Sub-threshold neuronal activity and the dynamical regime of cerebral cortex.

Cortical neurons exhibit temporally irregular spiking patterns and heterogeneous firing rates. These features arise in model circuits operating in a 'fluctuation-driven regime', in which fluctuations in membrane potentials emerge from the network dynamics. However, it is still debated whether the cortex operates in such a regime. We evaluated the fluctuation-driven hypothesis by analyzing spiking and sub-threshold membrane potentials of neurons in the frontal cortex of mice performing a decision-making task. We showed that while standard fluctuation-driven models successfully account for spiking statistics, they fall short in capturing the heterogeneity in sub-threshold activity. This limitation is an inevitable outcome of bombarding single-compartment neurons with a large number of pre-synaptic inputs, thereby clamping the voltage of all neurons to more or less the same average voltage. To address this, we effectively incorporated dendritic morphology into the standard models. Inclusion of dendritic morphology in the neuronal models increased neuronal selectivity and reduced error trials, suggesting a functional role for dendrites during decision-making. Our work suggests that, during decision-making, cortical neurons in high-order cortical areas operate in a fluctuation-driven regime.

Site- and frequency-specific enhancement of visual search performance with online individual alpha frequency (IAF) repetitive transcranial magnetic stimulation (rTMS) to the inferior frontal junction.

In this study, repetitive transcranial magnetic stimulation was applied to either the right inferior frontal junction or the right inferior parietal cortex during a difficult aerial reconnaissance search task to test its capacity to improve search performance. Two stimulation strategies previously found to enhance cognitive performance were tested: The first is called "addition by subtraction," and the second condition utilizes a direct excitatory approach by applying brief trains of high-frequency repetitive transcranial magnetic stimulation immediately before task trials. In a within-subjects design, participants were given active or sham repetitive transcranial magnetic stimulation at either 1 Hz or at 1 Hz above their individual peak alpha frequency (IAF + 1, mean 11.5 Hz), delivered to either the right inferior frontal junction or the right inferior parietal cortex, both defined with individualized peak functional magnetic resonance imaging (fMRI) activation obtained during the visual search task. Results indicated that among the 13 participants who completed the protocol, only active IAF + 1 stimulation to inferior frontal junction resulted in significant speeding of reaction time compared to sham. This site- and frequency-specific enhancement of performance with IAF + 1 repetitive transcranial magnetic stimulation applied immediately prior to task trials provides evidence for the involvement of inferior frontal junction in guiding difficult visual search, and more generally for the use of online repetitive transcranial magnetic stimulation directed at specific functional networks to enhance visual search performance.

Transforming text to music using artificial intelligence improves the frontal lobe function of normal older adults.

INTRODUCTION: Recent advances in artificial intelligence (AI) have been substantial. We investigated the effectiveness of an online meeting in which normal older adults (otokai) used a music-generative AI that transforms text to music (Music Trinity Generative Algorithm-Human Refined [MusicTGA-HR]). METHODS: One hundred eighteen community-dwelling, cognitively normal older adults were recruited through the internet (64 men, 54 women; mean age: 69.4 ± 4.4 years). Using MusicTGA-HR, the participants chose music that they thought was the most suitable to a given theme. We established 11 classes of 7-10 members and one instructor each. Each class held an online meeting once a week, and each participant presented the music they chose. The other participants and the instructor then commented on the music. Neuropsychological assessments were performed before and after the intervention for 6 months, and the results before and after the intervention were statistically analyzed. RESULTS: The category and letter word fluencies (WFs) were significantly improved (category WF: p = .003; letter WF: p = .036), and the time of the Trail-Making Test-B was also significantly shortened (p = .039). The Brain Assessment, an online cognitive test we developed, showed significant improvement in the memory of numbers (p < .001). CONCLUSION: The online meeting of the otokai, which used music-generative AI, improved the frontal lobe function and memory of independent normal older adults.

Medial to lateral frontal functional connectivity mapping reveals the organization of cingulate cortex.

The functional organization of the frontal lobe is a source of debate, focusing on broad functional subdivisions, large-scale networks, or local refined specificities. Multiple neurocognitive models have tried to explain how functional interactions between cingulate and lateral frontal regions contribute to decision making and cognitive control, but their neuroanatomical bases remain unclear. We provide a detailed description of the functional connectivity between cingulate and lateral frontal regions using resting-state functional MRI in rhesus macaques. The analysis focuses on the functional connectivity of the rostral part of the cingulate sulcus with the lateral frontal cortex. Data-driven and seed-based analysis revealed three clusters within the cingulate sulcus organized along the rostro-caudal axis: the anterior, mid, and posterior clusters display increased functional connectivity with, respectively, the anterior lateral prefrontal regions, face-eye lateral frontal motor cortical areas, and hand lateral frontal motor cortex. The location of these clusters can be predicted in individual subjects based on morphological landmarks. These results suggest that the anterior cluster corresponds to the anterior cingulate cortex, whereas the posterior clusters correspond to the face-eye and hand cingulate motor areas within the anterior midcingulate cortex. These data provide a comprehensive framework to identify cingulate subregions based on functional connectivity and local organization.

Encoding of 2D Self-Centered Plans and World-Centered Positions in the Rat Frontal Orienting Field.

The neural mechanisms of motor planning have been extensively studied in rodents. Preparatory activity in the frontal cortex predicts upcoming choice, but limitations of typical tasks have made it challenging to determine whether the spatial information is in a self-centered direction reference frame or a world-centered position reference frame. Here, we trained male rats to make delayed visually guided orienting movements to six different directions, with four different target positions for each direction, which allowed us to disentangle direction versus position tuning in neural activity. We recorded single unit activity from the rat frontal orienting field (FOF) in the secondary motor cortex, a region involved in planning orienting movements. Population analyses revealed that the FOF encodes two separate 2D maps of space. First, a 2D map of the planned and ongoing movement in a self-centered direction reference frame. Second, a 2D map of the animal's current position on the port wall in a world-centered reference frame. Thus, preparatory activity in the FOF represents self-centered upcoming movement directions, but FOF neurons multiplex both self- and world-reference frame variables at the level of single neurons. Neural network model comparison supports the view that despite the presence of world-centered representations, the FOF receives the target information as self-centered input and generates self-centered planning signals.

Transcranial photobiomodulation on the left inferior frontal gyrus enhances Mandarin Chinese L1 and L2 complex sentence processing performances.

This study investigated the causal enhancing effect of transcranial photobiomodulation (tPBM) over the left inferior frontal gyrus (LIFG) on syntactically complex Mandarin Chinese first language (L1) and second language (L2) sentence processing performances. Two (L1 and L2) groups of participants (thirty per group) were recruited to receive the double-blind, sham-controlled tPBM intervention via LIFG, followed by the sentence processing, the verbal working memory (WM), and the visual WM tasks. Results revealed a consistent pattern for both groups: (a) tPBM enhanced sentence processing performance but not verbal WM for linear processing of unstructured sequences and visual WM performances; (b) Participants with lower sentence processing performances under sham tPBM benefited more from active tPBM. Taken together, the current study substantiated that tPBM enhanced L1 and L2 sentence processing, and would serve as a promising and cost-effective noninvasive brain stimulation (NIBS) tool for future applications on upregulating the human language faculty.

Multiple faces of anxiety: a frontal lobe perspective.

Marked dysregulation of the human prefrontal cortex (PFC) and anterior cingulate cortex (ACC) characterises a variety of anxiety disorders, and its amelioration is a key feature of treatment success. Overall treatment response, however, is highly variable, and about a third of patients are resistant to treatment. In this review we hypothesise that a major contributor to this variation in treatment response are the multiple faces of anxiety induced by distinct forms of frontal cortex dysregulation. Comparison of findings from humans and non-human primates reveals marked similarity in the functional organisation of threat regulation across the frontal lobes. This organisation is discussed in relation to the 'predatory imminence continuum' model of threat and the differential engagement of executive functions at the core of both emotion generation and regulation strategies.

Frontal EEG alpha asymmetry predicts foreign language anxiety while speaking a foreign language.

Engaging in dialog requires interlocutors to coordinate sending and receiving linguistic signals to build a discourse based upon interpretations and perceptions interconnected with a range of emotions. Conversing in a foreign language may induce emotions such as anxiety which influence the quality communication. The neural processes underpinning these interactions are crucial to understanding foreign language anxiety (FLA). Electroencephalography (EEG) studies reveal that anxiety is often displayed via hemispheric frontal alpha asymmetry (FAA). To examine the neural mechanisms underlying FLA, we collected self-reported data on the listening and speaking sections of the Second language skill specific anxiety scale (L2AS) over behavioral, cognitive, and somatic domains and recorded EEG signals during participation in word chain turn-taking activities in first (L1, Chinese) and second (L2, English) languages. Regression analysis showed FAA for the L2 condition was a significant predictor primarily of the behavioral and somatic domains on the L2AS speaking section. The results are discussed along with implications for improving communication during L2 interactions.

Stimulating social interest: The translational value of basic investigations into frontal cortex function.

Fan et al. use electrical stimulation during a novel social interaction paradigm to demonstrate a role for the orbitofrontal cortex in directing social attention. Their results shed new light on the basic functions of the orbitofrontal cortex and have translational value in understanding circuit modulation for psychiatric disorders.

Dissociable functional responses along the posterior-anterior gradient of the frontal and parietal cortices revealed by parametric working memory and training.

While the storage capacity is limited, accumulating studies have indicated that working memory (WM) can be improved by cognitive training. However, understanding how exactly the brain copes with limited WM capacity and how cognitive training optimizes the brain remains inconclusive. Given the hierarchical functional organization of WM, we hypothesized that the activation profiles along the posterior-anterior gradient of the frontal and parietal cortices characterize WM load and training effects. To test this hypothesis, we recruited 51 healthy volunteers and adopted a parametric WM paradigm and training method. In contrast to exclusively strengthening the activation of posterior areas, a broader range of activation concurrently occurred in the anterior areas to cope with increased memory load for all subjects at baseline. Moreover, there was an imbalance in the responses of the posterior and anterior areas to the same increment of 1 item at different load levels. Although a general decrease in activation after adaptive training, the changes in the posterior and anterior areas were distinct at different memory loads. Particularly, we found that the activation gradient between the posterior and anterior areas was significantly increased at load 4-back after adaptive training, and the changes were correlated with improvement in WM performance. Together, our results demonstrate a shift in the predominant role of posterior and anterior areas in the frontal and parietal cortices when approaching WM capacity limits. Additionally, the training-induced performance improvement likely benefits from the elevated neural efficiency reflected in the increased activation gradient between the posterior and anterior areas.

Single-Trial Representations of Decision-Related Variables by Decomposed Frontal Corticostriatal Ensemble Activity.

The frontal cortex-striatum circuit plays a pivotal role in adaptive goal-directed behaviors. However, it remains unclear how decision-related signals are mediated through cross-regional transmission between the medial frontal cortex and the striatum by neuronal ensembles in making decision based on outcomes of past action. Here, we analyzed neuronal ensemble activity obtained through simultaneous multiunit recordings in the secondary motor cortex (M2) and dorsal striatum (DS) in rats performing an outcome-based left-or-right choice task. By adopting tensor component analysis (TCA), a single-trial-based unsupervised dimensionality reduction approach, for concatenated ensembles of M2 and DS neurons, we identified distinct three spatiotemporal neural dynamics (TCA components) at the single-trial level specific to task-relevant variables. Choice-position-selective neural dynamics reflected the positions chosen and was correlated with the trial-to-trial fluctuation of behavioral variables. Intriguingly, choice-pattern-selective neural dynamics distinguished whether the incoming choice was a repetition or a switch from the previous choice before a response choice. Other neural dynamics was selective to outcome and increased within-trial activity following response. Our results demonstrate how the concatenated ensembles of M2 and DS process distinct features of decision-related signals at various points in time. Thereby, the M2 and DS collaboratively monitor action outcomes and determine the subsequent choice, whether to repeat or switch, for action selection.

Frontoparietal Brain Network Plays a Crucial Role in Working Memory Capacity during Complex Cognitive Task.

Recent neurophysiological studies provide inconsistent results of frontoparietal network (FPN) stimulation for altering working memory (WM) capacity. This study aimed to boost WM capacity by manipulating the activity of the FPN via dual-site high-definition transcranial direct current stimulation. Forty-eight participants were randomly assigned to three stimulation groups, receiving either simultaneous anodal stimulation of the frontal and parietal areas (double stimulation), or stimulation of the frontal area only (single stimulation), or the placebo stimulation (sham) to frontal and parietal areas. After the stimulation, we used an operation span task to test memory accuracy, mathematical accuracy, time of calculation and memorizing, and recall response time across the three groups. The results revealed an enhancement of memory accuracy and a reduction of time of calculation in the double stimulation group compared with that in others. In addition, recall response time was significantly decreased in the double and single stimulation groups compared with that in sham. No differences in mathematical accuracy were observed. Our results confirm the pivotal role of the FPN in WM and suggest its functional dissociation, with the frontal component more implicated in the retrieval stage and the parietal component in the processing and retention stages.

Asymmetry of the Frontal Aslant Tract Depends on Handedness.

BACKGROUND AND PURPOSE: The human brain displays structural and functional disparities between its hemispheres, with such asymmetry extending to the frontal aslant tract. This plays a role in a variety of cognitive functions, including speech production, language processing, and executive functions. However, the factors influencing the laterality of the frontal aslant tract remain incompletely understood. Handedness is hypothesized to impact frontal aslant tract laterality, given its involvement in both language and motor control. In this study, we aimed to investigate the relationship between handedness and frontal aslant tract lateralization, providing insight into this aspect of brain organization. MATERIALS AND METHODS: The Automated Tractography Pipeline was used to generate the frontal aslant tract for both right and left hemispheres in a cohort of 720 subjects sourced from the publicly available Human Connectome Project in Aging database. Subsequently, macrostructural and microstructural parameters of the right and left frontal aslant tract were extracted for each individual in the study population. The Edinburgh Handedness Inventory scores were used for the classification of handedness, and a comparative analysis across various handedness groups was performed. RESULTS: An age-related decline in both macrostructural parameters and microstructural integrity was noted within the studied population. The frontal aslant tract demonstrated a greater volume and larger diameter in male subjects compared with female participants. Additionally, a left-side laterality of the frontal aslant tract was observed within the general population. In the right-handed group, the volume (P < .001), length (P < .001), and diameter (P = .004) of the left frontal aslant tract were found to be higher than those of the right frontal aslant tract. Conversely, in the left-handed group, the volume (P = .040) and diameter (P = .032) of the left frontal aslant tract were lower than those of the right frontal aslant tract. Furthermore, in the right-handed group, the volume and diameter of the frontal aslant tract showed left-sided lateralization, while in the left-handed group, a right-sided lateralization was evident. CONCLUSIONS: The laterality of the frontal aslant tract appears to differ with handedness. This finding highlights the complex interaction between brain lateralization and handedness, emphasizing the importance of considering handedness as a factor in evaluating brain structure and function.

Time to bury the chisel: a continuous dorsal association tract system.

The arcuate fasciculus may be subdivided into a tract directly connecting frontal and temporal lobes and a pair of indirect subtracts in which the fronto-temporal connection is mediated by connections to the inferior parietal lobe. This tripartition has been advanced as an improvement over the centuries-old consensus that the lateral dorsal association fibers form a continuous system with no discernible discrete parts. Moreover, it has been used as the anatomical basis for functional hypotheses regarding linguistic abilities. Ex hypothesi, damage to the indirect subtracts leads to deficits in the repetition of multi-word sequences, whereas damage to the direct subtract leads to deficits in the immediate reproduction of single multisyllabic words. We argue that this partitioning of the dorsal association tract system enjoys no special anatomical status, and the search for the anatomical substrates of linguistic abilities should not be constrained by it. Instead, the merit of any postulated partitioning should primarily be judged on the basis of whether it enlightens or obfuscates our understanding of the behavior of patients in which individual subtracts are damaged.

Dissociable Representations of Decision Variables within Subdivisions of the Macaque Orbital and Ventrolateral Frontal Cortex.

The ventral frontal cortex (VFC) in macaques is involved in many affective and cognitive processes and has a key role in flexibly guiding reward-based decision-making. VFC is composed of a set of anatomically distinct subdivisions that are within the orbitofrontal cortex, ventrolateral prefrontal cortex, and anterior insula. In part, because prior studies have lacked the resolution to test for differences, it is unclear if neural representations related to decision-making are dissociable across these subdivisions. Here we recorded the activity of thousands of neurons within eight anatomically defined subdivisions of VFC in male macaque monkeys performing a two-choice probabilistic task for different fruit juice outcomes. We found substantial variation in the encoding of decision variables across these eight subdivisions. Notably, ventrolateral Area 12l was unique relative to the other areas that we recorded from as the activity of single neurons integrated multiple attributes when monkeys evaluated the different choice options. Activity within Area 12o, in contrast, more closely represented reward probability and whether reward was received on a given trial. Orbitofrontal Area 11m/l contained more specific representations of the quality of the outcome that could be earned later on. We also found that reward delivery encoding was highly distributed across all VFC subdivisions, while the properties of the reward, such as its flavor, were more strongly represented in Areas 11m/l and 13m. Taken together, our work reveals the diversity of encoding within the various anatomically distinct subdivisions of VFC in primates.

Domain-general cognitive control processes in bilingual switching: Evidence from midfrontal theta oscillations.

Language control in bilingual speakers is thought to be implicated in effectively switching between languages, inhibiting the non-intended language, and continuously monitoring what to say and what has been said. It has been a matter of controversy concerning whether language control operates in a comparable manner to cognitive control processes in non-linguistic domains (domain-general) or if it is exclusive to language processing (domain-specific). As midfrontal theta oscillations have been considered as an index of cognitive control, examining whether a midfrontal theta effect is evident in tasks requiring bilingual control could bring new insights to the ongoing debate. To this end, we reanalysed the EEG data from two previous bilingual production studies where Dutch-English bilinguals named pictures based on colour cues. Specifically, we focused on three fundamental control processes in bilingual production: switching between languages, inhibition of the nontarget language, and monitoring of speech errors. Theta power increase was observed in switch trials compared to repeat trials, with a midfrontal scalp distribution. However, no theta power difference was observed in switch trials following a shorter sequence of same-language trials compared to a longer sequence, suggesting a missing modulation of inhibitory control. Similarly, increased midfrontal theta power was observed when participants failed to switch to the intended language compared to correct responses. Altogether, these findings tentatively support the involvement of domain-general cognitive control mechanisms in bilingual switching.

Frontoparietal and salience network synchronizations during nonsymbolic magnitude processing predict brain age and mathematical performance in youth.

The development and refinement of functional brain circuits crucial to human cognition is a continuous process that spans from childhood to adulthood. Research increasingly focuses on mapping these evolving configurations, with the aim to identify markers for functional impairments and atypical development. Among human cognitive systems, nonsymbolic magnitude representations serve as a foundational building block for future success in mathematical learning and achievement for individuals. Using task-based frontoparietal (FPN) and salience network (SN) features during nonsymbolic magnitude processing alongside machine learning algorithms, we developed a framework to construct brain age prediction models for participants aged 7-30. Our study revealed differential developmental profiles in the synchronization within and between FPN and SN networks. Specifically, we observed a linear increase in FPN connectivity, concomitant with a decline in SN connectivity across the age span. A nonlinear U-shaped trajectory in the connectivity between the FPN and SN was discerned, revealing reduced FPN-SN synchronization among adolescents compared to both pediatric and adult cohorts. Leveraging the Gradient Boosting machine learning algorithm and nested fivefold stratified cross-validation with independent training datasets, we demonstrated that functional connectivity measures of the FPN and SN nodes predict chronological age, with a correlation coefficient of .727 and a mean absolute error of 2.944 between actual and predicted ages. Notably, connectivity within the FPN emerged as the most contributing feature for age prediction. Critically, a more matured brain age estimate is associated with better arithmetic performance. Our findings shed light on the intricate developmental changes occurring in the neural networks supporting magnitude representations. We emphasize brain age estimation as a potent tool for understanding cognitive development and its relationship to mathematical abilities across the critical developmental period of youth. PRACTITIONER POINTS: This study investigated the prolonged changes in the brain's architecture across childhood, adolescence, and adulthood, with a focus on task-state frontoparietal and salience networks. Distinct developmental pathways were identified: frontoparietal synchronization strengthens consistently throughout development, while salience network connectivity diminishes with age. Furthermore, adolescents show a unique dip in connectivity between these networks. Leveraging advanced machine learning methods, we accurately predicted individuals' ages based on these brain circuits, with a more mature estimated brain age correlating with better math skills.

Comparative basolateral amygdala connectomics reveals dissociable single-neuron projection patterns to frontal cortex in macaques and mice.

Basolateral amygdala (BLA) is a key hub for affect in the brain,1,2,3 and dysfunction within this area contributes to a host of psychiatric disorders.4,5 BLA is extensively and reciprocally interconnected with frontal cortex,6,7,8,9 and some aspects of its function are evolutionarily conserved across rodents, anthropoid primates, and humans.10 Neuron density in BLA is substantially lower in primates compared to murine rodents,11 and frontal cortex (FC) is dramatically expanded in primates, particularly the more anterior granular and dysgranular areas.12,13,14 Yet, how these anatomical differences influence the projection patterns of single BLA neurons to frontal cortex across rodents and primates is unknown. Using a barcoded connectomic approach, we assessed the single BLA neuron connections to frontal cortex in mice and macaques. We found that BLA neurons are more likely to project to multiple distinct parts of FC in mice than in macaques. Further, while single BLA neuron projections to nucleus accumbens were similarly organized in mice and macaques, BLA-FC connections differed substantially. Notably, BLA connections to subcallosal anterior cingulate cortex (scACC) in macaques were least likely to branch to other medial frontal cortex areas compared to perigenual ACC (pgACC). This pattern of connections was reversed in the mouse homologues of these areas, infralimbic and prelimbic cortex (IL and PL), mirroring functional differences between rodents and non-human primates. Taken together, these results indicate that BLA connections to FC are not linearly scaled from mice to macaques and instead the organization of single-neuron BLA connections is distinct between these species.

Dynamic spatial representation of self and others' actions in the macaque frontal cortex.

Modulation of neuronal firing rates by the spatial locations of physical objects is a widespread phenomenon in the brain. However, little is known about how neuronal responses to the actions of biological entities are spatially tuned and whether such spatially tuned responses are affected by social contexts. These issues are of key importance for understanding the neural basis of embodied social cognition, such as imitation and perspective-taking. Here, we show that spatial representation of actions can be dynamically changed depending on others' social relevance and agents of action. Monkeys performed a turn-taking choice task with a real monkey partner sitting face-to-face or a filmed partner in prerecorded videos. Three rectangular buttons (left, center, and right) were positioned in front of the subject and partner as their choice targets. We recorded from single neurons in two frontal nodes in the social brain, the ventral premotor cortex (PMv) and the medial prefrontal cortex (MPFC). When the partner was filmed rather than real, spatial preference for partner-actions was markedly diminished in MPFC, but not PMv, neurons. This social context-dependent modulation in the MPFC was also evident for self-actions. Strikingly, a subset of neurons in both areas switched their spatial preference between self-actions and partner-actions in a diametrically opposite manner. This observation suggests that these cortical areas are associated with coordinate transformation in ways consistent with an actor-centered perspective-taking coding scheme. The PMv may subserve such functions in context-independent manners, whereas the MPFC may do so primarily in social contexts.

Multiscale chemogenetic dissection of fronto-temporal top-down regulation for object memory in primates.

Visual object memory is a fundamental element of various cognitive abilities, and the underlying neural mechanisms have been extensively examined especially in the anterior temporal cortex of primates. However, both macroscopic large-scale functional network in which this region is embedded and microscopic neuron-level dynamics of top-down regulation it receives for object memory remains elusive. Here, we identified the orbitofrontal node as a critical partner of the anterior temporal node for object memory by combining whole-brain functional imaging during rest and a short-term object memory task in male macaques. Focal chemogenetic silencing of the identified orbitofrontal node downregulated both the local orbitofrontal and remote anterior temporal nodes during the task, in association with deteriorated mnemonic, but not perceptual, performance. Furthermore, imaging-guided neuronal recordings in the same monkeys during the same task causally revealed that orbitofrontal top-down modulation enhanced stimulus-selective mnemonic signal in individual anterior temporal neurons while leaving bottom-up perceptual signal unchanged. Furthermore, similar activity difference was also observed between correct and mnemonic error trials before silencing, suggesting its behavioral relevance. These multifaceted but convergent results provide a multiscale causal understanding of dynamic top-down regulation of the anterior temporal cortex along the ventral fronto-temporal network underpinning short-term object memory in primates.