Neural Activity In Prefrontal Cortex Research Articles

Neural dynamics of reversal learning in the prefrontal cortex and recurrent neural networks.

In probabilistic reversal learning, the choice option yielding reward at higher probability switches at a random trial. To perform optimally in this task, one has to accumulate evidence across trials to infer the probability that a reversal has occurred. In this study, we investigated how this reversal probability is represented in cortical neurons by analyzing the neural activity in prefrontal cortex of monkeys and recurrent neural networks trained on the task. We found that neural trajectories encoding reversal probability had substantial dynamics associated with intervening behaviors necessary to perform the task. Furthermore, the neural trajectories were translated systematically in response to whether outcomes were rewarded, and their position in the neural subspace captured information about reward outcomes. These findings suggested that separable dynamic trajectories, instead of fixed points on a line attractor, provided a better description of neural representation of reversal probability. Near the behavioral reversal, in particular, the trajectories shifted monotonically across trials with stable ordering, representing varying estimates of reversal probability around the reversal point. Perturbing the neural trajectory of trained networks biased when the reversal trial occurred, showing the role of reversal probability activity in decision-making. In sum, our study shows that cortical neurons encode reversal probability in a family of dynamic neural trajectories that accommodate flexible behavior while maintaining separability to represent distinct probabilistic values.

Proactive Versus Reactive Control Strategies Differentially Mediate Alcohol Drinking in Male Wistars and P Rats.

Problematic alcohol consumption is associated with deficits in decision-making and alterations in prefrontal cortex neural activity likely contribute. We hypothesized that the differences in cognitive control would be evident between male Wistars and a model of genetic risk: alcohol-preferring P rats. Cognitive control is split into proactive and reactive components. Proactive control maintains goal-directed behavior independent of a stimulus, whereas reactive control elicits goal-directed behavior at the time of a stimulus. We hypothesized that Wistars would show proactive control over alcohol seeking whereas P rats would show reactive control over alcohol seeking. Neural activity was recorded from the prefrontal cortex during an alcohol seeking task with two session types. On congruent sessions, the conditioned stimulus (CS+) was on the same side as alcohol access. Incongruent sessions presented alcohol opposite the CS+. Wistars, but not P rats, made more incorrect approaches during incongruent sessions, suggesting that Wistars utilized the previously learned rule. This motivated the hypothesis that neural activity reflecting proactive control would be observable in Wistars but not P rats. While P rats showed differences in neural activity at times of alcohol access, Wistars showed differences prior to approaching the sipper. These results support our hypothesis that Wistars are more likely to engage in proactive cognitive control strategies whereas P rats are more likely to engage in reactive cognitive control strategies. Although P rats were bred to prefer alcohol, the differences in cognitive control may reflect a sequela of behaviors that mirror those in humans at risk for an AUD.

Decoding spatial locations from primate lateral prefrontal cortex neural activity during virtual navigation

Objective. Decoding the intended trajectories from brain signals using a brain-computer interface system could be used to improve the mobility of patients with disabilities. Approach. Neuronal activity associated with spatial locations was examined while macaques performed a navigation task within a virtual environment. Main results. Here, we provide proof of principle that multi-unit spiking activity recorded from the lateral prefrontal cortex (LPFC) of non-human primates can be used to predict the location of a subject in a virtual maze during a navigation task. The spatial positions within the maze that require a choice or are associated with relevant task events can be better predicted than the locations where no relevant events occur. Importantly, within a task epoch of a single trial, multiple locations along the maze can be independently identified using a support vector machine model. Significance. Considering that the LPFC of macaques and humans share similar properties, our results suggest that this area could be a valuable implant location for an intracortical brain-computer interface system used for spatial navigation in patients with disabilities.

Prefrontal cortex neural activity predicts reduction of non-suicidal self-injury in adolescents with major depressive disorder: An event related potential study.

Non-suicidal self-injury (NSSI) is common in adolescent MDD, which is also a risk factor for suicide. However, there is few research on biomarkers and predictors about treatment response of NSSI. The purpose of this study was to find the difference of P300 between adolescent MDD with NSSI and healthy controls, and to explore whether the baseline electrophysiological level can predict the change of NSSI after treatment. We collected 62 first-episode drug-naïve MDD adolescents with NSSI (MDD with NSSI group) and 44 healthy controls (HC group). The demographic data, HAMD score, self-injury frequency and electrophysiological level of NSSI group and HC group were collected. The HAMD score, frequency of NSSI in was also collected after 8 weeks of antidepressant treatment. Compared to HC, the latency of the N2, P3a, and P3b components were significantly prolonged, whereas the amplitude of P3a and P3b were decreased in the MDD with NSSI group (P < 0.001). The frequency of self-injury decreased significantly after treatment (P < 0.001). Regression analysis showed that the amplitudes of P3b had a significant positive predictive effect on the rate of change of NSSI frequency after 8 weeks. P3b at baseline can be used as potential predictor for the reduction of NSSI in adolescent MDD.

Does an acute bout of breathing awareness meditation improve breathing stability correlated with regulatory prefrontal cortex neural activity in obstructive sleep apnea?

Does an acute bout of breathing awareness meditation improve breathing stability correlated with regulatory prefrontal cortex neural activity in obstructive sleep apnea?

A method for determining groups in nonparametric regression curves: Application to prefrontal cortex neural activity analysis.

Generalized additive models provide a flexible and easily-interpretable method for uncovering a nonlinear relationship between response and covariates. In many situations, the effect of a continuous covariate on the response varies across groups defined by the levels of a categorical variable. When confronted with a considerable number of groups defined by the levels of the categorical variable and a factor-by-curve interaction is detected in the model, it then becomes important to compare these regression curves. When the null hypothesis of equality of curves is rejected, leading to the clear conclusion that at least one curve is different, we may assume that individuals can be grouped into a number of classes whose members all share the same regression function. We propose a method that allows determining such groups with an automatic selection of their number by means of bootstrapping. The validity and behavior of the proposed method were evaluated through simulation studies. The applicability of the proposed method is illustrated using real data from an experimental study in neurology.

Shared mechanisms underlie the control of working memory and attention.

Cognitive control guides behaviour by controlling what, when, and how information is represented in the brain1. For example, attention controls sensory processing; top-down signals from prefrontal and parietal cortex strengthen the representation of task-relevant stimuli2-4. A similar 'selection' mechanism is thought to control the representations held 'in mind'-in working memory5-10. Here we show that shared neural mechanisms underlie the selection of items from working memory and attention to sensory stimuli. We trained rhesus monkeys to switch between two tasks, either selecting one item from a set of items held in working memory or attending to one stimulus from a set of visual stimuli. Neural recordings showed that similar representations in prefrontal cortex encoded the control of both selection and attention, suggesting that prefrontal cortex acts as a domain-general controller. By contrast, both attention and selection were represented independently in parietal and visual cortex. Both selection and attention facilitated behaviour by enhancing and transforming the representation of the selected memory or attended stimulus. Specifically, during the selection task, memory items were initially represented in independent subspaces of neural activity in prefrontal cortex. Selecting an item caused its representation to transform from its own subspace to a new subspace used to guide behaviour. A similar transformation occurred for attention. Our results suggest that prefrontal cortex controls cognition by dynamically transforming representations to control what and when cognitive computations are engaged.

Сравнительный анализ активности нейронов префронтальной коры мозга крыс в состоянии продуктивной и непродуктивной работы

The goal of the work was to study the prefrontal cortex neural activity in the different neuropsychological conditions of the animal. Extracellular neuron activity of the prefrontal cortex rat brain was recorded in rats performing the behavioral task of choice in the two-ring maze. On each experimental day, in the sequence of trials, periods of efficient and ineffective work were distinguished, differing in the prevalence of correct or incorrect choice. A comparative analysis of the neuron activity in six different variants of behavior revealed a significant difference in one pattern of neural activity accompanying reinforced trials to the one side in the ineffective condition. It is assumed that this is due to the activation of a previously formed pattern of behavior such leads to a probabilistic choice strategy. A dynamic mechanism of changing some decision-making strategies depending on the neuropsychological conditions of the animal is assumed, manifested in the inhibition of old models during training in a efficient state and a weakening of such a control mechanism in an ineffective state.

Excitation of the Pre-frontal and Primary Visual Cortex in Response to Transcorneal Electrical Stimulation in Retinal Degeneration Mice

Retinal degeneration (rd) is one of the leading causes of blindness in the modern world today. Various strategies including electrical stimulation are being researched for the restoration of partial or complete vision. Previous studies have demonstrated that the effectiveness of electrical stimulation in somatosensory, frontal and visual cortices is dependent on stimulation parameters including stimulation frequency and brain states. The aim of the study is to investigate the effect of applying a prolonged electrical stimulation on the eye of rd mice with various stimulation frequencies, in awake and anesthetized brain states. We recorded spontaneous electrocorticogram (ECoG) neural activity in prefrontal cortex and primary visual cortex in a mouse model of retinitis pigmentosa (RP) after prolonged (5-day) transcorneal electrical stimulation (pTES) at various frequencies (2, 10, and 20 Hz). We evaluated the absolute power and coherence of spontaneous ECoG neural activities in contralateral primary visual cortex (contra Vcx) and contralateral pre-frontal cortex (contra PFx). Under the awake state, the absolute power of theta, alpha and beta oscillations in contra Vcx, at 10 Hz stimulation, was higher than in the sham group. Under the anesthetized state, the absolute power of medium-, high-, and ultra-high gamma oscillations in the contra PFx, at 2 Hz stimulation, was higher than in the sham group. We also observed that the ultra-high gamma band coherence in contra Vcx-contra PFx was higher than in the sham group, with both 10 and 20 Hz stimulation frequencies. Our results showed that pTES modulates rd brain oscillations in a frequency and brain state-dependent manner. These findings suggest that non-invasive electrical stimulation of retina changes patterns of neural oscillations in the brain circuitry. This also provides a starting point for investigating the sustained effect of electrical stimulation of the retina to brain activities.

Effect of acute and chronic restraint stress on electrical activity of prefrontal cortex neurons in the reinstatement of extinguished methamphetamine-induced conditioned place preference: An electrophysiological study

Increased vulnerability to drug abuse has been observed after exposure to stress and the prefrontal cortex (PFC) plays a major role in the control of the stress response and reward pathway. The current study was conducted to clarify the effects of acute and chronic restraint stress on PFC neural activity during the reinstatement of methamphetamine (METH)-induced conditioned place preference (CPP) in rats. Following the establishment of CPP (METH 0.5 mg/kg; s.c. for 3 days) and the extinction phase, male Wistar rats were divided into threshold (0.25 mg/kg; s.c.) and sub-threshold (0.125 mg/kg; s.c.) METH-treated super groups to induce reinstatement. Each super group contained control (non-stressed), acute restraint stress (ARS) and chronic restraint stress (CRS) groups. in vivo single unit recordings were performed on the urethane-anesthetized rats in these groups. After baseline recordings (10-min period) of the neurons in the PFC, their firing activity was recorded for 50 min during the reinstatement phase after injection of METH. The results showed that the threshold dose, but not the sub-threshold dose, of METH significantly increased PFC neural activity in the non-stressed animals. The sub-threshold dose of METH notably changed this activity in both the ARS and CRS groups. These changes in the excited neurons after the sub-threshold dose in the ARS and CRS groups were significantly higher than those in the non-stressed group. It appears that the PFC is implicated in the associated reward pathway and stress functions. METH affected the firing rate of PFC neurons and stress amplified the effect of METH on changes in the neuronal firing rate in the PFC.

Nucleus incertus ablation disrupted conspecific recognition and modified immediate early gene expression patterns in ‘social brain’ circuits of rats

Social interaction involves neural activity in prefrontal cortex, septum, hippocampus, amygdala and hypothalamus. Notably, these areas all receive projections from the nucleus incertus (NI) in the pontine tegmentum. Therefore, we investigated the effect of excitotoxic lesions of NI neurons in adult male, Wistar rats on performance in a social discrimination test, and associated changes in immediate-early gene protein levels. NI was lesioned with quinolinic acid, and after recovery, rats underwent two trials in the 3-chamber test. In the first trial, NI-lesioned and sham-lesioned rats spent longer exploring a conspecific than an inanimate object. By contrast, in the second trial, NI-lesioned rats visited the familiar and novel conspecific chambers equally, whereas sham-lesioned rats spent longer engaging with the novel rat. Quantification of Fos- and Egr-1-immunoreactivity (IR) levels in brain areas implicated in social behaviour, revealed that social encounter and NI lesion produced complex, differential changes. For example, Egr-1-IR was broadly decreased in several amygdala nuclei in NI-lesioned rats relative to sham, but Fos-IR levels were unaltered. In hippocampus, NI-lesioned rats displayed decreased Fos-IR in CA2 and CA3, while Egr-1-IR was increased in the polymorphic dentate gyrus, CA1, CA2 and subiculum of NI-lesioned rats, relative to sham. Social encounter-related Egr-1-IR was also decreased in septum and anterior and lateral hypothalamus of NI-lesioned rats. Overall, these data suggest NI networks can modulate the activity of sensory, emotional and executive brain areas involved in social recognition, with a likely involvement of neuronal Egr-1 activation in amygdala, septum and hypothalamus, and Erg-1 inhibition in hippocampus.

Rearrangement of the Prefrontal Cortex Neural Activity in Both Hemispheres during Learning.

Neuronal activity of both right and left hemispheres of the rat prefrontal brain cortex was recorded in the two-ring maze during animal learning to operate in response to signals. At the beginning of learning, pairwise comparison of neural activity that accompanied correct and incorrect choice of the right and left sides showed significant differences in the left hemisphere and the lack of differences in the right one. With increasing percentage of correct choices during a session of learning, the differences in neuronal responses appeared in the right hemispheres and were reduced in the left one. The opposite trends in rearrangement of the total impulse activity are believed to be related to different roles of hemispheres in the construction of the internal behavioral model.

Rearrangement of Prefrontal Cortex Neural Activity Both Hemispheres During the Learning

Rearrangement of Prefrontal Cortex Neural Activity Both Hemispheres During the Learning

Just above Chance: Is It Harder to Decode Information from Prefrontal Cortex Hemodynamic Activity Patterns?

The prefrontal cortex (PFC) is central to flexible, goal-directed cognition, and understanding its representational code is an important problem in cognitive neuroscience. In humans, multivariate pattern analysis (MVPA) of fMRI blood oxygenation level-dependent (BOLD) measurements has emerged as an important approach for studying neural representations. Many previous studies have implicitly assumed that MVPA of fMRI BOLD is just as effective in decoding information encoded in PFC neural activity as it is in visual cortex. However, MVPA studies of PFC have had mixed success. Here we estimate the base rate of decoding information from PFC BOLD activity patterns from a meta-analysis of published MVPA studies. We show that PFC has a significantly lower base rate (55.4%) than visual areas in occipital (66.6%) and temporal (71.0%) cortices and one that is close to chance levels. Our results have implications for the design and interpretation of MVPA studies of PFC and raise important questions about its functional organization.

Age-Related Declines in Prefrontal Cortical Expression of Metabotropic Glutamate Receptors that Support Working Memory.

Glutamate signaling is essential for the persistent neural activity in prefrontal cortex (PFC) that enables working memory. Metabotropic glutamate receptors (mGluRs) are a diverse class of proteins that modulate excitatory neurotransmission via both presynaptic regulation of extracellular glutamate levels and postsynaptic modulation of ion channels on dendritic spines. This receptor class is of significant therapeutic interest for treatment of cognitive disorders associated with glutamate dysregulation. Working memory impairment and cortical hypoexcitability are both associated with advanced aging. Whether aging modifies PFC mGluR expression, and the extent to which any such alterations are regionally or subtype specific, however, is unknown. Moreover, it is unclear whether specific mGluRs in PFC are critical for working memory, and thus, whether altered mGluR expression in aging or disease is sufficient to play a causative role in working memory decline. Experiments in the current study first evaluated the effects of age on medial PFC (mPFC) mGluR expression using biochemical and molecular approaches in rats. Of the eight mGluRs examined, only mGluR5, mGluR3, and mGluR4 were significantly reduced in the aged PFC. The reductions in mGluR3 and mGluR5 (but not mGluR4) were observed in both mRNA and protein and were selectively localized to the prelimbic (PrL), but not infralimbic (IL), subregion of mPFC. Finally, pharmacological blockade of mGluR5 or mGluR2/3 using selective antagonists directed to PrL significantly impaired working memory without influencing non-mnemonic aspects of task performance. Together, these data implicate attenuated expression of PFC mGluR5 and mGluR3 in the impaired working memory associated with advanced ages.

Stable and Dynamic Coding for Working Memory in Primate Prefrontal Cortex.

Working memory (WM) provides the stability necessary for high-level cognition. Influential theories typically assume that WM depends on the persistence of stable neural representations, yet increasing evidence suggests that neural states are highly dynamic. Here we apply multivariate pattern analysis to explore the population dynamics in primate lateral prefrontal cortex (PFC) during three variants of the classic memory-guided saccade task (recorded in four animals). We observed the hallmark of dynamic population coding across key phases of a working memory task: sensory processing, memory encoding, and response execution. Throughout both these dynamic epochs and the memory delay period, however, the neural representational geometry remained stable. We identified two characteristics that jointly explain these dynamics: (1) time-varying changes in the subpopulation of neurons coding for task variables (i.e., dynamic subpopulations); and (2) time-varying selectivity within neurons (i.e., dynamic selectivity). These results indicate that even in a very simple memory-guided saccade task, PFC neurons display complex dynamics to support stable representations for WM.SIGNIFICANCE STATEMENT Flexible, intelligent behavior requires the maintenance and manipulation of incoming information over various time spans. For short time spans, this faculty is labeled “working memory” (WM). Dominant models propose that WM is maintained by stable, persistent patterns of neural activity in prefrontal cortex (PFC). However, recent evidence suggests that neural activity in PFC is dynamic, even while the contents of WM remain stably represented. Here, we explored the neural dynamics in PFC during a memory-guided saccade task. We found evidence for dynamic population coding in various task epochs, despite striking stability in the neural representational geometry of WM. Furthermore, we identified two distinct cellular mechanisms that contribute to dynamic population coding.

Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention

Nicotine has strong addictive as well as procognitive properties. While a large body of research on nicotine continues to inform us about mechanisms related to its reinforcing effects, less is known about clinically relevant mechanisms that subserve its cognitive-enhancing properties. Understanding the latter is critical for developing optimal strategies for treating cognitive deficits. The primary brain region implicated in cognitive functions improved by nicotine is the prefrontal cortex (PFC). Here we assessed the impact of nicotine on unit activity and local field potential oscillations in the PFC of behaving rats. An acute dose of nicotine produced a predominantly inhibitory influence on population activity, a small increase in gamma oscillations, and a decrease in theta and beta oscillations. After a daily dosing regimen, a shift to excitatory–inhibitory balance in single-unit activity and stronger gamma oscillations began to emerge. This pattern of plasticity was specific to the gamma band as lower frequency oscillations were suppressed consistently across daily nicotine treatments. Gamma oscillations are associated with enhanced attentional capacity. Consistent with this mechanism, the repeat dosing regimen in a separate cohort of subjects led to improved performance in an attention task. These data suggest that procognitive effects of nicotine may involve development of enhanced gamma oscillatory activity and a shift to excitatory–inhibitory balance in PFC neural activity. In the context of the clinical use of nicotine and related agonists for treating cognitive deficits, these data suggest that daily dosing may be critical to allow for development of robust gamma oscillations.

NR2A-Containing NMDARs in the Prefrontal Cortex Are Required for Working Memory and Associated with Age-Related Cognitive Decline.

Working memory, the ability to hold information "in mind," requires persistent activity of pyramidal neurons in prefrontal cortex (PFC) mediated by NMDA receptor (NMDAR) activation. NMDAR loss in PFC may account for working memory impairments in aging and psychiatric disease. Our studies demonstrate that NMDARs containing the NR2A subunit, but not the NR2B subunit, are required for working memory and that loss of NR2A predicts severity of age-related working memory impairment. The importance of NR2A to working memory is likely due its abundant contribution to pyramidal neuron activity and location at synaptic sites in PFC. This information is useful in designing new therapies to treat working memory impairments by enhancing the function of NR2A-containing NMDARs.

Catechol-O-methyltransferase Val158met polymorphism interacts with early experience to predict executive functions in early childhood.

Numerous studies demonstrate that the Methionine variant of the catechol-O-methyltransferase Val158Met polymorphism, which confers less efficient catabolism of catecholamines, is associated with increased focal activation of prefrontal cortex (PFC) and higher levels of executive function abilities. By and large, however, studies of COMT Val158Met have been conducted with adult samples and do not account for the context in which development is occurring. Effects of early adversity on stress response physiology and the inverted U shape relating catecholamine levels to neural activity in PFC indicate the need to take into account early experience when considering relations between genes such as COMT and executive cognitive ability. Consistent with this neurobiology, we find in a prospective longitudinal sample of children and families (N = 1292) that COMT Val158Met interacts with early experience to predict executive function abilities in early childhood. Specifically, the Valine variant of the COMT Val158Met polymorphism, which confers more rather than less efficient catabolism of catecholamines is associated with higher executive function abilities at child ages 48 and 60 months and with faster growth of executive function for children experiencing early adversity, as indexed by cumulative risk factors in the home at child ages 7, 15, 24, and 36 months. Findings indicate the importance of the early environment for the relation between catecholamine genes and developmental outcomes and demonstrate that the genetic moderation of environmental risk is detectable in early childhood.

I think therefore I am: Rest-related prefrontal cortex neural activity is involved in generating the sense of self.

The sense of self has always been a major focus in the psychophysical debate. It has been argued that this complex ongoing internal sense cannot be explained by any physical measure and therefore substantiates a mind-body differentiation. Recently, however, neuro-imaging studies have associated self-referential spontaneous thought, a core-element of the ongoing sense of self, with synchronous neural activations during rest in the medial prefrontal cortex (PFC), as well as the medial and lateral parietal cortices. By applying deep transcranial magnetic stimulation (TMS) over human PFC before rest, we disrupted activity in this neural circuitry thereby inducing reports of lowered self-awareness and strong feelings of dissociation. This effect was not found with standard or sham TMS, or when stimulation was followed by a task instead of rest. These findings demonstrate for the first time a critical, causal role of intact rest-related PFC activity patterns in enabling integrated, enduring, self-referential mental processing.