Task-related Activation Patterns Research Articles

Population-level coding of avoidance learning in medial prefrontal cortex.

The medial prefrontal cortex (mPFC) has been proposed to link sensory inputs and behavioral outputs to mediate the execution of learned behaviors. However, how such a link is implemented has remained unclear. To measure prefrontal neural correlates of sensory stimuli and learned behaviors, we performed population calcium imaging during a new tone-signaled active avoidance paradigm in mice. We developed an analysis approach based on dimensionality reduction and decoding that allowed us to identify interpretable task-related population activity patterns. While a large fraction of tone-evoked activity was not informative about behavior execution, we identified an activity pattern that was predictive of tone-induced avoidance actions and did not occur for spontaneous actions with similar motion kinematics. Moreover, this avoidance-specific activity differed between distinct avoidance actions learned in two consecutive tasks. Overall, our results are consistent with a model in which mPFC contributes to the selection of goal-directed actions by transforming sensory inputs into specific behavioral outputs through distributed population-level computations.

The subthalamic nucleus contributes causally to perceptual decision-making in monkeys.

The subthalamic nucleus (STN) plays critical roles in the motor and cognitive function of the basal ganglia (BG), but the exact nature of these roles is not fully understood, especially in the context of decision-making based on uncertain evidence. Guided by theoretical predictions of specific STN contributions, we used single-unit recording and electrical microstimulation in the STN of healthy monkeys to assess its causal, computational roles in visual-saccadic decisions based on noisy evidence. The recordings identified subpopulations of STN neurons with distinct task-related activity patterns that related to different theoretically predicted functions. Microstimulation caused changes in behavioral choices and response times that reflected multiple contributions to an "accumulate-to-bound"-like decision process, including modulation of decision bounds and evidence accumulation, and to non-perceptual processes. These results provide new insights into the multiple ways that the STN can support higher brain function.

Emergence of task-related spatiotemporal population dynamics in transplanted neurons

Loss of nervous system tissue after severe brain injury is a main determinant of poor functional recovery. Cell transplantation is a promising method to restore lost tissue and function, yet it remains unclear if transplanted neurons can demonstrate the population level dynamics important for movement control. Here we present a comprehensive approach for long-term single neuron monitoring and manipulation of transplanted embryonic cortical neurons after cortical injury in adult male mice performing a prehension task. The observed patterns of population activity in the transplanted network strongly resembled that of healthy networks. Specifically, the task-related spatiotemporal activity patterns of transplanted neurons could be represented by latent factors that evolve within a low dimensional manifold. We also demonstrate reliable modulation of the transplanted networks using minimally invasive epidural stimulation. Our approach may allow greater insight into how restoration of cell-type specific network dynamics in vivo can restore motor function.

48 Should I Stay or Should I Go? Neural Circuits Underlying Decisions to Explore or Exploit

Objective:Adaptive decision-making is necessary to sustain functional independence. Maladaptive decisions are among the most prevalent features of psychological and neurological disorders. One crucial aspect of decision-making involves arbitrating between exploring new avenues with risky but potentially lucrative outcomes or exploiting prior knowledge and endorsing predictable outcomes. Balancing this dichotomy creates a behavioral tension that shapes all decisions and is termed the exploration-exploitation trade-off. This trade-off has been linked to reward and affective drives and associated neural circuitry as well as neuropsychological dysfunction. However, the neural mechanisms underlying the exploration-exploitation trade-off are still uncertain, due to the scarcity of literature and the heterogeneity of paradigms. This study aimed to systematically quantify and disambiguate neuroanatomical correlates of the exploration-exploitation tradeoff in a normative adult sample. These findings provide a necessary starting point for future investigations of this fundamental aspect of decision-making across clinical populations, with potential implications for assessment and intervention.Participants and Methods:We used the effect-location method of meta-analysis to analyze data from 10 functional neuroimaging studies investigating the exploration-exploitation tradeoff in non-clinical samples. We analyzed the location and frequency of significant neural activations across studies for both explorative and exploitative decisions and characterized them as core and non-core regions. Core activations were defined as those reported in over 50% of studies. Secondary and tertiary activations were defined as those reported in 40% and 30% of studies, respectively. The present review was conducted in accordance with the guidelines of the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Results:The results revealed that explorative and exploitative choice behaviours differed markedly with respect to associated patterns of task-related brain activity. Exploration was associated with activity in brain regions implicated in externally directed, goal-based attentional processing and reward-related uncertainty, mainly tapping bilateral parietal and frontal circuitry, with relatively high consistency across studies. A core explorative network was revealed, consisting of activity in the frontal polar cortex, the dorsal anterior cingulate cortex, the bilateral medial frontal gyrus, the bilateral precuneus, and the bilateral intraparietal sulcus. Secondary and tertiary regions were also detected, including the bilateral anterior insula, the left precentral gyrus, the bilateral superior frontal gyrus, the right inferior frontal gyrus, the left supplementary motor area, the bilateral superior parietal lobule, and the bilateral thalamus. Exploitation was associated with brain regions implicated in internally directed processes including reward valuation, motivation, and memory. Core exploitative activations included the ventromedial prefrontal cortex, the bilateral anterior cingulate cortex, and the bilateral orbitofrontal cortex. Secondary and tertiary activations included the bilateral hippocampus, the left middle temporal gyrus, the bilateral angular gyrus, the left posterior cingulate cortex, the left superior frontal gyrus, and the bilateral superior temporal gyrus.Conclusions:The exploration-exploitation trade-off provides a novel paradigmatic approach to study adaptive and maladaptive decision-making behaviour in humans. Our findings support the neural dichotomization of exploration and exploitation and illuminate potential neural networks underlying this fundamental feature of decision-making. Understanding these mechanistic networks opens a new avenue of inquiry into decision-making deficits in clinical populations, including neurodegenerative, neurodevelopmental, and neuropsychiatric syndromes.

Grasping with a twist: Dissociating action goals from motor actions in human frontoparietal circuits.

In daily life, prehension is typically not the end goal of hand-object interactions but a precursor for manipulation. Nevertheless, functional MRI (fMRI) studies investigating manual manipulation have primarily relied on prehension as the end goal of an action. Here, we used slow event-related fMRI to investigate differences in neural activation patterns between prehension in isolation and prehension for object manipulation. Sixteen (7 males and 9 females) participants were instructed either to simply grasp the handle of a rotatable dial (isolated prehension) or to grasp and turn it (prehension for object manipulation). We used representational similarity analysis to investigate whether the experimental conditions could be discriminated from each other based on differences in task-related brain activation patterns. We also used temporal multivoxel pattern analysis to examine the evolution of regional activation patterns over time. Importantly, we were able to differentiate isolated prehension and prehension for manipulation from activation patterns in the early visual cortex, the caudal intraparietal sulcus, and the superior parietal lobule. Our findings indicate that object manipulation extends beyond the putative cortical grasping network (anterior intraparietal sulcus, premotor and motor cortices) to include the superior parietal lobule and early visual cortex.Significance statement:A simple act such as turning an oven dial requires not only that the central nervous system encode the initial state (starting dial orientation) of the object but also the appropriate posture to grasp it in order to achieve the desired end state (final dial orientation) and the motor commands to achieve that state. Using advanced temporal neuroimaging analysis techniques, we reveal how such actions unfold over time and how they differ between object manipulation (turning a dial) vs. grasping alone. We find that a combination of brain areas implicated in visual processing and sensorimotor integration can distinguish between the complex and simple tasks during planning, with neural patterns that approximate those during the actual execution of the action.

Modulation of cortical resting state functional connectivity during a visuospatial attention task in Parkinson's disease.

Visual dysfunction is a recognized early symptom of Parkinson's disease (PD) that partly scales motor symptoms, yet its background is heterogeneous. With additional deficits in visuospatial attention, the two systems are hard to disentangle and it is not known whether impaired functional connectivity in the visual cortex is translative in nature or disrupted attentional modulation also contributes. In this study, we investigate functional connectivity modulation during a visuospatial attention task in patients with PD. In total, 15 PD and 16 age-matched healthy controls performed a visuospatial attention task while undergoing fMRI, in addition to a resting-state fMRI scan. Tensorial independent component analysis was used to investigate task-related network activity patterns. Independently, an atlas-based connectivity modulation analysis was performed using the task potency method. Spearman's rank correlation was calculated between task-related network expression, connectivity modulation, and clinical characteristics. Task-related networks including mostly visual, parietal, and prefrontal cortices were expressed to a significantly lesser degree in patients with PD (p < 0.027). Resting-state functional connectivity did not differ between the healthy and diseased cohorts. Connectivity between the precuneus and ventromedial prefrontal cortex was modulated to a higher degree in patients with PD (p < 0.004), while connections between the posterior parietal cortex and primary visual cortex, and also the superior frontal gyrus and opercular cortex were modulated to a lesser degree (p < 0.001 and p < 0.011). Task-related network expression and superior frontal gyrus–opercular cortex connectivity modulation were significantly associated with UPDRSIII motor scores and the Hoehn–Yahr stages (R = −0.72, p < 0.006 and R = −0.90, p < 0.001; R = −0.68, p < 0.01 and R = −0.71, p < 0.007). Task-related networks function differently in patients with PD in association with motor symptoms, whereas impaired modulation of visual and default-mode network connectivity was not correlated with motor function.

Task-Related Modulation of Sensorimotor GABA+ Levels in Association with Brain Activity and Motor Performance: A Multimodal MRS-fMRI Study in Young and Older Adults.

Recent studies suggest an important role of the principal inhibitory neurotransmitter GABA for motor performance in the context of aging. Nonetheless, as previous magnetic resonance spectroscopy (MRS) studies primarily reported resting-state GABA levels, much less is known about transient changes in GABA levels during motor task performance and how these relate to behavior and brain activity patterns. Therefore, we investigated GABA+ levels of left primary sensorimotor cortex (SM1) acquired before, during, and after execution of a unimanual/bimanual action selection task in 30 (human) young adults (YA; age 24.5 ± 4.1, 15 male) and 30 older adults (OA; age 67.8 ± 4.9, 14 male). In addition to task-related MRS data, task-related functional magnetic resonance imaging (fMRI) data were acquired. Behavioral results indicated lower motor performance in OA as opposed to YA, particularly in complex task conditions. MRS results demonstrated lower GABA+ levels in OA as compared with YA. Furthermore, a transient task-related decrease of GABA+ levels was observed, regardless of age. Notably, this task-induced modulation of GABA+ levels was linked to task-related brain activity patterns in SM1 such that a more profound task-induced instantaneous lowering of GABA+ was related to higher SM1 activity. Additionally, higher brain activity was related to better performance in the bimanual conditions, despite some age-related differences. Finally, the modulatory capacity of GABA+ was positively related to motor performance in OA but not YA. Together, these results underscore the importance of transient dynamical changes in neurochemical content for brain function and behavior, particularly in the context of aging.SIGNIFICANCE STATEMENT Emerging evidence designates an important role to regional GABA levels in motor control, especially in the context of aging. However, it remains unclear whether changes in GABA levels emerge when executing a motor task and how these changes relate to brain activity patterns and performance. Here, we identified a transient decrease of sensorimotor GABA+ levels during performance of an action selection task across young adults (YA) and older adults (OA). Interestingly, whereas a more profound GABA+ modulation related to higher brain activity across age groups, its association with motor performance differed across age groups. Within OA, our results highlighted a functional merit of a task-related release from inhibitory tone, i.e. lowering regional GABA+ levels was associated with task-relevant brain activity.

Type 1 diabetes affects the brain functional connectivity underlying working memory processing.

Visuospatial working memory (VSWM) deficits have been demonstrated to occur during the development of type-1-diabetes (T1D). Despite confirming the early appearance of distinct task-related brain activation patterns in T1D patients compared to healthy controls, the effect of VSWM load on functional brain connectivity during task performance is still unknown. Using electroencephalographic methods, the present study evaluated this topic in clinically well-controlled T1D young patients and healthy individuals, while they performed a VSWM task with different memory load levels during two main VSWM processing phases: encoding and maintenance. The results showed a significantly lower number of correct responses and longer reaction times in T1D while performing the task. Besides, higher and progressively increasing functional connectivity indices were found for T1D patients in response to cumulative degrees of VSWM load, from the beginning of the VSWM encoding phase, without notably affecting the VSWM maintenance phase. In contrast, healthy controls managed to solve the task, showing lower functional brain connectivity during the initial VSWM processing steps with more gradual task-related adjustments. Present results suggest that T1D patients anticipate high VSWM load demands by early recruiting supplementary processing resources as the probable expression of a more inefficient, though paradoxically better adjusted to task demands cognitive strategy.

Learning differentially shapes prefrontal and hippocampal activity during classical conditioning.

The ability to use sensory cues to inform goal-directed actions is a critical component of behavior. To study how sounds guide anticipatory licking during classical conditioning, we employed high-density electrophysiological recordings from the hippocampal CA1 area and the prefrontal cortex (PFC) in mice. CA1 and PFC neurons undergo distinct learning-dependent changes at the single-cell level and maintain representations of cue identity at the population level. In addition, reactivation of task-related neuronal assemblies during hippocampal awake Sharp-Wave Ripples (aSWRs) changed within individual sessions in CA1 and over the course of multiple sessions in PFC. Despite both areas being highly engaged and synchronized during the task, we found no evidence for coordinated single cell or assembly activity during conditioning trials or aSWR. Taken together, our findings support the notion that persistent firing and reactivation of task-related neural activity patterns in CA1 and PFC support learning during classical conditioning.

Brain Activation of Patients With Obsessive-Compulsive Disorder During a Mental Rotation Task: A Functional MRI Study.

Functional neuroimaging studies have implicated alterations in frontostriatal and frontoparietal circuits in obsessive-compulsive disorder (OCD) during various tasks. To date, however, brain activation for visuospatial function in conjunction with symptoms in OCD has not been comprehensively evaluated. To elucidate the relationship between neural activity, cognitive function, and obsessive-compulsive symptoms, we investigated regional brain activation during the performance of a visuospatial task in patients with OCD using functional magnetic resonance imaging (fMRI). Seventeen medication-free patients with OCD and 21 age-, sex-, and IQ-matched healthy controls participated in this study. Functional magnetic resonance imaging data were obtained while the subjects performed a mental rotation (MR) task. Brain activation during the task was compared between the two groups using a two-sample t-test. Voxel-wise whole-brain multiple regression analyses were also performed to examine the relationship between obsessive-compulsive symptom severity and neural activity during the task. The two groups did not differ in MR task performance. Both groups also showed similar task-related activation patterns in frontoparietal regions with no significant differences. Activation in the right dorsolateral prefrontal cortex in patients with OCD during the MR task was positively associated with their total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. This study identified the specific brain areas associated with the interaction between symptom severity and visuospatial cognitive function during an MR task in medication-free patients with OCD. These findings may serve as potential neuromodulation targets for OCD treatment.

Assessing the Effect of Training on the Cognition and Brain of Older Adults: Protocol for a Three-Arm Randomized Double-Blind Controlled Trial (ACTOP).

BackgroundTo prevent age-related cognitive impairment, many intervention programs offer exercises targeting different central cognitive processes. However, the effects of different process-based training programs are rarely compared within equivalent experimental designs.ObjectiveUsing a randomized double-blind controlled trial, this project aims to examine and compare the impact of 2 process-based interventions, inhibition and updating, on the cognition and brain of older adults.MethodsA total of 90 healthy older adults were randomly assigned to 1 of 3 training conditions: (1) inhibition (Stroop-like exercises), (2) updating (N-back-type exercises), and (3) control active (quiz game exercise). Training was provided in 12 half-hour sessions over 4 weeks. First, the performance gain observed will be measured on the trained tasks. We will then determine the extent of transfer of gain on (1) untrained tasks that rely on the same cognitive process, (2) complex working memory (WM) measurements hypothesized to involve 1 of the 2 trained processes, and (3) virtual reality tasks that were designed to mimic real-life situations that require WM. We will assess whether training increases cortical volume given that the volume of the cortex is determined by cortical area and thickness in regions known to be involved in WM or changes task-related brain activation patterns measured with functional magnetic resonance imaging. Dose effects will be examined by measuring outcomes at different time points during training. We will also determine whether individual characteristics moderate the effect of training on cognitive and cerebral outcomes. Finally, we will evaluate whether training reduces the age-related deficit on transfer and brain outcomes, by comparing study participants to a group of 30 younger adults.ResultsThe project was funded in January 2017; enrollment began in October 2017 and data collection was completed in April 2019. Data analysis has begun in June 2020 and the first results should be published by the end of 2020 or early 2021.ConclusionsThe results of this study will help understand the relative efficacy of 2 attentional control interventions on the cognition and the brain of older adults, as well as the moderating role of individual characteristics on training efficiency and transfer.Trial RegistrationClinicalTrials.gov NCT03532113; https://clinicaltrials.gov/ct2/show/NCT03532113International Registered Report Identifier (IRRID)DERR1-10.2196/20430

Functional connectivity in a triple-network saliency model is associated with real-life self-control

Despite its significance for health and education, the neurocognitive mechanism of real-life self-control remains unclear. While recent studies focused on task-related brain activation patterns as predictors of self-control, the contribution and relevance of functional connectivity between large-scale brain networks mediating higher-order cognition is largely unknown. Using a saliency-based triple-network model of cognitive control, we tested the hypothesis that cross-network interactions among the salience network (SN), the central executive network (CEN), and the default mode network (DMN) are associated with real-life self-control. To this end, a large community sample (N = 294) underwent ecological momentary assessment of daily self-control as well as task-free fMRI to examine intrinsic inter-network organization and determine a SN-centered network interaction index (NII). Logistic multilevel regression analysis showed that higher NII scores were associated with increased real-life self-control. This suggests that the assumed role of the SN in initiating switching between the DMN and CEN is an important part of self-control.

Functional magnetic resonance imaging in primary hyperparathyroidism.

The neurophysiological mechanisms underlying cognitive dysfunction in primary hyperparathyroidism (PHPT) and the brain regions affected are not clear. We assessed neural activation during cognitive testing (matrix reasoning, paired associates, and logical memory) using functional MRI (fMRI) in 23 patients with PHPT and 23 healthy controls. A subset with PHPT was re-assessed 6 months post-parathyroidectomy (PTX). This is an observational study comparing neural activation by fMRI in patients with PHPT to normative controls. Postmenopausal women were studied at a tertiary referral center. There were no between-group differences in cognitive task performance. Patients with PHPT had lower neural activation vs controls (max Z = 4.02, all P < 0.01) during matrix reasoning in brain regions involved in executive function (left frontal lobe (k = 57) and right medial frontal gyrus (k = 72)) and motor function (right precentral gyrus (k = 51)). During paired associates (verbal memory), those with PHPT had greater activation in the right inferior parietal lobule (language/mathematical operations; k = 65, P < 0.01). Greater activation in this region bilaterally correlated with higher PTH (k = 96, P < 0.01). Post-PTX, activation decreased during matrix reasoning, but in different regions than those affected pre-PTX. PHPT is associated with differences in task-related neural activation patterns, but no difference in cognitive performance. While this may indicate compensation to maintain the same cognitive function, there was no clear improvement in neural activation after PTX. Larger, longitudinal studies that include PHPT patients followed without surgery are needed to determine if PTX could prevent worsening of altered neural activation patterns in PHPT.

Working memory training increases neural efficiency in Parkinson's disease: a randomized controlled trial.

Impairment of working memory and executive functions is already frequently observed in early stages of Parkinson’s disease. Improvements in working memory performance in this cohort could potentially be achieved via working memory training. However, the specific neural mechanisms underlying different working memory processes such as maintenance as opposed to manipulation are largely under-investigated in Parkinson’s disease. Moreover, the plasticity of these correlates as a function of working memory training is currently unknown in this population. Thus, the working memory subprocesses of maintenance and manipulation were assessed in 41 cognitively healthy patients with Parkinson’s disease using a newly developed working memory paradigm and functional MRI. Nineteen patients were randomized to a 5-week home-based digital working memory training intervention while the remaining patients entered a control, wait list condition. Working memory task-related activation patterns and context-dependent functional connectivity, as well as the change of these neural correlates as a function of training, were assessed. While both working memory processes activated an extended frontoparietal–cerebellar network, only the manipulation of items within working memory also recruited the anterior striatum. The intervention effect on the neural correlates was small, but decreased activation in areas relevant for working memory could be observed, with activation changes correlating with behavioural change. Moreover, training seemed to result in decreased functional connectivity when pure maintenance was required, and in a reorganization of functional connectivity when items had to be manipulated. In accordance with the neural efficacy hypothesis, training resulted in overall reduced activation and reorganized functional connectivity, with a differential effect on the different working memory processes under investigation. Now, larger trials including follow-up examinations are needed to further explore the long-term effects of such interventions on a neural level and to estimate the clinical relevance to potentially delay cognitive decline in cognitively healthy patients with Parkinson’s disease.

Identifying and removing widespread signal deflections from fMRI data: Rethinking the global signal regression problem

One of the most controversial procedures in the analysis of resting-state functional magnetic resonance imaging (rsfMRI) data is global signal regression (GSR): the removal, via linear regression, of the mean signal averaged over the entire brain. On one hand, the global mean signal contains variance associated with respiratory, scanner-, and motion-related artifacts, and its removal via GSR improves various quality-control metrics, enhances the anatomical specificity of functional-connectivity patterns, and can increase the behavioral variance explained by such patterns. On the other hand, GSR alters the distribution of regional signal correlations in the brain, can induce artifactual anticorrelations, may remove real neural signal, and can distort case-control comparisons of functional-connectivity measures. Global signal fluctuations can be identified visually from a matrix of colour-coded signal intensities, called a carpet plot, in which rows represent voxels and columns represent time. Prior to GSR, large, periodic bands of coherent signal changes that affect most of the brain are often apparent; after GSR, these apparently global changes are greatly diminished. Here, using three independent datasets, we show that reordering carpet plots to emphasize cluster structure in the data reveals a greater diversity of spatially widespread signal deflections (WSDs) than previously thought. Their precise form varies across time and participants, and GSR is only effective in removing specific kinds of WSDs. We present an alternative, iterative correction method called Diffuse Cluster Estimation and Regression (DiCER), that identifies representative signals associated with large clusters of coherent voxels. DiCER is more effective than GSR at removing diverse WSDs as visualized in carpet plots, reduces correlations between functional connectivity and head-motion estimates, reduces inter-individual variability in global correlation structure, and results in comparable or improved identification of canonical functional-connectivity networks. Using task fMRI data across 47 contrasts from 7 tasks in the Human Connectome Project, we also present evidence that DiCER is more successful than GSR in preserving the spatial structure of expected task-related activation patterns. Our findings indicate that care must be exercised when examining WSDs (and their possible removal) in rsfMRI data, and that DiCER is a viable alternative to GSR for removing anatomically widespread and temporally coherent signals. All code for implementing DiCER and replicating our results is available at https://github.com/BMHLab/DiCER.

Chronic stability of single-channel neurophysiological correlates of gross and fine reaching movements in the rat.

While substantial task-related neural activity has been observed during motor tasks in rodent primary motor cortex and premotor cortex, the long-term stability of these responses in healthy rats is uncertain, limiting the interpretability of longitudinal changes in the specific patterns of neural activity associated with learning or motor recovery following injury. This study examined the stability of task-related neural activity associated with execution of two distinct reaching tasks in healthy rodents. A novel automated rodent behavioral apparatus was constructed and rats were trained to perform a reaching task combining a ‘gross’ lever press and a ‘fine’ pellet retrieval. In each animal, two chronic microelectrode arrays were implanted in motor cortex spanning the caudal forelimb area (rodent primary motor cortex) and the rostral forelimb area (rodent premotor cortex). We recorded multiunit spiking and local field potential activity from 10 days to 7–10 weeks post-implantation to characterize the patterns of neural activity observed during each task component and analyzed the consistency of channel-specific task-related neural activity. Task-related changes in neural activity were observed on the majority of channels. While the task-related changes in multi-unit spiking and local field potential spectral power were consistent over several weeks, spectral power changes were more stable, despite the trade-off of decreased spatial and temporal resolution. These results show that neural activity in rodent primary and premotor cortex is associated with specific phases of reaching movements with stable patterns of task-related activity across time, establishing the relevance of the rodent for future studies designed to examine changes in task-related neural activity during recovery from focal cortical lesions.

Distinct Properties of Layer 3 Pyramidal Neurons from Prefrontal and Parietal Areas of the Monkey Neocortex.

In primates, working memory function depends on activity in a distributed network of cortical areas that display different patterns of delay task-related activity. These differences are correlated with, and might depend on, distinctive properties of the neurons located in each area. For example, layer 3 pyramidal neurons (L3PNs) differ significantly between primary visual and dorsolateral prefrontal (DLPFC) cortices. However, to what extent L3PNs differ between DLPFC and other association cortical areas is less clear. Hence, we compared the properties of L3PNs in monkey DLPFC versus posterior parietal cortex (PPC), a key node in the cortical working memory network. Using patch-clamp recordings and biocytin cell filling in acute brain slices, we assessed the physiology and morphology of L3PNs from monkey DLPFC and PPC. The L3PN transcriptome was studied using laser microdissection combined with DNA microarray or quantitative PCR. We found that in both DLPFC and PPC, L3PNs were divided into regular spiking (RS-L3PNs) and bursting (B-L3PNs) physiological subtypes. Whereas regional differences in single-cell excitability were modest, B-L3PNs were rare in PPC (RS-L3PN:B-L3PN, 94:6), but were abundant in DLPFC (50:50), showing greater physiological diversity. Moreover, DLPFC L3PNs display larger and more complex basal dendrites with higher dendritic spine density. Additionally, we found differential expression of hundreds of genes, suggesting a transcriptional basis for the differences in L3PN phenotype between DLPFC and PPC. These data show that the previously observed differences between DLPFC and PPC neuron activity during working memory tasks are associated with diversity in the cellular/molecular properties of L3PNs.SIGNIFICANCE STATEMENT In the human and nonhuman primate neocortex, layer 3 pyramidal neurons (L3PNs) differ significantly between dorsolateral prefrontal (DLPFC) and sensory areas. Hence, L3PN properties reflect, and may contribute to, a greater complexity of computations performed in DLPFC. However, across association cortical areas, L3PN properties are largely unexplored. We studied the physiology, dendrite morphology and transcriptome of L3PNs from macaque monkey DLPFC and posterior parietal cortex (PPC), two key nodes in the cortical working memory network. L3PNs from DLPFC had greater diversity of physiological properties and larger basal dendrites with higher spine density. Moreover, transcriptome analysis suggested a molecular basis for the differences in the physiological and morphological phenotypes of L3PNs from DLPFC and PPC.

Evaluating task-based brain network activity in pediatric subjects with an mTBI: mechanisms of functional compensation are symptom-level dependent

ABSTRACTThe diagnosis of a mild traumatic brain injury (mTBI) places large emphasis on patient-reported symptoms which has restricted our ability to evaluate patients. Task-based functional magnetic resonance imaging has the potential to act as an objective measurement of abnormal brain activity and inform clinical decision-making; however, there is little research evaluating pediatric subjects as a function of mTBI-related symptoms. The objective of this study was to evaluate the extent to which brain activity during a spatial navigation task is different between children with mTBI and a group of healthy controls (HCs) based on symptom reporting. A group of patients with mTBI (n = 27) were divided into low- and high-symptom cohorts and compared with HCs (n = 27) on a task that required participants to locate specific landmarks. No difference was found in the level of symptoms reported between patients with low-symptom participants and HCs despite the low-symptom group showing increased activity within the frontal and occipital cortices. In participants with high-symptoms, an increase in the number of reported symptoms was found relative to HCs alongside an increase in the number of active brain regions. Findings suggest that persons with an mTBI may display unique symptom-dependent patterns of altered task-related brain activity.

Improved Volitional Recall of Motor-Imagery-Related Brain Activation Patterns Using Real-Time Functional MRI-Based Neurofeedback.

Motor imagery (MI), a covert cognitive process where an action is mentally simulated but not actually performed, could be used as an effective neurorehabilitation tool for motor function improvement or recovery. Recent approaches employing brain–computer/brain–machine interfaces to provide online feedback of the MI during rehabilitation training have promising rehabilitation outcomes. In this study, we examined whether participants could volitionally recall MI-related brain activation patterns when guided using neurofeedback (NF) during training. The participants’ performance was compared to that without NF. We hypothesized that participants would be able to consistently generate the relevant activation pattern associated with the MI task during training with NF compared to that without NF. To assess activation consistency, we used the performance of classifiers trained to discriminate MI-related brain activation patterns. Our results showed significantly higher predictive values of MI-related activation patterns during training with NF. Additionally, this improvement in the classification performance tends to be associated with the activation of middle temporal gyrus/inferior occipital gyrus, a region associated with visual motion processing, suggesting the importance of performance monitoring during MI task training. Taken together, these findings suggest that the efficacy of MI training, in terms of generating consistent brain activation patterns relevant to the task, can be enhanced by using NF as a mechanism to enable participants to volitionally recall task-related brain activation patterns.

Whole-Brain Calcium Imaging Reveals an Intrinsic Functional Network in Drosophila

A long-standing goal of neuroscience has been tounderstand how computations are implemented across large-scale brain networks. By correlating spontaneous activity during "resting states" [1], studies of intrinsic brain networks in humans have demonstrated a correspondence with task-related activation patterns [2], relationships to behavior [3], and alterations in processes such asaging [4] and brain disorders [5], highlighting the importance of resting-state measurements forunderstanding brain function. Here, we develop methods to measure intrinsic functional connectivity in Drosophila, a powerful model for the study ofneural computation. Recent studies usingcalcium imaging have measured neural activity at high spatial and temporal resolution in zebrafish, Drosophila larvae, and worms [6-10]. For example, calcium imaging in the zebrafish brain recently revealed correlations between the midbrain and hindbrain, demonstrating the utility of measuring intrinsic functional connections in model organisms [8]. An important component ofhuman connectivity research is the use of brain atlases to compare findings across individuals and studies [11]. An anatomical atlas of the centraladult fly brain was recently described [12]; however, combining an atlas with whole-brain calcium imaging has yet to be performed invivo in adult Drosophila. Here, we measure intrinsic functional connectivity in Drosophila by acquiring calcium signals from the central brain. We developan alignment procedure to assign functional data to atlas regions and correlate activity between regions to generate brain networks. Thiswork reveals a large-scale architecture for neural communication and provides a framework for using Drosophila to study functional brain networks.