The "psychiatric" neuron: the psychic neuron of the cerebral cortex, revisited.

Nearly 25 years ago, Dr. Patricia Goldman-Rakic published her review paper, "The 'Psychic' Neuron of the Cerebral Cortex," outlining the circuit-level dynamics, neurotransmitter systems, and behavioral correlates of pyramidal neurons in the cerebral cortex, particularly as they relate to working memory. In the decades since the release of this paper, the existing literature and our understanding of the pyramidal neuron have increased tremendously, and research is still underway to better characterize the role of the pyramidal neuron in both healthy and psychiatric disease states. In this review, we revisit Dr. Goldman-Rakic's characterization of the pyramidal neuron, focusing on the pyramidal neurons of the prefrontal cortex (PFC) and their role in working memory. Specifically, we examine the role of PFC pyramidal neurons in the intersection of working memory and social function and describe how deficits in working memory may actually underlie the pathophysiology of social dysfunction in psychiatric disease states. We briefly describe the cortico-cortical and corticothalamic connections between the PFC and non-PFC brain regions, as well the microcircuit dynamics of the pyramidal neuron and interneurons, and the role of both these macro- and microcircuits in the maintenance of the excitatory/inhibitory balance of the cerebral cortex for working memory function. Finally, we discuss the consequences to working memory when pyramidal neurons and their circuits are dysfunctional, emphasizing the resulting social deficits in psychiatric disease states with known working memory dysfunction.

Predictability and Variation in Language Are Differentially Affected by Learning and Production.

General principles of human cognition can help to explain why languages are more likely to have certain characteristics than others: structures that are difficult to process or produce will tend to be lost over time. One aspect of cognition that is implicated in language use is working memory-the component of short-term memory used for temporary storage and manipulation of information. In this study, we consider the relationship between working memory and regularization of linguistic variation. Regularization is a well-documented process whereby languages become less variable (on some dimension) over time. This process has been argued to be driven by the behavior of individual language users, but the specific mechanism is not agreed upon. Here, we use an artificial language learning experiment to investigate whether limitations in working memory during either language learning or language production drive regularization behavior. We find that taxing working memory during production results in the loss of all types of variation, but the process by which random variation becomes more predictable is better explained by learning biases. A computational model offers a potential explanation for the production effect using a simple self-priming mechanism.

How BDNF affects working memory in acute sleep deprivation: The mediating role of spontaneous brain activity.

The brain-derived neurotrophic factor (BDNF) mediates the plasticity associated with memory processing, and compensatorily increases after acute sleep deprivation (SD). However, whether the altered spontaneous brain activity mediates the association between BDNF and working memory in SD remains unknown. Here, we aimed to probe the mediating role of the spontaneous brain activity between plasma BDNF and WM function in SD. A total of 30 healthy subjects with regular sleep were enrolled in this study. Resting-sate functional magnetic resonance imaging (fMRI) scans and the peripheral blood were collected before and after 24 h SD. All participants also received n-back task assessing working memory (WM) performance. The amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were calculated to reflect the intensity of regional spontaneous brain activity. Plasma BDNF was measured by sandwich ELISA. Our results revealed a significant decline in WM and increase in plasma BDNF level after SD, and negative association between the changed WM performance and plasma BDNF level. Specially, the ALFF of the left inferior parietal cortex and right inferior frontal cortex, and fALFF of the left anterior cingulate and medial prefrontal cortex and left posterior opercular cortex regulated the association between the BDNF and one-back reaction time respectively. Our results suggest that the association between BDNF and working memory may be mediated through regional spontaneous brain activity involving in the cerebral cortex, which may provide new sight into the interaction between neurotrophic factors and cognition, and potential targets for noninvasive brain stimulation on WM decline after acute SD.

The relationship between speech in noise perception and auditory working memory capacity in monolingual and bilingual adults.

OBJECTIVE: Speech-in-noise perception is dependent on the interaction between sensory and cognitive processes. One factor that can relate to both processes is bilingualism. This study aimed to determine the correlation between auditory-working-memory and speech-in-noise in Persian monolinguals and Kurdish-Persian bilinguals. DESIGN: Speech-in-noise tests (sentences-in-noise and syllables-in-noise) and auditory-working-memory tests (forward and backward digit span, and n-back) were performed. STUDY SAMPLE: Participants were 48 Kurdish-Persian bilinguals with a mean age of 24 (±4) years and 48 Persian monolinguals with a mean age of 25 (±2) years with normal hearing. RESULTS: Both language groups scored within normal limits in all memory and speech-in-noise tests. However, bilinguals performed significantly worse than monolinguals on all auditory-working-memory tests and the sentences-in-noise test. Monolinguals outperformed bilinguals in sentences-in-noise test (∼1.5 dB difference) and all auditory-working-memory tests (∼1 digit difference). The two groups did not significantly differ in syllables-in-noise test. Both groups had a significant correlation between working memory capacity and sentences-in-noise test. However, no significant correlation was found between syllables-in-noise and working memory capacity at any SNR. CONCLUSIONS: Cognitive factors such as auditory working memory appear to correlate with speech-in-noise perception ability (at least at the sentence level) in monolingual and bilinguals young adults.

Unpacking affect maintenance and its association with depressive symptoms: integrating positive and negative affects.

ABSTRACTDepression is associated with increased maintenance of negative affect (NA) and reduced - blunted and short-lived - maintenance of positive affect (PA). Studies have focused on factors associated with the maintenance of NA, specifically, the emotion regulation strategy of brooding and the capacity to hold negative affective experiences in working memory (WM). Despite its theoretical importance, less attention has been given to factors associated with the maintenance of PA in depression. This study aims to synthesise factors playing a role in the maintenance of both NA and PA. Specifically, we used self-reported assessment of PA and NA regulation and performance-based measures of NA and PA processing in WM to predict depressive symptoms severity. Participants (N = 219) completed the Affective Maintenance Task (AMT, Mikels et al., 2008), which provided performance-based measures of PA and NA maintenance, and filled out questionnaires assessing brooding, positive rumination and depressive severity. Brooding, positive rumination and AMT-based measures of positive (but not negative) affective information processing were independently associated with depressive symptoms. We highlight the unique contributions of PA processing, as well as of self-reported emotion regulation strategies in understanding depression maintenance.

Working memory training improves episodic memory in older people: transfer based on controlled retrieval processes.

Introduction: The results of working memory (WM) training to improve episodic memory in older people are inconsistent. This inconsistency could be due to the fact that the episodic memory tests used do not share the same cognitive resources as the trained WM task. The aim of this study was to assess whether performance on an episodic memory test will improve only when this test requires controlled processes of retrieval of information from secondary memory or recollection, similar to the processes exercised during WM training. Method: Fifty-five people over 60 years of age participated in the study: 27 were randomly assigned to the experimental group (EG) and the rest to the control group (CG). The EG was trained in complex span tasks. Before and after training, both groups were tested on episodic memory tests (a verbal and a visuospatial recognition test) and WM span tasks (reading, digit and spatial location). Results: ANOVAs revealed a greater improvement of recollection estimates in the EG than in the CG for both verbal recognition (p = 0.023) and visuospatial recognition (p = 0.014). Discussion: Our results provide support for a cognitive mechanism whose shared presence favored transfer from training on a WM task to a test of episodic memory. Consistent with our predictions, training on complex span tasks improved performance on recognition tests only when recall required a controlled search process in secondary memory, or recollection. We therefore stress the importance of identifying other cognitive resources that are susceptible to transfer from a training task to other untrained tasks. A better understanding of the phenomenon of transfer is crucial for the design of increasingly effective intervention programs for older people.

OpenWMB: An open-source and automated working memory task battery for OpenSesame.

Working memory capacity (WMC) has been measured with a plethora of cognitive tasks. Several preeminent automated batteries of working memory (WM) tasks have been developed recently. However, despite all their advantages, most batteries were programmed in paid platforms and/or only included a single WM paradigm. To address these issues, we developed the OpenWMB, an automated battery comprising seven tasks from three distinct paradigms (complex spans, updating tasks, and binding tasks) that tap into several functional aspects of WM (simultaneous storage and processing, updating, and binding). The battery runs on open-source software (OpenSesame) and is freely available online in a ready-to-download format. The OpenWMB possesses flexible features and includes a data processing script (that converts data into a format ready for statistical analysis). The instrument is available in Portuguese and English. However, we only assessed the psychometric properties of the former version. The Portuguese version presented good internal consistency and considerable internal and predictive validity: all tasks loaded into a single factor. Additionally, the WMC estimate was strongly correlated with a fluid intelligence factor. This study also tried to contribute to the ongoing debate regarding the best method to assess WMC. We computed a permutation analysis to compare the amount of variance shared between a fluid intelligence factor and (1) each WM task, (2) homogenous WMC factors (based on multiple tasks from the same paradigm), and (3) heterogeneous WMC factors (derived from triplets of tasks from different paradigms). Our results suggested that heterogeneous factors provided the best estimates of WMC.

Effects of optogenetic silencing the anterior cingulate cortex in a delayed non-match to trajectory task.

Working memory is a fundamental cognitive ability, allowing us to keep information in memory for the time needed to perform a given task. A complex neural circuit fulfills these functions, among which is the anterior cingulate cortex (CG). Functionally and anatomically connected to the medial prefrontal, retrosplenial, midcingulate and hippocampus, as well as motor cortices, CG has been implicated in retrieving appropriate information when needed to select and control appropriate behavior. The role of cingulate cortex in working memory-guided behaviors remains unclear due to the lack of studies reversibly interfering with its activity during specific epochs of working memory. We used eNpHR3.0 to silence cingulate neurons while animals perform a standard delayed non-match to trajectory task, and found that, while not causing an absolute impairment in working memory, silencing cingulate neurons during retrieval decreases the mean performance if compared to silencing during encoding. Such retrieval-associated changes are accompanied by longer delays observed when light is delivered to control animals, when compared to eNpHR3.0+ ones, consistent with an adaptive recruitment of additional cognitive resources.

The assessment of executive function abilities in healthy and neurodegenerative aging-A selective literature review.

Numerous studies have examined executive function (EF) abilities in cognitively healthy older adults and those living with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Currently, there are no standard accepted protocols for testing specific EFs; thus, researchers have used their preferred tool, which leads to variability in assessments of decline in a particular ability across studies. Therefore, there is a need for guidance as to the most sensitive tests for assessing EF decline. A search of the most current literature published between 2000 and 2022 on EF studies assessing cognitively healthy older adults and individuals living with MCI and AD was conducted using PubMed/Medline, PsycINFO, Embase, Web of Science, and Google Scholar. Emphasis was placed on the EF's dual-tasking, inhibition, shifting or switching, and working memory updating. Many tasks and their outcomes were reviewed. Of particular importance was the difference in outcomes for tasks applied to the same group of participants. These various EF assessment tools demonstrate differences in effectively identifying decline in EF ability due to the aging process and neurodegenerative conditions, such as MCI and AD. This review identifies various factors to consider in using particular EF tasks in particular populations, including task demand and stimuli factors, and also when comparing differing results across studies.

Role of executive functions in the relations of state- and trait-math anxiety with math performance.

The detrimental effect of math anxiety on math performance is thought to be mediated by executive functions. Previous studies have primarily focused on trait-math anxiety rather than state-math anxiety and have typically examined a single executive function rather than comprehensively evaluating all of them. Here, we used a structural equation modeling approach to concurrently determine the potential mediating roles of different executive functions (i.e., inhibition, switching, and updating) in the relationships between both state- and trait-math anxiety and math performance. A battery of computer-based tasks and questionnaires were administered to 205 university students. Two relevant results emerged. First, confirmatory factor analysis suggests that math anxiety encompassed both trait and state dimensions and, although they share substantial variance, trait-math anxiety predicted math performance over and above state-math anxiety. Second, working memory updating was the only executive function that mediated the relationship between math anxiety and math performance; neither inhibition nor switching played mediating roles. This calls into question whether some general proposals about the relationship between anxiety and executive functions can be extended specifically to math anxiety. We also raise the possibility that working memory updating or general cognitive difficulties might precede individual differences in math anxiety.

Decomposing neurophysiological underpinnings of age-related decline in visual working memory.

Exploring the neural basis of age-related decline in working memory is vital in our aging society. Previous electroencephalographic studies suggested that the contralateral delay activity (CDA) may be insensitive to age-related decline in lateralized visual working memory (VWM) performance. Instead, recent evidence indicated that task-induced alpha power lateralization decreases in older age. However, the relationship between alpha power lateralization and age-related decline of VWM performance remains unknown, and recent studies have questioned the validity of these findings due to confounding factors of the aperiodic signal. Using a sample of 134 participants, we replicated the age-related decrease of alpha power lateralization after adjusting for the aperiodic signal. Critically, the link between task performance and alpha power lateralization was found only when correcting for aperiodic signal biases. Functionally, these findings suggest that age-related declines in VWM performance may be related to the decreased ability to prioritize relevant over irrelevant information. Conversely, CDA amplitudes were stable across age groups, suggesting a distinct neural mechanism possibly related to preserved VWM encoding or early maintenance.

A working memory intervention for children with prenatal alcohol exposure: Pilot study.

Cogmed© is a computerized working memory training program designed to improve attention and working memory. We examined the short- and long-term impacts of a 25-session Cogmed© intervention on working memory and other cognitive and learning domains in children with prenatal alcohol exposure (PAE) and typically developing children. Participants included 38 children (4 - 13 years old) from Alberta, Canada in two groups: PAE (n = 20) and typically developing (n = 18). Significant improvements in areas of working memory and attentional control for both the PAE and the typically developing group were reported immediately after intervention completion (short-term impact). The gains on some measures were retained at five-week follow up (long-term impact). Preliminary findings indicate that computerized interventions may positively impact WM and attention control and that these changes may be maintained after a delay period.

Enhanced expression of activity-regulated cytoskeleton-associated protein in the medial prefrontal cortex is involved in working memory performance.

Working memory (WM) is a cognitive function important for guiding the on-going or upcoming behavior. A memory-related protein Arc (activity-regulated cytoskeleton-associated protein) is implicated in long-term memory consolidation. Recent evidence further suggests the involvement of hippocampal Arc in spatial WM. The medial prefrontal cortex (mPFC) is a key brain region mediating WM. However, the role of mPFC Arc in WM is still uncertain. To investigate whether mPFC Arc protein is involved in WM performance, delayed non-match to sample (DNMS) T-maze task was performed in rats with or without blocking new synthesis of mPFC Arc. In DNMS task, a 10-s or 30-s delay between the sample run and the choice run was given to evaluate WM performance. To block new Arc protein synthesis during the DNMS task, Arc antisense oligodeoxynucleotides (ODNs) were injected to the bilateral mPFC. The results show that, in rats without surgery for cannula implantation and subsequent intracerebral injection of ODNs, WM was functioning well during the DNMS task with a delay of 10 s but not 30 s, which was accompanied with a significantly increased level of mPFC Arc protein, indicating a possible link between enhanced Arc protein expression and the performance of WM. After preventing the enhancement of mPFC Arc protein expression with Arc antisense ODNs, rat's WM performance was impaired. These findings support enhanced mPFC Arc protein expression playing a role during WM performance.

Repertoire of timescales in uni - and transmodal regions mediate working memory capacity.

Working memory (WM) describes the dynamic process of maintenance and manipulation of information over a certain time delay. Neuronally, WM recruits a distributed network of cortical regions like the visual and dorsolateral prefrontal cortex as well as the subcortical hippocampus. How the input dynamics and subsequent neural dynamics impact WM remains unclear though. To answer this question, we combined the analysis of behavioral WM capacity with measuring neural dynamics through task-related power spectrum changes, e.g., median frequency (MF) in functional magnetic resonance imaging (fMRI). We show that the processing of the input dynamics, e.g., the task structure's specific timescale, leads to changes in the unimodal visual cortex's corresponding timescale which also relates to working memory capacity. While the more transmodal hippocampus relates to working memory capacity through its balance across multiple timescales or frequencies. In conclusion, we here show the relevance of both input dynamics and different neural timescales for WM capacity in uni - and transmodal regions like visual cortex and hippocampus for the subject's WM performance.

Healthcare Cost of Cochlear Implantation in India.

Making evidence-based policy decisions is challenging when there is a lack of information, especially when deciding provider payment rates for publicly funded health insurance plans. Therefore, the goal of this study was to estimate the cost of a cochlear implant operation in a tertiary care setting in India. We also looked at the patients' out-of-pocket (OOP) expenses for the cochlear implant surgery. From the perspectives of the patients and the healthcare systems, we assessed the financial costs of the cochlear implantation procedure. A bottom-up pricing model was used to assess the cost that the healthcare system would bear for a cochlear implant procedure. Information on all the resources (both capital and ongoing) required to offer cochlear implantation services for hearing loss was gathered over the course of a year. 120 individuals with hearing loss who had cochlear implantation surgery disclosed their out-of-pocket (OOP) costs, which included both direct medical and non-medical expenses. All costs for the budgetary year 2018-2019 were anticipated. The unit health system spent ₹ 151($2), ₹ 578($7.34) and ₹ 37,449($478) on ear exams, audiological evaluations, and cochlear implant surgeries, respectively. Per bed-day in the otolaryngology ward, hospitalization cost ₹ 202($2.6), or ₹ 1211($15.5). The estimated average out-of-pocket cost for a cochlear implant operation was ₹ 682,230($8710). Our research can be used to establish package rates for publicly funded insurance plans in India, plan the growth of public sector hearing care services, and do cost-effectiveness assessments on various hearing care models. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04389-7.

One Size Does Not Fit All: Idiographic Computational Models Reveal Individual Differences in Learning and Meta-Learning Strategies.

Complex skill learning depends on the joint contribution of multiple interacting systems: working memory (WM), declarative long-term memory (LTM) and reinforcement learning (RL). The present study aims to understand individual differences in the relative contributions of these systems during learning. We built four idiographic, ACT-R models of performance on the stimulus-response learning, Reinforcement Learning Working Memory task. The task consisted of short 3-image, and long 6-image, feedback-based learning blocks. A no-feedback test phase was administered after learning, with an interfering task inserted between learning and test. Our four models included two single-mechanism RL and LTM models, and two integrated RL-LTM models: (a) RL-based meta-learning, which selects RL or LTM to learn based on recent success, and (b) a parameterized RL-LTM selection model at fixed proportions independent of learning success. Each model was the best fit for some proportion of our learners (LTM: 68.7%, RL: 4.8%, Meta-RL: 13.25%, bias-RL:13.25% of participants), suggesting fundamental differences in the way individuals deploy basic learning mechanisms, even for a simple stimulus-response task. Finally, long-term declarative memory seems to be the preferred learning strategy for this task regardless of block length (3- vs 6-image blocks), as determined by the large number of subjects whose learning characteristics were best captured by the LTM only model, and a preference for LTM over RL in both of our integrated-models, owing to the strength of our idiographic approach.

Contributions of narrow- and broad-spiking prefrontal and parietal neurons on working memory tasks.

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.

Stress priming transcranial direct current stimulation (tDCS) enhances updating of emotional content in working memory.

Transcranial direct current stimulation (tDCS) targeting the prefrontal cortex has emerged as a valuable tool in psychiatric research. Understanding the impact of affective states, such as stress at the time of stimulation, on the efficacy of prefrontal tDCS is crucial for advancing tDCS interventions. Stress-primed tDCS, wherein stress is used as a priming agent, has the potential to modulate neural plasticity and enhance cognitive functions, particularly in emotional working memory. However, prior research using stress-primed tDCS focused solely on non-emotional working memory performance, yielding mixed results. In this sham-controlled study, we addressed this gap by investigating the effects of stress-primed bifrontal tDCS (active versus sham) on both non-emotional and emotional working memory performance. The study was conducted in 146 healthy individuals who were randomly assigned to four experimental groups. The Trier Social Stress Test (TSST) or a control variant of the test was used to induce a stress versus control state. The results showed that stress priming significantly enhanced the effects of tDCS on the updating of emotional content in working memory, as evidenced by improved accuracy. Notably, no significant effects of stress priming were found for non-emotional working memory performance. These findings highlight the importance of an individual's prior affective state in shaping their response to tDCS, especially in the context of emotional working memory.

Comparison of Executive Function Skills between Patients with Cerebral Palsy and Typically Developing Populations: A Systematic Review and Meta-Analysis.

Background: Children with CP show deficits in executive function compared to their typically developing peers, based on the majority of the available evidence. However, the magnitude of these deficits, as well as the proportions of the shortfalls in the three main components, have not yet been examined. This is the first meta-analysis to synthesize evidence on the magnitude of differences between patients with cerebral palsy (CP) and typically developing populations in different components of executive function skills (working memory, inhibitory control and cognitive flexibility), and thus makes recommendations on which areas of executive functioning are in greatest need of intervention. Methods: We conducted a systematic literature search of four databases for studies that measured executive functions in these two groups until 31 August 2023. We calculated the standardized mean difference (Hedges' g), an average effect size overall, and for the three components of executive function skills separately, we used several moderator analyses, including methodological differences between the primary studies. Results: Fifteen articles were included in the meta-analysis. The average mean difference in executive functioning overall was large (g+ = -0.82). Furthermore, large significant differences were found in working memory (g+ = -0.92) and inhibitory control (g+ = -0.82) and a moderate difference was identified in cognitive flexibility (g+ = -0.57). In addition, results of moderator analyses reveal the importance of a rigorous matching of control group participants and CP patients. Conclusions: The results demonstrate a severe impairment in all executive functions among CP patients compared to typically developing peers, which do not decrease over time.

Alterations in brain functional connectivity in patients with mild cognitive impairment: A systematic review and meta-analysis of functional near-infrared spectroscopy studies.

Emerging evidences suggest that cognitive deficits in individuals with mild cognitive impairment (MCI) are associated with disruptions in brain functional connectivity (FC). This systematic review and meta-analysis aimed to comprehensively evaluate alterations in FC between MCI individuals and healthy control (HC) using functional near-infrared spectroscopy (fNIRS). Thirteen studies were included in qualitative analysis, with two studies synthesized for quantitative meta-analysis. Overall, MCI patients exhibited reduced resting-state FC, predominantly in the prefrontal, parietal, and occipital cortex. Meta-analysis of two studies revealed a significant reduction in resting-state FC from the right prefrontal to right occipital cortex (standardized mean difference [SMD] = -.56; p < .001), left prefrontal to left occipital cortex (SMD = -.68; p < .001), and right prefrontal to left occipital cortex (SMD = -.53; p < .001) in MCI patients compared to HC. During naming animal-walking task, MCI patients exhibited enhanced FC in the prefrontal, motor, and occipital cortex, whereas a decrease in FC was observed in the right prefrontal to left prefrontal cortex during calculating-walking task. In working memory tasks, MCI predominantly showed increased FC in the medial and left prefrontal cortex. However, a decreased in prefrontal FC and a shifted in distribution from the left to the right prefrontal cortex were noted in MCI patients during a verbal frequency task. In conclusion, fNIRS effectively identified abnormalities in FC between MCI and HC, indicating disrupted FC as potential markers for the early detection of MCI. Future studies should investigate the use of task- and region-specific FC alterations as a sensitive biomarker for MCI.