Cortical Activity Research Articles

ARViS: a bleed-free multi-site automated injection robot for accurate, fast, and dense delivery of virus to mouse and marmoset cerebral cortex

Genetically encoded fluorescent sensors continue to be developed and improved. If they could be expressed across multiple cortical areas in non-human primates, it would be possible to measure a variety of spatiotemporal dynamics of primate-specific cortical activity. Here, we develop an Automated Robotic Virus injection System (ARViS) for broad expression of a biosensor. ARViS consists of two technologies: image recognition of vasculature structures on the cortical surface to determine multiple injection sites without hitting them, and robotic control of micropipette insertion perpendicular to the cortical surface with 50 μm precision. In mouse cortex, ARViS sequentially injected virus solution into 100 sites over a duration of 100 min with a bleeding probability of only 0.1% per site. Furthermore, ARViS successfully achieved 266-site injections over the frontoparietal cortex of a female common marmoset. We demonstrate one-photon and two-photon calcium imaging in the marmoset frontoparietal cortex, illustrating the effective expression of biosensors delivered by ARViS.

Cochlear implant induced changes in cortical networks associated with tinnitus severity

We investigated tinnitus-related cortical networks in cochlear implant users who experience tinnitus and whose perception of tinnitus changes with use of their implant. &#xD;&#xD;Tinnitus, the perception of unwanted sounds which are not present externally, can be a debilitating condition. In individuals with cochlear implants, use of the implant is known to modulate tinnitus, often improving symptoms but worsening them in some cases. Little is known about underlying cortical changes with use of the implant, which lead to changes in tinnitus perception. In this study we investigated whether changes in brain networks with the cochlear implant turned on and off, were associated with changes in tinnitus perception, as rated subjectively.&#xD;&#xD;Approach: Using functional near-infrared spectroscopy (fNIRS), we recorded cortical activity at rest, from 14 cochlear implant users who experienced tinnitus. Recordings were performed with the cochlear implant turned off and on. For each condition, participants rated the loudness and annoyance of their tinnitus using a visual rating scale. Changes in neural synchrony have been reported in humans and animal models of tinnitus. To assess neural synchrony, functional connectivity networks with the implant turned on and off, were compared using two network features: node strength and diversity coefficient. &#xD;&#xD;Main results: Changes in subjective ratings of loudness were significantly correlated with changes in node strength, averaged across occipital channels (r=-0.65,p = 0.01). Changes in both loudness and annoyance were significantly correlated with changes in diversity coefficient averaged across all channels (r=-0.79,p<0.001 and r = -0.86,p<0.001). More distributed connectivity with the implant on, compared to implant off, was associated with a reduction in tinnitus loudness and annoyance. &#xD;&#xD;Significance: A better understanding of neural mechanisms underlying tinnitus suppression with cochlear implant use, could lead to their application as a tinnitus treatment and pave the way for effective use of other less invasive stimulation-based treatments. &#xD.

Restoration of abnormal sleep EEG power in patients with insomnia disorder after 1Hz rTMS over left DLPFC.

Hyperarousal has been a significant pathophysiological theory related to insomnia disorder (ID), characterized by excessive cortical activation and abnormal electroencephalogram (EEG) power during daytime or sleep. However, there is currently insufficient attention to the EEG power during rapid eye movement (REM) sleep and different stages of non-rapid eye movement (NREM) sleep. Additionally, whether the abnormal sleep EEG power in ID patients can be restored by repetitive transcranial magnetic stimulation (rTMS) remains unclear. Data of 26 ID patients and 26 healthy controls (HCs) were included in the current observational study. The comparisons of relative power between patients and HCs at baseline in each band of each sleep stage and the changes in patients before and after rTMS treatment were performed. The correlations between relative power and behavioral measures of the patients were also investigated. Abnormalities in sleep EEG relative power in the delta, beta and gamma bands of the patients were observed in NREM2, NREM3 and REM sleep. Correlations were identified between relative power and behavioral measures in ID group, primarily encompassing sleep efficiency, sleep onset latency and depression scores. Post-treatment improvements in relative power of the delta and beta band were observed in NREM2 sleep. The relative power of sleep EEG exhibited a significant correlation with sleep measures in ID patients, and demonstrated notable differences from HCs across the delta, beta, and gamma frequency bands. Furthermore, our findings suggest that rTMS treatment may partially ameliorate relative power abnormalities in patients with ID.

Hemodynamics of the Frontopolar and Dorsolateral Pre-Frontal Cortex in People with Multiple Sclerosis During Walking, Cognitive Subtraction, and Cognitive-Motor Dual-Task.

Higher cortical activity has been observed in people with multiple sclerosis (pwMS) during walking and dual-tasking. However, further studies in overground walking and considering pre-frontal cortex (PFC) sub-areas are necessary. To investigate PFC activity during a cognitive-motor dual-task (DT) and its single component tasks, in combination with behavioral outcomes in pwMS. Fifteen pwMS (EDSS 3.5 [2-5.5], 42 ± 11 years) and 16 healthy controls (HC, 45.2 ± 13.2 years) performed 3 conditions: single motor-walking (SWT), single cognitive - subtracting sevens (SCT), and a DT. Meters walked and the number of correct answers were obtained from which, respectively, the motor (mDTC) and cognitive (cDTC) DT costs were calculated. A functional Near-Infrared Spectroscopy covering the frontopolar and dorsolateral PFC (DLPFC) areas was used to concentration of relative oxyhemoglobin (ΔHbO2) and deoxyhemoglobin (ΔHHb) in the PFC. A repeated 2-way ANOVA (group × conditions) was used to compare ΔHbO2/ΔHHb and behavioral outcomes. PwMS walked shorter distances (P < .002) and answered fewer correct numbers (P < .03) than HC in all conditions, while cDTC and mDTC were similar between groups. PwMS presented higher ΔHbO2 in the frontopolar area than HC in the SWT (P < .001). HC increased ΔHbO2 in frontopolar during the SCT (P < .029) and DT (P < .037) compared with the SWT. Higher frontopolar activity in pwMS compared to HC in the SWT suggests reduced gait automaticity. Furthermore, it seems that only HC increased neural activity in the frontopolar in the SCT and DT, which might suggest a limit of cognitive resources to respond to DT in pwMS.

Restoring transient connectivity during development improves dysfunctions in fragile X mice.

Early-generated circuits are critical for the maturation of cortical network activity and the formation of excitation/inhibition (E/I) balance. This process involves the maturation of specific populations of inhibitory neurons. While parvalbumin (PV)-expressing neurons have been associated with E/I impairments observed in neurodevelopmental disorders, somatostatin-expressing (SST) neurons have recently been shown to regulate PV neuron maturation by controlling neural dynamics in the developing cortex. SST neurons receive transient connections from the sensory thalamus, yet the implications of transient connectivity in neurodevelopmental disorders remain unknown. Here, we show that thalamocortical connectivity to SST neurons is persistent rather than transient in a mouse model of Fragile X syndrome. We were able to restore the transient dynamics using chemogenetics, which led to the recovery of fragile X-associated dysfunctions in circuit maturation and sensory-dependent behavior. Overall, our findings unveil the role of early transient dynamics in controlling downstream maturation of sensory functions.

Study on the impact of aging on the brain activity patterns in auditory speech comprehension dual-route regions

Objective: To elucidate the patterns of neural activity alterations associated with auditory speech comprehension across the lifespan and the impact of varying listening environments on these dynamics. Methods: Functional near-infrared spectroscopy (fNIRS) was employed to measure the concentration of oxygenated hemoglobin in the brains of 93 adults aged from 20 to 70 with normal hearing. These participants were recruited from Beijing Tongren Hospital, affiliated with Capital Medical University, between March 2021 and February 2023. Brain activity was recorded as subjects passively listened to sentences in both silent and noise conditions with varying signal-to-noise ratios (SNR). The alterations in brain activity were analyzed to delineate the age-related trends under different auditory conditions. Statistical analysis was performed using SPSS 22.0 software. Results: The bilateral primary auditory cortex, superior temporal gyrus, and Wernicke's area, critical for sound signal discrimination and perception, exhibited enhanced activity post-stimulus presentation. Broca's area, pivotal for speech production, demonstrated an initial decrease in activity followed by an increment after stimulus onset. The ventral middle temporal gyrus and dorsal postcentral gyrus showed augmented activity in later time windows. Furthermore, it was observed that in quiet conditions and at low noise levels (SNR=10 dB), auditory cortical activity diminished with age. With increasing noise levels (SNR=5 dB), compensatory brain regions (right ventral middle temporal gyrus and dorsal postcentral gyrus) showed enhanced activity with advancing age. As noise intensity further escalated (SNR=0, SNR=-5 dB), not only did auditory cortical activity decline, but also the activity in regions associated with semantic processing and motor functions reduced with age. Conclusion: During auditory speech comprehension, dual-pathway brain regions exhibit distinct activity patterns. With heightened noise exposure, an increasing number of brain regions are influenced by aging, manifesting as a general decline in activity in most dual-pathway regions, alongside a selective augmentation in some compensatory regions on the right hemisphere.

Dissociative and prioritized modeling of behaviorally relevant neural dynamics using recurrent neural networks

Understanding the dynamical transformation of neural activity to behavior requires new capabilities to nonlinearly model, dissociate and prioritize behaviorally relevant neural dynamics and test hypotheses about the origin of nonlinearity. We present dissociative prioritized analysis of dynamics (DPAD), a nonlinear dynamical modeling approach that enables these capabilities with a multisection neural network architecture and training approach. Analyzing cortical spiking and local field potential activity across four movement tasks, we demonstrate five use-cases. DPAD enabled more accurate neural–behavioral prediction. It identified nonlinear dynamical transformations of local field potentials that were more behavior predictive than traditional power features. Further, DPAD achieved behavior-predictive nonlinear neural dimensionality reduction. It enabled hypothesis testing regarding nonlinearities in neural–behavioral transformation, revealing that, in our datasets, nonlinearities could largely be isolated to the mapping from latent cortical dynamics to behavior. Finally, DPAD extended across continuous, intermittently sampled and categorical behaviors. DPAD provides a powerful tool for nonlinear dynamical modeling and investigation of neural–behavioral data.

Wide-field calcium imaging of cortical activation and functional connectivity in externally- and internally-driven locomotion

The role of the cerebral cortex in self-initiated versus sensory-driven movements is central to understanding volitional action. Whether the differences in these two movement classes are due to specific cortical areas versus more cortex-wide engagement is debated. Using wide-field Ca2+ imaging, we compared neural dynamics during spontaneous and motorized treadmill locomotion, determining the similarities and differences in cortex-wide activation and functional connectivity (FC). During motorized locomotion, the cortex exhibits greater activation globally prior to and during locomotion starting compared to spontaneous and less during steady-state walking, during stopping, and after termination. Both conditions are characterized by FC increases in anterior secondary motor cortex (M2) nodes and decreases in all other regions. There are also cortex-wide differences; most notably, M2 decreases in FC with all other nodes during motorized stopping and after termination. Therefore, both internally- and externally-generated movements widely engage the cortex, with differences represented in cortex-wide activation and FC patterns.

Restricted Cortical Activity Involving Parietal Lobe and Sublobar Region Leads to Generalized Spike-Wave Discharges of Juvenile Myoclonic Epilepsy: Evidence from an EEG Source Localization Study.

Previous studies have localized the origin of "generalized" spike-wave discharges of idiopathic generalized epilepsies to specific brain regions. Although there are studies in juvenile myoclonic epilepsy (JME) which have investigated the origin of spike-wave discharges, reports on the propagation of discharges are sparse. The current study investigated the propagation of spike-wave discharges in JME, which was investigated by statistically comparing the electroencephalography (EEG)-derived cortical source activity during (a) various phases of spike-wave discharge versus background (eyes closed) activity, and (b) various phases of the first spike wave versus the corresponding phase of subsequent spike waves. Fourteen patients with JME who had generalized spike/polyspike and slow wave discharges in interictal EEG were included in the study. A total of 179 spike waves (first discernible spike wave - 55; subsequent spike waves - 124) were selected for source localization. Source analysis was carried out using exact low-resolution electromagnetic tomography (eLORETA). Statistical analyses to estimate the probability distribution of differences in cortical activity between (a) eight phases of epileptic discharge versus background (eyes closed) activity and (b) phases of the first spike wave versus the corresponding phases of subsequent spike waves were performed by paired t-tests and corrected for multiple testing using LORETA-KEY software. Widespread activation of cortical voxels (more than 94%) was observed during all phases of epileptic discharge except the initial phase (pre-first spike) and terminal phase (post-peak of the subsequent wave). The parietal lobe, which was the most activated lobe during the pre-first spike, was found to be the least activated during the post-peak of first and subsequent waves. More than 93% of voxels in the sublobar region were consistently activated during all eight phases of discharge. The study findings suggest that the activity generated from the restricted brain network involving parietal lobe could be propagated through sublobar structures to cause widespread cortical activation during the subsequent phases of the spike-wave cycle.

Abstract P189: Maternal Hyperandrogenemia Programs Hypoandrogenemia and Intrarenal Activation of Histone Deacetylase in Adult Male Offspring

Polycystic ovary syndrome ( PCOS ) is the most common endocrinopathy in young women. In-utero, children of ~80% of PCOS women in the US are exposed to maternal “hyperandrogenemia and obesity”. It remains unclear whether this exposure affects their cardiovascular ( CV ) health later in life. Using a well-characterized rat model of maternal PCOS, the hyperandrogenemic obese ( HAO ) dams, we previously showed that adult male, not female, offspring ( HAO F1 ) have enhanced blood pressure ( BP ) response to chronic angiotensin ( Ang ) II compared to sex-matched control offspring ( CON F1 ), suggesting their increased risk of later CV disease. Sex steroids have the potential to modulate epigenetics. Histone deacetylase ( HDAC ) and histone acetyltransferase ( HAT ) are markers of epigenetic modifications. HDACs have been shown to promote tumor necrosis factor ( TNF )-α expression and play a role in Ang II-induced hypertension. The present study was designed to test the hypothesis that male HAO F1 have intra-renal activation of HDAC and increased TNF-α that could play a role in their Ang II BP response. Methods: At 4 weeks ( wks ) of age, female SD rats were implanted (s.c.) with either 5α-dihydrotestosterone pellets (7.5 mg/90 d; HAO) or placebo pellets (CON) and mated at 9-12 wks. Offspring were obtained and weaned at 3 wks. Serum testosterone ( T; by LC/MS-MS), renal cortical TNF-α (Bioplex) and renal cortical nuclear HDAC and HAT activities (colorimetric assays) were measured in male offspring (1/litter, 16-24 wks, n=5-9). Results: Male HAO F1 had significantly lower serum T, higher renal cortical HDAC activity and TNF-α (430.2±124 vs 120.6±14 ng/dl, 0.97±0.1 vs 4.51±0.96 OD/min/mg protein and 423.7±47 vs 579.8±47 pg/g tissue, in male CON F1 vs male HAO F1 , respectively, p&lt;0.05), and no change in their renal cortical HAT activity (vs male CON F1 ). Conclusion: Male offspring born to HAO dams develop hypoandrogenemia that is associated with intra-renal activation of HDAC that could be mediating their increased intra-renal inflammation (TNF-α expression) and mediating their exaggerated BP response to Ang II. Future studies will determine the causative relationship between hypoandrogenemia, HDAC activation and TNF-a and their role in the exaggerated pressor response to Ang II in those male offspring. Funding: AHA-24DIVSUP1273026 (JA), NIH-NIGMS P20GM121334 (JFR, NMS), R01HL135089 &amp; R01AG075963 (JFR), AHA-22CDA938320 and 2024 Dean Franklin Award (NMS).

Activation of the mPFC-NAc Pathway Reduces Motor Impulsivity but Does Not Affect Risk-Related Decision-Making in Innately High-Impulsive Male Rats.

Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUD) are characterized by exacerbated motor and risk-related impulsivities, which are associated with decreased cortical activity. In rodents, the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) have been separately implicated in impulsive behaviors, but studies on the specific role of the mPFC-NAc pathway in these behaviors are limited. Here, we investigated whether heightened impulsive behaviors are associated with reduced mPFC activity in rodents and determined the involvement of the mPFC-NAc pathway in motor and risk-related impulsivities. We used the Roman High- (RHA) and Low-Avoidance (RLA) rat lines, which display divergent phenotypes in impulsivity. To investigate alterations in cortical activity in relation to impulsivity, regional brain glucose metabolism was measured using positron emission tomography and [18F]-fluorodeoxyglucose ([18F]FDG). Using chemogenetics, the activity of the mPFC-NAc pathway was either selectively activated in high-impulsive RHA rats or inhibited in low-impulsive RLA rats, and the effects of these manipulations on motor and risk-related impulsivity were concurrently assessed using the rat gambling task. We showed that basal [18F]FDG uptake was lower in the mPFC and NAc of RHA compared to RLA rats. Activation of the mPFC-NAc pathway in RHA rats reduced motor impulsivity, without affecting risk-related decision-making. Conversely, inhibition of the mPFC-NAc pathway had no effect in RLA rats. Our results suggest that the mPFC-NAc pathway controls motor impulsivity, but has limited involvement in risk-related decision-making in our current model. Our findings suggest that reducing fronto-striatal activity may help attenuate motor impulsivity in patients with impulse control dysregulation.

Differential analgesic effects of high-frequency or accelerated intermittent theta burst stimulation of M1 on experimental tonic pain: Correlations with cortical activity changes assessed by TMS-EEG

Accelerated intermittent theta burst stimulation (AiTBS) has attracted much attention in the past few years as a new form of brain stimulation paradigm. However, it is unclear the relative efficacy of AiTBS on cortical excitability compared to conventional high-frequency rTMS. Using concurrent TMS and electroencephalogram (TMS-EEG), this study systematically compared the efficacy on cortical excitability and a typical clinical application (i.e. pain), between AiTBS with different intersession interval (ISIs) and 10-Hz rTMS. Participants received 10-Hz rTMS, AiTBS-15 (3 iTBS sessions with a 15-min ISI), AiTBS-50 (3 iTBS sessions with a 50-min ISI), or Sham stimulation over the primary motor cortex on four separate days. All four protocols included a total of 1800 pulses but with different session durations (10-Hz rTMS ​= ​18, AiTBS-15 ​= ​40, and AiTBS-50 ​= ​110 ​min). AiTBS-50 and 10-Hz rTMS were more effective in pain reduction compared to AiTBS-15. Using single-pulse TMS-induced oscillation, our data revealed low gamma oscillation as a shared cortical excitability change across all three active rTMS protocols but demonstrated completely opposite directions. Changes in low gamma oscillation were further associated with changes in pain perception across the three active conditions. In contrast, a distinct pattern of TMS-evoked potentials (TEPs) was revealed, with 10-Hz rTMS decreasing inhibitory N100 amplitude and AiTBS-15 reducing excitatory P60 amplitude. These changes in TEPs were also covarying with low gamma power changes. Sham stimulation indicated no significant effect on either cortical excitability or pain perception. These results are relevant only for provoked experimental pain, without being predictive for chronic pain, and revealed a change in low gamma oscillation, particularly around the very particular frequency of 40 ​Hz, shared between AiTBS and high-frequency rTMS. Conversely, cortical excitability (balance between excitation and inhibition) assessed by TEP recording was modulated differently by AiTBS and high-frequency rTMS paradigms.

Cycle-frequency content EEG analysis improves the assessment of respiratory-related cortical activity

Objective. Time-frequency (T-F) analysis of electroencephalographic (EEG) is a common technique to characterise spectral changes in neural activity. This study explores the limitations of utilizing conventional spectral techniques in examining cyclic event-related cortical activities due to challenges, including high inter-trial variability.Approach. Introducing the cycle-frequency (C-F) analysis, we aim to enhance the evaluation of cycle-locked respiratory events. For synthetic EEG that mimicked cycle-locked pre-motor activity, C-F had more accurate frequency and time localization compared to conventional T-F analysis, even for a significantly reduced number of trials and a variability of breathing rhythm.Main results. Preliminary validations using real EEG data during both unloaded breathing and loaded breathing (that evokes pre-motor activity) suggest potential benefits of using the C-F method, particularly in normalizing time units to cyclic activity phases and refining baseline placement and duration.Significance. The proposed approach could provide new insights for the study of rhythmic neural activities, complementing T-F analysis.

Cerebral Synchronization Between Mothers and Their Newborns During Breastfeeding.

Introduction: Breastfeeding is a fundamental biological function in mammals, allowing the progeny to develop in a physiological way. A physical and emotional dialog between mothers and offspring during breastfeeding has been described as part of the attachment relationship, and a synchronicity between maternal and neonatal brains can be hypothesized. This study aimed to assess if neonatal and maternal cortical areas activated during breastfeeding are functionally synchronized since the second day of life. Materials and Methods: Twenty mothers and their term newborns were enrolled. Cortical activation during breastfeeding was identified by multichannel near-infrared spectroscopy, which detects changes in haemoglobin concentration from multiple cortical regions. Functional activity was simultaneously detected (hyperscanning) in mothers and newborns' frontal and motor/primary somatosensory cortical areas during the first 5 minutes of breastfeeding. Cluster analysis and Student's t test were used to detect oxygenated haemoglobin increase, as cortical activation estimate. Wavelet transform coherence (WTC) analysis was used to identify a possible synchronization between maternal and neonatal activated cortical regions. Results: Mothers showed an activation of the central motor/primary somatosensory cortex, above the sagittal fissure. In newborns, the bilateral frontal cortex was activated. WTC analysis revealed two different cyclical synchronizations between mothers and infants' activated cortical regions. Conclusions: Such evidence may reflect a very early common sharing of experiences, possibly associated with reciprocal dynamic motor adjustments, hormonal coregulation, and somatic stimulations and sensations. The observed cyclical neural synchronization, between the mother and her newborn's cortex during breastfeeding, may play an important role in promoting their bonding.

Cognitive functioning in adults with chronic insomnia disorder- A cross-sectional study

Background: Chronic insomnia, affecting 15.9% of the population, is characterized by sustained hyperarousal and heightened somatic, cognitive, and cortical activity. Despite its prevalence, the precise impact of chronic insomnia on cognitive domains, particularly attention, working memory, and executive function, remains inadequately understood. Aim: This study aims to systematically investigate the cognitive functioning of adults with chronic insomnia. Methodology: A meticulously matched cohort of 80 participants, comprising 40 with chronic insomnia and 40 controls, participated in this cross-sectional study. The diagnosis followed strict criteria outlined in the International Classification of Sleep Disorders-3. Neuropsychological assessments, including the Digit Span Test, Stroop Test, and Trail Making Test, were employed to scrutinize attention, working memory, and executive function. Robust metrics, such as the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9), supported the investigative approach. Results: Analysis revealed notable deficits in backward digit span, digit symbol substitution test, and Stroop Test (cards B and C) among chronic insomnia subjects compared to non-insomniac counterparts. Trail Making Test B indicated prolonged completion times in the chronic insomnia cohort. Despite comparable levels of anxiety and depressive symptoms, the chronic insomnia group exhibited higher ISI and PSQI scores, indicating the severity of their sleep disturbances. Conclusion: This cross-sectional analysis reveals cognitive deficits associated with chronic insomnia, specifically impacting attention, working memory, and executive function. Even with meticulous demographic controls, chronic insomnia leaves a discernible impact on cognitive functions. The study underscores the need for precise cognitive evaluations to reveal the latent impact of chronic insomnia, offering insights for targeted interventions.

Association of Levels of CSF Osteopontin With Cortical Atrophy and Disability in Early Multiple Sclerosis.

To evaluate CSF inflammatory markers with accumulation of cortical damage as well as disease activity in patients with early relapsing-remitting MS (RRMS). CSF levels of osteopontin (OPN) and 66 inflammatory markers were assessed using an immune-assay multiplex technique in 107 patients with RRMS (82 F/25 M, mean age 35.7 ± 11.8 years). All patients underwent regular clinical assessment and yearly 3T MRI scans for 2 years while 39 patients had a 4-year follow-up. White matter lesion number and volume, cortical lesions (CLs) and volume, and global cortical thickness (CTh) were evaluated together with the 'no evidence of disease activity' (NEDA-3) status, defined by no relapses, no disability worsening, and no MRI activity, including CLs. The random forest algorithm selected OPN, CXCL13, TWEAK, TNF, IL19, sCD30, sTNFR1, IL35, IL16, and sCD163 as significantly associated with changes in global CTh. OPN and CXCL13 were most related to accumulation of atrophy after 2 and 4 years. In a multivariate linear regression model on CSF markers, OPN (p < 0.001), CXCL13 (p = 0.001), and sTNFR1 (p = 0.024) were increased in those patients with accumulating atrophy (adjusted R-squared 0.615). The 10 markers were added in a model that included all clinical, demographic, and MRI variables: OPN (p = 0.002) and IL19 (p = 0.022) levels were confirmed to be significantly increased in patients developing more CTh change over the follow-up (adjusted R-squared 0.619). CXCL13 and OPN also revealed the best association with NEDA-3 after 2 years, with OPN significantly linked to disability accumulation (OR 2.468 [1.46-5.034], p = 0.004) at the multivariate logistic regression model. These data confirm and expand our knowledge on the prognostic role of the CSF inflammatory profile in predicting changes in cortical pathology and disease activity in early MS. The data emphasize a crucial role of OPN.

Adaptive closed-loop modulation of cortical theta oscillations: Insights into the neural dynamics of navigational decision-making

Navigational decision-making tasks, such as spatial working memory (SWM), rely highly on information integration from several cortical and sub-cortical regions. Performance in SWM tasks is associated with theta rhythm, including low-frequency oscillations related to movement and memory. The interaction of the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC), reflected in theta synchrony, is essential in various steps of information processing during SWM. We used a closed-loop neurofeedback (CLNF) system to upregulate theta power in the mPFC and investigate its effects on circuit dynamics and behavior in animal models. Specifically, we hypothesized that enhancing the power of the theta rhythm in the mPFC might improve SWM performance. Animals were divided into three groups: closed-loop (CL), random-loop (RL), and OFF (without stimulation). We recorded local field potential (LFP) in the mPFC while electrical reward stimulation contingent on cortical theta activity was delivered to the lateral hypothalamus (LH), which is considered one of the central reward-associated regions. We also recorded LFP in the vHPC to evaluate the related subcortical neural changes. Results revealed a sustained increase in the theta power in both mPFC and vHPC for the CL group. Our analysis also revealed an increase in mPFC-vHPC synchronization in the theta range over the stimulation sessions in the CL group, as measured by coherence and cross-correlation in the theta frequency band. The reinforcement of this circuit improved spatial decision-making performance in the subsequent behavioral results. Our findings provide direct evidence of the relationship between specific theta upregulation and SWM performance and suggest that theta oscillations are integral to cognitive processes. Overall, this study highlights the potential of adaptive CLNF systems in investigating neural dynamics in various brain circuits.

Functional segregation and dynamic integration of the corticotectal descending signal in rat

The superior colliculus (SC) receives inputs from various brain regions in a layer- and radial subregion-specific manner, but whether the SC exhibits subregion-specific dynamics remains unclear. To address this issue, we recorded the spiking activity of single SC neurons while photoactivating cortical areas in awake head-fixed Thy1-ChR2 rats. We classified 309 neurons that responded significantly into 8 clusters according to the response dynamics. Among them, neurons with monophasic excitatory responses (7–12 ms latency) that returned to baseline within 20 ms were commonly observed in the optic and intermediate gray layers of centromedial and centrolateral SC. In contrast, neurons with complex polyphasic responses were commonly observed in the deep layers of the anterolateral SC. Cross-correlation analysis suggested that the complex pattern could be only partly explained by an internal circuit of the deep gray layer. Our results indicate that medial to centrolateral SC neurons simply relay cortical activity, whereas neurons in the deep layers of the anterolateral SC dynamically integrate inputs from the cortex, SNr, CN, and local circuits. These findings suggest a spatial gradient in SC integration, with a division of labor between simple relay circuits and those integrating complex dynamics.

Physical exercise on cortical brain activity in patients with mild cognitive impairment: A meta-analysis.

Physical exercise is recognized as a potential strategy to mitigate the cognitive decline associated with mild cognitive impairment (MCI). This systematic review aims to examine the specific effects of physical exercise on cortical brain activity in patients with MCI, an area that has not been thoroughly explored. We conducted a search across 9 electronic databases for randomized controlled trials assessing the impact of physical exercise on the cortical activity of patients with MCI. The search covered the period from database inception to September 2023. Literature screening, data extraction, and quality assessments were carried out by 2 independent researchers. Meta-analyses were conducted using RevMan 5.3, and publication bias was evaluated using STATA 17.0. This study primarily assessed P300 latency and amplitude, alongside cognitive evaluations using the mini-mental state examination and Montreal Cognitive Assessment. Six high-quality randomized controlled trials, involving a total of 360 participants, were included. Compared to the control group, significant enhancements were observed in the amplitude of central midline electrode (mean difference [MD] = 1.64 [95% confidence interval [CI], 0.92-2.36]; P < .00001), frontal midline electrode (MD = 2.70 [95% CI, 2.02-3.38]; P < .00001), and parietal midline electrode (MD = 2.42 [95% CI, 0.44-4.41]; P = .02). Latency periods of the central midline electrode (MD = -32.40 [95% CI, -40.27 to -24.54]; P < .00001), frontal midline electrode (MD = -12.57 [95% CI, -30.83 to 5.69]; P = .18), and parietal midline electrode (MD = -12.57 [95% CI, -30.83 to 5.69]; P = .81) were also notably influenced. Moreover, overarching cognitive functions as measured by mini-mental state examination (MD = 1.02 [95% CI, 0.61-1.43]; P < .00001) and Montreal Cognitive Assessment (MD = 1.39 [95% CI, 0.67-2.12]; P = .0002) exhibited marked improvement. This meta-analysis suggests that physical exercise can augment the P300 amplitude, reduce the P300 latency period, and, overall, enhance cognitive functionality in individuals with MCI.

Change of Cerebral Hemodynamic Signals during the Process of Swallowing Water, Acetic Acid Solution and Salt Solution in Healthy Adults: An fNIRS Study.

The aim of this preliminary study was to investigate the similarities and differences in cortical activation patterns during the swallowing of water, acetic acid solution and salt solution in healthy adults using functional near-infrared spectroscopy (fNIRS). Eighteen right-handed healthy adults were recruited and fNIRS was used to measure changes in concentrations of oxygenated hemoglobin (HbO2) and deoxygenated hemoglobin (HbR) in 35 channels during the swallowing of water, acetic acid solution and salt solution. The task-based experiment used a block-design in which participants alternated between resting blocks of 30 s and task blocks (swallowing water, acetic acid solution, or salt solution) of 30 s, repeated six times. Participants remained still during the resting blocks and performed a swallowing action every 6 s during the task blocks. Data preprocessing was conducted using NirSpark software and statistical analyses were performed using either one-sample or paired t-tests to compare differences in cortical activation in healthy participants between swallowing a water and acetic acid solution, as well as swallowing a water and salt solution. Compared to the resting state, nine brain regions, including primary somatosensory cortex (S1), primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), Wernicke's area, premotor cortex (PMC), supplementary motor area (SMA), inferior frontal cortex (IFC), orbitofrontal cortex (OFC) and frontopolar area, were commonly activated during the process of swallowing water, acetic acid solution, and salt solution. The DLPFC, Broca's area, PMC and SMA showed higher activation levels during the swallowing of acetic acid solution when compared to swallowing water, with statistically significant differences (p < 0.05). The frontopolar area and OFC exhibited higher activation during the swallowing of salt solution when compared to water, also with statistically significant differences (p < 0.05). Multiple brain regions were activated during the swallowing of water, acetic acid solution and salt solution in healthy adults. Moreover, swallowing acetic acid solution leads to stronger activation of DLPFC, Broca's area, PMC and SMA, while swallowing salt solution leads to stronger activation of the frontopolar area and OFC.