Ipsilateral Activity Research Articles

Characterization of a rapid avoidance behavior in Manduca sexta larvae in response to noxious stimuli.

This study focuses on the nociceptive responses observed in the tobacco hornworm (Manduca sexta). While prior investigations have described the sensory neurons and muscle activation patterns associated with the 'strike' behavior, there remains a gap in our understanding of the alternative 'withdrawal' movement, wherein the animal bends its head and thorax away from the stimulus. Our results show that stimulus location determines which nocifensive behavior is elicited. Interestingly, stimulation of specific mid-body segments could result in either withdrawal or strike, indicating a decision process rather than a hard-wired circuit. The withdrawal behavior was characterized using high-speed videography and electromyography. The results show that withdrawal in Manduca is driven by contralateral ventral muscles, followed by an increase in ipsilateral muscle activation just before the bending stops. Dorsal muscles are co-activated throughout the movement. Although both withdrawal and strike behaviors involve sequential activation of lateral muscles, these behaviors involve different muscle groups. This discovery provides a novel model system to investigate the context-dependence and decision-making processes triggered by stressful or noxious stimuli.

Displacement and functional ultrasound (fUS) imaging of displacement-guided focused ultrasound (FUS) neuromodulation in mice

Focused ultrasound (FUS) stimulation is a promising neuromodulation technique with the merits of non-invasiveness, high spatial resolution, and deep penetration depth. However, simultaneous imaging of FUS-induced brain tissue displacement and the subsequent effect of FUS stimulation on brain hemodynamics has proven challenging thus far. In addition, earlier studies lack in situ confirmation of targeting except for the magnetic resonance imaging-guided FUS system-based studies. The purpose of this study is 1) to introduce a fully ultrasonic approach to in situ target, modulate neuronal activity, and monitor the resultant neuromodulation effect by respectively leveraging displacement imaging, FUS, and functional ultrasound (fUS) imaging, and 2) to investigate FUS-evoked cerebral blood volume (CBV) response and the relationship between CBV and displacement. We performed displacement imaging on craniotomized mice to confirm the in situ targeting for neuromodulation site. We recorded hemodynamic responses evoked by FUS while fUS imaging revealed an ipsilateral CBV increase that peaks at 4 s post-FUS. We report a stronger hemodynamic activation in the subcortical region than cortical, showing good agreement with a brain elasticity map that can also be obtained using a similar methodology. We observed dose-dependent CBV responses with peak CBV, activated area, and correlation coefficient increasing with the ultrasonic dose. Furthermore, by mapping displacement and hemodynamic activation, we found that displacement colocalized and linearly correlated with CBV increase. The findings presented herein demonstrated that FUS evokes ipsilateral hemodynamic activation in cortical and subcortical depths while the evoked hemodynamic responses colocalize and correlate with FUS-induced displacement. We anticipate that our findings will help consolidate accurate targeting as well as shedding light on one of the mechanisms behind FUS modulation, i.e., how FUS mechanically displaces brain tissue affecting cerebral hemodynamics and thereby its associated connectivity.

The vestigial pinna-orienting system in humans briefly suppresses superior auricular muscle activity during reflexive orienting toward auditory stimuli.

The vestigial pinna-orienting system in humans is capable of increasing the activity of several auricular muscles in response to lateralized transient auditory stimuli. For example, transient increases in electromyographic activity in the posterior auricular muscle (PAM) to an attention-capturing stimulus have been documented. For the current study, surface electromyograms (EMGs) were recorded from the PAMs and superior auricular muscles (SAMs) of 10 normal-hearing participants. During the experiments, lateralized transient auditory stimuli, such as a crying baby, a shattering vase, or the participant's first names, were presented. These transient stimuli were either presented in silence or when participants actively listened to a podcast. Although ipsilateral PAM activity increased in response to transient stimuli, the SAM displayed the opposite behavior, i.e., a brief, ipsilateral suppression of activity. This suppression of ipsilateral SAM activity was more frequent on the right (75%) than left side (35%), whereas an ipsilateral PAM increase was roughly equal in prevalence on the two sides (left: 90%, right: 95%). During the active listening task, SAM suppression on the right ear was significantly larger in response to ipsilateral stimuli, compared with contralateral ones (P = 0.002), whereas PAM activity increased significantly (P = 0.002). Overall, this study provides evidence of a systematic transient suppression of the SAM during exogenous attention. This could suggest a more complex system than previously assumed, as the presence of synchronized excitatory and inhibitory components in different auricular muscles points toward a coordinated attempt at reflexively orienting the pinna toward a sound.NEW & NOTEWORTHY This study provides evidence that two auricular muscles in humans, the posterior and superior auricular muscles (PAM, SAM), react fundamentally different to lateralized transient auditory stimuli, especially during active listening. Although the PAM reacts with a transient increase in ipsilateral activity, ongoing ipsilateral SAM activity is briefly suppressed at the same time. This indicates the presence of a more complex and nuanced pinna-orienting system, with synchronized excitatory and inhibitory components in humans, than previously suspected.

The systemic impact of different COVID-19 vaccines in 2-[18F] FDG-PET/CT

Austria started its COVID-19-vaccination program in December 2020 with three different vaccines. As the vaccination program continues, we encountered increased 2-[18F] FDG-activity not only in axillary lymph nodes ipsilateral to the injection site but also in other organs. The aim of this retrospective study is to present results of the metabolic activity of ipsilateral axillary lymph nodes, liver, blood pool, spleen, and bone marrow after three different vaccines. To our knowledge, this is the first study to examine systemic response changes in relation to time after COVID-19 vaccination using three different vaccines. The collected data of 220 eligible vaccinated patients (127 with BioNTech/Pfizer BNT162b2, 61 with Moderna, and 32 with AstraZeneca) examined with 2-[18F] FDG-PET/CT were enrolled. The PET/CT examinations were evaluated from day 1 to day 135 (SD: 23.2, median: 26) after different vaccinations. Seventy-one out of these 220 patients underwent a pre-vaccination 2-[18F] FDG -PET/CT. SUVmax of axillary node(s), and blood pool, liver, spleen, and bone marrow as reference organs were calculated. The ratio of SUVmax activity of axillary lymph node to reference organs was also compared in all patients. The tracer activity dynamics were investigated in three different vaccines. After BioNTech/Pfizer vaccination 2-[18F] FDG activity in axillary lymph nodes shows a steady decrease in all patients. Ten days after vaccination the 2-[18F] FDG uptake was at its highest activity. Seventy days after vaccination, tracer activity is not different from the background activity of 2-[18F] FDG in the axillary region. This result also applies to other two vaccines; however, in the 4th week after Moderna vaccination SUVmax in lymph nodes showed the highest peak of tracer activity. With AstraZeneca the highest activity was at the earlier days. There was no significant statistical difference of SUVmax of lymph nodes or its ratios to other reference organs between three groups of vaccines. SUVmax in lymph nodes was statistically significant lower than SUVmax in the liver, spleen, and bone marrow with p-values of < 0.001, 0.044, and 0.001, respectively. In the group of 71 patients with a pre-vaccination PET/CT examination, the median SUVmax of lymph nodes increased significantly after vaccination from 0.82 (IQR 0.59–1.38) to 1.80 (IQR 1.07–3.89)(p < 0.001). In contrast median tracer activity in the liver decreased from 3.37 (IQR 2.83–3.91) to 3.11 (2.56–3.70) (p = 0.032). There was no significant change of tracer activity after vaccination in other reference regions (mediastinum, spleen, and bone marrow). In this group of 71 patients, there was also no significant difference in tracer activity in different types of vaccines. Local site and ipsilateral axillary lymph node activity in 2-[18F] FDG PET/CT after COVID19-vaccination is suggested in many studies. The main challenge is recognizing the changes in lymph nodes during time after vaccination to minimize false interpretation, foremost in patients with oncological diagnoses. Moreover, different vaccines cause different system metabolic changes. The knowledge of vaccine type, the time interval between vaccination and PET/CT scan is essential, especially in therapy evaluation.

Does Ipsilateral Remapping Following Hand Loss Impact Motor Control of the Intact Hand?

What happens once a cortical territory becomes functionally redundant? We studied changes in brain function and behavior for the remaining hand in humans (male and female) with either a missing hand from birth (one-handers) or due to amputation. Previous studies reported that amputees, but not one-handers, show increased ipsilateral activity in the somatosensory territory of the missing hand (i.e., remapping). We used a complex finger task to explore whether this observed remapping in amputees involves recruiting more neural resources to support the intact hand to meet greater motor control demands. Using basic fMRI analysis, we found that only amputees had more ipsilateral activity when motor demand increased; however, this did not match any noticeable improvement in their behavioral task performance. More advanced multivariate fMRI analyses showed that amputees had stronger and more typical representation-relative to controls' contralateral hand representation-compared with one-handers. This suggests that in amputees, both hand areas work together more collaboratively, potentially reflecting the intact hand's efference copy. One-handers struggled to learn difficult finger configurations, but this did not translate to differences in univariate or multivariate activity relative to controls. Additional white matter analysis provided conclusive evidence that the structural connectivity between the two hand areas did not vary across groups. Together, our results suggest that enhanced activity in the missing hand territory may not reflect intact hand function. Instead, we suggest that plasticity is more restricted than generally assumed and may depend on the availability of homologous pathways acquired early in life.

Functional Dissection of Ipsilateral and Contralateral Neural Activity Propagation Using Voltage-Sensitive Dye Imaging in Mouse Prefrontal Cortex.

Prefrontal cortex (PFC) intrahemispheric activity and the interhemispheric connection have a significant impact on neuropsychiatric disorder pathology. This study aimed to generate a functional map of FC intrahemispheric and interhemispheric connections. Functional dissection of mouse PFCs was performed using the voltage-sensitive dye (VSD) imaging method with high speed (1 ms/frame), high resolution (256 × 256 pixels), and a large field of view (∼10 mm). Acute serial 350 μm slices were prepared from the bregma covering the PFC and numbered 1-5 based on their distance from the bregma (i.e., 1.70, 1.34, 0.98, 0.62, and 0.26 mm) with reference to the Mouse Brain Atlas (Paxinos and Franklin, 2008). The neural response to electrical stimulation was measured at nine sites and then averaged, and a functional map of the propagation patterns was created. Intracortical propagation was observed in slices 3-5, encompassing the anterior cingulate cortex (ACC) and corpus callosum (CC). The activity reached area 33 of the ACC. Direct white matter stimulation activated area 33 in both hemispheres. Similar findings were obtained via DiI staining of the CC. Imaging analysis revealed directional biases in neural signals traveling within the ACC, whereby the signal transmission speed and probability varied based on the signal direction. Specifically, the spread of neural signals from cg2 to cg1 was stronger than that from cingulate cortex area 1(cg1) to cingulate cortex area 2(cg2), which has implications for interhemispheric functional connections. These findings highlight the importance of understanding the PFC functional anatomy in evaluating neuromodulators like serotonin and dopamine, as well as other factors related to neuropsychiatric diseases.

Inflammatory activity of vulnerable plaques in asymptomatic, non-hemodynamically significant carotid artery stenoses: preliminary results of the carotid artery multi-modality imaging prognostic study

Abstract Background [18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a valid technique to quantify carotid plaque inflammation and can improve identification of patients at high risk for stroke. There are few data on the inflammatory plaque activity in asymptomatic patients and of its association with other characteristics of plaque vulnerability. Purpose To assess the inflammatory carotid plaque activity and its correlations with patient characteristics and features of plaque vulnerability detected by other imaging techniques in a population of patients with asymptomatic mild/moderate degree of stenosis. Methods Seventy-five asymptomatic patients with 40-60% unilateral carotid stenosis at Doppler ultrasound (DUS) were prospectively evaluated with [18F]FDG-PET, computed tomography angiography (CTA), and magnetic resonance angiography (MRA). Regions of interests were drawn using fused PET/CT slices on the most diseased segment (MDS), defined as the single hottest slice of [18F]FDG uptake. Background blood pool activity was obtained from regions of interests placed in the lumen of the jugular vein. The target-to-background ratio (TBR) was calculated by dividing maximum standardized uptake value (SUVmax) of the MDS to SUVmax of ipsilateral blood pool activity. Plaque vulnerability was defined as the presence of an echolucent plaque at DUS, plaque ulceration at CTA, intraplaque hemorrhage, and lipid-rich necrotic core at MRA. Results Patients with a TBR ≥median (1.75), compared with those below the median, were significantly more frequently male and on statin therapy, had higher prevalence of ulcerated plaque at CTA (61% vs 35%, p=0.03) and intraplaque hemorrhage at MRA (33% vs 10%, p=0.03), while the prevalence of a lipid-rich necrotic core at MRA was not significantly different (p=0.16). TBR and SUVmax of the MDS were similar in those with or without a ≥50% stenosis, and peak velocities indices at DUS were not significantly correlated with TBR or SUVmax. Log(TBR) was significantly higher in ulcerated, rather than non-ulcerated, plaque (0.27 vs 0.21, p=0.03) and numerically higher in plaques with an intraplaque hemorrhage (0.22 vs 0.30, p=0.06). Log(TBR) and Log(SUVmax) were similar in plaques with and without a lipid-rich necrotic core (p=0.86 for both). Conclusions Higher TBR or SUVmax, indicating a high inflammatory activity, are associated with an ulcerated plaque and the presence of intraplaque hemorrhage but not with either the degree of stenosis or the presence of a lipid-rich necrotic core.

Bilateral ictal EEG is associated with better memory outcome after hippocampal sclerosis surgery.

To compare memory outcomes after surgery for unilateral hippocampal sclerosis (HS)-associated epilepsy in patients with unilateral and bilateral ictal electrographic involvement. We prospectively evaluated HS patients, aged 18-55 years and IQ ≥70. Left (L) and right (R) surgical groups underwent noninvasive video-EEG monitoring and Wada test. We classified patients as Ipsilateral if ictal EEG was restricted to the HS side, or Bilateral, if at least one seizure onset occurred contralaterally to the HS, or if ictal discharge evolved to the opposite temporal region. Patients who declined surgery served as controls. Memory was evaluated on two occasions with Rey Auditory-Verbal Learning Test and Rey Visual-Design Learning Test. Baseline neuropsychological test scores were compared between groups. Pre- and postoperative scores were compared within each group. Reliable change index Z-scores (RCI) were obtained using controls as references, and compared between surgical groups. We evaluated 64 patients. Patients were classified as: L-Ipsilateral (9), L-Bilateral (15), L-Control (9), R-Ipsilateral (10), R-Bilateral (9), and R-Control (12). On preoperative evaluation, memory performance did not differ among surgical groups. Right HS patients did not present postoperative memory decline. L-Ipsilateral group presented postoperative decline on immediate (P = 0.036) and delayed verbal recall (P = 0.011), while L-Bilateral did not decline. L-Ipsilateral had lower RCI Z-scores, indicating delayed verbal memory decline compared to L-Bilateral (P = 0.012). Dominant HS patients with bilateral ictal involvement presented less pronounced postoperative verbal memory decline compared to patients with exclusive ipsilateral ictal activity. Surgery was indicated in these patients regardless of memory impairment on neuropsychological testing, since resection of the left sclerotic hippocampus could result in cessation of contralateral epileptiform activity, and, therefore, improved memory function.

Predictive Contribution of the Superficial Neck Muscles to Short-Latency Rate of Force Development of the Head and Neck.

To evaluate the contribution of splenius capitis, sternocleidomastoid, and upper fibers of trapezius activation to the gains in rate of force development (RFD) of the head and neck during maximum voluntary ballistic contractions. RFD gain was facilitated by a single-session intervention for maximum voluntary ballistic contractions in the anterior direction, oriented at 45° to the midsagittal plane, which require active restraint of axial rotation. Muscle activation for the agonist (sternocleidomastoid) and 2 antagonists (splenius capitis and upper fibers of trapezius) was evaluated. The study sample included 12 physically active men (mean age, 22.6y). RFD (N·m·s-1; 0-100ms) and integrated muscle activity (50ms before and 100ms after force onset) were measured at 10 minutes, 20 minutes, and 2 days postintervention, relative to baseline. Muscle activation predictive of RFD gains was evaluated by linear regression analysis. RFD reproducibility was evaluated using the coefficient of variation of the typical error. The intervention yielded a 1.95- to 2.39-fold RFD gain (P ≤ .05), with greater RFD gain for participants with a lower peak moment of force (<10.9N·m) than those with a higher peak moment (≥10.9N·m) at baseline (P ≤ .002). For the low group, 65% to 74% of the RFD gain was predicted by ipsilateral sternocleidomastoid activation, with ipsilateral splenius capitis activation predicting 77% to 92% of RFD gain for the high group. Absolute peak and impulse of static force were greater for the high than for the low group (P ≤ .04). RFD reproducibility was high (coefficient of variation of the typical error ≤ 14.4%). The agonist- and antagonist-focused synergies might reflect different functional priorities, higher RFD gain compared with higher head-neck force.

Children With Bilateral Cerebral Palsy Exhibit Bimanual Asymmetric Motor Deficits and EEG Evidence of Dominant Sensorimotor Hemisphere Overreliance During Reaching.

Reaching is a fundamental motor skill often impaired in cerebral palsy (CP). Studies on manual function, intervention, and underlying brain mechanisms largely focus on unilateral CP. This first electroencephalography (EEG) evaluation of reaching exclusively in bilateral CP aims to quantify and relate brain activation patterns to bimanual deficits in this population. A total of 15 children with bilateral CP (13.4 ± 2.9 years) and 13 with typical development (TD: 14.3 ± 2.4 years) performed 45 reaches per hand while recording motion capture and EEG data. The Box and Blocks test was administered bilaterally. Cortical sources were identified using independent component analysis and clustered using k-means. Alpha (8-12 Hz) and beta (13-30 Hz) band event-related desynchronization (ERD) values were compared across groups and hands within clusters, between dominant and non-dominant sensorimotor clusters, and related to reach kinematics and the Box and Block test. The group with CP demonstrated bimanual motor deficits with slower reaches, lower Box and Blocks scores, and stronger hand preference than in TD. Beta ERD, representing motor execution, was notably higher in the dominant sensorimotor cluster in CP compared to TD. Both groups demonstrated more contralateral than ipsilateral activity in both hands and clusters, with CP showing a less lateralized (more bilateral) alpha response. Higher brain activation was generally related to better function. Bimanual deficits in bilateral CP and related EEG differences warrant more clinical and research attention particularly earlier in life when greater potential for neural and functional recovery exists.

Role of Neural Plasticity of Motor Cortex in Gliomas Evaluated by Brain Imaging and Mapping Techniques in Pre- and Postoperative Period: A Systematic Review.

Resection of infiltrative neuroepithelial primary brain tumors, such as low-grade gliomas (LGGs) remains a neurosurgical challenge. Usual lack of clinical deficit despite LGGs growing in eloquent brain areas may be explained by reshaping and reorganization of functional networks. The development of modern diagnostic imaging techniques could disclose better understanding of the rearrangement of the brain cortex; however, mechanisms underlying such compensation and how it occurs in the motor cortex remain unclear. This systematic review aims to analyze the neuroplasticity of motor cortex in patients with LGGs, as determined by neuroimaging and functional techniques. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, medical subject headings (MeSH) and the following terms related to neuroimaging, LGGs and neuroplasticity were used with the Boolean operators AND and OR to synonymous terms in the PubMed database. Among the 118 results, 19 studies were included in the systematic review. Motor function in patients with LGG was characterized by a compensation in the contralateral and supplementary motor areas and premotor functional networks. Furthermore, ipsilateral activation in these types of gliomas was rarely described. Moreover, some studies did not reveal statistical significance in association between functional reorganization and the postoperative period, which can be explained by the low number of patients. Our findings suggest a high pattern of reorganization per different eloquent motor areas and gliomas diagnosis. Understanding this process is useful to guide safe surgical resection and to develop protocols that assess the plasticity, even though functional network rearrangement needs to be better characterized by more studies.

Cervical spinal hemisection effects on spinal tissue oxygenation and long-term facilitation of phrenic, renal and splanchnic sympathetic nerve activity

HypothesesModerate acute intermittent hypoxia (mAIH) elicits plasticity in both respiratory (phrenic long-term facilitation; pLTF) and sympathetic nerve activity (sympLTF) in rats. Although mAIH produces pLTF in normal rats, inconsistent results are reported after cervical spinal cord injury (cSCI), possibly due to greater spinal tissue hypoxia below the injury site. There are no reports concerning cSCI effects on sympLTF. Since mAIH is being explored as a therapeutic modality to restore respiratory and non-respiratory movements in humans with chronic SCI, both effects are important. To understand cSCI effects on mAIH-induced pLTF and sympLTF, partial or complete C2 spinal hemisections (C2Hx) were performed and, 2 weeks later, we assessed: 1) ipsilateral cervical spinal tissue oxygen tension; 2) ipsilateral & contralateral pLTF; and 3) ipsilateral sympLTF in splanchnic and renal sympathetic nerves. MethodsMale Sprague-Dawley rats were studied intact, or after partial (single slice) or complete C2Hx (slice with ∼1 mm aspiration). Two weeks post-C2Hx, rats were anesthetized and prepared for recordings of bilateral phrenic nerve activity and spinal tissue oxygen pressure (PtO2). Splanchnic and renal sympathetic nerve activity was recorded in intact and complete C2Hx rats. ResultsSpinal PtO2 near phrenic motor neurons was decreased after C2Hx, an effect most prominent with complete vs. partial injuries; baseline PtO2 was positively correlated with mean arterial pressure. Complete C2Hx impaired ipsilateral but not contralateral pLTF; with partial C2Hx, ipsilateral pLTF was unaffected. In intact rats, mAIH elicited splanchnic and renal sympLTF. Complete C2Hx had minimal impact on baseline ipsilateral splanchnic or renal sympathetic nerve activity and renal, but not splanchnic, sympLTF remained intact. ConclusionGreater tissue hypoxia likely impairs pLTF and splanchnic sympLTF post-C2Hx, although renal sympLTF remains intact. Increased sympathetic nerve activity post-mAIH may have therapeutic benefits in individuals living with chronic SCI since anticipated elevations in systemic blood pressure may mitigate hypotension characteristic of people living with SCI.

The role of ipsilateral motor network in upper limb movement.

The execution of voluntary movements is primarily governed by the cerebral hemisphere contralateral to the moving limb. Previous research indicates that the ipsilateral motor network, comprising the primary motor cortex (M1), supplementary motor area (SMA), and premotor cortex (PM), plays a crucial role in the planning and execution of limb movements. However, the precise functions of this network and its interplay in different task contexts have yet to be fully understood. Twenty healthy right-handed participants (10 females, mean age 26.1 ± 4.6years) underwent functional MRI scans while performing biceps brachii representations such as bilateral, unilateral flexion, and bilateral flexion-extension. Ipsilateral motor evoked potentials (iMEPs) were obtained from the identical set of participants in a prior study using transcranial magnetic stimulation (TMS) targeting M1 while employing the same motor tasks. The voxel time series was extracted based on the region of interest (M1, SMA, ventral PM and dorsal PM). Directed functinal connectivity was derived from the extracted time series using time-resolved partial directed coherence. We found increased connectivity from left-PMv to both sides M1, as well as right-PMv to both sides SMA, in unilateral flexion compared to bilateral flexion. Connectivity from left M1 to left-PMv, and left-SMA to right-PMd, also increased in both unilateral flexion and bilateral flexion-extension compared to bilateral flexion. However, connectivity between PMv and right-M1 to left-PMd decreased during bilateral flexion-extension compared to unilateral flexion. Additionally, during bilateral flexion-extension, the connectivity from right-M1 to right-SMA had a negative relationship with the area ratio of iMEP in the dominant side. Our results provide corroborating evidence for prior research suggesting that the ipsilateral motor network is implicated in the voluntary movements and underscores its involvement in cognitive processes such as movement planning and coordination. Moreover, ipsilateral connectivity from M1 to SMA on the dominant side can modulate the degree of ipsilateral M1 activation during bilateral antagonistic contraction.

Long-term high-altitude exposure influences task-related representations in visual working memory.

Human working memory is impaired when individuals are exposed to high altitudes, however, whether the capacity of visual working memory is affected remains unclear. This study combined a lateralized change detection task and event-related potentials analysis to explore changes in visual working memory capacity among individuals who emigrated from a low-altitude environment to Tibet (a high-altitude environment). Thirty-five college students were recruited from Tibet University as the high-altitude (HA) group, and thirty-six low-altitude (LA) students were enrolled from South China Normal University (sea level) as the LA group. We measured participants' contralateral delay activity (CDA) under different memory loads. ERP component analysis showed that both the HA and LA groups reached an asymptote at memory load four. However, the contralateral and ipsilateral activity of the HA and LA groups shows different patterns. The results showed a significantly larger contralateral activity for the LA group than for the HA group at memory load one (p = 0.04, Cohen's d = 0.52) and load three (p = 0.02, Cohen's d = 0.61). Additionally, we found marginally larger contralateral activity at memory load four for the LA group (p = 0.06, Cohen's d = 0.47), but not at memory load two (p = 0.10) or load five (p = 0.12). No significant differences were observed for ipsilateral activity. In addition, we observed that the HA group performed larger ipsilateral activity than contralateral activity under each memory load, compared with the LA group. These findings demonstrated that the attentional resource of long-term HA exposure is more captured by task-irrelevant information, potentially due to impaired inhibitory control, which makes it difficult for them to exclude the interference of task-irrelevant information.

Closed-loop electrical epidural stimulation restores ipsilesional in-phase diaphragm activity in spontaneously breathing rats after acute C2-hemisection

Epidural electrical stimulation has great promise for recovering many functions after spinal cord injury, including breathing. High-frequency stimulation of the thoracic [DiMarco and Kowalski, 2009] and cervical cord [Gonzalez-Rothi et al. 2017] recovers some phrenic and diaphragm activity. However, open-loop stimulation paradigms induce tonic activity and, thus far, have not elicited recovery of breathing function independent of the stimulation period. We have shown in C2-hemisected rats, closed-loop epidural stimulation (CLES; paced from contralateral diaphragm EMG activity) increases excitability in the respiratory motor network [Malone et al. 2022]; still, the ability of CLES to recover respiratory function following spinal cord injury has not been explored. Here, we hypothesized that CLES can elicit phasic ipsilesional diaphragm activity in C2-hemisected rats without tonic output. To test this, 3-5 month female Sprague-Dawley rats were anesthetized via inhaled isoflurane anesthetic, implanted with stimulating wire electrodes on the dorsal dura at C4 and recording electrodes bilaterally on the diaphragm, and C2-hemisected. After injury, a 15-30 minute recovery to ensure abolishment of ipsilateral diaphragm activity was followed by measurement of spinal motor evoked potentials of the diaphragm, and a baseline recording of diaphragm EMG activity. Biphasic CLES (n=3), set to an amplitude of ¼ the motor threshold, or a sham waiting period (n=3) was delivered for 20 minutes. EMG post processing was done in Spike2 using custom scripts. Stimulated animals received on average 101.8 +/- 22.8 Hz of stimulation during breaths. In stimulated animals, phasic ipsilesional diaphragm EMG activity significantly increased during stimulation (23.7 +/- 1.9 spikes per breath vs 4.32 +/- 1.9 at baseline, p &lt; 0.005). Stimulation did not increase tonic activity of the ipsilesional diaphragm, and ipsilesional diaphragm activity stopped with cessation of stim indicating no spontaneous recovery of activity. Additionally, there was no significant recovery of sham animals during the same period (5.2 +/- 1.9 vs 4.5 +/- 1.9 spikes per breath). Peak EMG activity and modulus of the contralesional diaphragm were significantly elevated from baseline during stimulation (peak value 0.19 +/- 0.015 V vs 0.15 +/- 0.005 V baseline p &lt; 0.05, % change modulus 34.9 +/- 5.9%, p &lt; 0.03). This work represents the first report that CLES can increase phasic diaphragm EMG activity both ipsi- and contralaterally after acute C2-hemisection. Further study is necessary to determine if CLES can elicit similar effects in a chronic model of injury. Additionally, work to determine the mechanism underlying these changes is essential to tailor this therapy for improving breathing function in individuals with spinal cord injury. T32HL134621, R01HL153102, SPARC OT2OD023854 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Post-ictal Rhythmic Thalamic Activity of the Centromedian Nucleus.

Deep brain stimulation of the centromedian nucleus of the thalamus (CMN) to treat drug-resistant epilepsy has been of interest for decades. However, little is known about the electrophysiological activity of the CMN during seizures. We describe a novel CMN EEG finding associated with seizure: post-ictal rhythmic thalamic activity. Five patients with drug-resistant epilepsy of unknown etiology with focal onset seizures underwent stereoelectroencephalography monitoring as part of evaluation for potential resective surgery or neuromodulation. Two patients had previously undergone complete corpus callosotomy and vagus nerve stimulation. A standardized plan for implantation included targets in the bilateral CMN. Each patient had frontal onset seizures, and two patients had additional insular, parietal, or mesial temporal onset seizures. Contacts of CMN were involved synchronously or rapidly after onset in most recorded seizures, particularly those with frontal onset. Focal onset hemiclonic and bilateral tonic-clonic seizures spread to involve cortical contacts with high-amplitude rhythmic spiking followed by abrupt offset with diffuse voltage attenuation. A post-ictal rhythmic 1.5 to 2.5 Hz delta frequency pattern, post-ictal rhythmic thalamic activity, emerged in CMN contacts amid the suppression of background activity in cortical contacts. In the two patients with corpus callosotomy, unilateral seizure spread and ipsilateral post-ictal rhythmic thalamic activity were observed. We observed post-ictal rhythmic thalamic activity in five patients with stereoelectroencephalography monitoring of the CMN with convulsive seizures. This rhythm appears late in ictal evolution and may signal an important role of the CMN in seizure termination. Furthermore, this rhythm may help identify CMN involvement in the epileptic network.

Continuous versus discrete robotic feedback for brain-computer interfaces aimed for neurorehabilitation.

Brain-Computer Interfaces (BCI) can allow control of external devices using motor imagery (MI) decoded from electroencephalography (EEG). Although BCI have a wide range of applications including neurorehabilitation, the low spatial resolution of EEG, coupled to the variability of cortical activations during MI, make control of BCI based on EEG a challenging task. An assessment of BCI control with different feedback timing strategies was performed. Two different feedback timing strategies were compared, comprised by passive hand movement provided by a robotic hand orthosis. One of the timing strategies, the continuous, involved the partial movement of the robot immediately after the recognition of each time segment in which hand MI was performed. The other feedback, the discrete, was comprised by the entire movement of the robot after the processing of the complete MI period. Eighteen healthy participants performed two sessions of BCI training and testing, one with each feedback. Significantly higher BCI performance (65.4 ± 17.9% with the continuous and 62.1 ± 18.6% with the discrete feedback) and pronounced bilateral alpha and ipsilateral beta cortical activations were observed with the continuous feedback. It was hypothesized that these effects, although heterogenous across participants, were caused by the enhancement of attentional and closed-loop somatosensory processes. This is important, since a continuous feedback timing could increase the number of BCI users that can control a MI-based system or enhance cortical activations associated with neuroplasticity, important for neurorehabilitation applications.

Revisiting differential control of sympathetic outflow by the rostral ventrolateral medulla.

The rostral ventrolateral medulla (RVLM) is an important brain region involved in both resting and reflex regulation of the sympathetic nervous system. Anatomical evidence suggests that as a bilateral structure, each RVLM innervates sympathetic preganglionic neurons on both sides of the spinal cord. However, the functional importance of ipsilateral versus contralateral projections from the RVLM is lacking. Similarly, during hypotension, the RVLM is believed to rely primarily on withdrawal of tonic gamma aminobutyric acid (GABA) inhibition to increase sympathetic outflow but whether GABA withdrawal mediates increased activity of functionally different sympathetic nerves is unknown. We sought to test the hypothesis that activation of the ipsilateral versus contralateral RVLM produces differential increases in splanchnic versus adrenal sympathetic nerve activities, as representative examples of functionally different sympathetic nerves. We also tested whether GABA withdrawal is responsible for hypotension-induced increases in splanchnic and adrenal sympathetic nerve activity. To test our hypothesis, we measured splanchnic and adrenal sympathetic nerve activity simultaneously in Inactin-anesthetized, male Sprague-Dawley rats during ipsilateral or contralateral glutamatergic activation of the RVLM. We also produced hypotension (sodium nitroprusside, i.v.) before and after bilateral blockade of GABAA receptors in the RVLM (bicuculline, 5mM 90nL). Glutamate (100mM, 30nL) injected into the ipsilateral or contralateral RVLM produced equivalent increases in splanchnic sympathetic nerve activity, but increased adrenal sympathetic nerve activity by more than double with ipsilateral injections versus contralateral injections (p < 0.05; n = 6). In response to hypotension, increases in adrenal sympathetic nerve activity were similar after bicuculline (p > 0.05), but splanchnic sympathetic nerve activity responses were eliminated (p < 0.05; n = 5). These results provide the first functional evidence that the RVLM has predominantly ipsilateral innervation of adrenal nerves. In addition, baroreflex-mediated increases in splanchnic but not adrenal sympathetic nerve activity are mediated by GABAA receptors in the RVLM. Our studies provide a deeper understanding of neural control of sympathetic regulation and insight towards novel treatments for cardiovascular disease involving sympathetic nervous system dysregulation.

Functional Neuroplasticity and Motor Skill Change Following Gross Motor Interventions for Children With Diplegic Cerebral Palsy

Background Gross motor intervention designs for children with diplegic cerebral palsy (DCP) require an improved understanding of the children’s potential for neuroplasticity. Objective To identify relations between functional neuroplasticity and motor skill changes following gross motor interventions for children with DCP. Methods There were 17 participants with DCP (ages 8-16 years; 6 females; Gross Motor Function Classification System Level I [n = 9] and II [n = 8]). Each completed a 6-week gross motor intervention program that was directed toward achievement of individualized motor/physical activity goals. Outcomes were assessed pre/post and 4 to 6 months post-intervention (follow-up). An active ankle dorsiflexion task was completed during functional magnetic resonance imaging. The ratio of motor cortical activation volume in each hemisphere was calculated using a laterality index. The Challenge was the primary gross motor skill measure. Change over time and relations among outcomes were evaluated. Results Challenge scores improved post-intervention (4.57% points [SD 4.45], P = .004) and were maintained at follow-up (0.75% [SD 6.57], P = 1.000). The laterality index for dominant ankle dorsiflexion increased (P = .033), while non-dominant change was variable (P = .534). Contralateral activation (laterality index ≥+0.75) was most common for both ankles. Challenge improvements correlated with increased ipsilateral activity (negative laterality index) during non-dominant dorsiflexion (r = −.56, P = .045). Smaller activation volume during non-dominant dorsiflexion predicted continued gross motor gains at follow-up (R2 = .30, P = .040). Conclusions Motor cortical activation during non-dominant ankle dorsiflexion is a modest indicator of the potential for gross motor skill change. Further investigation of patterns of neuroplastic change will improve our understanding of effects. ClinicalTrials.gov Registry: NCT02584491 and NCT02754128

In vivo inhibition of epileptiform afterdischarges in rat hippocampus by light-activated chloride channel, stGtACR2.

The blue light-sensitive chloride-conducting opsin, stGtACR2, provides potent optogenetic silencing of neurons. The present study investigated whether activation of stGtACR2 in granule cells of the dentate gyrus (DG) inhibits epileptic afterdischarges in a rat model. Rats were bilaterally injected with 0.9 μl of AAV2/7-CaMKIIα-stGtACR2-fusionred in the DG. Three weeks later, afterdischarges were recorded from the DG by placing an optrode at the injection site and a stimulation electrode in the perforant path (PP). Afterdischarges were evoked every 10 min by unilateral electrical stimulation of the PP (20 Hz, 10 s). During every other afterdischarge, the DG was illuminated for 5 or 30 s, first ipsilaterally and then bilaterally to the PP stimulation. The line length metric of the afterdischarges was compared between illumination conditions. Ipsilateral stGtACR2 activation during afterdischarges decreased the local field potential line length only during illumination and specifically at the illuminated site but did not reduce afterdischarge duration. Bilateral illumination did not terminate the afterdischarges. Optogenetic inhibition of excitatory neurons using the blue-light sensitive chloride channel stGtACR2 reduced the amplitude of electrically induced afterdischarges in the DG at the site of illumination, but this local inhibitory effect was insufficient to reduce the duration of the afterdischarge.