Synchronization Of Neuronal Activity Research Articles

Neuronal extracellular vesicles and associated microRNAs induce circuit connectivity downstream BDNF.

Extracellular vesicles (EVs) have emerged as mediators of cellular communication, in part via the delivery of associated microRNAs (miRNAs), small non-coding RNAs that regulate gene expression. We show that brain-derived neurotrophic factor (BDNF) mediates the sorting of miR-132-5p, miR-218-5p, and miR-690 in neuron-derived EVs. BDNF-induced EVs in turn increase excitatory synapse formation in recipient hippocampal neurons, which is dependent on the inter-neuronal delivery of these miRNAs. Transcriptomic analysis further indicates the differential expression of developmental and synaptogenesis-related genes by BDNF-induced EVs, many of which are predicted targets of miR-132-5p, miR-218-5p, and miR-690. Furthermore, BDNF-induced EVs up-regulate synaptic vesicle (SV) clustering in a transmissible manner, thereby increasing synaptic transmission and synchronous neuronal activity. As BDNF and EV-miRNAs miR-218 and miR-132 were previously implicated in neuropsychiatric disorders such as anxiety and depression, our results contribute to a better understanding of disorders characterized by aberrant neural circuit connectivity.

Ripples in macaque V1 and V4 are modulated by top-down visual attention

Sharp-wave ripples (SWRs) are highly synchronous neuronal activity events. They have been predominantly observed in the hippocampus during offline states such as pause in exploration, slow-wave sleep, and quiescent wakefulness. SWRs have been linked to memory consolidation, spatial navigation, and spatial decision-making. Recently, SWRs have been reported during visual search, a form of remote spatial exploration, in macaque hippocampus. However, the association between SWRs and multiple forms of awake conscious and goal-directed behavior is unknown. We report that ripple activity occurs in macaque visual areas V1 and V4 during focused spatial attention. The occurrence of ripples is modulated by stimulus characteristics, increased by attention toward the receptive field, and by the size of the attentional focus. During attention cued to the receptive field, the monkey's reaction time in detecting behaviorally relevant events was reduced by ripples. These results show that ripple activity is not limited to hippocampal activity during offline states, rather they occur in the neocortex during active attentive states and vigilance behaviors.

Feohromocitom kao potencijalni uzrok napada epilepsije

Epileptic seizures are defined as the transient appearance of signs or symptoms due to excessive or synchronous neuronal activity in the cerebral cortex. Pheochromocytomas and paragangliomas (PPGL) are tumors of chromaffin cells that arise from the medulla of the adrenal gland in 80-85% of patients and from the extra-adrenal sympathetic tissue of the abdomen, pelvis and chest in 10-20% of patients. The clinical picture of PPGL is variable and ranges from the absence of symptoms to severe clinical picture, depending on the biochemical profile. They are most often manifested by paroxysmal hypertension, followed by episodes of severe headache or diaphoresis, while epileptic attacks are rare. Neurological symptoms are present in many patients with PPGL. Also, paroxysmal neurological conditions such as vasodilating headache, intracranial tumors, diencephalic-autonomic epilepsy, hypertensive encephalopathy, focal arterial disease of the brain and anxiety state have been described, which may have similar clinical manifestations with pheochromocytomas. We present a 44-year-old woman, who has been diagnosed with pheochromocytoma as possible etiological basis of epileptic seizures. Pheochromocytoma, with its low incidence and "chameleon" clinical spectrum, should be considered as a potential etiological factor of convulsions.

Prelimbic Ensembles Mediate Cocaine Seeking After Behavioral Acquisition and Once Rats Are Well-Trained.

Substance use disorder (SUD) is a chronic relapsing condition characterized by continued use of drugs despite negative consequences. SUD is thought to involve disordered learning and memory wherein drug-paired cues gain increased salience, and ultimately drive craving and relapse. These types of associations are thought to be encoded within sparsely distributed sets of neurons, called neuronal ensembles, that drive encoded behaviors through synchronous activity of the participant neurons. We have previously found that Fos-expressing neuronal ensembles within the prefrontal cortex are required for well-trained cocaine seeking. However, less is known about how quickly cortical neuronal ensembles form during the initiation of cocaine seeking behavior. Here, we seek to further elucidate the role of Fos-expressing neuronal ensembles within the prelimbic cortex (PL) after the initial acquisition of cocaine self-administration (SA), or, after 10 days of additional SA training (well-trained). We trained Fos-LacZ transgenic rats to lever press for cocaine under an FR1 schedule of reinforcement. Once rats met acquisition criteria for cocaine self-administration, we ablated Fos-expressing neuronal ensembles in the PL using the Daun02 inactivation method, either 1 or 10 days after the rats met the acquisition criteria. Targeted ablation of Fos-expressing neuronal ensembles in the PL attenuated active lever pressing both 1 day and 10 days after rats acquired cocaine self-administration. Together, this suggests that Fos-expressing neuronal ensembles rapidly form in the PL and continue to mediate maintained cocaine seeking behavior.

Repetitive nociceptive stimulation increases spontaneous neural activation similar to nociception-induced activity in mouse insular cortex

Recent noninvasive neuroimaging technology has revealed that spatiotemporal patterns of cortical spontaneous activity observed in chronic pain patients are different from those in healthy subjects, suggesting that the spontaneous cortical activity plays a key role in the induction and/or maintenance of chronic pain. However, the mechanisms of the spontaneously emerging activities supposed to be induced by nociceptive inputs remain to be established. In the present study, we investigated spontaneous cortical activities in sessions before and after electrical stimulation of the periodontal ligament (PDL) by applying wide-field and two-photon calcium imaging to anesthetized GCaMP6s transgenic mice. First, we identified the sequential cortical activation patterns from the primary somatosensory and secondary somatosensory cortices to the insular cortex (IC) by PDL stimulation. We, then found that spontaneous IC activities that exhibited a similar spatiotemporal cortical pattern to evoked activities by PDL stimulation increased in the session after repetitive PDL stimulation. At the single-cell level, repetitive PDL stimulation augmented the synchronous neuronal activity. These results suggest that cortical plasticity induced by the repetitive stimulation leads to the frequent PDL stimulation-evoked-like spontaneous IC activation. This nociception-induced spontaneous activity in IC may be a part of mechanisms that induces chronic pain.

Modelos experimentales en el estudio de la epileptogénesis

Epilepsy is a chronic neurological disease characterized by spontaneous recurrently occurring epileptic seizures as a consequence of abnormal, excessive and synchronous neuronal activity in the brain. Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy in adults, being characterized by hippocampal sclerosis, reactive gliosis, neurodegeneration, and synaptic reorganization. Animal models of TLE based on the administration of convulsive agents trigger a status epilepticus (SE) that progresses towards the occurrence of spontaneous recurrent seizures. Among these models are those induced by the systemic administration of pilocarpine or by intrahippocampal injection of kainic acid, both being characterized by 3 clearly defined phases: (i) acute SE seizures; (ii) latent period and (iii) occurrence of recurrent spontaneous seizures. These models not only reproduce most of the neuropathological TLE features but also allow for the identification of biomarkers of epileptogenesis and potential pharmacological targets. The use of neuroimaging techniques such as positron emission tomography (PET) with the radiotracer 18F-Fluorodeoxyglucose (18F-FDG) identifies brain hypometabolism in the latent period that not only localizes the epileptic focus but is also an biomarker of early diagnosis. Other neuroimaging techniques allow for detecting, among others, biomarkers of neuroinflammation, alterations in the permeability of the blood-brain barrier and astrocytic activation, all of them associated with epileptogenesis. Finally, the use of chemogenetics through DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) technology in murine models leads to targeted modulation of astrocytic activity, being a novel tool that considers the contribution of the astrocytes role in brain metabolic alterations in epileptogenesis.

The broad edge of synchronization: Griffiths effects and collective phenomena in brain networks.

Many of the amazing functional capabilities of the brain are collective properties stemming from the interactions of large sets of individual neurons. In particular, the most salient collective phenomena in brain activity are oscillations, which require the synchronous activation of many neurons. Here, we analyse parsimonious dynamical models of neural synchronization running on top of synthetic networks that capture essential aspects of the actual brain anatomical connectivity such as a hierarchical-modular and core-periphery structure. These models reveal the emergence of complex collective states with intermediate and flexible levels of synchronization, halfway in the synchronous-asynchronous spectrum. These states are best described as broad Griffiths-like phases, i.e. an extension of standard critical points that emerge in structurally heterogeneous systems. We analyse different routes (bifurcations) to synchronization and stress the relevance of 'hybrid-type transitions' to generate rich dynamical patterns. Overall, our results illustrate the complex interplay between structure and dynamics, underlining key aspects leading to rich collective states needed to sustain brain functionality. This article is part of the theme issue 'Emergent phenomena in complex physical and socio-technical systems: from cells to societies'.

Distinct ensembles in the noradrenergic locus coeruleus are associated with diverse cortical states

The noradrenergic locus coeruleus (LC) is a controller of brain and behavioral states. Activating LC neurons en masse by electrical or optogenetic stimulation promotes a stereotypical “activated” cortical state of high-frequency oscillations. However, it has been recently reported that spontaneous activity of LC cell pairs has sparse yet structured time-averaged cross-correlations, which is unlike the highly synchronous neuronal activity evoked by stimulation. Therefore, LC population activity could consist of distinct multicell ensembles each with unique temporal evolution of activity. We used nonnegative matrix factorization (NMF) to analyze large populations of simultaneously recorded LC single units in the rat LC. NMF identified ensembles of spontaneously coactive LC neurons and their activation time courses. Since LC neurons selectively project to specific forebrain regions, we hypothesized that distinct ensembles activate during different cortical states. To test this hypothesis, we calculated band-limited power and spectrograms of local field potentials in cortical area 24a aligned to spontaneous activations of distinct LC ensembles. A diversity of state modulations occurred around activation of different LC ensembles, including a typical activated state with increased high-frequency power as well as other states including decreased high-frequency power. Thus—in contrast to the stereotypical activated brain state evoked by en masse LC stimulation—spontaneous activation of distinct LC ensembles is associated with a multitude of cortical states.

Evaluating spatial and network properties of NMDA-dependent neuronal connectivity in mixed cortical cultures

A technique combining fluorescence imaging with Ca2+ indicators and single-cell laser scanning photostimulation of caged glutamate (LSPS) allowed identification of functional connections between individual neurons in mixed cultures of rat neocortical cells as well as observation of synchronous spontaneous activity among neurons. LSPS performed on large numbers of neurons yielded maps of functional connections between neurons and allowed calculation of neuronal network parameters. LSPS also provided an indirect measure of excitability of neurons targeted for photostimulation. By repeating LSPS sessions with the same neurons, stability of connections and change in the number and strength of connections were also determined. Experiments were conducted in the presence of bicuculline to study in detail the properties of excitatory neurotransmission. The AMPA receptor inhibitor, 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX), abolished synchronous neuronal activity but had no effect on connections mapped by LSPS. In contrast, the NMDA receptor inhibitor, 2-Amino-5-phosphono-pentanoic acid (APV), dramatically decreased the number of functional connections between neurons while also affecting synchronous spontaneous activity. Functional connections were also decreased by increasing extracellular Mg2+ concentration. These data demonstrated that LSPS mapping interrogates NMDA receptor-dependent connectivity between neurons in the network. In addition, a GluN2A-specific inhibitor, NVP-AAM077, decreased the number and strength of connections between neurons as well as neuron excitability. Conversely, the GluN2A-specific positive modulator, GNE-0723, increased these same properties. These data showed that LSPS can be used to directly study perturbations in the properties of NMDA receptor-dependent connectivity in neuronal networks. This approach should be applicable in a wide variety of in vitro and in vivo experimental preparations.

Broadband-NIRS System Identifies Epileptic Focus in a Child with Focal Cortical Dysplasia-A Case Study.

Epileptic seizures are transiently occurring symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Previous functional near-infrared spectroscopy (fNIRS) studies during seizures have focused in only monitoring the brain oxygenation and haemodynamic changes. However, few tools are available to measure actual cellular metabolism during seizures, especially at the bedside. Here we use an in-house developed multichannel broadband NIRS (or bNIRS) system, that, alongside the changes in oxy-, deoxy- haemoglobin concentration (HbO2, HHb), also quantifies the changes in oxidised cytochrome-c-oxidase Δ(oxCCO), a marker of cellular oxygen metabolism, simultaneously over 16 different brain locations. We used bNIRS to measure metabolic activity alongside brain tissue haemodynamics/oxygenation during 17 epileptic seizures at the bedside of a 3-year-old girl with seizures due to an extensive malformation of cortical development in the left posterior quadrant. Simultaneously Video-EEG data was recorded from 12 channels. Whilst we did observe the expected increase in brain tissue oxygenation (HbD) during seizures, it was almost diminished in the area of the focal cortical dysplasia. Furthermore, in the area of seizure origination (epileptic focus) ΔoxCCO decreased significantly at the time of seizure generalization when compared to the mean change in all other channels. We hypothesize that this indicates an incapacity to sustain and increase brain tissue metabolism during seizures in the region of the epileptic focus.

EFFECT OF DIFFERENT ANTICONVULSANTS ON LIVER ENZYME ACTIVITIES IN PATIENTS WITH SEIZURE DISORDER

Background: Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures, which has transient signs and/or symptoms of abnormal, synchronous neuronal activity in the brain. Antiepileptic drugs (AEDs) used for the prevention of seizure have been found to be an inducer of liver enzyme activity. So, the purpose of this study was to see the effect of antiepileptic drugs on hepatic enzymes activity. Methods: An observational study was carried out in Kathmandu Medical College from October 2020 to April 2021 at neurology department. Sixty-seven seizure patients aged 19-89 years were included in the study. Liver function test was performed before medication, followed up and monitored for three and six months. Paired sample t-test was used to compare the means by using SPSS version 15. Results: Among carbamazepine (CBZ) and sodium valproate (VPA) treated cases, 4.5% and 9.1% respectively showed raised Alanine aminotransferase (ALT) activity whereas, 13.6% and 4.5% respectively showed raised Alkaline Phosphatase (ALP) activity. ALT activity was higher in VPA treated patient compared to CBZ treated patient. However, ALP activity was raised in CBZ treated patient compared to VPA treated patients. No, change in liver enzyme activities was observed in patient treated with Levetiracetam Conclusions: Anticonvulsant drugs used during the treatment have mild to moderate hepatotoxicity. Liver enzyme activity more than two to three-fold may increase. Levetiracetam has minimal hepatic metabolism while sodium valproate is more hepatotoxic. Therefore, routine screening of hepatic enzymes is recommended to the patients under antiepileptic therapy.

POST-COVID 19 ENCEPHALITIS IN PATIENT WITH DE NOVO MUTATION IN THE SCN1A GENE, A CASE REPORT

Seizures are defined as a transient occurrence of signs and symptoms due to an abnormal, excessive or synchronous neuronal activity in the brain, characterized by abrupt and involuntary skeletal muscle activity. The presence of cephalgic syndrome, infectious-toxic encephalopathy, hypo- and anosmia and ageusia are pathognomonic conditions in COVID-19 infected patients. Post-Covid 19 encephalitis develops to encephalopathy in children with epilepsy. Based on the clinical appearance and the parameters that showed past Covid-19 infection, a diagnosis of post-COVID19 encephalopathy was confirmed. To confirm the diagnosis, clinical examinations, MRI of the brain, electroencephalography, lumbar puncture, laboratory tests (including CBC, CRP, basic metabolic panel, liver panel, hemostasis with D-dimer) are necessary. Based on the brain changes registered on the EEG record, the physical findings and the presence of SARS CoV 2 IgG antibodies, it was concluded that a child with an initial diagnosis of epilepsy, developed encephalopathy after asymptomatic COVID 19 infection. Keywords: Post-COVID19 complications, encephalitis, Dravet syndrome, epilepsy, de novo mutation, children

Long-term development of dynamic changes in neurovascular coupling after acute temporal lobe epilepsy

Epilepsy is an abnormal brain state that may be induced by synchronous neuronal activation and also abnormalities in energy metabolism or the oxygen supply vascular system. Neurovascular coupling (NVC), the relationship between neuron, capillary, and penetrating artery, remains unexplored on a fine-scale with respect to the pathology process after acute temporal lobe epilepsy (TLE). Here we use two-photon microscopy (TPM) to provide high temporal-spatial resolution imaging to identify changes in NVC during spontaneous and electro-stimulated (ES) states in awake mice. Implantation of a long-term craniotomy window allowed TPM recording of the pathological development after the acute Kainic Acid temporal lobe epilepsy model. Our results provide direct evidence that the capillary and penetrating artery are not correlated to rhythmic neuronal activity during acute epilepsy. During the CSD period, NVC shows a strong correlation. We demonstrate that NVC exhibits nonlinear dynamics after status epilepticus. Furthermore, the vascular correlation to neuronal signals in spontaneous and ES states shows dynamic changes which correlate to the evolution after acute TLE. Understanding NVC in all TLE stages, from the acute through the TLE pathological development, may provide new therapeutic pathways.

Astrocytic Gap Junctions Contribute to Aberrant Neuronal Synchronization in a Mouse Model of MeCP2 Duplication Syndrome.

Abnormal synchronous neuronal activity has been widely detected by brain imaging of autistic patients, but its underlying neural mechanism remains unclear. Compared with wild-type mice, our in vivo two-photon imaging showed that transgenic (Tg1) mice over-expressing human autism risk gene MeCP2 exhibited higher neuronal synchrony in the young but lower synchrony in the adult stage. Whole-cell recording of neuronal pairs in brain slices revealed that higher neuronal synchrony in young postnatal Tg1 mice was attributed mainly to more prevalent giant slow inward currents (SICs). Both in vivo and slice imaging further demonstrated more dynamic activity and higher synchrony in astrocytes from young Tg1 mice. Blocking astrocytic gap junctions markedly decreased the generation of SICs and overall cell synchrony in the Tg1 brain. Furthermore, the expression level of Cx43 protein and the coupling efficiency of astrocyte gap junctions remained unchanged in Tg1 mice. Thus, astrocytic gap junctions facilitate but do not act as a direct trigger for the abnormal neuronal synchrony in young Tg1 mice, revealing the potential role of the astrocyte network in the pathogenesis of MeCP2 duplication syndrome.

Abstract WP234: Age And Type 2 Diabetes Reduce The Coherence Of Theta And Gamma Oscillations Between Brain Networks

Introduction: The integrity of the functional connectivity across networks relies on synchronous activation of neurons, which reduces with age. Type 2 diabetes (T2DM) is a major risk factor for stroke and cognitive decline and also a precocious aging, yet the electrophysiological changes in T2DM and its interaction with aging is not well understood. The current study sought to delineate the age and diabetic effect on the resting state field potential in regions crucial for cognition. Methods: Local field potential was recorded under urethane anesthesia with multichannel electrodes spanning the cortex and hippocampus (HPC) in control (db/+) and diabetic (db/db) mice, at 200 or 400 days of age. Brain state and neural activity in signal power of δ, θ, γ waves and sharp-wave associated ripples (SWRs) were determined. Coherence and phase-amplitude coupling (PAC) within the HPC or between cortex and HPC were computed to reflect the level of functional communication across brain networks. Results: Our results show that age decreased the θ/δ amplitude (T/D) ratio and the signal power of the theta, gamma and high gamma in the cortex and the HPC. Both age and diabetes prolonged the average duration of SWR clusters and inter-ripple intervals. The greatest SWR signal power was detected in db/db mice at 200 ds of age compared to the other 3 groups, so were the γ power in the cortex and HPC during SWRs. Both age and diabetes reduced θ coherence between cortex and HPC. Age also reduced γ coherence within the hippocampus. Interestingly, while age reduced the coherence of high γ band between hippocampus and CTX, diabetes significantly increased it. To the contrary, age increased coherence in δ within the hippocampal layers. Diabetes decreased the θ-low γ PAC between CA1 and cortex and within CA1. However, diabetes increased δ-γ PAC within the slm, while both age and diabetes increased the δ-γ PAC between the hippocampus and the cortex. Conclusion: The neural activity and synchrony in brain regions crucial for cognitive function is impaired by age and further confounded by T2DM. The perturbation of resting state field potential signal power and coherence may underlie age and diabetes induced loss of functional connectivity and cognitive decline.

Clinical and Social Findings of Childhood Epilepsy

Background: Seizures are defined as a transient occurrence of signs and symptoms due to the abnormal, excessive, or synchronous neuronal activity in the brain characterized by abrupt and involuntary skeletal muscle activity. Seizure is related to specific risk factors like positive family history, fever, infections, neurological comorbidity, premature birth, mother’s alcohol abuse, and smoking in pregnancy. Epilepsy is the most frequent chronic neurologic condition in children. Studies have suggested declining incidence rates of childhood epilepsy in high-income countries during the last decades. Objective: To describe the clinical features and social findings of epilepsy in children, and to evaluate some risk factors associated with control of epilepsy. Patients and Methods: This cross-sectional study was conducted in the pediatric department of Albatool teaching hospital in Diyala province, Iraq. A total of 100 children were included in the study from February 2020 to May 2020. All children diagnosed with epilepsy in this study. Results: One hundred children with epilepsy, their mean age was 5.96± 3.33 years (range 1-14 years). Of the 48(48%) children were male and 52(52%). Of the total patients, 79% were free from seizure on AED, 21% of them were refractory to treatment.Patients without developmental delay (88.7%, p=0.012) can be controlled by AED. Patients who had idiopathic seizures (87.5%, p=0.04) can be controlled by AED. Patients who had seizure attacks can be controlled by AED more than patients who had weekly or monthly seizure attacks (97.4%) (p<0.001). Patients who had been treated by monotherapy (94.7%, p=0.012) can be controlled more than patients who were treated by multidrug therapy. Affected social interaction and need more supervision were factors that detected more in patients with refractory epilepsy, p=0.04, 0.01 respectively. While there was no association between frightened other people and epilepsy control. Conclusion: Most of the patients are characterized by: treatment approach monotherapy, less affected by social interaction and need less supervision. Patients with refractory epilepsy had opposite factors. Keywords: Epilepsy, Albatool teaching hospital.

How does the Alzheimer’s disease brain respond to optomechanical stimuli? A narrative review

Abstract Alzheimer's disease (AD) is a neurodegenerative condition with enormous social and economic impact at a global scale. Given the inefficacy of the pharmacological treatments developed so far in decelerating/blocking AD pathology, the study and development of so-called alternative (i.e., non-pharmacological) and non-invasive therapies has become one of the major focuses of biomedical research on AD in recent years. Indeed, several researchers have demonstrated the therapeutic potential of optical and mechanical (i.e., optomechanical) stimuli in brain lesions. Among them, photobiomodulation (PBM, the application of modulated red/NIR light for therapeutic purposes) and tailored ultrasonic waves applied to the brain through transcranial ultrasound stimulation (TUSS) are at the forefront of clinical interventions with the potential to improve associated neuropathology and symptomatology of AD (e.g., reduction of protein aggregates deposition in the brain, increased functional connectivity and synchronization of neuronal activity, cognitive improvements), both at the preclinical and clinical levels. However, the biologic mechanisms differentially activated/stimulated during optomechanical stimulation are far from being understood. There are no proven data about the bioavailability of the stimulus energy and their bioeffects on signaling pathways, inflammation and clearance mechanisms, as well as on how these alterations relate with the behavioral improvement observed. Thus, this review compiles and describes possible biological mechanisms and alterations through which optomechanical stimuli can be effective in mitigating AD neuropathology and clinical symptoms. The topics reviewed here will be crucial for further development in the field of alternative, noninvasive brain stimulation approaches against AD, also contributing to all therapeutic interventions by transcranial stimulation in the future, enabling the development of customized therapies. Keywords: Alzheimer’s disease, optomechanical stimuli, immunoregulation, neuroprotection

Distributed cell assemblies spanning prefrontal cortex and striatum

Highly synchronous neuronal assembly activity is deemed essential for cognitive brain function. In theory, such synchrony could coordinate multiple brain areas performing complementary processes. However, cell assemblies have been observed only in single structures, typically cortical areas, and little is known about their synchrony with downstream subcortical structures, such as the striatum. Here, we demonstrate distributed cell assemblies activated at high synchrony (∼10ms) spanning prefrontal cortex and striatum. In addition to including neurons at different brain hierarchical levels, surprisingly, they synchronized functionally distinct limbic and associative sub-regions. These assembly activations occurred when members shifted their firing phase relative to ongoing 4 Hz and theta rhythms, in association with high gamma oscillations. This suggests that these rhythms could mediate the emergence of cross-structural assemblies. To test for the role of assemblies in behavior, we trained the rats to perform a task requiring cognitive flexibility, alternating between two different rules in a T-maze. Overall, assembly activations were correlated with task-relevant parameters, including impending choice, reward, rule, or rule order. Moreover, these behavioral correlates were more robustly expressed by assemblies than by their individual member neurons. Finally, to verify whether assemblies can be endogenously generated, we found that they were indeed spontaneously reactivated during sleep and quiet immobility. Thus, cell assemblies are a more general coding mechanism than previously envisioned, linking distributed neocortical and subcortical areas at high synchrony.

The Association between Body Mass Index and Intra-Cortical Myelin: Findings from the Human Connectome Project.

Intra-cortical myelin is a myelinated part of the cerebral cortex that is responsible for the spread and synchronization of neuronal activity in the cortex. Recent animal studies have established a link between obesity and impaired oligodendrocyte maturation vis-à-vis cells that produce and maintain myelin; however, the association between obesity and intra-cortical myelination remains to be established. To investigate the effects of obesity on intra-cortical myelin in living humans, we employed a large, demographically well-characterized sample of healthy young adults drawn from the Human Connectome Project (n = 1066). Intra-cortical myelin was assessed using a novel T1-w/T2-w ratio method. Linear regression analysis was used to investigate the association between body mass index (BMI), an indicator of obesity, and intra-cortical myelination, adjusting for covariates of no interest. We observed BMI was related to lower intra-cortical myelination in regions previously identified to be involved in reward processing (i.e., medial orbitofrontal cortex, rostral anterior cingulate cortex), attention (i.e., visual cortex, inferior/middle temporal gyrus), and salience detection (i.e., insula, supramarginal gyrus) in response to viewing food cues (corrected p < 0.05). In addition, higher BMIs were associated with more intra-cortical myelination in regions associated with somatosensory processing (i.e., the somatosensory network) and inhibitory control (i.e., lateral inferior frontal gyrus, frontal pole). These findings were also replicated after controlling for key potential confounding factors including total intracranial volume, substance use, and fluid intelligence. Findings suggested that altered intra-cortical myelination may represent a novel microstructure-level substrate underlying prior abnormal obesity-related brain neural activity, and lays a foundation for future investigations designed to evaluate how living habits, such as dietary habit and physical activity, affect intra-cortical myelination.

Mapping Regional Homogeneity and Functional Connectivity of the Visual Cortex in Resting-State fMRI

A combined regional homogeneity (ReHo) and functional connectivity (FC) method, a type of noninvasive functional magnetic resonance imaging (fMRI) method, has been used to evaluate synchronous neuronal activity changes in retinitis pigmentosa (RP). The purpose of this study is to describe our method for analysis of intra- and interregional synchronizations of changes in neuronal activity in RP patients. The advantages of the combined ReHo and FC method are that it is both noninvasive and sufficiently sensitive to investigate changes in cerebral synchronous neuronal activity changes in vivo. Here, 16 RP patients and 14 healthy controls closely matched in age, sex, and education underwent resting-state fMRI scans. Two sample t-tests were conducted to compare ReHo and FC across groups. Our results showed that visual network disconnection and reorganization of the retino-thalamocortical pathway and dorsal visual stream occurred in the RP patients. Here, we describe the details of this method, its use, and the impact of its key parameters in a step-by-step manner.