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1.
Nat Rev Neurosci ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937654

RESUMEN

The lateral prefrontal cortex (PFC) in humans and other primates is critical for immediate, goal-directed behaviour and working memory, which are classically considered distinct from the cognitive and neural circuits that support long-term learning and memory. Over the past few years, a reconsideration of this textbook perspective has emerged, in that different timescales of memory-guided behaviour are in constant interaction during the pursuit of immediate goals. Here, we will first detail how neural activity related to the shortest timescales of goal-directed behaviour (which requires maintenance of current states and goals in working memory) is sculpted by long-term knowledge and learning - that is, how the past informs present behaviour. Then, we will outline how learning across different timescales (from seconds to years) drives plasticity in the primate lateral PFC, from single neuron firing rates to mesoscale neuroimaging activity patterns. Finally, we will review how, over days and months of learning, dense local and long-range connectivity patterns in PFC facilitate longer-lasting changes in population activity by changing synaptic weights and recruiting additional neural resources to inform future behaviour. Our Review sheds light on how the machinery of plasticity in PFC circuits facilitates the integration of learned experiences across time to best guide adaptive behaviour.

2.
Front Syst Neurosci ; 18: 1365622, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577690

RESUMEN

Neurons that generate persistent activity in the primate dorsolateral prefrontal and posterior parietal cortex have been shown to be predictive of behavior in working memory tasks, though subtle differences between them have been observed in how information is represented. The role of different neuron types in each of these areas has not been investigated at depth. We thus compared the activity of neurons classified as narrow-spiking, putative interneurons, and broad-spiking, putative pyramidal neurons, recorded from the dorsolateral prefrontal and posterior parietal cortex of male monkeys, to analyze their role in the maintenance of working memory. Our results demonstrate that narrow-spiking neurons are active during a range of tasks and generate persistent activity during the delay period over which stimuli need to be maintained in memory. Furthermore, the activity of narrow-spiking neurons was predictive of the subject's recall no less than that of broad-spiking neurons, which are exclusively projection neurons in the cortex. Our results show that putative interneurons play an active role during the maintenance of working memory and shed light onto the fundamental neural circuits that determine subjects' memories and judgments.

3.
J Neurosci ; 44(23)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38641409

RESUMEN

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.


Asunto(s)
Memoria a Corto Plazo , Modelos Neurológicos , Corteza Prefrontal , Memoria Espacial , Corteza Prefrontal/fisiología , Memoria a Corto Plazo/fisiología , Memoria Espacial/fisiología , Animales , Acetilcolina/metabolismo , Masculino , Neuronas Colinérgicas/fisiología , Neuronas Colinérgicas/efectos de los fármacos , Núcleo Basal de Meynert/fisiología
4.
bioRxiv ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38645237

RESUMEN

Risk taking behavior is a symptom of multiple neuropsychiatric disorders and often lacks effective treatments. Reward circuitry regions including the amygdala, orbitofrontal cortex, insula, and anterior cingulate have been implicated in risk-taking by neuroimaging studies. Electrophysiological activity associated with risk taking in these regions is not well understood in humans. Further characterizing the neural signalling that underlies risk-taking may provide therapeutic insight into disorders associated with risk-taking. Eleven patients with pharmacoresistant epilepsy who underwent stereotactic electroencephalography with electrodes in the amygdala, orbitofrontal cortex, insula, and/or anterior cingulate participated. Patients participated in a gambling task where they wagered on a visible playing card being higher than a hidden card, betting $5 or $20 on this outcome, while local field potentials were recorded from implanted electrodes. We used cluster-based permutation testing to identify reward prediction error signals by comparing oscillatory power following unexpected and expected rewards. We also used cluster-based permutation testing to compare power preceding high and low bets in high-risk (<50% chance of winning) trials and two-way ANOVA with bet and risk level to identify signals associated with risky, risk averse, and optimized decisions. We used linear mixed effects models to evaluate the relationship between reward prediction error and risky decision signals across trials, and a linear regression model for associations between risky decision signal power and Barratt Impulsiveness Scale scores for each patient. Reward prediction error signals were identified in the amygdala (p=0.0066), anterior cingulate (p=0.0092), and orbitofrontal cortex (p=6.0E-4, p=4.0E-4). Risky decisions were predicted by increased oscillatory power in high-gamma frequency range during card presentation in the orbitofrontal cortex (p=0.0022), and by increased power following bet cue presentation across the theta-to-beta range in the orbitofrontal cortex ( p =0.0022), high-gamma in the anterior cingulate ( p =0.0004), and high-gamma in the insula ( p =0.0014). Risk averse decisions were predicted by decreased orbitofrontal cortex gamma power ( p =2.0E-4). Optimized decisions that maximized earnings were preceded by decreases within the theta to beta range in orbitofrontal cortex ( p =2.0E-4), broad frequencies in amygdala ( p =2.0E-4), and theta to low-gamma in insula ( p =4.0E-4). Insula risky decision power was associated with orbitofrontal cortex high-gamma reward prediction error signal ( p =0.0048) and with patient impulsivity ( p =0.00478). Our findings identify and help characterize reward circuitry activity predictive of risk-taking in humans. These findings may serve as potential biomarkers to inform the development of novel treatment strategies such as closed loop neuromodulation for disorders of risk taking.

5.
iScience ; 27(3): 109130, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38380249

RESUMEN

Oscillatory activity in the local field potential (LFP) is thought to be a marker of cognitive processes. To understand how it differentiates tasks and brain areas in humans, we recorded LFPs in 15 adults with intracranial depth electrodes, as they performed visual-spatial and shape working memory tasks. Stimulus appearance produced widespread, broad-band activation, including in occipital, parietal, temporal, insular, and prefrontal cortex, and the amygdala and hippocampus. Occipital cortex was characterized by most elevated power in the high-gamma (100-150 Hz) range during the visual stimulus presentation. The most consistent feature of the delay period was a systematic pattern of modulation in the beta frequency (16-40 Hz), which included a decrease in power of variable timing across areas, and rebound during the delay period. These results reveal the widespread nature of oscillatory activity across a broad brain network and region-specific signatures of oscillatory processes associated with visual working memory.

6.
bioRxiv ; 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38293215

RESUMEN

The behavioral and neural effects of the endogenous release of acetylcholine following stimulation of the Nucleus Basalis of Meynert (NB) have been recently examined (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 PFC.

7.
J Neurosci ; 44(2)2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-37973375

RESUMEN

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.


Asunto(s)
Memoria a Corto Plazo , Corteza Prefrontal , Animales , Masculino , Memoria a Corto Plazo/fisiología , Corteza Prefrontal/fisiología , Macaca , Neuronas/fisiología , Primates
8.
J Neurosci ; 43(45): 7523-7529, 2023 11 08.
Artículo en Inglés | MEDLINE | ID: mdl-37940591

RESUMEN

Rapid progress in our understanding of the brain's learning mechanisms has been accomplished over the past decade, particularly with conceptual advances, including representing behavior as a dynamical system, large-scale neural population recordings, and new methods of analysis of neuronal populations. However, motor and cognitive systems have been traditionally studied with different methods and paradigms. Recently, some common principles, evident in both behavior and neural activity, that underlie these different types of learning have become to emerge. Here we review results from motor and cognitive learning, relying on different techniques and studying different systems to understand the mechanisms of learning. Movement is intertwined with cognitive operations, and its dynamics reflect cognitive variables. Training, in either motor or cognitive tasks, involves recruitment of previously unresponsive neurons and reorganization of neural activity in a low dimensional manifold. Mapping of new variables in neural activity can be very rapid, instantiating flexible learning of new tasks. Communication between areas is just as critical a part of learning as are patterns of activity within an area emerging with learning. Common principles across systems provide a map for future research.


Asunto(s)
Aprendizaje , Movimiento , Aprendizaje/fisiología , Cognición/fisiología
9.
J Neurophysiol ; 130(6): 1392-1402, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37910532

RESUMEN

Persistent activity of neurons in the prefrontal cortex has been thought to represent the information maintained in working memory, though alternative models have challenged this idea. Theories that depend on the dynamic representation of information posit that stimulus information may be maintained by the activity pattern of neurons whose firing rate is not significantly elevated above their baseline during the delay period of working memory tasks. We thus tested the ability of neurons that do and do not generate persistent activity in the prefrontal cortex of monkeys to represent spatial and object information in working memory. Neurons that generated persistent activity represented more information about the stimuli in both spatial and object working memory tasks. The amount of information that could be decoded from neural activity depended on the choice of decoder and parameters used but neurons with persistent activity outperformed non-persistent neurons consistently. Averaged across all neurons and stimuli, the firing rate did not appear clearly elevated above baseline during the maintenance of neural activity particularly for object working memory; however, this grand average masked neurons that generated persistent activity selective for their preferred stimuli, which carried the majority of stimulus information. These results reveal that prefrontal neurons that generate persistent activity maintain information more reliably during working memory.NEW & NOTEWORTHY Competing theories suggest that neurons that generate persistent activity or do not are primarily responsible for the maintenance of information, particularly regarding object working memory. Although the two models have been debated on theoretical terms, direct comparison of empirical results has been lacking. Analysis of neural activity in a large database of prefrontal recordings revealed that neurons that generate persistent activity were primarily responsible for the maintenance of both spatial and object working memory.


Asunto(s)
Memoria a Corto Plazo , Corteza Prefrontal , Animales , Memoria a Corto Plazo/fisiología , Macaca mulatta , Corteza Prefrontal/fisiología , Neuronas/fisiología
10.
J Neurophysiol ; 130(4): 980-989, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37703490

RESUMEN

Adolescent development is characterized by an improvement in cognitive abilities, such as working memory. Neurophysiological recordings in a nonhuman primate model of adolescence have revealed changes in neural activity that mirror improvement in behavior, including higher firing rate during the delay intervals of working memory tasks. The laminar distribution of these changes is unknown. By some accounts, persistent activity is more pronounced in superficial layers, so we sought to determine whether changes are most pronounced there. We therefore analyzed neurophysiological recordings from the young and adult stage of male monkeys, at different cortical depths. Superficial layers exhibited an increased baseline firing rate in the adult stage. Unexpectedly, we also detected substantial increases in delay period activity in the middle layers after adolescence, which was confirmed even after excluding penetrations near sulci. Finally, improved discriminability around the saccade period was most evident in the deeper layers. These results reveal the laminar pattern of neural activity maturation that is associated with cognitive improvement.NEW & NOTEWORTHY Structural brain changes are evident during adolescent development particularly in the cortical thickness of the prefrontal cortex, at a time when working memory ability increases markedly. The depth distribution of neurophysiological changes during adolescence is not known. Here, we show that neurophysiological changes are not confined to superficial layers, which have most often been implicated in the maintenance of working memory. Contrary to expectations, substantial changes were evident in intermediate layers of the prefrontal cortex.


Asunto(s)
Desarrollo del Adolescente , Memoria a Corto Plazo , Humanos , Animales , Masculino , Memoria a Corto Plazo/fisiología , Corteza Prefrontal/fisiología , Neuronas/fisiología , Cognición/fisiología
11.
bioRxiv ; 2023 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-37732263

RESUMEN

Oscillatory activity is thought to be a marker of cognitive processes, although its role and distribution across the brain during working memory has been a matter of debate. To understand how oscillatory activity differentiates tasks and brain areas in humans, we recorded local field potentials (LFPs) in 12 adults as they performed visual-spatial and shape-matching memory tasks. Tasks were designed to engage working memory processes at a range of delay intervals between stimulus delivery and response initiation. LFPs were recorded using intracranial depth electrodes implanted to localize seizures for management of intractable epilepsy. Task-related LFP power analyses revealed an extensive network of cortical regions that were activated during the presentation of visual stimuli and during their maintenance in working memory, including occipital, parietal, temporal, insular, and prefrontal cortical areas, and subcortical structures including the amygdala and hippocampus. Across most brain areas, the appearance of a stimulus produced broadband power increase, while gamma power was evident during the delay interval of the working memory task. Notable differences between areas included that occipital cortex was characterized by elevated power in the high gamma (100-150 Hz) range during the 500 ms of visual stimulus presentation, which was less pronounced or absent in other areas. A decrease in power centered in beta frequency (16-40 Hz) was also observed after the stimulus presentation, whose magnitude differed across areas. These results reveal the interplay of oscillatory activity across a broad network, and region-specific signatures of oscillatory processes associated with visual working memory.

12.
bioRxiv ; 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37693584

RESUMEN

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, e.g., from parietal to prefrontal and cingulate cortex, pointing to their role in cortical computations. It is currently unknown whether these timescales depend on training in a specific task and/or are an inherent property of neurons, and whether more fine-grained hierarchies of timescales exist within specific cortical regions. 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. Significance statement: Recent studies have demonstrated that neural responses exhibit dynamics with different timescales that follow a certain order or hierarchy across cortical areas. While the hierarchy of timescales is consistent across different tasks, it is unknown if these timescales emerge only after training or if they represent inherent properties of neurons. To answer this question, we estimated multiple timescales in neural response across five subregions of the monkeys' lateral prefrontal cortex before and after training on a working-memory task. Our results provide evidence for fine-grained gradients related to certain neural dynamics. Moreover, we show that these timescales depend on and can be modulated by training in a cognitive task, and contribute to encoding of task-relevant information at single-cell and population levels.

13.
bioRxiv ; 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37693624

RESUMEN

While the current understanding of sensory and motor cortical areas has been defined topographical maps across the surface of these areas, higher cortical areas, such as the prefrontal cortex, seem to lack an equivalent organization, with only limited evidence of functional clustering of neurons with similar stimulus properties. We sought to examine whether neurons that represent similar spatial and object information are clustered in the monkey prefrontal cortex and whether such an organization only emerges as a result of training. We analyzed neurophysiological recordings from male macaque monkeys before and after they were trained to perform cognitive tasks. Neurons with similar spatial or shape selectivity were more likely than chance to be encountered at short distances from each other. This pattern of organization was present even in naïve animals, prior to any cognitive training. Our results reveal that prefrontal microstructure automatically supports orderly representations of spatial and object information.

14.
J Neurophysiol ; 130(3): 694-705, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37609703

RESUMEN

Information represented in working memory is reflected in the firing rate of neurons in the prefrontal cortex and brain areas connected to it. In recent years, there has been an increased realization that population measures capture more accurately neural correlates of cognitive functions. We examined how single neuron firing in the prefrontal and posterior parietal cortex of two male monkeys compared with population measures in spatial working memory tasks. Persistent activity was observed in the dorsolateral prefrontal and posterior parietal cortex and firing rate predicted working memory behavior, particularly in the prefrontal cortex. These findings had equivalents in population measures, including trajectories in state space that became less separated in error trials. We additionally observed rotations of stimulus representations in the neuronal state space for different task conditions, which were not obvious in firing rate measures. These results suggest that population measures provide a richer view of how neuronal activity is associated with behavior, largely confirming that persistent activity is the core phenomenon that maintains visual-spatial information in working memory.NEW & NOTEWORTHY Recordings from large numbers of neurons led to a reevaluation of neural correlates of cognitive functions, which traditionally were defined based on responses of single neurons or averages of firing rates. Analysis of neuronal recordings from the dorsolateral prefrontal and posterior parietal cortex revealed that properties of neuronal firing captured in classical studies of persistent activity can account for population representations, though some population characteristics did not have clear correlates in single neuron activity.


Asunto(s)
Memoria a Corto Plazo , Neuronas , Masculino , Animales , Encéfalo , Cognición , Lóbulo Parietal
15.
bioRxiv ; 2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37546782

RESUMEN

Persistent activity of neurons in the prefrontal cortex has been thought to represent the information maintained in working memory, though alternative models have recently challenged this idea. Activity-silent theories posit that stimulus information may be maintained by the activity pattern of neurons that do not produce firing rate significantly elevated about their baseline during the delay period of working memory tasks. We thus tested the ability of neurons that do and do not generate persistent activity in the prefrontal cortex of monkeys to represent spatial and object information in working memory. Neurons that generated persistent activity represented more information about the stimuli in both spatial and object working memory tasks. The amount of information that could be decoded from neural activity depended on the choice of decoder and parameters used but neurons with persistent activity outperformed non-persistent neurons consistently. Although averaged across all neurons and stimuli, firing rate did not appear clearly elevated above baseline during the maintenance of neural activity particularly for object working memory, this grant average masked neurons that generated persistent activity selective for their preferred stimuli, which carried the majority of information about the stimulus identity. These results reveal that prefrontal neurons with generate persistent activity constitute the primary mechanism of working memory maintenance in the cortex. NEW AND NOTEWORTHY: Competing theories suggest that neurons that generate persistent activity or do not are primarily responsible for the maintenance of information, particularly regarding object working memory. While the two models have been debated on theoretical terms, direct comparison of empirical results have been lacking. Analysis of neural activity in a large database of prefrontal recordings revealed that neurons that generate persistent activity were primarily responsible for the maintenance of both spatial and object working memory.

16.
bioRxiv ; 2023 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-37546979

RESUMEN

Adolescent development is characterized by an improvement in cognitive abilities, such as working memory. Neurophysiological recordings in a non-human primate model of adolescence have revealed changes in neural activity that mirror improvement in behavior, including higher firing rate during the delay intervals of working memory tasks. The laminar distribution of these changes is unknown. By some accounts, persistent activity is more pronounced in superficial layers, so we sought to determine whether changes are most pronounced there. We therefore analyzed neurophysiological recordings from neurons recorded in the young and adult stage, at different cortical depths. Superficial layers exhibited increased baseline firing rate in the adult stage. Unexpectedly, changes in persistent activity were most pronounced in the middle layers. Finally, improved discriminability of stimulus location was most evident in the deeper layers. These results reveal the laminar pattern of neural activity maturation that is associated with cognitive improvement. NEW AND NOTEWORTHY: Structural brain changes are evident during adolescent development particularly in the cortical thickness of the prefrontal cortex, at a time when working memory ability increases markedly. The depth distribution of neurophysiological changes during adolescence is not known. Here we show that neurophysiological changes are not confined to superficial layers, which have most often been implicated in the maintenance of working memory. Contrary to expectations, greatest changes were evident in intermediate layers of the prefrontal cortex.

17.
Brain Sci ; 13(6)2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37371395

RESUMEN

Acetylcholine is a critical modulatory neurotransmitter for cognitive function. Cholinergic drugs improve cognitive performance and enhance neuronal activity in the sensory and association cortices. An alternative means of improving cognitive function is through the use of deep brain stimulation. Prior animal studies have demonstrated that stimulation of the nucleus basalis of Meynert through DBS improves cognitive performance on a visual working memory task to the same degree as cholinesterase inhibitors. Additionally, unlike current pharmacological treatments for neurocognitive disorders, DBS does not lose efficacy over time and adverse effects are rare. These findings suggest that DBS may be a promising alternative for treating cognitive impairments in neurodegenerative disorders such as Alzheimer's disease. Thus, further research and human trials should be considered to assess the potential of DBS as a therapeutic treatment for these disorders.

18.
Commun Biol ; 6(1): 505, 2023 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-37169826

RESUMEN

Local field potential (LFP) power in the gamma frequency is modulated by cognitive variables during task execution. We sought to examine whether such modulations only emerge when task rules are established. We therefore analyzed neuronal firing and LFPs in different prefrontal subdivisions before and after the same monkeys were trained to perform cognitive tasks. Prior to task rule learning, sites containing neurons selective for stimuli already exhibited increased gamma power during and after the passive viewing of stimuli compared to the baseline period. Unexpectedly, when the same monkeys learned to maintain these stimuli in working memory, the elevation of gamma power above the baseline was diminished, despite an overall increase in firing rate. Learning and executing the task further decoupled LFP power from single neuron firing. Gamma power decreased at the time when subjects needed to make a judgment about whether two stimuli were the same or not, and differential gamma power was observed for matching and nonmatching stimuli. Our results indicate that prefrontal gamma power emerges spontaneously, not necessarily tied to a cognitive task being executed.


Asunto(s)
Aprendizaje , Neuronas , Animales , Potenciales de Acción/fisiología , Macaca mulatta , Neuronas/fisiología , Aprendizaje/fisiología , Memoria a Corto Plazo/fisiología
19.
bioRxiv ; 2023 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-38529503

RESUMEN

Human and non-human primate data clearly implicate the dorsolateral prefrontal cortex (dlPFC) as critical for advanced cognitive functions 1,2 . It is thought that intracortical synaptic architectures within dlPFC are the integral neurobiological substrate that gives rise to these processes, including working memory, inferential reasoning, and decision-making 3-7 . In the prevailing model, each cortical column makes up one fundamental processing unit composed of dense intrinsic connectivity, conceptualized as the 'canonical' cortical microcircuit 3,8 . Each cortical microcircuit receives sensory and cognitive information from a variety of sources which are represented by sustained activity within the microcircuit, referred to as persistent or recurrent activity 4,9 . Via recurrent connections within the microcircuit, activity can propagate for a variable length of time, thereby allowing temporary storage and computations to occur locally before ultimately passing a transformed representation to a downstream output 4,5,10 . Competing theories regarding how microcircuit activity is coordinated have proven difficult to reconcile in vivo where intercortical and intracortical computations cannot be fully dissociated 5,9,11,12 . Here, we interrogated the intrinsic features of isolated microcircuit networks using high-density calcium imaging of macaque dlPFC ex vivo . We found that spontaneous activity is intrinsically maintained by microcircuit architecture, persisting at a high rate in the absence of extrinsic connections. Further, using perisulcal stimulation to evoke persistent activity in deep layers, we found that activity propagates through stochastically assembled intracortical networks, creating predictable population-level events from largely non-overlapping ensembles. Microcircuit excitability covaried with individual cognitive performance, thus anchoring heuristic models of abstract cortical functions within quantifiable constraints imposed by the underlying synaptic architecture.

20.
iScience ; 25(9): 104929, 2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36065179

RESUMEN

Learning to perform a new cognitive task induces plasticity of the prefrontal cortex generally involving activation of more neurons and increases in firing rate; however, its effects on single neurons are diverse and complex. We sought to understand how training affects global measures of neural activity by recording and analyzing local field potentials (LFPs) in monkeys before and after they learned to perform working memory tasks. LFP power after training was characterized by a reduction in power in 20-40 Hz during the stimulus presentations and delay periods of the task. Both evoked power, synchronized to task events, and induced power exhibited this decrease after training. The effect was consistent across tasks requiring memory of spatial location and stimulus shape. Error trials were characterized by a lack of LFP power ramping around the fixation onset. Our results reveal signatures of cortical plasticity in LFPs associated with learning to perform cognitive tasks.

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