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Motivation: Mechanisms underlying the variation in the appearance of electroencephalogram (EEG) over human head are not well characterized. We hypothesized that spatial variation of the EEG, being ...

Semantic (svPPA) and nonfluent (nfvPPA) variants of primary progressive aphasia (PPA) have recently been associated with distinct patterns of white matter and functional network alterations in left frontoinsular and anterior temporal regions, respectively. Little information exists, however, about the topological characteristics of gray matter covariance networks in these two PPA variants. In the present study, we used a graph theory approach to describe the structural covariance network organization in 34 patients with svPPA, 34 patients with nfvPPA and 110 healthy controls. All participants underwent a 3 T structural MRI. Next, we used cortical thickness values and subcortical volumes to define subject-specific connectivity networks. Patients with svPPA and nfvPPA were characterized by higher values of normalized characteristic path length compared with controls. Moreover, svPPA patients had lower values of normalized clustering coefficient relative to healthy controls. At a regional level, patients with svPPA showed a reduced connectivity and impaired information processing in temporal and limbic brain areas relative to controls and nfvPPA patients. By contrast, local network changes in patients with nfvPPA were focused on frontal brain regions such as the pars opercularis and the middle frontal cortex. Of note, a predominance of local metric changes was observed in the left hemisphere in both nfvPPA and svPPA brain networks. Taken together, these findings provide new evidences of a suboptimal topological organization of the structural covariance networks in svPPA and nfvPPA patients. Moreover, we further confirm that distinct patterns of structural network alterations are related to neurodegenerative mechanisms underlying each PPA variant.

We studied structural organization of cortical area 10 of the prefrontal cortex in the left and right hemispheres of the brain of an outstanding scientist and inventor (age 78 years). To this end, continuous series of 20-μm Nissl-stained frontal slices were compared with cortex sections of the same area from senile men (control group). It was found that the cytoarchitectonic organization of the cortical area 10 of the prefrontal cortex of the brain of an outstanding scientist-inventor is characterized by more pronounced vertical striation, greater thickness of the cortex and association layer III, higher density and size of pyramid neurons and higher density of satellite glia.

Across species, adolescence is a period of growing independence that is associated with the maturation of cognitive, social, and affective processing. Reorganization of neural circuits within the frontal cortex is believed to contribute to the emergence of adolescent changes in cognition and behavior. While puberty coincides with adolescence, relatively little is known about which aspects of frontal cortex maturation are driven by pubertal development and gonadal hormones. In this review, we highlight existing work that suggests puberty plays a role in the maturation of specific cell types in the medial prefrontal cortex (mPFC) of rodents, and highlight possible routes by which gonadal hormones influence frontal cortical circuit development.

The technology, methodology and models used by visual neuroscientists have provided great insights into the structure and function of individual brain areas. However, complex cognitive functions arise in the brain due to networks comprising multiple interacting cortical areas that are wired together with precise anatomical connections. A prime example of this phenomenon is the frontal–parietal network and two key regions within it: the frontal eye fields (FEF) and lateral intraparietal area (area LIP). Activity in these cortical areas has independently been tied to oculomotor control, motor preparation, visual attention and decision-making. Strong, bidirectional anatomical connections have also been traced between FEF and area LIP, suggesting that the aforementioned visual functions depend on these inter-area interactions. However, advancements in our knowledge about the interactions between area LIP and FEF are limited with the main animal model, the rhesus macaque, because these key regions are buried in the sulci of the brain. In this review, we propose that the common marmoset is the ideal model for investigating how anatomical connections give rise to functionally-complex cognitive visual behaviours, such as those modulated by the frontal–parietal network, because of the homology of their cortical networks with humans and macaques, amenability to transgenic technology, and rich behavioural repertoire. Furthermore, the lissencephalic structure of the marmoset brain enables application of powerful techniques, such as array-based electrophysiology and optogenetics, which are critical to bridge the gaps in our knowledge about structure and function in the brain.

A group of 27 healthy young adults solved a task involving the working memory (WM) activation, consisting of the comparison between the spatial orientations of two sequentially presented square-wave luminance gratings. We investigated the effective (directed) connectivity patterns between the frontal and postcentral cortical regions related to the visual system. The connectivity was assessed using vector autoregression modeling of EEG. It was shown that the strength of the top-down right-hemispheric connectivity patterns directed from the frontal cortex to the visual areas in θ frequency was significantly lower at the stage of stimulus retention in the WM than at the stage of stimulus anticipation. On the contrary, in the α band the descending influences were slightly more intense. The results of the study showed the frequency-dependent dynamics of the descending influences of the frontal cortex on visual areas and confirm that the frontal cortex plays the role of a controlling and modulating center in the brain system underlying WM.

Working memory (WM) supports the persistent representation of transient sensory information. Visual and auditory stimuli place different demands on WM and recruit different brain networks. Separate auditory- and visual-biased WM networks extend into the frontal lobes, but several challenges confront attempts to parcellate human frontal cortex, including fine-grained organization and between-subject variability. Here, we use differential intrinsic functional connectivity from 2 visual-biased and 2 auditory-biased frontal structures to identify additional candidate sensory-biased regions in frontal cortex. We then examine direct contrasts of task functional magnetic resonance imaging during visual versus auditory 2-back WM to validate those candidate regions. Three visual-biased and 5 auditory-biased regions are robustly activated bilaterally in the frontal lobes of individual subjects (N = 14, 7 women). These regions exhibit a sensory preference during passive exposure to task stimuli, and that preference is stronger during WM. Hierarchical clustering analysis of intrinsic connectivity among novel and previously identified bilateral sensory-biased regions confirms that they functionally segregate into visual and auditory networks, even though the networks are anatomically interdigitated. We also observe that the frontotemporal auditory WM network is highly selective and exhibits strong functional connectivity to structures serving non-WM functions, while the frontoparietal visual WM network hierarchically merges into the multiple-demand cognitive system.

Efficient foraging is essential to survival and depends on frontal cortex in mammals. Because of its role in psychiatric disorders, frontal cortex and its contributions to reward procurement have been studied extensively in both rodents and non-human primates. How frontal cortex of these animal models compares is a source of intense debate. Here we argue that translating findings from rodents to non-human primates requires an appreciation of both the niche in which each animal forages as well as the similarities in frontal cortex anatomy and function. Consequently, we highlight similarities and differences in behavior and anatomy, before focusing on points of convergence in how parts of frontal cortex contribute to distinct aspects of foraging in rats and macaques, more specifically. In doing so, our aim is to emphasize where translation of frontal cortex function between species is clearer, where there is divergence, and where future work should focus. We finish by highlighting aspects of foraging for which have received less attention but we believe are critical to uncovering how frontal cortex promotes survival in each species.

Cognitive flexibility is an essential prerequisite for goal-directed behavior, and daily observations already show that it deteriorates when one is engaged in a task for a (too) long time. Yet, the neural mechanisms underlying such fatigability effect in cognitive flexibility are poorly understood. We examined how theta, alpha, and beta frequency event-related synchronization and desynchronization processes during cued memory-based task switching are modulated by time-on-task effects. We put special emphasis on the examination of functional neuroanatomical regions being associated with these modulations, using EEG beamforming. We show clear declines in task switching performance (increased switch costs) with time on task. For processes occurring before rule switching or repetition processes, we show that anticipatory attentional sampling and selection mechanisms associated with fronto-parietal structures are modulated by time-on-task effects but sensory areas (occipital cortex) also show fatigability-dependent modulations. After target stimulus presentation, the allocation of processing resources for response selection as reflected by theta-related activity in parietal cortices is compromised with time on task and similarly a concomitant increase in alpha and beta band-related attentional processing or gating mechanisms in frontal and occipital regions. Yet, considering the behavioral data showing an apparent decline in performance, this probably compensatory increase is still insufficient to allow reasonable performance. The same is likely the case for processes occurring before rule switching or repetition processes. Comparative analyses show that modulations of alpha band activity are as strongly modulated by fatigability as theta band activity. Implications of these findings for theoretical concepts on fatigability are discussed.

Prior research has demonstrated that the frontal lobes play a critical role in the top–down control of behavior, and damage to the frontal cortex impairs performance on tasks that require executive control [Burgess, P. W., & Stuss, D. T. Fifty years of prefrontal cortex research: Impact on assessment. Journal of the International Neuropsychological Society, 23, 755–767, 2017; Stuss, D. T., & Levine, B. Adult clinical neuropsychology: Lessons from studies of the frontal lobes. Annual Review of Psychology, 53, 401–433, 2002]. Across executive functioning tasks, performance deficits are often quantified as the number of false alarms per total number of nontarget trials. However, most studies of frontal lobe function focus on individual task performance and do not discuss commonalities of errors committed across different tasks. Here, we describe a neurocognitive account that explores the link between deficient frontal lobe function and increased false alarms across an array of experimental tasks from a variety of task domains. We review evidence for heightened false alarms following frontal deficits in episodic long-term memory tests, working memory tasks (e.g., n-back), attentional tasks (e.g., continuous performance tasks), interference control tasks (e.g., recent probes), and inhibitory control tasks (e.g., go/no-go). We examine this relationship via neuroimaging studies, lesion studies, and across age groups and pathologies that impact the pFC, and we propose 11 issues in cognitive processing that can result in false alarms. In our review, some overlapping neural regions were implicated in the regulation of false alarms. Ultimately, however, we find evidence for the fractionation and localization of certain frontal processes related to the commission of specific types of false alarms. We outline avenues for additional research that will enable further delineation of the fractionation of the frontal lobes' regulation of false alarms.

Sensory modality, widely accepted as a key factor in the functional organization of posterior cortical areas, also shapes the organization of human frontal lobes. ‘Deep imaging,’ or the practice of collecting a sizable amount of data on individual subjects, offers significant advantages in revealing fine-scale aspects of functional organization of the human brain. Here, we review deep imaging approaches to mapping multiple sensory-biased and multiple-demand regions within human lateral frontal cortex. In addition, we discuss how deep imaging methods can be transferred to large public data sets to further extend functional mapping at the group level. We also review how ‘connectome fingerprinting’ approaches, combined with deep imaging, can be used to localize fine-grained functional organization in individual subjects using resting-state data. Finally, we summarize current ‘best practices’ for deep imaging.

Decisions are held in memory until enacted, which makes them potentially vulnerable to distracting sensory input. Gating of information flow from sensory to motor areas could protect memory from interference during decision-making, but the underlying network mechanisms are not understood. Here, we trained mice to detect optogenetic stimulation of the somatosensory cortex, with a delay separating sensation and action. During the delay, distracting stimuli lost influence on behavior over time, even though distractor-evoked neural activity percolated through the cortex without attenuation. Instead, choice-encoding activity in the motor cortex became progressively less sensitive to the impact of distractors. Reverse engineering of neural networks trained to reproduce motor cortex activity revealed that the reduction in sensitivity to distractors was caused by a growing separation in the neural activity space between attractors that encode alternative decisions. Our results show that communication between brain regions can be gated via attractor dynamics, which control the degree of commitment to an action. The flow of information in the brain is regulated over space and time. The authors show that mice can adaptively filter stimuli originating in the sensory cortex. The stimuli are gated by attractor dynamics in the frontal cortex, revealing a mechanism of gating of neural information.

In cervical dystonia, functional MRI (fMRI) evidence indicates changes in several resting state networks, which revert in part following the botulinum neurotoxin A (BoNT) therapy. Recently, the involvement of the cerebellum in dystonia has gained attention. The aim of our study was to compare connectivity between cerebellar subdivisions and the rest of the brain before and after BoNT treatment. Seventeen patients with cervical dystonia indicated for treatment with BoNT were enrolled (14 female, aged 50.2 ± 8.5 years, range 38–63 years). Clinical and fMRI examinations were carried out before and 4 weeks after BoNT injection. Clinical severity was evaluated using TWSTRS. Functional MRI data were acquired on a 1.5 T scanner during 8 min rest. Seed-based functional connectivity analysis was performed using data extracted from atlas-defined cerebellar areas in both datasets. Clinical scores demonstrated satisfactory BoNT effect. After treatment, connectivity decreased between the vermis lobule VIIIa and the left dorsal mesial frontal cortex. Positive correlations between the connectivity differences and the clinical improvement were detected for the right lobule VI, right crus II, vermis VIIIb and the right lobule IX. Our data provide evidence for modulation of cerebello-cortical connectivity resulting from successful treatment by botulinum neurotoxin.

Visually guided behavior begins with inputs to sensory cortices, but the decision to initiate actions engages the frontal cortex. A new study dissects a microcircuit for visual-to-motor transformation in the anterior cingulate cortex of the mouse with implications for impulsivity and disease states.

Summary To navigate social environments, people must simultaneously hold representations about their own and others’ abilities. During self-other mergence, people estimate others’ abilities not only on the basis of the others’ past performance, but the estimates are also influenced by their own performance. For example, if we perform well, we overestimate the abilities of those with whom we are co-operating and underestimate competitors. Self-other mergence is associated with specific activity patterns in the dorsomedial prefrontal cortex (dmPFC). Using a combination of non-invasive brain stimulation, functional magnetic resonance imaging, and computational modeling, we show that dmPFC neurostimulation silences these neural signatures of self-other mergence in relation to estimation of others’ abilities. In consequence, self-other mergence behavior increases, and our assessments of our own performance are projected increasingly onto other people. This suggests an inherent tendency to form interdependent social representations and a causal role of the dmPFC in separating self and other representations., Highlights • During self-other mergence (SOM), people confuse one’s own with another’s performance • Brain stimulation over dorsomedial prefrontal cortex (dmPFC) alters neural SOM • Brain stimulation over dmPFC simultaneously alters behavioral SOM • This suggests a causal role of dmPFC in separating self and other representations, Wittmann et al. find that, after disrupting activity in the dorsomedial prefrontal cortex, humans merge performance estimates concerning other people with performance estimates about themselves. This suggests that representations of self and others are inherently interlinked and that intact dmPFC activity is needed for separating the two.

Consciously and subliminally processed information can both lead to conflicts that hinder goal-directed behaviour. Conflict monitoring processes are required to cope with situations where one or multiple conflicts occur. It has been suggested, that medial-frontal theta oscillations are associated with the implementation of cognitive control and that conflicts increase theta band activity. Still, a causal mechanistic understanding of theta oscillations during the resolution of combined subliminal and conscious conflicts is missing. To investigate this, we combined EEG signal decomposition methods with EEG beamforming approaches and used the obtained information to modulate theta oscillations with tACS in a second experiment. This showed that theta oscillations in the superior frontal cortex (BA6) and the left paracentral lobule encoded stimulus-related processes during the resolution of conflicts arising from both conscious and subliminal information processing. Response selection and motor-related processes encoded by theta oscillations were not similarly modulated. Thus, the joint modulation of conflicts by conscious and subliminal information affects very specific aspects of the information coded in theta oscillations. Results indicate, that entraining theta-oscillations using tACS modulates conflict resolution depending on the already existing theta activity level. In summary, the study provides further evidence that frontal theta oscillations play a crucial role in conflict monitoring and control.

Decades of electrophysiological research on top–down control converge on the role of the lateral frontal cortex in facilitating attention to behaviorally relevant external inputs. However, the involvement of frontal cortex in the top–down control of attention directed to the external versus internal environment remains poorly understood. To address this, we recorded intracranial electrocorticography while subjects directed their attention externally to tones and responded to infrequent target tones, or internally to their own thoughts while ignoring the tones. Our analyses focused on frontal and temporal cortices. We first computed the target effect, as indexed by the difference in high frequency activity (70–150 Hz) between target and standard tones. Importantly, we then compared the target effect between external and internal attention, reflecting a top–down attentional effect elicited by task demands, in each region of interest. Both frontal and temporal cortices showed target effects during external and internal attention, suggesting this effect is present irrespective of attention states. However, only the frontal cortex showed an enhanced target effect during external relative to internal attention. These findings provide electrophysiological evidence for top–down attentional modulation in the lateral frontal cortex, revealing preferential engagement with external attention.

Childhood trauma (CT) is a well‐established risk factor for major depressive disorder (MDD). However, the underlying mechanism linking CT and MDD remains not fully understood. The present study tested the hypothesis that CT have effects on specific types of anhedonia in depression via reward system. To do so, we evaluated different aspects of anhedonia and resting‐state functional connectivity (FC) in reward system among 66 patients with MDD (44 with moderate‐to‐severe and 22 with no or low CT), and 57 healthy controls (HC; 23 with moderate‐to‐severe and 34 with no or low CT). Results showed that MDD patients with moderate‐to‐severe CT suffered more severe state anhedonic depression than patients with no or low level of CT. Individuals with moderate‐to‐severe CT, irrespective of MDD diagnosis, had elevated physical, social and anticipatory but not consummatory trait anhedonia, and demonstrated decreased left nucleus accumbens (NAcc)‐right orbital frontal cortex (OFC) and left ventral caudate‐left OFC connectivity compared to those with no or low exposure. Left NAcc‐right OFC connectivity mediated relationship between CT and state anhedonia in MDD. The total altered ventral striatum (VS)‐OFC connectivity mediated links between CT and physical trait anhedonia in HC. These findings highlight specific types of anhedonia and the core reward system as targets of CT. Blunted hedonic responses via decreased coupling within core reward system may be involved in the mechanism of depression following CT. Implications for clinical interventions are also discussed.

Synaptic interactions between parvalbumin-positive γ-aminobutyric acid (GABA)-ergic interneurons and pyramidal neurons evoke cortical gamma oscillations, which are known to be abnormal in schizophrenia. These cortical gamma oscillations can be indexed by the gamma-band auditory steady-state response (ASSR), a robust electroencephalographic (EEG) biomarker that is increasingly used to advance the development of novel therapeutics for schizophrenia, and other related brain disorders. Despite promise of ASSR, the neural substrates of ASSR have not yet been characterized. This study investigated the sources underlying ASSR in healthy subjects and schizophrenia patients. In this study, a novel method for noninvasively characterizing source locations was developed and applied to EEG recordings obtained from 293 healthy subjects and 427 schizophrenia patients who underwent ASSR testing. Results revealed a distributed network of temporal and frontal sources in both healthy subjects and schizophrenia patients. In both groups, primary contributing ASSR sources were identified in the right superior temporal cortex and the orbitofrontal cortex. In conjunction with normal activity in these areas, schizophrenia patients showed significantly reduced source dipole density of gamma-band ASSR (ITC > 0.25) in the left superior temporal cortex, orbitofrontal cortex, and left superior frontal cortex. In conclusion, a distributed network of temporal and frontal brain regions supports gamma phase synchronization. We demonstrated that failure to mount a coherent physiologic response to simple 40-Hz stimulation reflects disorganized network function in schizophrenia patients. Future translational studies are needed to more fully understand the neural mechanisms underlying gamma-band ASSR network abnormalities in schizophrenia.

The right inferior frontal cortex (IFC) is critical to response inhibition. The right IFC referred in the human studies of response inhibition is located in the posterior part of the inferior frontal gyrus and the surrounding regions and consists of multiple areas that implement distinct functions. Recent studies using resting-state functional connectivity have parcellated the cerebral cortex and revealed across-subject variability of parcel-based cerebrocortical networks. However, how the right IFC of individual brains is functionally organized and what functional properties the IFC parcels possess regarding response inhibition remain elusive. In the present functional magnetic resonance imaging study, precision functional mapping of individual human brains was adopted to the parcels in the right IFC to evaluate their functional properties related to response inhibition. The right IFC consisted of six modules or subsets of subregions, and the spatial organization of the modules varied considerably across subjects. Each module revealed unique characteristics of brain activity and its correlation to behavior related to response inhibition. These results provide updated functional features of the IFC and demonstrate the importance of individual-focused approaches in studying response inhibition in the right IFC.

Several recent studies have interpreted multivariate evidence for stimulus-specific patterns of activity in parietal and/or frontal cortex as evidence for a representational function in those regions that is qualitatively similar to the representational functions of the visual system. Here we argue that although evidence that a brain system takes on a different configuration for each stimulus in a stimulus set is a necessary property for that system having a role in perceptual representation, such evidence is not specific for this function. Drawing on several recent examples from the recent literature, we offer alternative accounts for understanding stimulus-specificity in parietal and frontal cortex that are consistent with longstanding ideas that activity these regions is best understood as implementing control-related, rather than inherently representational, functions.

Contains fulltext : 218491.pdf (Publisher’s version ) (Open Access) Electroencephalogram (EEG) studies suggest an association between beta (13-30 Hz) power and reversal learning performance. In search for direct evidence concerning the involvement of beta oscillations in reversal learning, transcranial alternating current stimulation (tACS) was applied in a double-blind, sham-controlled and between-subjects design. Exogenous oscillatory currents were administered bilaterally to the frontal cortex at 20 Hz with an intensity of 1 mA peak-to-peak and the effects on reward-punishment based reversal learning were evaluated in hundred-and-eight healthy volunteers. Pre- and post-tACS resting state EEG recordings were analyzed. Results showed that beta-tACS improved rule implementation during reversal learning and decreases left and right resting-state frontal theta/beta EEG ratios following tACS. Our findings provide the first behavioral and electrophysiological evidence for exogenous 20 Hz oscillatory electric field potentials administered over to the frontal cortex to improve reversal learning. 10 p.

Recent studies of the neurobiology of the dorsal frontal cortex (FC) of the ferret have illuminated its key role in the attention network, top-down cognitive control of sensory processing, and goal directed behavior. To elucidate the neuroanatomical regions of the dorsal FC, and delineate the boundary between premotor cortex (PMC) and dorsal prefrontal cortex (dPFC), we placed retrograde tracers in adult ferret dorsal FC anterior to primary motor cortex and analyzed thalamo-cortical connectivity. Cyto- and myeloarchitectural differences across dorsal FC and the distinctive projection patterns from thalamic nuclei, especially from the subnuclei of the medial dorsal (MD) nucleus and the ventral thalamic nuclear group, make it possible to clearly differentiate three separate dorsal FC fields anterior to primary motor cortex: polar dPFC (dPFCpol), dPFC, and PMC. Based on the thalamic connectivity, there is a striking similarity of the ferret’s dorsal FC fields with other species. This possible homology opens up new questions for future comparative neuroanatomical and functional studies.

The use of allocentric cues for movement guidance is complex because it involves the integration of visual targets and independent landmarks and the conversion of this information into egocentric commands for action. Here, we focus on the mechanisms for encoding reach targets relative to visual landmarks in humans. First, we consider the behavioral results suggesting that both of these cues influence target memory, but are then transformed-at the first opportunity-into egocentric commands for action. We then consider the cortical mechanisms for these behaviors. We discuss different allocentric versus egocentric mechanisms for coding of target directional selectivity in memory (inferior temporal gyrus versus superior occipital gyrus) and distinguish these mechanisms from parieto-frontal activation for planning egocentric direction of actual reach movements. Then, we consider where and how the former allocentric representations of remembered reach targets are converted into the latter egocentric plans. In particular, our recent neuroimaging study suggests that four areas in the parietal and frontal cortex (right precuneus, bilateral dorsal premotor cortex, and right presupplementary area) participate in this allo-to-ego conversion. Finally, we provide a functional overview describing how and why egocentric and landmark-centered representations are segregated early in the visual system, but then reintegrated in the parieto-frontal cortex for action.

Structural modifications in the dendritic morphology of neurons occur following many forms of experience, including exposure to drugs, complex housing, and training in specific behavioral tasks. The present study examined morphological changes in orbitofrontal (OFC) and medial prefrontal cortex (mPFC) neurons of female rats following experience with a variety of social partners or nonsocial olfactory stimuli. We reasoned that experience with various social partners or olfactory stimuli, and the associated behavioral adaptations, would drive structural modifications in prefrontal cortex neurons engaged by these stimuli. Social experience was manipulated by providing rats with a novel cage-mate or housing the animal with the same cage-mate throughout the study. Similarly, olfactory experience was manipulated by introducing novel, nonsocial odors in the home cage or exposing the animals to the same home-cage odor throughout the study. Both forms of experience resulted in altered dendritic morphology in OFC neurons, whereas morphological changes in mPFC were comparatively small and limited to changes in spine density. These observations indicate that OFC and mPFC neurons respond differently to social and nonsocial olfactory stimulation in adulthood and join the growing body of data illustrating differential effects of experience on structural plasticity in OFC and mPFC. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The anterior cingulate cortex (ACC) is implicated in effort exertion and choices based on effort cost, but it is still unclear how it mediates this cost-benefit evaluation. Here, male rats were trained to exert effort for a high-value reward (sucrose pellets) in a progressive ratio lever pressing task. Trained rats were then tested in two conditions: a no-choice condition where lever pressing for sucrose was the only available food option, and a choice condition where a low-value reward (lab chow) was freely available as an alternative to pressing for sucrose. Disruption of ACC—via either chemogenetic inhibition or excitation—reduced lever pressing in the choice, but not in the no-choice, condition. We next looked for value coding cells in ACC during effortful behavior and reward consumption phases during choice and no-choice conditions. For this, we utilized in vivo miniaturized fluorescence microscopy to reliably track responses of the same cells and compare how ACC neurons respond during the same effortful behavior where there was a choice versus when there was no-choice. We found that lever-press and sucrose-evoked responses were significantly weaker during choice compared to no-choice sessions, which may have rendered them more susceptible to chemogenetic disruption. Taken together, findings from our interference experiments and neural recordings suggest that a mechanism by which ACC mediates effortful decisions is in the discrimination of the utility of available options. ACC regulates these choices by providing a stable population code for the relative value of different options.Significance StatementThe anterior cingulate cortex (ACC) is implicated in effort-based decision making. Here, we used chemogenetics and in vivo calcium imaging to explore its mechanism. Rats were trained to lever press for a high-value reward and tested in two conditions: a no-choice condition where lever pressing for the high-value reward was the only option, and a choice condition where a low-value reward was also available. Inhibition or excitation of ACC reduced effort toward the high value option, but only in the choice condition. Neural responses in ACC were weaker in the choice compared to the no-choice condition. A mechanism by which ACC regulates effortful decisions is in providing a stable population code for the discrimination of the utility of available options.

In the last years, some studies have shown that behavior disorder seems in frontotemporal dementia is related to dysfunction in the fronto-subcortical circuitry. Objectives: We did a narrative literature review concerning fronto-subcortical circuitry and frontotemporal dementia (FTD). Methods: Manuscripts related to fronto-subcortical network and frontotemporal dementia were selected for further analysis. Results: From the executions of simple motor actions to the most complex behaviors like goal-direct behavior and social cognition, the fronto-subcortical circuitry involves an intrigued network of fibers that reaches to basal ganglia nuclei. Recently, researchers have shown five parallel fronto-subcortical circuits integrating and segregating information from the frontal cortex to basal ganglia. Understanding the relationship between the fronto-subcortical circuit dysfunctions and neurodegenerative diseases requires studying the functional anatomy and neurochemical basis involved. Conclusions: In this view, it is essential to review the functional anatomy of the fronto-subcortical network, and it’s correlated with clinical aspects to pursuing a better therapeutic approach.

PURPOSE The present study investigated possible associations between cortical dysfunction/degeneration as measured by F-FDG PET and nigrostriatal degeneration according to the specific I-FP-CIT binding ratio (SBR) in striatal subregions defined by striato-cortical anatomical connectivity in Parkinson disease (PD) patients. MATERIALS AND METHODS The study included 41 patients (61.4 ± 12.8 years) with PD-typical reduction of striatal FP-CIT SBR and no sign of atypical parkinsonian syndrome on FDG PET. FP-CIT SBR was determined separately in the cognitive (composite of executive and limbic) and sensorimotor part of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Scaled FDG uptake was tested voxelwise for correlation with FP-CIT SBR (familywise error corrected P < 0.05). RESULTS A large cluster (17.6 mL) of significant correlation of scaled FDG uptake with FP-CIT SBR in the cognitive part of the striatum, corrected for SBR in the sensorimotor part, was detected in the bilateral medial frontal cortex and the anterior cingulate cortex (partial correlation coefficient R = 0.767); small clusters were detected in ipsilateral caudate and ipsilateral thalamus. There was a small contralateral occipital cluster (3.0 mL) of significant correlation between FDG uptake and sensorimotor SBR corrected for cognitive SBR (R = 0.709). CONCLUSIONS The correlation between nigrostriatal degeneration in the cognitive striatum and reduced cerebral glucose metabolism in the medial parts of the frontal cortex including the anterior cingulate suggests that nigrostriatal degeneration is specifically involved in the pathogenesis of cognitive deficits associated with medial frontal dysfunction such as impaired inhibitory control.

Reactivation of newly acquired memories during sleep across hippocampal and neocortical systems is proposed to underlie systems memory consolidation. Here, we investigate spontaneous memory reprocessing during sleep by applying machine learning to source space-transformed magnetoencephalographic data in a two-step exploratory and confirmatory study design. We decode memory-related activity from slow oscillations in hippocampus, frontal cortex and precuneus, indicating parallel memory processing during sleep. Moreover, we show complementary roles of hippocampus and neocortex: while gamma activity indicated memory reprocessing in hippocampus, delta and theta frequencies allowed decoding of memory in neocortex. Neocortex and hippocampus were linked through coherent activity and modulation of high-frequency gamma oscillations by theta, a dynamic similar to memory processing during wakefulness. Overall, we noninvasively demonstrate localized, coordinated memory reprocessing in human sleep.

Neurons in frontal and parietal cortex encode task variables during decision-making, but causal manipulations of the two regions produce strikingly different results. For example, silencing the posterior parietal cortex (PPC) in rats and monkeys produces minimal effects in perceptual decisions requiring integration of sensory evidence, but silencing frontal cortex profoundly impairs the same decisions. Here, we tested the causal roles of the rat frontal orienting field (FOF) and PPC in economic choice under risk. On each trial, rats chose between a lottery and a small but guaranteed surebet. The magnitude of the lottery was independently varied across trials and was indicated to the rat by the pitch of an auditory cue. As in perceptual decisions, both unilateral and bilateral PPC muscimol inactivations produced minimal effects. FOF inactivations produced substantial changes in behavior even though our task had no working memory component. We quantified control and bilateral inactivation behavior with a multi-agent model consisting of a mixture of a ‘rational’ utility-maximizing agent (U=Vρ) with two ‘habitual’ agents that either choose surebet or lottery. Effects of FOF silencing were best accounted for by a decrease inρ, the exponent of the utility function. The decrease inρcould be parsimoniously explained by a dynamical model where the FOF is part of a network that represents the value of the lottery to compare against a remembered boundary representing the value of the surebet. This dynamical model predicted that neurons in the FOF should increase their activity with increasing lottery values. In line with our predictions, single neurons recorded in the FOF encoded the value of the lottery even when controlling for choice. These results together demonstrate that FOF is a critical node in the neural circuit for decision under risk.

To date, it is still unclear how word structure might impact lexical processing in the brain for morphological impoverished language like Chinese. In this study, concurrent EEG and fNIRS recordings were performed to inspect the temporal and spatial brain activity that are related to the morphological priming effect (compound/derivation constitute priming vs. non-morphological priming) and word structure (compound vs. derivation) modulation. Interestingly, it was discovered that the morphological priming effect was mainly detected by the behavioral performance and spatial brain activation in the left prefrontal cortex, while word structure effect was revealed by the behavioral data as well as the temporal and spatial brain activation patterns. In addition, Chinese derivations exhibited significantly enhanced brain activation in the frontal cortex and involved more brain networks as compared to lexicalized compounds. The results were interpreted by the differing connection patterns between constitute morphemes within a given word structure from spreading activation perspective. More importantly, we demonstrated that Chinese word structure effect showed a distinct brain activation pattern as compared to that from the dual-route mechanism in alphabetic languages. Therefore, this pilot work paves a new avenue for comprehensively understanding the underlying cognitive neural mechanism associated with Chinese derivations and coordinate compounds.

Striatal loci are connected to both the ipsilateral and contralateral frontal cortex. Normative quantitation of the dissimilarity between striatal loci’s hemispheric connection profiles and its spatial variance across the striatum, and assessment of how interindividual differences relate to function, stands to further the understanding of the role of corticostriatal circuits in lateralized functions and the role of abnormal corticostriatal laterality in neurodevelopmental and other neuropsychiatric disorders. A resting-state functional connectivity fingerprinting approach (n = 261) identified “laterality hotspots”—loci whose profiles of connectivity with ipsilateral and contralateral frontal cortex were disproportionately dissimilar—in the right rostral ventral putamen, left rostral central caudate, and bilateral caudal ventral caudate. Findings were replicated in an independent sample and were robust to both preprocessing choices and the choice of cortical atlas used for parcellation definitions. Across subjects, greater rightward connectional laterality at the right ventral putamen hotspot and greater leftward connectional laterality at the left rostral caudate hotspot were associated with higher performance on tasks engaging lateralized functions (i.e., response inhibition and language, respectively). In sum, we find robust and reproducible evidence for striatal loci with disproportionately lateralized connectivity profiles where interindividual differences in laterality magnitude are associated with behavioral capacities on lateralized functions.

Brain G-protein coupled receptors have been hypothesized to be potential targets for maintaining or restoring cognitive function in normal aged individuals or in patients with neurodegenerative disease. A number of recent reports suggest that activation of melanocortin receptors (MCRs) in the brain can significantly improve cognitive functions of normal rodents and of different rodent models of the Alzheimer’s disease. However, the potential impact of normative aging on the expression of MCRs and their potential roles for modulating cognitive function remains to be elucidated. In the present study, we first investigated the expression of these receptors in six different brain regions of young (6 months) and aged (23 months) rats following assessment of their cognitive status. Correlation analysis was further performed to reveal potential contributions of MCR subtypes to spatial learning and memory. Our results revealed statistically significant correlations between the expression of several MCR subtypes in the frontal cortex/hypothalamus and the hippocampus regions and the rats’ performance in spatial learning and memory only in the aged rats. These findings support the hypothesis that aging has a direct impact on the expression and function of MCRs, establishing MCRs as potential drug targets to alleviate aging-induced decline of cognitive function.

Objective: Our aim was to investigate the dynamics of functional connectivity (FC) networks during seizure termination in patients with childhood absence epilepsy (CAE) using magnetoencephalography (MEG) and graph theory (GT) analysis.Methods: MEG data were recorded from 22 drug-naïve patients diagnosed with CAE. FC analysis was performed to evaluate the FC networks in seven frequency bands of the MEG data. GT analysis was used to assess the topological properties of FC networks in different frequency bands.Results: The patterns of FC networks involving the frontal cortex were altered significantly during seizure termination compared with those during the ictal period. Changes in the topological parameters of FC networks were observed in specific frequency bands during seizure termination compared with those in the ictal period. In addition, the connectivity strength at 250–500 Hz during the ictal period was negatively correlated with seizure frequency.Conclusions: FC networks associated with the frontal cortex were involved in the termination of absence seizures. The topological properties of FC networks in different frequency bands could be used as new biomarkers to characterize the dynamics of FC networks related to seizure termination.

The theory of predictive processing posits that the nervous system uses expectations to process information predictively. Direct empirical evidence in support of this theory however has been scarce and largely limited to sensory areas. Here, we report a precise and adaptive neural mechanism in the frontal cortex of non-human primates consistent with predictive processing of temporal events. We found that the speed at which neural states evolve over time is inversely proportional to the statistical mean of the temporal distribution of an expected stimulus. This lawful relationship was evident across multiple experiments and held true during learning: when temporal statistics underwent covert changes, neural responses underwent predictable changes that reflected the new mean. Together, these results highlight a precise mathematical relationship between temporal statistics in the environment and neural activity in the frontal cortex that could serve as a mechanistic foundation for predictive temporal processing.

Flexible reward learning relies on frontal cortex, with substantial evidence indicating the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) play important roles. Recent studies in both rat and macaque suggest theta oscillations (5-10 Hz) may be a spectral signature that coordinates this learning. However, causal network-level interactions between ACC and OFC in flexible learning remain unclear. We investigated the learning of stimulus-outcome (S-O) and action-outcome (A-O) associations using a combination of simultaneous in-vivo electrophysiology in dorsal ACC and ventral OFC, partnered with bilateral inhibitory DREADDs in ACC. In freely-behaving male and female rats and using a within-subject design, we examined accuracy and speed of response across distinct and precisely-defined trial epochs including correct choice, incorrect choice, and reward collection. We report significant modulation of accuracy by theta power in both ACC and OFC. Both ACC and OFC theta oscillations consistently signaled accuracy in the initial discrimination phase, whereas it was OFC theta alone in the reversal phases of both S-O and A-O learning. Theta power in either region was not correlated with deliberation speed. Indeed, theta modulation of accuracy was dissociable from its involvement in speed of response which was affected by ACC inhibition, most prominently in A-O learning. Results are discussed with reference to the nonhuman primate literature, where there is by contrast more reported specialization of OFC and ACC in flexible learning of stimuli and actions. The present results also point to a specific role of OFC theta in signaling a reversal of either kind.

Anti-saccades are eye movements that require inhibition to stop the automatic saccade to the visual target and to perform instead a saccade in the opposite direction. The inhibitory processes underlying anti-saccades have been primarily associated with frontal cortex areas for their role in executive control. Impaired performance in anti-saccades has also been associated with the parietal cortex, but its role in inhibitory processes remains unclear. Here, we tested the assumption that the dorsal parietal cortex contributes to spatial inhibition processes of contralateral visual target. We measured anti-saccade performance in 2 unilateral optic ataxia patients and 15 age-matched controls. Participants performed 90 degree (across and within visual fields) and 180 degree inversion anti-saccades, as well as pro-saccades. The main result was that our patients took longer to inhibit visually guided saccades when the visual target was presented in the ataxic hemifield and the task required a saccade across hemifields. This was observed through anti-saccades latencies and error rates. These deficits show the crucial role of the dorsal posterior parietal cortex in spatial inhibition of contralateral visual target representations to plan an accurate anti-saccade toward the ipsilesional side.

The functionality of central vision is different from peripheral vision. Central vision is used for fixation and has higher acuity, making it useful for everyday activities such as reading and object identification. The central and peripheral representations in primary visual cortex (V1) also differ in how higher-order processing areas modulate their responses. For example, attention and expectation are top-down processes (i.e., high-order cognitive functions) that influence visual information processing during behavioral tasks. This top-down control is different for central vs. peripheral vision. Since functional networks can influence visual information processing in different ways, networks (such as the Fronto-Parietal (FPN), Default Mode (DMN), and Cingulo-Opercular (CON)) likely differ in how they connect to representations of the visual field across V1. Prior work indicated the central representing portion of V1 was more functionally connected to regions belonging to the FPN, and the far-peripheral representing portion of V1 was more functionally connected to regions belonging to the DMN. Our goals were (1) Assess the reproducibility and generalizability of retinotopic effects on functional connections between V1 and functional networks. (2) Extend this work to understand structural connections of central vs. peripheral representations in V1. (3) Examine the overlapping eccentricity differences in functional and structural connections of V1. (4) Examine the major white matter tracks connecting central V1 to frontal regions. We used resting-state BOLD fMRI and DWI to examine whether portions of V1 that represent different visual eccentricities differ in their functional and structural connectivity to functional networks. All data were acquired and minimally preprocessed by the Human Connectome Project. We identified central and far-peripheral representing regions from a retinotopic template. Functional connectivity was measured by correlated activity between V1 and functional networks, and structural connectivity was measured by probabilistic tractography and converted to track probability. In both modalities, differences between V1 eccentricity segment connections were compared by paired, two-tailed t-test. A spatial permutation approach was used to determine the statistical significance of the spatial overlap between modalities. The identified spatial overlap was then used in a deterministic tractography approach to identify the white matter pathways connecting the overlap to central V1. We found (1) Centrally representing portions of V1 are more strongly functionally connected to frontal regions than are peripherally representing portions of V1, (2) Structural connections also show stronger connections between central V1 and frontal regions, (3) Patterns of structural and functional connections overlaps in the lateral frontal cortex, (4) This lateral frontal overlap is connected to central V1 via the IFOF. In summary, the work's main contribution is a greater understanding of higher-order functional networks' connectivity to V1. There are stronger structural connections to central representations in V1, particularly for lateral frontal regions, implying that the functional relationship between central V1 and frontal regions is built upon direct, long-distance connections via the IFOF. Overlapping structural and functional connections reflect differences in V1 eccentricities, with central V1 preferentially connected to attention-associated regions. Understanding how V1 is functionally and structurally connected to higher-order brain areas contributes to our understanding of how the human brain processes visual information and forms a baseline for understanding any modifications in processing that might occur with training or experience.

Vocal communication is essential for social behaviors in humans and many non-human primates. While the frontal cortex has been shown to play a crucial role in human speech production, its role in vocal production in non-human primates has long been questioned. Recent studies have shown activation in single neurons in the monkey frontal cortex during vocal production in relatively isolated environment. However, little is known about how the frontal cortex is engaged in vocal production in ethologically relevant social context, where different types of vocal signals are produced for various communication purposes. Here we studied single neuron activities and local field potentials (LFP) and in the frontal cortex of marmoset monkeys while the animal engaged in vocal exchanges with other conspecifics in a social environment. Marmosets most frequently produced four types of vocalizations with distinct acoustic structures, three of which were typically not produced in isolation. We found that both single neuron activities and LFP were modulated by the production of each of the four call types. Moreover, the neural modulations in the frontal cortex showed distinct patterns for different call types, suggesting a representation of vocal signal features. In addition, we found that theta-band LFP oscillations were phase-locked to the phrases of twitter calls, which indicates the coordination of temporal structures of vocalizations. Our results suggested important functions of the marmoset frontal cortex in supporting the production of diverse vocalizations in vocal communication.

Goal-directed behavior often involves temporal separation and flexible context-dependent association between sensory input and motor output. The control of goal-directed behavior is proposed to lie in the frontoparietal network, but the computational architecture of this network remains elusive. Based on recent rodent studies that measured and manipulated projection neurons in the frontoparietal network together with findings from earlier primate studies, we propose a canonical scheme of information flows in this network. The parietofrontal pathway transmits the spatial information of a sensory stimulus or internal motor bias to drive motor programs in the frontal areas. This pathway might consist of multiple parallel connections, each controlling distinct motor effectors. The frontoparietal pathway sends the spatial information of cognitively processed motor plans through multiple parallel connections. Each of these connections could support distinct spatial functions that use the motor target information, including attention allocation, multi-body part coordination, and forward estimation of movement state (i.e., forward models). The parallel pathways in the frontoparietal network enable dynamic interactions between regions that are tuned for specific goal-directed behaviors. This scheme offers a promising framework within which the computational architecture of the frontoparietal network and the underlying circuit mechanisms can be delineated in a systematic way, providing a holistic understanding of information processing in this network. Clarifying this network may also improve the diagnosis and treatment of behavioral deficits associated with dysfunctional frontoparietal connectivity in various neurological disorders including Alzheimer’s disease.

Sleep deprivation (SD) is known to be associated with decreased cognitive performance; however, the underlying mechanisms are poorly understood. As interactions between distinct brain regions depend on mental state, functional brain networks established by these connections typically show a reorganization during task. Hence, analysis of functional connectivity (FC) could reveal the task‐related change in the examined frontal brain networks. Our objective was to assess the impact of SD on static FC in the prefrontal and motor cortices and find whether changes in FC correlate with changes in neuropsychological scores. Healthy young male individuals (n = 10, 27.6 ± 3.7 years of age) participated in the study. A battery of tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and 48 channel functional near‐infrared spectroscopy (fNIRS) measurements were performed before and after 24 hr of SD. Network metrics were obtained by graph theoretical analysis using the fNIRS records in resting state and during finger‐tapping sessions. During task, SD resulted in a significantly smaller decrease in the number and strength of functional connections (characterizing FC) in the frontal cortex. Changes in the global connection strengths correlated with decreased performance in the paired association learning test. These results indicate a global impact of SD on functional brain networks in the frontal lobes., To assess the impact of sleep deprivation on static functional connectivity in the frontal lobe, functional near‐infrared spectroscopy and graph theoretical analysis were utilized before and after 24 hr sleep deprivation in healthy young male participants. Deprivation of sleep resulted in a significantly smaller task‐related decrease in the number of functional connections that correlated with decreased performance in the paired association learning test. These results indicate the global impact of sleep deprivation on functional brain networks in the frontal lobes.

Correlates of sensory stimuli and motor actions are found in multiple cortical areas, but such correlates do not indicate whether these areas are causally relevant to task performance. We trained mice to discriminate visual contrast and report their decision by steering a wheel. Widefield calcium imaging and Neuropixels recordings in cortex revealed stimulus-related activity in visual (VIS) and frontal (MOs) areas, and widespread movement-related activity across the whole dorsal cortex. Optogenetic inactivation biased choices only when targeted at VIS and MOs,proportionally to each site's encoding of the visual stimulus, and at times corresponding to peak stimulus decoding. A neurometric model based on summing and subtracting activity in VIS and MOs successfully described behavioral performance and predicted the effect of optogenetic inactivation. Thus, sensory signals localized in visual and frontal cortex play a causal role in task performance, while widespread dorsal cortical signals correlating with movement reflect processes that do not play a causal role.

Working memory, the brain’s ability to retain and manipulate information internally, has been traditionally associated with persistent neural firing in localized brain areas such as those in the frontal cortex (Fuster 1973, Funahashi et al., 1989; Goldman-Rakic 1995; Romo et al., 1999; Rigotti et al., 2013; Kopec et al., 2015; Inagaki et al., 2019). However, self-sustained neural persistent activity during working memory is present in multiple brain regions (Romo et al., 2004; Christophel et al., 2017; Leavitt et al., 2017; Sreenivasan and D’Esposito, 2019), the underlying mechanism is unknown. We developed an anatomically constrained large-scale computational model of the macaque cortex endowed with a macroscopic gradient of synaptic excitation, to investigate the origin of distributed working memory representation. We found that long-range inter-areal reverberation can support the emergence of persistent activity patterns across multiple cortical regions, by virtue of a robust bifurcation in space, even when none of isolated local areas is capable of generating persistent activity. The model uncovered a host of distinct persistent activity patterns (attractor states), and provides experimentally testable predictions that cannot be explained in local circuit models. Simulating cortical lesions reveals that distributed activity patters are resilient against simultaneous lesions of multiple cortical areas, but depend on areas that form the core of the entire cortex. This work provides a theoretical framework for identifying large-scale brain mechanisms and computational principles of distributed cognitive processes.

Preparatory activity in the frontal cortex preceding movement onset is thought to represent a neuronal signature of motor planning. However, how excitatory and inhibitory synaptic inputs to frontal neurons are integrated during movement preparation remains unclear. Here we address this question by performing in vivo whole-cell patch-clamp recordings in the secondary motor cortex (MOs) of head-fixed mice moving on a treadmill. We find that both superficial and deep principal neurons show slowly increasing (~10 s) membrane potential and spike rate ramps preceding the onset of spontaneous, self-paced running periods. By contrast, in animals trained to perform a goal-directed task, both membrane potential and spike ramps are characterized by larger amplitudes and accelerated kinetics during preparation of goal-driven movement. To determine the role of local inhibitory neurons in shaping these task-dependent preparatory signals, we chemogenetically suppressed the activity of specific interneuron subpopulations in untrained animals. Inactivation of parvalbumin-positive (PV+) interneurons leads to depolarized membrane potential ramps with increased amplitudes during preparation of movement, while inactivation of somatostatin-positive (SOM+) interneurons abolishes membrane potential ramps. A computational model of the local MOs circuit shows that SOM+-mediated inhibition of PV+ interneurons in conjunction with recurrent connectivity among the principal neurons can reproduce slow ramping signals, while plasticity of excitatory synapses on SOM+ interneurons can explain the acceleration of these signals in trained animals. Together, our data reveal that local inhibitory neurons play distinct roles in controlling task-dependent preparatory ramping signals when MOs neurons integrate external inputs during motor planning.HighlightsPrincipal neurons in MOs show slow preparatory membrane potential and firing rate ramps preceding the onset of spontaneous, self-paced running periods.In animals trained to perform a goal-directed task, both membrane potential and spike ramps are faster and larger in amplitude.Inactivation of PV+ interneurons disinhibits MOs principal neurons and increases the amplitude of membrane potential ramps, while inactivation of SOM+ interneurons abolishes membrane potential ramps.Our modeling results suggest that the concerted action of external inputs and local inactivation shapes task-dependent preparatory motor signals in MOs neurons.

Consciousness, its neural underpinnings, and the role of frontal cortex are highly debated topics. New evidence shows that human frontal cortex can bias conscious perception. What does this really mean about its contribution to consciousness?

A remarkable feature of primate behavior is the ability to predict future events based on past experience and current sensory cues. To understand how the brain plans movements in the presence of unstable cues, we recorded gaze-related activity in the frontal cortex of two monkeys engaged in a quasi-predictable cue-conflict task. Animals were trained to look toward remembered visual targets in the presence of a landmark that shifted with fixed amplitude but randomized direction. As simulated by a probabilistic model based on known physiology/behavior, gaze end points assumed a circular distribution around the target, mirroring the possible directions of the landmark shift. This predictive strategy was reflected in frontal cortex activity (especially supplementary eye fields), which anticipated future gaze distributions before the actual landmark shift. In general, these results implicate prefrontal cortex in the predictive integration of environmental cues and their learned statistical properties to mitigate spatial uncertainty.