Reorganization Of Neural Networks Research Articles

Functional connectivity across the lifespan: a cross-sectional analysis of changes.

In the era of functional brain networks, our understanding of how they evolve across life in a healthy population remains limited. Here, we investigate functional connectivity across the human lifespan using magnetoencephalography in a cohort of 792 healthy individuals, categorized into young (13 to 30 yr), middle (31 to 54 yr), and late adulthood (55 to 80 yr). Employing corrected imaginary phase-locking value, we map the evolving landscapes of connectivity within delta, theta, alpha, beta, and gamma classical frequency bands among brain areas. Our findings reveal significant shifts in functional connectivity patterns across all frequency bands, with certain networks exhibiting increased connectivity and others decreased, dependent on the frequency band and specific age groups, showcasing the dynamic reorganization of neural networks as age increases. This detailed exploration provides, to our knowledge, the first all-encompassing view of how electrophysiological functional connectivity evolves at different life stages, offering new insights into the brain's adaptability and the intricate interplay of cognitive aging and network connectivity. This work not only contributes to the body of knowledge on cognitive aging and neurological health but also emphasizes the need for further research to develop targeted interventions for maintaining cognitive function in the aging population.

Physical reserve and its underpinning functional neural networks moderate the relationship between white matter hyperintensity and postural balance in older adults with subcortical ischemic vascular cognitive impairment

White matter hyperintensities (WMH) are markers of subcortical ischemic vascular cognitive impairment (SIVCI) associated with impaired postural balance. Physical reserve (PR) is a recently established construct that reflects one’s capacity to maintain physical function despite brain pathology. This cross-sectional study aims to map functional networks associated with PR, and examining the relationship between PR, WMH, and postural balance. PR was defined in 22 community-dwelling older adults with SIVCI. Functional networks of PR were computed using general linear model. Subsequent analyses examined whether PR and relevant networks moderated the relationship between WMH and postural balance under two conditions—eyes open while standing on foam (EOF) or on floor (EONF). We found that PR and the relevant networks—frontoparietal network (FPN) and default mode network (DMN)—significantly moderated the association between WMH and postural balance. For individuals with high PR, postural balance remained stable regardless of the extent of WMH load; whereas for those with low PR, postural balance worsened as WMH load increased. These results suggest the attenuated effects of WMH on postural stability due to PR may be underpinned by functional neural network reorganization in the FPN and DMN as a part of compensatory processes.

Developmental and lesion models of schizophrenia in rodents

Animal modeling of schizophrenia is essential for understanding the neurobiological basis of the disease, as well as for the development of new antipsychotic drugs with improved therapeutic efficacy and safety profile. The review aims at summarizing the methodology and practical aspects of schizophrenia modeling based on dysontogenetic disturbances of the central nervous system in rats and mice. Environmental factors or the destruction of brain structures during prenatal or postnatal periods of development cause reorganization of neural networks, leading to irreversible changes in the function of the central nervous system, which usually appear after puberty. Developmental and lesion models of schizophrenia are widely regarded as the most appropriate due to their ability to reproduce characteristic behavioral and cognitive impairments with a delayed onset of symptoms, which is consistent with the clinical presentation of schizophrenia in humans.

Adult Neurogenesis, Learning and Memory.

Neural plasticity can be defined as the ability of neural circuits to be shaped by external and internal factors. It provides the brain with a capacity for functional and morphological remodelling, with many lines of evidence indicating that these changes are vital for learning and memory formation. The basis of this brain plasticity resides in activity- and experience-driven modifications of synaptic strength, including synaptic formation, elimination or weakening, as well as of modulation of neuronal population, which drive the structural reorganization of neural networks. Recent evidence indicates that brain-resident glial cells actively participate in these processes, suggesting that mechanisms underlying plasticity in the brain are multifaceted. Establishing the 'tripartite' synapse, the role of astrocytes in modulating synaptic transmission in response to neuronal activity was recognized first. Further redefinition of the synapse as 'quad-partite' followed to acknowledge the contribution of microglia which were revealed to affect numerous brain functions via dynamic interactions with synapses, acting as 'synaptic sensors' that respond to neuronal activity and neurotransmitter release, as well as crosstalk with astrocytes. Early studies identified microglial ability to dynamically survey their local brain environment and established their integral role in the active interfacing of environmental stimuli (both internal and external), with brain plasticity and remodelling. Following the introduction to neurogenesis, this chapter details the role that microglia play in regulating neurogenesis in adulthood, specifically as it relates to learning and memory, as well as factors involved in modulation of microglia. Further, a microglial perspective is introduced for the context of environmental enrichment impact on neurogenesis, learning and memory across states of stress, ageing, disease and injury.

Temporal Ordering and Auditory Resolution in Individuals with Sensorineural Hearing Loss.

Introduction Peripheral hearing loss, besides causing inadequate auditory input, can lead to distortions in the tonotopic auditory map and reorganization of neural networks. Therefore, the processing of temporal aspects of a sound stimulus and, consequently, the effectiveness of human communication can be negatively impacted. Objective To test the temporal ordering and auditory resolution of people with mild and moderate sensorineural hearing loss and to compare them with the those of people with normal hearing. Methods A total of 19 right-handed individuals aged 16 to 59 years with mild to moderate postlingually acquired symmetric bilateral sensorineural hearing loss participated in the study. They were submitted to frequency and duration pattern tests and a random gap detection test. Results The mean correct response rate in the frequency pattern test was of 66.3%, and, in the duration pattern test, 71.7%. The mean threshold in the random gap detection test was of 14.1 ms. A comparison with the criteria established for normal subjects without peripheral hearing loss revealed that more than half the subjects had abnormal results in the temporal ordering test, while a smaller fraction had reduced temporal resolution. Conclusions The performance of the subjects with acquired sensorineural hearing loss was poorer than that of the participants without peripheral hearing loss. Their results on the temporal ordering test were also poorer than in the temporal resolution test, demonstrating the importance of analyzing both these auditory skills in people with peripheral hearing loss.

Dendritic reorganization in the hippocampus, anterior temporal lobe, and frontal neocortex of lithium-pilocarpine induced Status Epilepticus (SE)

Status Epilepticus (SE) is a distributed network disorder, which involves the hippocampus and extra-hippocampal structures. Epileptogenesis in SE is tightly associated with neurogenesis, plastic changes and neural network reorganization facilitating hyper-excitability. On the other hand, dendritic spines are known to be the excitatory synapse in the brain. Therefore, dendritic spine dynamics could play an intricate role in these network alterations. However, the exact reason behind these structural changes in SE are elusive. In the present study, we have investigated the aforementioned hypothesis in the lithium-pilocarpine treated rat model of SE. We have examined cytoarchitectural and morphological changes using hematoxylin-eosin and Golgi-Cox staining in three different brain regions viz. CA1 pyramidal layer of the dorsal hippocampus, layer V pyramidal neurons of anterior temporal lobe (ATL), and frontal neocortex of the same animals. We observed macrostructural and layer-wise alteration of the pyramidal layer mainly in the hippocampus and ATL of SE rats, which is associated with sclerosis in the hippocampus. Sholl analysis exhibited partial dendritic plasticity in apical and basal dendrites of pyramidal cells as compared to the saline-treated weight-/age-matched control group. These findings indicate that region-specific alterations in dendritogenesis may contribute to the development of independent epileptogenic networks in the hippocampus, ATL, and frontal neocortex of SE rats.

Neuropharmacological insight into preventive intervention in posttraumatic epilepsy based on regulating glutamate homeostasis.

Posttraumatic epilepsy (PTE) is one of the most critical complications of traumatic brain injury (TBI), significantly increasing TBI patients' neuropsychiatric symptoms and mortality. The abnormal accumulation of glutamate caused by TBI and its secondary excitotoxicity are essential reasons for neural network reorganization and functional neural plasticity changes, contributing to the occurrence and development of PTE. Restoring glutamate balance in the early stage of TBI is expected to play a neuroprotective role and reduce the risk of PTE. To provide a neuropharmacological insight for drug development to prevent PTE based on regulating glutamate homeostasis. We discussed how TBI affects glutamate homeostasis and its relationship with PTE. Furthermore, we also summarized the research progress of molecular pathways for regulating glutamate homeostasis after TBI and pharmacological studies aim to prevent PTE by restoring glutamate balance. TBI can lead to the accumulation of glutamate in the brain, which increases the risk of PTE. Targeting the molecular pathways affecting glutamate homeostasis helps restore normal glutamate levels and is neuroprotective. Taking glutamate homeostasis regulation as a means for new drug development can avoid the side effects caused by direct inhibition of glutamate receptors, expecting to alleviate the diseases related to abnormal glutamate levels in the brain, such as PTE, Parkinson's disease, depression, and cognitive impairment. It is a promising strategy to regulate glutamate homeostasis through pharmacological methods after TBI, thereby decreasing nerve injury and preventing PTE.

First Anatomy Annual Congress in Rwanda - October 13 – 15, 2022

Theme: Promoting anatomy to enlighten safe and effective clinical practice
 It is with a greater honor that I welcome you to this Anatomy Annual Congress, the first of its kind in Rwanda. Anatomy is an essential fundamental science in medical education and medical practice and it deserve to be vibrant scientifically. The S-CAR have been founded with the aim of growing the anatomy sciences and this congress is a wonderful outcome of this common commitment. The congress has 4 events that include: a pre-conference workshop on the peripheral nervous system, the S-CAR annual congress, the scientific conference and the world anatomy day (WAD).
 Reinforcing the importance of the PNS, Dr. David HAKIZIMANA, a Senior Consultant Neurosurgeon wrote this, I quote: “Peripheral nerve surgery is used to improve function and minimize pain and disability in people with peripheral nerve disorders, such as acute nerve injuries, entrapment neuropathies, and nerve sheath tumors. It involves rerouting healthy nerves to take over the function of the nerves affected by injury, disease, or condition. Surgical treatment for peripheral nerve injuries involves a team which may include: neurosurgeons, plastic surgeons, orthopedic surgeons. Globally the status of peripheral nerve surgery practice within the global landscape of surgery has long been in the shadow of the more prominent areas. The reasons are many, one of them plausibly being the conceptual frame of the very word “peripheral”, which evoke the notions of marginality and lesser importance especially for neurosurgeons. Some of the related common misconceptions are that neurological deficit in peripheral nerve injury is permanent and irreversible, that peripheral nerves do not have the ability to regenerate, that the results of surgical treatment are insignificant. In Rwanda and Africa in general peripheral nerve surgery in almost non-existing or at embryonic phase at best. Although peripheral nerve surgery is not a life-saving surgery, it has been proved to be a life-changing surgery, with a major impact on the quality of patient’s life, as it improves the patient’s ability to perform every day and professional activities and thus affects his/her physical and psychological well-being. Moreover, since most patients with peripheral nerve injuries and brachial plexus injuries belong to the working-age population, peripheral nerve surgery also has substantial socioeconomic implications. Contrary to the previously held view, the peripheral nerve system has been shown to have a huge regeneration potential, with significant results enhanced by different modalities of stimulation, whereby recent research on brain plasticity indicates that experience-dependent reorganization of neural networks plays an important role in functional recovery. For all these reasons, systematic research, education, and practice in peripheral nerve surgery is definitely worth the effort. The aim of this course will be to train residents and interested surgeons from Rwanda in peripheral nerve surgery skills”. The rich scientific conference program with 37 presentations subdivided in sessions on medical education, congenital defects, anatomy and anatomical variations, neurosciences, free presentations, closure lecture, scientific forum for PhD and MSC candidates, cadavers for education and research will give to you an excellent experience. On behalf of S-CAR, I am grateful to the sponsors (MoH, UR, UGHE, AUCA-ASOME, Operation Smile, CHUK and MMI).

Dysfunction of the Hippocampal-Lateral Septal Circuit Impairs Risk Assessment in Epileptic Mice.

Temporal lobe epilepsy, a chronic disease of the brain characterized by degeneration of the hippocampus, has impaired risk assessment. Risk assessment is vital for survival in complex environments with potential threats. However, the underlying mechanisms remain largely unknown. The intricate balance of gene regulation and expression across different brain regions is related to the structure and function of specific neuron subtypes. In particular, excitation/inhibition imbalance caused by hyperexcitability of glutamatergic neurons and/or dysfunction of GABAergic neurons, have been implicated in epilepsy. First, we estimated the risk assessment (RA) by evaluating the behavior of mice in the center of the elevated plus maze, and found that the kainic acid-induced temporal lobe epilepsy mice were specifically impaired their RA. This experiment evaluated approach-RA, with a forthcoming approach to the open arm, and avoid-RA, with forthcoming avoidance of the open arm. Next, results from free-moving electrophysiological recordings showed that in the hippocampus, ∼7% of putative glutamatergic neurons and ∼15% of putative GABAergic neurons were preferentially responsive to either approach-risk assessment or avoid-risk assessment, respectively. In addition, ∼12% and ∼8% of dorsal lateral septum GABAergic neurons were preferentially responsive to approach-risk assessment and avoid-risk assessment, respectively. Notably, during the impaired approach-risk assessment, the favorably activated dorsal dentate gyrus and CA3 glutamatergic neurons increased (∼9%) and dorsal dentate gyrus and CA3 GABAergic neurons decreased (∼7%) in the temporal lobe epilepsy mice. Then, we used RNA sequencing and immunohistochemical staining to investigate which subtype of GABAergic neuron loss may contribute to excitation/inhibition imbalance. The results show that temporal lobe epilepsy mice exhibit significant neuronal loss and reorganization of neural networks. In particular, the dorsal dentate gyrus and CA3 somatostatin-positive neurons and dorsal lateral septum cholecystokinin-positive neurons are selectively vulnerable to damage after temporal lobe epilepsy. Optogenetic activation of the hippocampal glutamatergic neurons or chemogenetic inhibition of the hippocampal somatostatin neurons directly disrupts RA, suggesting that an excitation/inhibition imbalance in the dHPC dorsal lateral septum circuit results in the impairment of RA behavior. Taken together, this study provides insight into epilepsy and its comorbidity at different levels, including molecular, cell, neural circuit, and behavior, which are expected to decrease injury and premature mortality in patients with epilepsy.

Effects of corticospinal tract integrity on upper limb motor function recovery in stroke patients treated with repetitive transcranial magnetic stimulation.

The bimodal balance-recovery model predicts that corticospinal tract (CST) integrity in the affected hemisphere influences the partterns of brain recovery after stroke. Repetitive transcranial magnetic stimulation (rTMS) has been used to promote functional recovery of stroke patients by modulating motor cortical excitability and inducing reorganization of neural networks. This study aimed to explore how to optimize the efficiency of repetitive transcranial magnetic stimulation to promote upper limb functional recovery after stroke according to bimodal balance-recovery model. 60 patients who met the inclusion criteria were enrolled to high CST integrity group (n = 30) or low CST integrity group (n = 30), and further assigned randomly to receive high-frequency rTMS (HF-rTMS), low-frequency rTMS (LF-rTMS) or sham rTMS in addition to routine rehabilitation, with 10 patients in each group. Outcome measures included Fugl-Meyer scale for upper extremity (FMA-UE), Wolf Motor Function (WMFT) scale and Modified Barthel Index (MBI) scale which were evaluated at baseline and after 21 days of treatment. For patients with high CST integrity, the LF group achieved higher FMA-UE, WMFT and MBI scores improvements after treatment when compared to the HF group and sham group. For patients with low CST integrity, after 21 days treatment, only the HF group showed significant improvements in FMA-UE and WMFT scores. For MBI assessment, the HF group revealed significantly better improvements than the LF group and sham group. For stroke patients with high CST integrity, low-frequency rTMS is superior to high-frequency rTMS in promoting upper limb motor function recovery. However, only high-frequency rTMS can improve upper limb motor function of stroke patients with low CST integrity.

Interrelation of cognitive functions and neural networks with blood flow velocity through the internal jugular vein in patients with chronic cerebral ischemia

Understanding age-related and functional changes in cerebral venous circulation is critical for the development of new preventive, diagnostic and therapeutic approaches to maintaining brain health in the elderly. Chronic cerebral ischemia is one of the widespread socially significant vascular diseases caused by a decrease in the level of blood circulation. To assess the role of venous outflow through the internal jugular veins in cognitive decline and neural networks in patients with chronic cerebral ischemia, 30 men and 40 women (average age 66.5 years), cognitive functions and organization of neural networks were studied at high and low levels of cerebral venous blood flow through the internal jugular veins. To assess the venous outflow, the systolic blood flow rate was measured by the internal jugular veins. A higher rate of venous outflow through internal jugular veins is associated with a more successful performance of the Luria test for verbal memory. A higher or lower blood flow rate affects the formation of neural networks of the brain. At a higher blood flow rate, the predominant areas of the resting neural networks (the passive mode network of the brain and the salient network) are localized in the frontal regions, at a low blood flow rate, the predominant neural network (frontal-parietal) is located in the left hemisphere. The state of faster and slower venous outflow forms neural networks using different neural formations that affect verbal memory. Reorganization of neural networks in this case, apparently, is the central mechanism responsible for cognitive decline in chronic cerebral ischemia (2 figs, 1 table, bibliography: 10 refs)

Transcutaneous Spinal Neuromodulation Reorganizes Neural Networks in Patients with Cerebral Palsy

Spinal neuromodulation and activity-based rehabilitation triggers neural network reorganization and enhances sensory-motor performances involving the lower limbs, the trunk, and the upper limbs. This study reports the acute effects of Transcutaneous Electrical Spinal Cord Neuromodulation (SCONE™, SpineX Inc.) on 12 individuals (ages 2 to 50) diagnosed with cerebral palsy (CP) with Gross Motor Function Classification Scale (GMFCS) levels ranging from I to V. Acute spinal neuromodulation improved the postural and locomotor abilities in 11 out of the 12 patients including the ability to generate bilateral weight bearing stepping in a 2-year-old (GMFCS level IV) who was unable to step. In addition, we observed independent head-control and weight bearing standing with stimulation in a 10-year-old and a 4-year old (GMFCS level V) who were unable to hold their head up or stand without support in the absence of stimulation. All patients significantly improved in coordination of flexor and extensor motor pools and inter and intralimb joint angles while stepping on a treadmill. While it is assumed that the etiologies of the disruptive functions of CP are associated with an injury to the supraspinal networks, these data are consistent with the hypothesis that spinal neuromodulation and functionally focused activity-based therapies can form a functionally improved chronic state of reorganization of the spinal-supraspinal connectivity. We further suggest that the level of reorganization of spinal-supraspinal connectivity with neuromodulation contributed to improved locomotion by improving the coordination patterns of flexor and extensor muscles by modulating the amplitude and firing patterns of EMG burst during stepping.

Neuropathophysiological Mechanisms and Treatment Strategies for Post-traumatic Epilepsy.

Traumatic brain injury (TBI) is a leading cause of death in young adults and a risk factor for acquired epilepsy. Severe TBI, after a period of time, causes numerous neuropsychiatric and neurodegenerative problems with varying comorbidities; and brain homeostasis may never be restored. As a consequence of disrupted equilibrium, neuropathological changes such as circuit remodeling, reorganization of neural networks, changes in structural and functional plasticity, predisposition to synchronized activity, and post-translational modification of synaptic proteins may begin to dominate the brain. These pathological changes, over the course of time, contribute to conditions like Alzheimer disease, dementia, anxiety disorders, and post-traumatic epilepsy (PTE). PTE is one of the most common, devastating complications of TBI; and of those affected by a severe TBI, more than 50% develop PTE. The etiopathology and mechanisms of PTE are either unknown or poorly understood, which makes treatment challenging. Although anti-epileptic drugs (AEDs) are used as preventive strategies to manage TBI, control acute seizures and prevent development of PTE, their efficacy in PTE remains controversial. In this review, we discuss novel mechanisms and risk factors underlying PTE. We also discuss dysfunctions of neurovascular unit, cell-specific neuroinflammatory mediators and immune response factors that are vital for epileptogenesis after TBI. Finally, we describe current and novel treatments and management strategies for preventing PTE.

Neuroplasticity and non-invasive brain stimulation in the developing brain.

The brain is a dynamic organ whose growth and organization varies according to each subject's life experiences. Through adaptations in gene expression and the release of neurotrophins and neurotransmitters, these experiences induce a process of cellular realignment and neural network reorganization, which consolidate what is called neuroplasticity. However, despite the brain's resilience and dynamism, neuroplasticity is maximized during the first years of life, when the developing brain is more sensitive to structural reorganization and the repair of damaged neurons. This review presents an overview of non-invasive brain stimulation (NIBS) techniques that have increasingly been a focus for experimental research and the development of therapeutic methods involving neuroplasticity, especially Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS). Due to its safety risk profile and extensive tolerability, several trials have demonstrated the benefits of NIBS as a feasible experimental alternative for the treatment of brain and mind disorders in children and adolescents. However, little is known about the late impact of neuroplasticity-inducing tools on the developing brain, and there are concerns about aberrant plasticity. There are also ethical considerations when performing interventions in the pediatric population. This article will therefore review these aspects and also obstacles related to the premature application of NIBS, given the limited evidence available concerning the extent to which these methods interfere with the developing brain.

Self‐reported quality of sleep is related to frontoparietal network connectivity in mild cognitive impairment

AbstractBackgroundSleep has been identified as a modifiable factor involved in both the development and progression of Alzheimer’s disease (AD). Previous findings have suggested that poor sleep may be associated with increased risk of AD. Conversely, higher quality of sleep may slow progression of pathophysiological mechanisms in mild cognitive impairment (MCI) through functional connectivity reorganization of neural networks underlying higher cognitive functions.MethodIn clinic, 38 MCI patients and 38 age‐matched controls completed structural magnetic resonance imaging (MRI), resting‐state functional MRI (rs‐fMRI), and a cognitive test battery, covering memory, executive functions, and language. The Sleep Continuity in Alzheimer’s Disease Scale (SCADS) was used to assess sleep quality. Patients were stratified into “good” (n=20) and “poor” (n=18) sleepers, using the median SCADS score as a cut‐point. Default mode (DMN) and left and right frontoparietal (FPN) networks were reconstructed through an independent component analysis approach. Differences in network connectivity across MCI groups were investigated with non‐parametric inference using FSL randomize (n=5000 permutations), corrected at a threshold‐free‐cluster enhancement level of pFWE < 0.025. Grey matter and sex were inserted as covariates in the analysis. The same model was implemented to investigate associations between connectivity and cognition in MCI. Finally, between‐network connectivity was assessed through partial correlation with sex as covariate.ResultMCI good sleepers showed increased FPN connectivity compared to MCI poor sleepers. Increased FPN connectivity was positively associated with language performance in the former group. Finally, we found a positive coupling connectivity between DMN and FPN and between left and right FPN in MCI good sleepers, while this pattern was disrupted in MCI patients with lower quality of sleep.ConclusionThese findings suggest a relationship between sleep quality and FPN connectivity in MCI, highlighting possible sleep‐induced compensatory mechanisms. Future studies in larger samples using longitudinal methods and objective measures of sleep will be necessary to confirm this finding. However, these results further support the concept that better sleep may be protective on the pathway to AD.

Reorganization of Bioelectrical Activity in the Neocortex after Stroke by Rehabilitation Using a Brain–Computer Interface Controlling a Wrist Exoskeleton

The process of the functional rearrangement of the motor cortex of the brain after stroke is due to neuroplasticity, and this underlies motor recovery. Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) are currently recognized as the most informative methods for studying these processes. The course of the neuroplastic process can be evaluated from the power levels of EEG rhythms during imagination of movements in the paralyzed arm in right-handed patients after stroke in the left hemisphere monitored at different times – before and after courses of neurorehabilitation using a brain–computer interface controlling a wrist exoskeleton. Powerful excitatory interactions in the primary motor cortex and frontoparietal areas in the lesioned and “intact” hemispheres are initially seen, and these probably reflect reorganization of neural networks. Rehabilitation courses were followed by restoration of bioelectrical activity in the primary motor cortex due to recovery of efficient connections with the premotor and superior parietal zones and decreases in the pathological influences of the contralateral hemisphere.

Statistical Analysis of fNIRS Data: Consideration of Spatial Varying Coefficient Model of Prefrontal Cortex Activity Changes During Speech Motor Learning in Apraxia of Speech

One of the key cognitive functions for new learning is cognitive flexibility. In a healthy system, the role of the prefrontal cortex (PFC) during speech is of growing interest. For individuals who have an impairment in the programing and planning of speech (apraxia of speech) secondary to a stroke or traumatic brain injury, the once hardwired activity is now a goal directed rule-based act. The literature falls short in PFC involvement for rehabilitation of speech following a brain injury. This repeated measures single case-design study involves two individuals with chronic acquired apraxia of speech. Hemodynamic changes in PFC activity during speech motor learning are measured using functional near-infrared spectroscopy. Two models - a generalized linear model (GLM) and a spatial varying coefficient model - are used to distinguish PFC activity differences corresponding the task, stage, and time of intervention. The significant differences in the pattern of activity for the regions of interest in the PFC are associated with structure of practice, feedback schedule, and the time of intervention. This pilot study provides evidence for the PFC role in speech motor learning and that neural reorganization can continue several years post-stroke. The implications include considerations for statistical methods used for fNIRS analysis with the potential to build tailored interventions to facilitate neural network reorganization for speech motor learning following an acquired brain injury.

Quality of sleep predicts increased frontoparietal network connectivity in patients with mild cognitive impairment

High quality of sleep may mitigate the impact of pathophysiological mechanisms in mild cognitive impairment (MCI) through functional connectivity reorganization of neural networks underlying higher cognitive functions. Thirty-eight patients with MCI stratified into high and low quality of sleep in accordance with a self-reported questionnaire for sleep habits, and 38 controls underwent resting-state functional magnetic resonance imaging. Independent component analysis was used to reconstruct the default mode network and frontoparietal network (FPN). High quality of sleep was associated with increased FPN connectivity among patients with MCI. Moreover, a positive coupling of connectivity between networks was found in MCI reporting high quality of sleep, congruently with the pattern observed in controls, whereas this coupling was disrupted in MCI with low quality of sleep. An association between FPN connectivity and language scores was observed in MCI. These findings suggest a relationship between sleep quality and FPN connectivity in MCI that may underlie compensatory mechanisms to overcome advancing neurodegeneration.

Motor Learning Induces Profound but Delayed Dendritic Plasticity in M1 Layer II/III Pyramidal Neurons

Motor learning depends on plastic reorganization of neural networks within the primary motor cortex (M1). In the circuitry of M1, integration and processing of afferent inputs is executed by pyramidal neurons of layer II/III. Thus, an involvement of these layer II/III pyramids in learning-induced changes is highly plausible. We therefore analyzed dendritic plasticity in layer II/III pyramidal cells on Golgi-Cox silver-impregnated sections after training of a forelimb reaching task. Based on their location within layer II/III, neurons were assigned to either a superficial or a deep population. After training, morphological changes occurred in both superficial and deep layer II/III pyramids. Overall, a decrease in dendritic length could be observed. In detail, superficial cells showed a significant reduction in the length of the apical dendrite after training ended in contrast to deep layer II/III pyramids, where dendritic length initially remained stable. Both types of neurons showed a transient increment in complexity of the distal apical dendrite 30 days after training. Findings were different in basal dendrites: length and complexity continuously decreased in superficial and deep layer II/III pyramids. Spine density increased in apical and basal dendrites of both superficial and deep layer II/III neurons, likely an effect of ageing that occurred independently from motor learning. This increase in spine density was accompanied with a morphological change towards stubby- and mushroom-like spines. Thus, profound but delayed changes occurred within the dendritic compartment of layer II/III pyramidal cells.

A systems approach delivers a functional microRNA catalog and expanded targets for seizure suppression in temporal lobe epilepsy

Temporal lobe epilepsy is the most common drug-resistant form of epilepsy in adults. The reorganization of neural networks and the gene expression landscape underlying pathophysiologic network behavior in brain structures such as the hippocampus has been suggested to be controlled, in part, by microRNAs. To systematically assess their significance, we sequenced Argonaute-loaded microRNAs to define functionally engaged microRNAs in the hippocampus of three different animal models in two species and at six time points between the initial precipitating insult through to the establishment of chronic epilepsy. We then selected commonly up-regulated microRNAs for a functional in vivo therapeutic screen using oligonucleotide inhibitors. Argonaute sequencing generated 1.44 billion small RNA reads of which up to 82% were microRNAs, with over 400 unique microRNAs detected per model. Approximately half of the detected microRNAs were dysregulated in each epilepsy model. We prioritized commonly up-regulated microRNAs that were fully conserved in humans and designed custom antisense oligonucleotides for these candidate targets. Antiseizure phenotypes were observed upon knockdown of miR-10a-5p, miR-21a-5p, and miR-142a-5p and electrophysiological analyses indicated broad safety of this approach. Combined inhibition of these three microRNAs reduced spontaneous seizures in epileptic mice. Proteomic data, RNA sequencing, and pathway analysis on predicted and validated targets of these microRNAs implicated derepressed TGF-β signaling as a shared seizure-modifying mechanism. Correspondingly, inhibition of TGF-β signaling occluded the antiseizure effects of the antagomirs. Together, these results identify shared, dysregulated, and functionally active microRNAs during the pathogenesis of epilepsy which represent therapeutic antiseizure targets.