood oxygenation level-dependent (BOLD) response, and moderate cognitive demand elicited widespread BOLD increases above baseline in the brainstem. Notably, these brainstem increases were not significantly greater than those in the mild demand condition, suggesting that a subthreshold brainstem BOLD increase occurred for mild cognitive demand as well. Subject-specific masks were group aligned to examine PAG response. In PAG, both mild and moderate demands elicited a well-defined response in ventrolateral PAG, a region thought to be functionally related to anticipated painful threat in humans and nonhuman animals-yet, the present task posed only the most minimal (if any) "threat," with the cognitive tasks used being approximately as challenging as remembering a phone number. These findings suggest that the PAG may play a more general role in visceromotor regulation, even in the absence of threat.
Assuntos
Imageamento por Ressonância Magnética , Memória de Curto Prazo , Substância Cinzenta Periaquedutal , Humanos , Substância Cinzenta Periaquedutal/fisiologia , Masculino , Feminino , Memória de Curto Prazo/fisiologia , Adulto , Imageamento por Ressonância Magnética/métodos , Adulto Jovem , Mapeamento EncefálicoRESUMO
The behavioral and neural effects of the endogenous release of acetylcholine following stimulation of the nucleus basalis (NB) of Meynert have been recently examined in two male monkeys (Qi et al., 2021). Counterintuitively, NB stimulation enhanced behavioral performance while broadening neural tuning in the prefrontal cortex (PFC). The mechanism by which a weaker mnemonic neural code could lead to better performance remains unclear. Here, we show that increased neural excitability in a simple continuous bump attractor model can induce broader neural tuning and decrease bump diffusion, provided neural rates are saturated. Increased memory precision in the model overrides memory accuracy, improving overall task performance. Moreover, we show that bump attractor dynamics can account for the nonuniform impact of neuromodulation on distractibility, depending on distractor distance from the target. Finally, we delve into the conditions under which bump attractor tuning and diffusion balance in biologically plausible heterogeneous network models. In these discrete bump attractor networks, we show that reducing spatial correlations or enhancing excitatory transmission can improve memory precision. Altogether, we provide a mechanistic understanding of how cholinergic neuromodulation controls spatial working memory through perturbed attractor dynamics in the PFC.
Assuntos
Memória de Curto Prazo , Modelos Neurológicos , Córtex Pré-Frontal , Memória Espacial , Córtex Pré-Frontal/fisiologia , Memória de Curto Prazo/fisiologia , Memória Espacial/fisiologia , Animais , Acetilcolina/metabolismo , Masculino , Neurônios Colinérgicos/fisiologia , Neurônios Colinérgicos/efeitos dos fármacos , Núcleo Basal de Meynert/fisiologiaRESUMO
While the exertion of mental effort improves performance on cognitive tasks, the neural mechanisms by which motivational factors impact cognition remain unknown. Here, we used fMRI to test how changes in cognitive effort, induced by changes in task difficulty, impact neural representations of working memory (WM). Participants (both sexes) were precued whether WM difficulty would be hard or easy. We hypothesized that hard trials demanded more effort as a later decision required finer mnemonic precision. Behaviorally, pupil size was larger and response times were slower on hard compared with easy trials suggesting our manipulation of effort succeeded. Neurally, we observed robust persistent activity during delay periods in the prefrontal cortex (PFC), especially during hard trials. Yet, details of the memoranda could not be decoded from patterns in prefrontal activity. In the patterns of activity in the visual cortex, however, we found strong decoding of memorized targets, where accuracy was higher on hard trials. To potentially link these across-region effects, we hypothesized that effort, carried by persistent activity in the PFC, impacts the quality of WM representations encoded in the visual cortex. Indeed, we found that the amplitude of delay period activity in the frontal cortex predicted decoded accuracy in the visual cortex on a trial-wise basis. These results indicate that effort-related feedback signals sculpt population activity in the visual cortex, improving mnemonic fidelity.
Assuntos
Cognição , Imageamento por Ressonância Magnética , Memória de Curto Prazo , Córtex Pré-Frontal , Humanos , Memória de Curto Prazo/fisiologia , Masculino , Feminino , Adulto Jovem , Adulto , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Cognição/fisiologia , Tempo de Reação/fisiologia , Mapeamento Encefálico , Córtex Visual/fisiologia , Córtex Visual/diagnóstico por imagem , Estimulação Luminosa/métodosRESUMO
NMDA receptors (NMDARs) may be crucial to working memory (WM). Computational models predict that they sustain neural firing and produce associative memory, which may underpin maintaining and binding information, respectively. We test this in patients with antibodies to NMDAR (n = 10, female) and compare them with healthy control participants (n = 55, 20 male, 35 female). Patients were tested after recovery with a task that separates two aspects of WM: sustaining attention and feature binding. Participants had to remember two colored arrows. Then attention was directed to one of them. After a variable delay, they reported the direction of either the same arrow (congruent cue) or of the other arrow (incongruent cue). We asked how congruency affected recall precision and measured types of error. Patients had difficulty in both sustaining attention to an item over time and feature binding. Controls were less precise after longer delays and incongruent cues. In contrast, patients did not benefit from congruent cues at longer delays [group × congruency (long condition); p = 0.041], indicating they could not sustain attention. Additionally, patients reported the wrong item (misbinding errors) more than controls after congruent cues [group × delay (congruent condition), main effect of group; p ≤ 0.001]. Our results suggest NMDARs are critical for both maintaining attention and feature binding.
Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Atenção , Memória de Curto Prazo , Humanos , Masculino , Feminino , Memória de Curto Prazo/fisiologia , Adulto , Atenção/fisiologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/fisiopatologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Adulto Jovem , Pessoa de Meia-Idade , Receptores de N-Metil-D-Aspartato/imunologia , Adolescente , Sinais (Psicologia)RESUMO
Recently, multi-voxel pattern analysis has verified that information can be removed from working memory (WM) via three distinct operations replacement, suppression, or clearing compared to information being maintained ( Kim et al., 2020). While univariate analyses and classifier importance maps in Kim et al. (2020) identified brain regions that contribute to these operations, they did not elucidate whether these regions represent the operations similarly or uniquely. Using Leiden-community-detection on a sample of 55 humans (17 male), we identified four brain networks, each of which has a unique configuration of multi-voxel activity patterns by which it represents these WM operations. The visual network (VN) shows similar multi-voxel patterns for maintain and replace, which are highly dissimilar from suppress and clear, suggesting this network differentiates whether an item is held in WM or not. The somatomotor network (SMN) shows a distinct multi-voxel pattern for clear relative to the other operations, indicating the uniqueness of this operation. The default mode network (DMN) has distinct patterns for suppress and clear, but these two operations are more similar to each other than to maintain and replace, a pattern intermediate to that of the VN and SMN. The frontoparietal control network (FPCN) displays distinct multi-voxel patterns for each of the four operations, suggesting that this network likely plays an important role in implementing these WM operations. These results indicate that the operations involved in removing information from WM can be performed in parallel by distinct brain networks, each of which has a particular configuration by which they represent these operations.
Assuntos
Encéfalo , Memória de Curto Prazo , Masculino , Humanos , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Mapeamento Encefálico , Estimulação Luminosa , Imageamento por Ressonância Magnética/métodosRESUMO
It is challenging to measure how specific aspects of coordinated neural dynamics translate into operations of information processing and, ultimately, cognitive functions. An obstacle is that simple circuit mechanisms-such as self-sustained or propagating activity and nonlinear summation of inputs-do not directly give rise to high-level functions. Nevertheless, they already implement simple the information carried by neural activity. Here, we propose that distinct functions, such as stimulus representation, working memory, or selective attention, stem from different combinations and types of low-level manipulations of information or information processing primitives. To test this hypothesis, we combine approaches from information theory with simulations of multi-scale neural circuits involving interacting brain regions that emulate well-defined cognitive functions. Specifically, we track the information dynamics emergent from patterns of neural dynamics, using quantitative metrics to detect where and when information is actively buffered, transferred or nonlinearly merged, as possible modes of low-level processing (storage, transfer and modification). We find that neuronal subsets maintaining representations in working memory or performing attentional gain modulation are signaled by their boosted involvement in operations of information storage or modification, respectively. Thus, information dynamic metrics, beyond detecting which network units participate in cognitive processing, also promise to specify how and when they do it, that is, through which type of primitive computation, a capability that may be exploited for the analysis of experimental recordings.
Assuntos
Encéfalo , Cognição , Cognição/fisiologia , Encéfalo/fisiologia , Memória de Curto Prazo/fisiologia , Atenção/fisiologia , Neurônios/fisiologiaRESUMO
Working memory (WM) maintenance relies on multiple brain regions and inter-regional communications. The hippocampus and entorhinal cortex (EC) are thought to support this operation. Besides, EC is the main gateway for information between the hippocampus and neocortex. However, the circuit-level mechanism of this interaction during WM maintenance remains unclear in humans. To address these questions, we recorded the intracranial electroencephalography from the hippocampus and EC while patients (N = 13, six females) performed WM tasks. We found that WM maintenance was accompanied by enhanced theta/alpha band (2-12â Hz) phase synchronization between the hippocampus to the EC. The Granger causality and phase slope index analyses consistently showed that WM maintenance was associated with theta/alpha band-coordinated unidirectional influence from the hippocampus to the EC. Besides, this unidirectional inter-regional communication increased with WM load and predicted WM load during memory maintenance. These findings demonstrate that WM maintenance in humans engages the hippocampal-entorhinal circuit, with the hippocampus influencing the EC in a load-dependent manner.
Assuntos
Hipocampo , Memória de Curto Prazo , Feminino , Humanos , Encéfalo , Eletrocorticografia , Córtex Entorrinal , Eletroencefalografia , Ritmo TetaRESUMO
Serial dependence has shown seemingly contradictory effects on visual perception and working memory. While serial dependence promotes perpetual and mnemonic stability, it biases behavioral reports toward prior information. The neural mechanisms that drive both biasing and adaptive stabilizing effects are not well understood. We proposed and tested a reactivation and integration mechanism that can account for these contradictory effects. We used multivariate pattern analyses of EEG data (26 human participants, 17 females, 9 males) to examine the reactivation of prior reported orientation during the delay period of a visual working memory task. The reactivation strength of prior reports, but not prior sensory items, was predictive of the magnitude of serial dependency biases. These reactivated representations integrated with the representation of the current memory item and improved the ability to decode the current contents of memory. Overall, our data provide convergent evidence suggesting that prior reports in a visual working memory task are reactivated on the subsequent trial and become integrated with current memory representations. This similarity-dependent reactivation mechanism drives both report biasing and stabilization effects attributed to serial dependence in working memory.
Assuntos
Eletroencefalografia , Memória de Curto Prazo , Percepção Visual , Humanos , Feminino , Masculino , Memória de Curto Prazo/fisiologia , Adulto , Adulto Jovem , Percepção Visual/fisiologia , Estimulação Luminosa/métodos , AdolescenteRESUMO
The N2pc and P3 event-related potentials (ERPs), used to index selective attention and access to working memory and conscious awareness, respectively, have been important tools in cognitive sciences. Although it is likely that these two components and the underlying cognitive processes are temporally and functionally linked, such links have not yet been convincingly demonstrated. Adopting a novel methodological approach based on dynamic time warping (DTW), we provide evidence that the N2pc and P3 ERP components are temporally linked. We analyzed data from an experiment where 23 participants (16 women) monitored bilateral rapid serial streams of letters and digits in order to report a target digit indicated by a shape cue, separately for trials with correct responses and trials where a temporally proximal distractor was reported instead (distractor intrusion). DTW analyses revealed that N2pc and P3 latencies were correlated in time, both when the target or a distractor was reported. Notably, this link was weaker on distractor intrusion trials. This N2pc-P3 association is discussed with respect to the relationship between attention and access consciousness. Our results demonstrate that our novel method provides a valuable approach for assessing temporal links between two cognitive processes and their underlying modulating factors. This method allows to establish links and their modulator for any two time-series across all domains of the field (general-purpose MATLAB functions and a Python module are provided alongside this paper).
Assuntos
Atenção , Estado de Consciência , Eletroencefalografia , Tempo de Reação , Humanos , Feminino , Atenção/fisiologia , Masculino , Estado de Consciência/fisiologia , Adulto , Adulto Jovem , Eletroencefalografia/métodos , Tempo de Reação/fisiologia , Potenciais Evocados P300/fisiologia , Estimulação Luminosa/métodos , Potenciais Evocados/fisiologia , Memória de Curto Prazo/fisiologiaRESUMO
Control over internal representations requires the prioritization of relevant information and suppression of irrelevant information. The frontoparietal network exhibits prominent neural oscillations during these distinct cognitive processes. Yet, the causal role of this network-scale activity is unclear. Here, we targeted theta-frequency frontoparietal coherence and dynamic alpha oscillations in the posterior parietal cortex using online rhythmic transcranial magnetic stimulation (TMS) in women and men while they prioritized or suppressed internally maintained working memory (WM) representations. Using concurrent high-density EEG, we provided evidence that we acutely drove the targeted neural oscillation and TMS improved WM capacity only when the evoked activity corresponded with the desired cognitive process. To suppress an internal representation, we increased the amplitude of lateralized alpha oscillations in the posterior parietal cortex contralateral to the irrelevant visual field. For prioritization, we found that TMS to the prefrontal cortex increased theta-frequency connectivity in the prefrontoparietal network contralateral to the relevant visual field. To understand the spatial specificity of these effects, we administered the WM task to participants with implanted electrodes. We found that theta connectivity during prioritization was directed from the lateral prefrontal to the superior posterior parietal cortex. Together, these findings provide causal evidence in support of a model where a frontoparietal theta network prioritizes internally maintained representations and alpha oscillations in the posterior parietal cortex suppress irrelevant representations.
Assuntos
Eletroencefalografia , Estimulação Magnética Transcraniana , Masculino , Humanos , Feminino , Ritmo Teta/fisiologia , Lobo Parietal/fisiologia , Córtex Pré-Frontal/fisiologia , Memória de Curto Prazo/fisiologiaRESUMO
How humans transform sensory information into decisions that steer purposeful behavior is a central question in psychology and neuroscience that is traditionally investigated during the sampling of external environmental signals. The decision-making framework of gradual information sampling toward a decision has also been proposed to apply when sampling internal sensory evidence from working memory. However, neural evidence for this proposal remains scarce. Here we show (using scalp EEG in male and female human volunteers) that sampling internal visual representations from working memory elicits a scalp EEG potential associated with gradual evidence accumulation-the central parietal positivity. Consistent with an evolving decision process, we show how this signal (1) scales with the time participants require to reach a decision about the cued memory content and (2) is amplified when having to decide among multiple contents in working memory. These results bring the electrophysiology of decision-making into the domain of working memory and suggest that variability in memory-guided behavior may be driven (at least in part) by variations in the sampling of our inner mental contents.
Assuntos
Tomada de Decisões , Eletroencefalografia , Memória de Curto Prazo , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Feminino , Tomada de Decisões/fisiologia , Adulto , Eletroencefalografia/métodos , Adulto Jovem , Estimulação Luminosa/métodos , Sinais (Psicologia) , Tempo de Reação/fisiologiaRESUMO
Most research in Parkinson's disease focuses on improving motor symptoms. Yet, up to 80% of patients present with non-motor symptoms that often have a large impact on patients' quality of life. Impairment in working memory, a fundamental cognitive process, is common in Parkinson's disease. While deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms in Parkinson's disease, its impact on cognitive functions is less well studied. Here, we examine the effect of DBS in the theta, beta, low and high gamma frequency on working memory in 20 Parkinson's disease patients with bilateral STN-DBS. A linear mixed effects model demonstrates that STN-DBS in the theta frequency improves working memory performance. This effect is frequency-specific and was absent for beta and gamma frequency stimulation. Further, this effect is specific to cognitive performance, as theta frequency DBS did not affect motor function. A non-parametric cluster-based permutation analysis of whole-brain normative structural connectivity shows that working memory enhancement by theta frequency stimulation is associated with higher connectivity between the stimulated subthalamic area and the right middle frontal gyrus. Again, this association is frequency- and task-specific. These findings highlight the potential of theta frequency STN-DBS as a targeted intervention to improve working memory in patients with Parkinson's disease.
Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Memória de Curto Prazo , Qualidade de VidaRESUMO
Transcranial direct current stimulation (tDCS) has garnered significant interest for its potential to enhance cognitive functions and as a therapeutic intervention in various cognitive disorders. However, the clinical application of tDCS has been hampered by significant variability in its cognitive outcomes. Furthermore, the widespread use of tDCS has raised concerns regarding its safety and efficacy, particularly due to our limited understanding of its underlying neural mechanisms at the cellular level. We still do not know 'where', 'when', and 'how' tDCS modulates information encoding by neurons, to lead to the observed changes in cognitive functions. Without elucidating these fundamental unknowns, the root causes of its outcome variability and long-term safety remain elusive, challenging the effective application of tDCS in clinical settings. Addressing this gap, our study investigates the effects of tDCS, applied over the dorsolateral prefrontal cortex (dlPFC), on cognitive abilities and individual neuron activity in macaque monkeys performing cognitive tasks. Like humans performing a Delayed Match-to-Sample task, monkeys exhibited practice-related slowing in their responses (within-session behavioural adaptation). Concurrently, there were practice-related changes in simultaneously recorded activity of prefrontal neurons (within-session neuronal adaptation). Anodal tDCS attenuated both these behavioural and neuronal adaptations when compared to sham. Furthermore, tDCS abolished the correlation between monkeys' response time and neuronal firing rate. At a single-cell level, we also found that following tDCS, neuronal firing rate was more likely to exhibit task-specific modulation than after sham stimulation. These tDCS-induced changes in both behaviour and neuronal activity persisted even after the end of tDCS stimulation. Importantly, multiple applications of tDCS did not alter burst-like firing rates of individual neurons when compared to sham stimulation. This suggests that tDCS modulates neural activity without enhancing susceptibility to epileptiform activity, confirming a potential for safe use in clinical settings. Our research contributes unprecedented insights into the 'where', 'when', and 'how' of tDCS effects on neuronal activity and cognitive functions by showing that modulation of monkeys' behaviour by the tDCS of the prefrontal cortex is accompanied by alterations in prefrontal cortical cell activity ('where') during distinct trial phases ('when'). Importantly, tDCS led to task-specific and state-dependent alterations in prefrontal cell activities ('how'). Our findings suggest a significant shift from the view that the tDCS effects are merely due to polarity-specific shifts in cortical excitability and instead, propose a more complex mechanism of action for tDCS that encompasses various aspects of cortical neuronal activity without increasing burst-like epileptiform susceptibility.