Intracortical Connections Research Articles

Embryonically active piriform cortex neurons promote intracortical recurrent connectivity during development

Neuronal activity plays a critical role in the maturation of circuits that propagate sensory information into the brain. How widely does early activity regulate circuit maturation across the developing brain? Here, we used targeted recombination in active populations (TRAP) to perform a brain-wide survey for prenatally active neurons in mice and identified the piriform cortex as an abundantly TRAPed region. Whole-cell recordings in neonatal slices revealed preferential interconnectivity within embryonically TRAPed piriform neurons and their enhanced synaptic connectivity with other piriform neurons. Invivo Neuropixels recordings in neonates demonstrated that embryonically TRAPed piriform neurons exhibit broad functional connectivity within piriform and lead spontaneous synchronized population activity during a transient neonatal period, when recurrent connectivity is strengthening. Selectively activating or silencing these neurons in neonates enhanced or suppressed recurrent synaptic strength, respectively. Thus, embryonically TRAPed piriform neurons represent an interconnected hub-like population whose activity promotes recurrent connectivity in early development.

The Effects of Acute Stress on Evoked-cortical Connectivity through Wide-field Optical Mapping of Neural and Hemodynamic Signals.

A single exposure to stress can induce functional changes in neurons, potentially leading to acute stress disorder or post-traumatic stress disorder. In this study, we used in vivo wide-field optical mapping to simultaneously measure neural calcium signals and hemodynamic responses over the whole cortical area. We found that cortical mapping to whisker stimuli was altered under acute stress conditions. In particular, callosal projections in the anterior cortex (primary/secondary motor, somatosensory forelimb cortex) relative to barrel field (S1BF) of somatosensory cortex were weakened. On the contrary, the projections in posterior cortex relative to S1BF were mostly unchanged or were only occasionally strengthened. In addition, changes in intra-cortical connection were opposite to those in inter-cortical connection. Thus, the S1BF connections to the anterior cortex were strengthened while those to the posterior cortex were weakened. This suggests that the well-known barrel cortex projection route was enhanced. In summary, our in vivo wide-field optical mapping study indicates that a single acute stress can impact whole-brain networks, affecting both neural and hemodynamic responses.

Spatial and temporal pattern of structure-function coupling of human brain connectome with development.

Brain structural circuitry shapes a richly patterned functional synchronization, supporting for complex cognitive and behavioural abilities. However, how coupling of structural connectome (SC) and functional connectome (FC) develops and its relationships with cognitive functions and transcriptomic architecture remain unclear. We used multimodal magnetic resonance imaging data from 439 participants aged 5.7-21.9 years to predict functional connectivity by incorporating intracortical and extracortical structural connectivity, characterizing SC-FC coupling. Our findings revealed that SC-FC coupling was strongest in the visual and somatomotor networks, consistent with evolutionary expansion, myelin content, and functional principal gradient. As development progressed, SC-FC coupling exhibited heterogeneous alterations dominated by an increase in cortical regions, broadly distributed across the somatomotor, frontoparietal, dorsal attention, and default mode networks. Moreover, we discovered that SC-FC coupling significantly predicted individual variability in general intelligence, mainly influencing frontoparietal and default mode networks. Finally, our results demonstrated that the heterogeneous development of SC-FC coupling is positively associated with genes in oligodendrocyte-related pathways and negatively associated with astrocyte-related genes. This study offers insight into the maturational principles of SC-FC coupling in typical development.

Spatial and temporal pattern of structure–function coupling of human brain connectome with development

Brain structural circuitry shapes a richly patterned functional synchronization, supporting for complex cognitive and behavioural abilities. However, how coupling of structural connectome (SC) and functional connectome (FC) develops and its relationships with cognitive functions and transcriptomic architecture remain unclear. We used multimodal magnetic resonance imaging data from 439 participants aged 5.7–21.9 years to predict functional connectivity by incorporating intracortical and extracortical structural connectivity, characterizing SC–FC coupling. Our findings revealed that SC–FC coupling was strongest in the visual and somatomotor networks, consistent with evolutionary expansion, myelin content, and functional principal gradient. As development progressed, SC–FC coupling exhibited heterogeneous alterations dominated by an increase in cortical regions, broadly distributed across the somatomotor, frontoparietal, dorsal attention, and default mode networks. Moreover, we discovered that SC–FC coupling significantly predicted individual variability in general intelligence, mainly influencing frontoparietal and default mode networks. Finally, our results demonstrated that the heterogeneous development of SC–FC coupling is positively associated with genes in oligodendrocyte-related pathways and negatively associated with astrocyte-related genes. This study offers insight into the maturational principles of SC–FC coupling in typical development.

Current perspectives on neuromodulation in ALS patients: A systematic review and meta-analysis.

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, paralysis, and eventually patient mortality. In recent years, neuromodulation techniques have emerged as promising potential therapeutic approaches to slow disease progression and improve the quality of life of ALS patients. A systematic review was conducted until August 8, 2023, to evaluate the neuromodulation methods used and their potential in the treatment of ALS. The search strategy was applied in the Cochrane Central database, incorporating results from other databases such as PubMed, Embase, CTgov, CINAHL, and ICTRP. Following the exclusion of papers that did not fulfil the inclusion criteria, a total of 2090 records were found, leaving a total of 10 studies. R software was used to conduct meta-analyses based on the effect sizes between the experimental and control groups. This revealed differences in muscle stretch measures with manual muscle testing (p = 0.012) and resting motor threshold (p = 0.0457), but not with voluntary isometric contraction (p = 0.1883). The functionality of ALS was also different (p = 0.007), but not the quality of life. Although intracortical facilitation was not seen in motor cortex 1 (M1) (p = 0.1338), short-interval intracortical inhibition of M1 was significant (p = 0.0001). BDNF showed no differences that were statistically significant (p = 0.2297). Neuromodulation-based treatments are proposed as a promising therapeutic approach for ALS that can produce effects on muscle function, spasticity, and intracortical connections through electrical, magnetic, and photonic stimulation. Photobiomodulation stands out as an innovative approach that uses specific wavelengths to influence mitochondria, with the aim of improving mitochondrial function and reducing excitotoxicity. The lack of reliable placebo controls and the variation in stimulation frequency are some of the drawbacks of neuromodulation.

Spike synchrony as a measure of Gestalt structure

The function of spike synchrony is debatable: some researchers view it as a mechanism for binding perceptual features, others – as a byproduct of brain activity. We argue for an alternative computational role: synchrony can estimate the prior probability of incoming stimuli. In V1, this can be achieved by comparing input with previously acquired visual experience, which is encoded in plastic horizontal intracortical connections. V1 connectivity structure can encode the acquired visual experience in the form of its aggregate statistics. Since the aggregate statistics of natural images tend to follow the Gestalt principles, we can assume that V1 is more often exposed to Gestalt-like stimuli, and this is manifested in its connectivity structure. At the same time, the connectivity structure has an impact on spike synchrony in V1. We used a spiking model with V1-like connectivity to demonstrate that spike synchrony reflects the Gestalt structure of the stimulus. We conducted simulation experiments with three Gestalt laws: proximity, similarity, and continuity, and found substantial differences in firing synchrony for stimuli with varying degrees of Gestalt-likeness. This allows us to conclude that spike synchrony indeed reflects the Gestalt structure of the stimulus, which can be interpreted as a mechanism for prior probability estimation.

Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phase

BackgroundAmyotrophic lateral sclerosis (ALS) is a progressive disease for which no curative treatment is currently available. ObjectiveThis study aimed to investigate whether cortico-spinal transcranial direct current stimulation (tDCS) could mitigate symptoms in ALS patients via a randomized, double-blind, sham-controlled trial, followed by an open-label phase. MethodsThirty-one participants were randomized into two groups for the initial controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS), while Group 2 received cortico-spinal stimulation (real tDCS) for five days/week for two weeks (T1), with an 8-week (T2) follow-up (randomized, double-blind, sham-controlled phase). At the 24-week follow-up (T3), all participants (Groups 1 and 2) received a second treatment of anodal bilateral motor cortex and cathodal spinal stimulation (real tDCS) for five days/week for two weeks (T4). Follow-up evaluations were performed at 32-weeks (T5) and 48-weeks (T6) (open-label phase). At each time point, clinical assessment, blood sampling, and intracortical connectivity measures using transcranial magnetic stimulation (TMS) were evaluated. Additionally, we evaluated survival rates. ResultsCompared to sham stimulation, cortico-spinal tDCS significantly improved global strength, caregiver burden, and quality of life scores, which correlated with the restoration of intracortical connectivity measures. Serum neurofilament light levels decreased among patients who underwent real tDCS but not in those receiving sham tDCS. The number of completed 2-week tDCS treatments significantly influenced patient survival. ConclusionsCortico-spinal tDCS may represent a promising therapeutic and rehabilitative approach for patients with ALS. Further larger-scale studies are necessary to evaluate whether tDCS could potentially impact patient survival. Clinical trial registrationNCT04293484.

Learning-dependent structural plasticity of intracortical and sensory connections to functional domains of the olfactory tubercle.

The olfactory tubercle (OT), which is a component of the olfactory cortex and ventral striatum, has functional domains that play a role in odor-guided motivated behaviors. Learning odor-guided attractive and aversive behavior activates the anteromedial (am) and lateral (l) domains of the OT, respectively. However, the mechanism driving learning-dependent activation of specific OT domains remains unknown. We hypothesized that the neuronal connectivity of OT domains is plastically altered through olfactory experience. To examine the plastic potential of synaptic connections to OT domains, we optogenetically stimulated intracortical inputs from the piriform cortex or sensory inputs from the olfactory bulb to the OT in mice in association with a food reward for attractive learning and electrical foot shock for aversive learning. For both intracortical and sensory connections, axon boutons that terminated in the OT domains were larger in the amOT than in the lOT for mice exhibiting attractive learning and larger in the lOT than in the amOT for mice exhibiting aversive learning. These results indicate that both intracortical and sensory connections to the OT domains have learning-dependent plastic potential, suggesting that this plasticity underlies learning-dependent activation of specific OT domains and the acquisition of appropriate motivated behaviors.

Intracortical functional connectivity dynamics induced by reflex seizures

Functional connectivity analysis is gaining more interest due to its promising clinical applications. To study network mechanisms underlying seizure termination and postictal depression, we explore dynamics of interhemispheric functional connectivity near the offset of focal and bilateral seizures in the experimental model of reflex audiogenic epilepsy. In the model, seizures and spreading depression are induced by sound stimulation of genetically predisposed rodents. We characterize temporal evolution of seizure-associated coupling dynamics in the frontoparietal cortex during late ictal, immediate postictal and interictal resting states, using two measures applied to local field potentials recorded in awake epileptic rats. Signals were analyzed with mean phase coherence index in delta (1–4 Hz), theta (4–10 Hz) beta (10–25 Hz) and gamma (25–50 Hz) frequency bands and mutual information function. The study shows that reflex seizures elicit highly dynamic changes in interhemispheric functional coupling with seizure-, region- and frequency-specific patterns of increased and decreased connectivity during late ictal and immediate postictal periods. Also, secondary generalization of recurrent seizures (kindling) is associated with pronounced alterations in resting-state functional connectivity – an early wideband decrease and a subsequent beta-gamma increase. The findings show that intracortical functional connectivity is dynamically modified in response to seizures on short and long timescales, suggesting the existence of activity-dependent plastic network alterations that may promote or prevent seizure propagation within the cortex and underlie postictal behavioral impairments.

A comprehensive atlas of perineuronal net distribution and colocalization with parvalbumin in the adult mouse brain

Perineuronal nets (PNNs) surround specific neurons in the brain and are involved in various forms of plasticity and clinical conditions. However, our understanding of the PNN role in these phenomena is limited by the lack of highly quantitative maps of PNN distribution and association with specific cell types. Here, we present a comprehensive atlas of Wisteria floribunda agglutinin (WFA)-positive PNNs and colocalization with parvalbumin (PV) cells for over 600 regions of the adult mouse brain. Data analysis shows that PV expression is a good predictor of PNN aggregation. In the cortex, PNNs are dramatically enriched in layer 4 of all primary sensory areas in correlation with thalamocortical input density, and their distribution mirrors intracortical connectivity patterns. Gene expression analysis identifies many PNN-correlated genes. Strikingly, PNN-anticorrelated transcripts are enriched in synaptic plasticity genes, generalizing PNNs' role as circuit stability factors.

Machine Learning-assisted Quantitative Mapping of Intracortical Axonal Plasticity Following a Focal Cortical Stroke in Rodents.

Stroke destroys neurons and their connections leading to focal neurological deficits. Although limited, many patients exhibit a certain degree of spontaneous functional recovery. Structural remodeling of the intracortical axonal connections is implicated in the reorganization of cortical motor representation maps, which is considered to be an underlying mechanism of the improvement in motor function. Therefore, an accurate assessment of intracortical axonal plasticity would be necessary to develop strategies to facilitate functional recovery following a stroke. The present study developed a machine learning-assisted image analysis tool based on multi-voxel pattern analysis in fMRI imaging. Intracortical axons originating from the rostral forelimb area (RFA) were anterogradely traced using biotinylated dextran amine (BDA) following a photothrombotic stroke in the mouse motor cortex. BDA-traced axons were visualized in tangentially sectioned cortical tissues, digitally marked, and converted to pixelated axon density maps. Application of the machine learning algorithm enabled sensitive comparison of the quantitative differences and the precise spatial mapping of the post-stroke axonal reorganization even in the regions with dense axonal projections. Using this method, we observed a substantial extent of the axonal sprouting from the RFA to the premotor cortex and the peri-infarct region caudal to the RFA. Therefore, the machine learningassisted quantitative axonal mapping developed in this study can be utilized to discover intracortical axonal plasticity that may mediate functional restoration following stroke.

Cortical recurrence supports resilience to sensory variance in the primary visual cortex

Our daily endeavors occur in a complex visual environment, whose intrinsic variability challenges the way we integrate information to make decisions. By processing myriads of parallel sensory inputs, our brain is theoretically able to compute the variance of its environment, a cue known to guide our behavior. Yet, the neurobiological and computational basis of such variance computations are still poorly understood. Here, we quantify the dynamics of sensory variance modulations of cat primary visual cortex neurons. We report two archetypal neuronal responses, one of which is resilient to changes in variance and co-encodes the sensory feature and its variance, improving the population encoding of orientation. The existence of these variance-specific responses can be accounted for by a model of intracortical recurrent connectivity. We thus propose that local recurrent circuits process uncertainty as a generic computation, advancing our understanding of how the brain handles naturalistic inputs.

Cerebral cortical regions always connect with each other via the shortest paths.

In human society, the choice of transportation mode between two cities is largely influenced by the distance between the regions. Similarly, when neurons communicate with each other within the cerebral cortex, do they establish their connections based on their physical distance? In this study, we employed a data-driven approach to explore the relationships between fiber length and corresponding geodesic distance between the fiber's two endpoints on brain surface. Diffusion-MRI-derived fiber streamlines were used to represent extra-cortical axonal connections between neurons or cortical regions, while geodesic paths between cortical points were employed to simulate intra-cortical connections. The results demonstrated that the geodesic distance between two cortical regions connected by a fiber streamline was greater than the fiber length most of the time, indicating that cortical regions tend to choose the shortest path for connection; whether it be an intra-cortical or extra-cortical route, especially when intra-cortical routes within cortical regions are longer than potential extrinsic fiber routes, there is an increased probability to establish fiber routes to connect the both regions. These findings were validated in a group of human brains and may provide insights into the underlying mechanisms of neuronal growth, connection, and wiring.

Investigation of brain mechanisms underlying upper limb function in bilateral cerebral palsy using EEG

ObjectiveFew studies focus on upper limbs in bilateral cerebral palsy (CP) despite potential bimanual deficits. Electroencephalography (EEG) was utilized to investigate brain mechanisms underlying upper limb tasks in bilateral CP and typical development (TD) and relationships to function. Methods26 (14 CP; 12 TD) completed the Box and Blocks Test and transport task with paper, sponge or mixed blocks, while recording EEG and motion data. ResultsGroup effects for path time, path length and Box and Blocks Test revealed bimanual deficits. Four sensorimotor-related EEG clusters were identified. Group effects were found in premotor and dominant motor clusters with greater beta event-related desynchronization (ERD) in CP. Hand and hand by group effects were found in the dominant motor cluster, showing greater ERD with the more affected hand in CP. Condition effects were prominent in the posterior parietal cluster with higher ERD reflecting greater difficulty in force modulation. ConclusionsHigher brain activation associated with greater bimanual deficits is similar to our lower limb findings but contrasts studies in TD or unilateral CP linking higher ERD to greater proficiency. SignificanceBilateral CP shows overreliance on the dominant hemisphere with the less functional hand and higher brain activity presumably related to excessive intracortical connectivity.

Normal connectivity of thalamorecipient networks in barrel equivalents of the reeler cortex.

The reeler mouse mutant has long served as a primary model to study the development of cortical layers, which is governed by the extracellular glycoprotein reelin secreted by Cajal-Retzius cells. Because layers organize local and long-range circuits for sensory processing, we investigated whether intracortical connectivity is compromised by reelin deficiency in this model. We generated a transgenic reeler mutant (we used both sexes), in which layer 4-fated spiny stellate neurons are labeled with tdTomato and applied slice electrophysiology and immunohistochemistry with synaptotagmin-2 to study the circuitry between the major thalamorecipient cell types, namely excitatory spiny stellate and inhibitory fast-spiking (putative basket) cells. In the reeler mouse, spiny stellate cells are clustered into barrel equivalents. In these clusters, we found that intrinsic physiology, connectivity, and morphology of spiny stellate and fast-spiking, putative basket cells does not significantly differ between reeler and controls. Properties of unitary connections, including connection probability, were very comparable in excitatory cell pairs and spiny stellate/fast-spiking cell pairs, suggesting an intact excitation-inhibition balance at the first stage of cortical sensory information processing. Together with previous findings, this suggests that thalamorecipient circuitry in the barrel cortex develops and functions independently of proper cortical lamination and postnatal reelin signaling.

Cortical activation and functional connectivity during locomotion tasks in Parkinson's disease with freezing of gait.

Freezing of gait (FoG) is a severely disabling symptom in Parkinson's disease (PD). The cortical mechanisms underlying FoG during locomotion tasks have rarely been investigated. We aimed to compare the cerebral haemodynamic response during FoG-prone locomotion tasks in patients with PD and FoG (PD-FoG), patients with PD but without FoG (PD-nFoG), and healthy controls (HCs). Twelve PD-FoG patients, 10 PD-nFoG patients, and 12 HCs were included in the study. Locomotion tasks included normal stepping, normal turning and fast turning ranked as three difficulty levels based on kinematic requirements and probability of provoking FoG. During each task, we used functional near-infrared spectroscopy to capture concentration changes of oxygenated haemoglobin (ΔHBO2) and deoxygenated haemoglobin (ΔHHB) that reflected cortical activation, and recorded task performance time. The cortical regions of interest (ROIs) were prefrontal cortex (PFC), supplementary motor area (SMA), premotor cortex (PMC), and sensorimotor cortex (SMC). Intra-cortical functional connectivity during each task was estimated based on correlation of ΔHBO2 between ROIs. Two-way multivariate ANOVA with task performance time as a covariate was conducted to investigate task and group effects on cerebral haemodynamic responses of ROIs. Z statistics of z-scored connectivity between ROIs were used to determine task and group effects on functional connectivity. PD-FoG patients spent a nearly significant longer time completing locomotion tasks than PD-nFoG patients. Compared with PD-nFoG patients, they showed weaker activation (less ΔHBO2) in the PFC and PMC. Compared with HCs, they had comparable ΔHBO2 in all ROIs but more negative ΔHHB in the SMC, whereas PD-nFoG showed SMA and PMC hyperactivity but more negative ΔHHB in the SMC. With increased task difficulty, ΔHBO2 increased in each ROI except in the PFC. Regarding functional connectivity during normal stepping, PD-FoG patients showed positive and strong PFC-PMC connectivity, in contrast to the negative PFC-PMC connectivity observed in HCs. They also had greater PFC-SMC connectivity than the other groups. However, they exhibited decreased SMA-SMC connectivity when task difficulty increased and had lower SMA-PMC connectivity than HCs during fast turning. Insufficient compensatory cortical activation and depletion of functional connectivity during complex locomotion in PD-FoG patients could be potential mechanisms underlying FoG. Chinese clinical trial registry (URL: http://www.chictr.org.cn, registration number: ChiCTR2100042813).

Pairing Transcranial Magnetic Stimulation and Loud Sounds Produces Plastic Changes in Motor Output.

Most current methods for neuromodulation target the cortex. Approaches for inducing plasticity in subcortical motor pathways, such as the reticulospinal tract, could help to boost recovery after damage (e.g., stroke). In this study, we paired loud acoustic stimulation (LAS) with transcranial magnetic stimulation (TMS) over the motor cortex in male and female healthy humans. LAS activates the reticular formation; TMS activates descending systems, including corticoreticular fibers. Two hundred paired stimuli were used, with 50 ms interstimulus interval at which LAS suppresses TMS responses. Before and after stimulus pairing, responses in the contralateral biceps muscle to TMS alone were measured. Ten, 20, and 30 min after stimulus pairing ended, TMS responses were enhanced, indicating the induction of LTP. No long-term changes were seen in control experiments which used 200 unpaired TMS or LAS, indicating the importance of associative stimulation. Following paired stimulation, no changes were seen in responses to direct corticospinal stimulation at the level of the medulla, or in the extent of reaction time shortening by a loud sound (StartReact effect), suggesting that plasticity did not occur in corticospinal or reticulospinal synapses. Direct measurements in female monkeys undergoing a similar paired protocol revealed no enhancement of corticospinal volleys after paired stimulation, suggesting no changes occurred in intracortical connections. The most likely substrate for the plastic changes, consistent with all our measurements, is an increase in the efficacy of corticoreticular connections. This new protocol may find utility, as it seems to target different motor circuits compared with other available paradigms.SIGNIFICANCE STATEMENT Induction of plasticity by neurostimulation protocols may be promising to enhance functional recovery after damage such as following stroke, but current protocols mainly target cortical circuits. In this study, we developed a novel paradigm which may generate long-term changes in connections between cortex and brainstem. This could provide an additional tool to modulate and improve recovery.

Prevalence of hypertension and correlation with mental health in women with burning mouth syndrome: A case-control study.

The relationship between hypertension (HTN) and chronic pain is still a matter of debate, and its prevalence in patients with burning mouth syndrome (BMS) has never been evaluated. This study aimed to assess the prevalence of HTN in women with BMS and to evaluate its relationship with potential predictors such as risk factors for cardiovascular diseases, pain, and mental health status analyzing differences with healthy women. In total, 250 women with BMS (WBMS) were prospectively recruited and compared with an equal number of healthy women (HW) matched for age. Education, body mass index, smoke and alcohol consumption, intensity and quality of pain, and psychological profile were further investigated to identify the potential predictors of HTN. Specifically, pain assessment [the Numeric Rating Scale (NRS) and Short-Form McGill Pain Questionnaire (SF-MPQ)] and psychological assessment [Hamilton Rating Scale for Depression and Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS)] was carried out for the participants. HTN was found in 128 (51.2%) WBMS and 76 (30.4%) HW (p < 0.001**). The scores of the NRS, SF-MPQ, HAM-D, HAM-A, and PSQI were statistically significantly higher in the WBMS than in the HW (p < 0.001**). A strongly linear correlation between HTN and employment status, systemic diseases, and education level (p < 0.001**) was found in WBMS, while a strong correlation between HTN and employment status, hypercholesterolemia, systemic diseases, and drug consumption was found in HW (p < 0.001**). No statistically significant correlation was found between HTN and pain, anxiety, depression, and sleep disturbances. These results suggest that WBMS showed a higher prevalence of HTN compared with controls. Unemployed WBMS with lower education and other systemic comorbidities are at an increased risk of developing HTN. HTN is associated with alteration in the vascular structure and function of the brain, and these processes accelerate brain aging, which contributes to a reduction in intracortical connectivity, thus affecting the modulatory system of control of pain in patients with BMS, independently of their mental health assessment. Predictors that may underlie this association remain unclear, taking into account the differences found in HW, and should be further elucidated.

Paired associative stimulation applied to the cortex can increase resting-state functional connectivity: A proof of principle study

IntroductionThere is emerging evidence that high Beta coherence (hBc) between prefrontal and motor corticies, measured with resting-state electroencephalography (rs-EEG), can be an accurate predictor of motor skill learning and stroke recovery. However, it remains unknown whether and how intracortical connectivity may be influenced using neuromodulation. Therefore, a cortico–cortico PAS (ccPAS) paradigm may be used to increase resting-state intracortical connectivity (rs-IC) within a targeted neural circuit. PurposeOur purpose is to demonstrate proof of principle that ccPAS can be used to increase rs-IC between a prefrontal and motor cortical region. MethodsEleven non-disabled adults were recruited (mean age 26.4, sd 5.6, 5 female). Each participant underwent a double baseline measurement, followed by a real and control ccPAS condition, counter-balanced for order. Control and ccPAS conditions were performed over electrodes of the right prefrontal and motor cortex. Both ccPAS conditions were identical apart from the inter-stimulus interval (i.e ISI 5 ms: real ccPAS and 500 ms: control ccPAS). Whole brain rs-EEG of high Beta coherence (hBc) was acquired before and after each ccPAS condition and then analyzed for changes in rs-IC along the targeted circuit. ResultsCompared to ccPAS500 and baseline, ccPAS5 induced a significant increase in rs-IC, measured as coherence between electrodes over right prefrontal and motor cortex, (p <.05). ConclusionThese findings demonstrate proof of principle that ccPAS with an STDP derived ISI, can effectively increase hBc along a targeted circuit.

A Computational Model of Direction Selectivity in Macaque V1 Cortex Based on Dynamic Differences between On and Off Pathways.

This paper is about neural mechanisms of direction selectivity (DS) in macaque primary visual cortex, V1. We present data (on male macaque) showing strong DS in a majority of simple cells in V1 layer 4Cα, the cortical layer that receives direct afferent input from the magnocellular division of the lateral geniculate nucleus (LGN). Magnocellular LGN cells are not direction-selective. To understand the mechanisms of DS, we built a large-scale, recurrent model of spiking neurons called DSV1. Like its predecessors, DSV1 reproduces many visual response properties of V1 cells including orientation selectivity. Two important new features of DSV1 are (1) DS is initiated by small, consistent dynamic differences in the visual responses of OFF and ON Magnocellular LGN cells, and (2) DS in the responses of most model simple cells is increased over those of their feedforward inputs; this increase is achieved through dynamic interaction of feedforward and intracortical synaptic currents without the use of intracortical direction-specific connections. The DSV1 model emulates experimental data in the following ways: (1) most 4Cα Simple cells were highly direction-selective but 4Cα Complex cells were not; (2) the preferred directions of the model's direction-selective Simple cells were invariant with spatial and temporal frequency (TF); (3) the distribution of the preferred/opposite ratio across the model's population of cells was very close to that found in experiments. The strong quantitative agreement between DS in data and in model simulations suggests that the neural mechanisms of DS in DSV1 may be similar to those in the real visual cortex.SIGNIFICANCE STATEMENT Motion perception is a vital part of our visual experience of the world. In monkeys, whose vision resembles that of humans, the neural computation of the direction of a moving target starts in the primary visual cortex, V1, in layer 4Cα that receives input from the eye through the lateral geniculate nucleus (LGN). How direction selectivity (DS) is generated in layer 4Cα is an outstanding unsolved problem in theoretical neuroscience. In this paper, we offer a solution based on plausible biological mechanisms. We present a new large-scale circuit model in which DS originates from slightly different LGN ON/OFF response time-courses and is enhanced in cortex without the need for direction-specific intracortical connections. The model's DS is in quantitative agreement with experiments.