Cortical Level Research Articles

Neuronavigation maximizes accuracy and precision in TMS positioning: Evidence from 11,230 distance, angle, and electric field modeling measurements

BackgroundResearchers and clinicians have traditionally relied on elastic caps with markings to reposition the transcranial magnetic stimulation (TMS) coil between trains and sessions. Newer neuronavigation technology co-registers the patient's head and structural magnetic resonance imaging (MRI) scan, providing the researcher with real-time feedback about how to adjust the coil to be on-target. However, there has been no head to head comparison of accuracy and precision across treatment sessions. Objective/Hypothesis: In this two-part study, we compared elastic cap and neuronavigation targeting methodologies on distance, angle, and electric field (E-field) magnitude values. MethodsIn 42 participants receiving up to 50 total accelerated rTMS sessions in 5 days, we compared cap and neuronavigation targeting approaches in 3408 distance and 6816 angle measurements. In Experiment 1, TMS administrators saved an on-target neuronavigation location at Beam F3, which served as the landmark for all other measurements. Next, the operators placed the TMS coil based on cap markings or neuronavigation software to measure the distance and angle differences from the on-target sample. In Experiment 2, we saved each XYZ coordinate of the TMS coil from cap and neuronavigation targeting in 12 participants to compare the E-field magnitude differences at the cortical prefrontal target in 1106 cap and neuronavigation models. ResultsCap targeting was significantly off-target for distance, placing the coil an average of 10.66 mm off-target (Standard error of the mean; SEM = 0.19 mm) compared to 0.3 mm (SEM = 0.03 mm) for neuronavigation (p < 0.0001). Cap targeting also significantly deviated for angles off-target, averaging 7.79 roll/pitch degrees (SEM = 1.07°) off-target and 5.99 yaw degrees (SEM = 0.12°) off-target; in comparison, neuronavigation targeting positioned the coil 0.34 roll/pitch degrees (SEM = 0.01°) and 0.22 yaw (SEM = 0.004°) off-target (both p < 0.0001). Further analyses revealed that there were significant inter-operator differences on distance and angle positioning for F3 (all p < 0.05), but not neuronavigation. Lastly, cap targeting resulted in significantly lower E-fields at the intended prefrontal cortical target, with equivalent E-fields as 110.7% motor threshold (MT; range = 58.3–127.4%) stimulation vs. 119.9% MT (range = 115–123.3%) from neuronavigated targeting with 120% MT stimulation applied (p < 0.001). ConclusionsCap-based targeting is an inherent source of target variability compared to neuronavigation. Additionally, cap-based coil placement is more prone to differences across operators. Off-target coil placement secondary to cap-based measurements results in significantly lower amounts of stimulation reaching the cortical target, with some individuals receiving only 48.6% of the intended on-target E-field. Neuronavigation technology enables more precise and accurate TMS positioning, resulting in the intended stimulation intensities at the targeted cortical level.

Low test-retest reliability of a protocol for assessing somatosensory cortex excitability generated from sensory nerves of the lower back.

In people with chronic low back pain (CLBP), maladaptive structural and functional changes on a cortical level have been identified. On a functional level, somatosensory cortical excitability has been shown to be reduced in chronic pain conditions, resulting in cortical disinhibition. The occurrence of structural and/or functional maladaptive cortical changes in people with CLBP could play a role in maintaining the pain. There is currently no measurement protocol for cortical excitability that employs stimulation directly to the lower back. We developed a protocol for the measurement of single pulse somatosensory evoked potential (SEP) waveforms and paired-pulse behavior (PPB) generated from sensory nerves of the lower back and quantified its test–retest reliability in a sample of 30 healthy individuals to gain insights into the normal variability of cortical responses, which could then be compared to results from people with CLBP. We investigated cortical excitability by measuring SEPs and PPB. PPB was defined as the ratio of the amplitude of the second cortical response (A2s) divided by the first cortical response (A1). A2s was determined by subtracting the response to single-pulse stimuli from the paired pulse stimuli response to account for linear superposition effects. The test–retest reliability of the protocol was very poor with no evidence of systematic bias but a high amount of random variability between sessions. There was no significant difference in the right side PPB for session 1 (Mean ratio A2s/A1 = 0.66, SD = 0.54) and session 2 (Mean ratio A2s/A1 = 0.94, SD = 1.56); mean session difference [(95% CI) = −0.44 (−1.23 to 0.34); t (22) = −1.17, p = 0.26]. The ICC3.1 (absolute agreement) for the outlier-removed right side PPB were 0.19 (95% CI: −0.84 to 0.66) and 0.43 for left side PPB (95% CI: −0.37 to 0.76). This finding potentially has wider implications for PPB protocols. If these findings were replicated in other groups and other nerves, it would question the validity of this measure more generally. However, these findings are restricted to healthy people and sensory nerves of the lower back and may not be generalizable.

Comparison of machine learning methods for the detection of focal cortical dysplasia lesions: decision tree, support vector machine and artificial neural network

ABSTRACT Background Accurate classification of focal cortical dysplasia (FCD) has been challenging due to the problematic visual detection in magnetic resonance imaging (MRI). Hence, recently, there has been a necessity for employing new techniques to solve the problem. Among the new techniques for FCD lesion diagnosis, classification techniques can be of great help in FCD patient’s detection from healthy individuals. Methods MRI data were collected from 58 participants (30 subjects with FCD type II and 28 normal subjects). Morphological and intensity-based characteristics were calculated for each cortical level and then the performance of the three classifiers: decision tree (DT), support vector machine (SVM) and artificial neural network (ANN) was evaluated. Results Metrics for evaluating classification methods, sensitivity, specificity and accuracy for the DT were 90%, 100% and 95.8%, respectively; it was 95%, 100% and 97.9% for the SVM and 96.7%, 100% and 98.6% for the ANN. Conclusion Comparison of the performance of the three classifications used in this study showed that all three have excellent performance in specificity, but in terms of classification sensitivity and accuracy, the artificial neural network method has worked better.

Neural responses in human superior temporal cortex support coding of voice representations.

The ability to recognize abstract features of voice during auditory perception is an intricate feat of human audition. For the listener, this occurs in near-automatic fashion to seamlessly extract complex cues from a highly variable auditory signal. Voice perception depends on specialized regions of auditory cortex, including superior temporal gyrus (STG) and superior temporal sulcus (STS). However, the nature of voice encoding at the cortical level remains poorly understood. We leverage intracerebral recordings across human auditory cortex during presentation of voice and nonvoice acoustic stimuli to examine voice encoding at the cortical level in 8 patient-participants undergoing epilepsy surgery evaluation. We show that voice selectivity increases along the auditory hierarchy from supratemporal plane (STP) to the STG and STS. Results show accurate decoding of vocalizations from human auditory cortical activity even in the complete absence of linguistic content. These findings show an early, less-selective temporal window of neural activity in the STG and STS followed by a sustained, strongly voice-selective window. Encoding models demonstrate divergence in the encoding of acoustic features along the auditory hierarchy, wherein STG/STS responses are best explained by voice category and acoustics, as opposed to acoustic features of voice stimuli alone. This is in contrast to neural activity recorded from STP, in which responses were accounted for by acoustic features. These findings support a model of voice perception that engages categorical encoding mechanisms within STG and STS to facilitate feature extraction.

Acetyl-dl-leucine in cerebellar ataxia ([18F]-FDG-PET study): how does a cerebellar disorder influence cortical sensorimotor networks?

ObjectiveThe aim of the study was to deepen our insights into central compensatory processes of brain networks in patients with cerebellar ataxia (CA) before and with treatment with acetyl-dl-leucine (AL) by means of resting-state [18F]-FDG-PET brain imaging.MethodsRetrospective analyses of [18F]-FDG-PET data in 22 patients with CA (with vestibular and ocular motor disturbances) of different etiologies who were scanned before (PET A) and on AL treatment (PET B). Group subtraction analyses, e.g., for responders and non-responders, comparisons with healthy controls and correlation analyses of regional cerebral glucose metabolism (rCGM) with symptom duration, ataxia (SARA) and quality of life (QoL) scores were calculated.ResultsPrior to treatment rCGM was consistently downregulated at the cerebellar level and increased in multisensory cortical areas, e.g., somatosensory, primary and secondary visual (including V5, precuneus), secondary vestibular (temporal gyrus, anterior insula), and premotor/supplementary motor areas. With AL (PET B vs. A) cerebellar hypometabolism was deepened and sensorimotor hypermetabolism increased only in responders with clinical benefit, but not for the non-responders and the whole CA group. A positive correlation of ataxia improvement with rCGM was found in visual and vestibular cortices, a negative correlation in cerebellar and brainstem areas. QoL showed a positive correlation with rCGM in the cerebellum and symptom duration in premotor and somatosensory areas.ConclusionsCentral compensatory processes in CA mainly involve multisensory visual, vestibular, and somatosensory networks as well as premotor/primary motor areas at the cortical level. The enhanced divergence of cortical sensorimotor up- and cerebellar downregulation with AL in responders could reflect amplification of inhibitory cerebellar mechanisms.

Relation between Cortical Activation and Effort during Robot-Mediated Walking in Healthy People: A Functional Near-Infrared Spectroscopy Neuroimaging Study (fNIRS).

Force and effort are important components of a motor task that can impact rehabilitation effectiveness. However, few studies have evaluated the impact of these factors on cortical activation during gait. The purpose of the study was to investigate the relation between cortical activation and effort required during exoskeleton-mediated gait at different levels of physical assistance in healthy individuals. Twenty-four healthy participants walked 10 m with an exoskeleton that provided four levels of assistance: 100%, 50%, 0%, and 25% resistance. Functional near-infrared spectroscopy (fNIRS) was used to measure cerebral flow dynamics with a 20-channel (plus two reference channels) device that covered most cortical motor regions bilaterally. We measured changes in oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR). According to HbO2 levels, cortical activation only differed slightly between the assisted conditions and rest. In contrast, bilateral and widespread cortical activation occurred during the two unassisted conditions (somatosensory, somatosensory association, primary motor, premotor, and supplementary motor cortices). A similar pattern was seen for HbR levels, with a smaller number of significant channels than for HbO2. These results confirmed the hypothesis that there is a relation between cortical activation and level of effort during gait. This finding should help to optimize neurological rehabilitation strategies to drive neuroplasticity.

Light-induced charge generation in polymeric nanoparticles restores vision in advanced-stage retinitis pigmentosa rats

Retinal dystrophies such as Retinitis pigmentosa are among the most prevalent causes of inherited legal blindness, for which treatments are in demand. Retinal prostheses have been developed to stimulate the inner retinal network that, initially spared by degeneration, deteriorates in the late stages of the disease. We recently reported that conjugated polymer nanoparticles persistently rescue visual activities after a single subretinal injection in the Royal College of Surgeons rat model of Retinitis pigmentosa. Here we demonstrate that conjugated polymer nanoparticles can reinstate physiological signals at the cortical level and visually driven activities when microinjected in 10-months-old Royal College of Surgeons rats bearing fully light-insensitive retinas. The extent of visual restoration positively correlates with the nanoparticle density and hybrid contacts with second-order retinal neurons. The results establish the functional role of organic photovoltaic nanoparticles in restoring visual activities in fully degenerate retinas with intense inner retina rewiring, a stage of the disease in which patients are subjected to prosthetic interventions.

Response of the somatosensory cortex following thermal stimuli to dental implants

In the current study, we investigated the cortical response of the somatosensory cortex following thermal stimuli to dental implants. Five implants were inserted at the site of the left upper canine with immediate implant placement protocols in five cats. Intrinsic signal optical imaging was applied to measure the cortical responses evoked by thermal sensing via dental implants. The cortical response evoked by 60 g of tactile stimulus to implants was also examined. The response strength and activated location were compared between implants and natural teeth. Thermal stimuli via the implant could evoke reliable cortical responses in the tooth-related region. However, the response amplitude evoked by the cold stimuli applied to the implants was significantly lower than that evoked by the cold stimuli applied to the natural teeth, indicating that the implants were less sensitive to thermal change than the natural tooth. The response evoked by tactile stimuli to implants was significantly stronger than that evoked by cold stimuli. Thermal and tactile stimuli activated the same location of the tooth-related somatosensory cortex in both the implants and natural teeth. Therefore, the thermal change in implants could be detected at the cortical response level. Multimodal sensory integration of thermal and tactile functions existed for implants.

Cortical Reorganization Following Psychoeducational Counselling and Residual Inhibition Therapy (RIT) in Individuals with Tinnitus.

Introduction Psychoeducational counselling and residual inhibition therapy (RIT) are traditional approaches used in many clinics to manage tinnitus. However, neurophysiological studies to evaluate posttreatment perceptual and functional cortical changes in humans are scarce. Objectives The present study aims to explore whether cortical auditory-evoked potentials (CAEPs; N1 and P3) reflect the effect of modified RIT and psychoeducational counselling, and whether there is a correlation between the behavioral and electrophysiological measures. Methods Ten participants with continuous and bothersome tinnitus underwent a session of psychoeducational counselling and modified RIT. Perceptual measures and CAEPs were recorded pre- and posttreatment. Further, the posttreatment measures were compared with age and gender-matched historical control groups. Results Subjectively, 80% of the participants reported a reduction in the loudness of their tinnitus. Objectively, there was a significant reduction in the posttreatment amplitude of N1 and P3, with no alterations in latency. There was no correlation between the perceived difference in tinnitus loudness and the difference in P3 amplitude (at Pz). Conclusion The perceptual and functional (as evidenced by sensory, N1, and cognitive, P3 reduction) changes after a single session of RIT and psychoeducational counselling are suggestive of plastic changes at the cortical level. The current study serves as preliminary evidence that event-related potentials (ERPs) can be used to quantify the physiological changes that occur after the intervention for tinnitus.

Short-Latency Afferent Inhibition Correlates with Stage of Disease in Parkinson's Patients.

Sensory-motor decoupling at the cortical level involving cholinergic circuitry has also been reported in Parkinson's Disease (PD). Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) paradigm that has been used previously to probe cortical cholinergic circuits in well-characterised subgroups of patients with PD. In the current study, we compared SAI in a cohort of PD patients at various stages of disease and explored correlations between SAI and various clinical measures of disease severity. The modified Hoehn and Yahr (H&Y) scale was used to stage disease in 22 patients with PD. Motor and cognitive function were assessed using the MDS-UPDRS (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale) part III and MoCA (Montreal Cognitive Assessment) score, respectively. Objective gait assessment was performed using an electronic walkway (GAITRite®). SAI was measured as the average percentage inhibition of test motor-evoked potentials (MEPs) conditioned by electrical stimulation of the contralateral median nerve at the wrist. SAI was significantly reduced in patients with advanced PD (H&Y stage 3) compared to early PD patients (H&Y stage 1) on pairwise comparison. The visuospatial executive function and orientation domains of cognition demonstrated significant negative associations with SAI. Cortical sensory-motor integration is progressively diminished as disease progresses. The observation that a reduction in SAI is associated with a reduction in cognitive function possibly reflects the progressive involvement of cortical cholinergic circuits in PD with increasing motor stage. Future longitudinal studies are necessary to confirm this preliminary result.

Microgravity induced resting state networks and metabolic alterations during sleep onset

There is concrete evidence that weightlessness and microgravity may affect sleep quality. However, most of the studies failed to provide an integrative understanding of sleep disorders. This study proposes a novel, multi-modal, data-driven model for identifying the detrimental factors that are crucial for sleep quality. Its aim is to quantify the impact of weightlessness on cortical functional connectivity and metabolic blood biomarkers. It also investigates the efficacy of the Reactive Sledge Jump as a countermeasure.The study involves healthy volunteers assigned either to a control or to a sledge group. The data include polysomnographic recordings and blood biomarkers. Reconstruction of the cortical resting-state networks through the sLORETA methodology is performed. Then, functional connectivity is obtained, and regression models are developed to explain the variance of the sleep macro-architecture characteristics.The study results indicate that neither the bed rest nor the countermeasure affect sleep macro-architecture or the biomarkers under consideration. There are statistically significant functional connectivity alterations within the alpha band. There are significant correlations among all the three biomarkers and sleep quality characteristics. Glucose and prolactin values can predict the sleep onset latency, whereas insulin and group (countermeasure or control) predict the number of awakenings. Finally, the biomarker values are significantly correlated with functional connectivity interactions.Our findings provide evidence that sleep disorders occur firstly at a cortical level following a non-uniform pattern. These disorders are evident as cortical connectivity disruptions before their clinical manifestation as biomarkers’ alterations or deterioration in terms of sleep characteristics. The proposed methodology highlights the significance of a personalized, multi-parametric evaluation of sleep quality which is able to identify sleep disorders prior to their clinical onset.

Imagery and perception: where is the phenomenological line?

IntroductionThe overlap between imagery and perception has long fascinated philosophers and scientists. Many scientists considered how the mind is capable of constructing an internal world without intervention of the external environment. Descriptions of their core characteristics often draw attention to differential features, but other currents reveal that many of these are shared rather than unique and differential.ObjectivesThe authors aim to analyse and discuss conceptualisation, similarities and differences of imagery and perception at the level of phenomenology, at the intersection with other psychopathological concepts, and thus reassemble them within a common framework.MethodsA brief literature review was developed based on relevant works containing subject matter most relevant to the topic.ResultsPerception is conceived as a transformation of raw sensory stimuli into sensory information that is then decoded into meaningful at the cortical level. Imagery, in turn, corresponds to the internal mental representation of the world, actively drawn from memory. The differentiation between these concepts at a phenomenological level is analysed and discussed. Additionally, their individual role is evaluated in the pshycopathological expression of alterations of perception such as hallucinations, pseudohallucinations, pareidolic illusions, abnormal imagery, sensory deprivation and also of dreams, in an analytical perspective of integration and simultaneous conceptual differentiation.ConclusionsUnderstanding imagery, its nature and formal characteristics is required for better recognising the nature of perceptions and related psychopathological alterations, as well as the mechanisms uniting these concepts. Further research is needed as these entities represent features of useful clinical and diagnostic significance.DisclosureNo significant relationships.

The monoclonal CGRP-receptor blocking antibody erenumab has different effects on brainstem and cortical sensory-evoked responses.

It is unclear whether the electrophysiological effects of erenumab, a monoclonal antibody against the calcitonin gene-related peptide receptor, occur only at the periphery of the trigeminal system or centrally and at the cortical level. We prospectively enrolled 20 patients with migraine who had failed at least two preventative treatments. We measured the nociceptive blink reflex and non-noxious somatosensory evoked potentials in all participants. The area under the curve and habituation of the second polysynaptic nociceptive blink reflex component (R2) as well as the amplitude and habituation of somatosensory evoked potentials N20-P25 were measured. Electrophysiological data were collected at baseline (T0), 28 days (T1), and 56 days (T2) before each injection of erenumab (70 mg). Erenumab reduced the patients' mean monthly headache days, headache intensity, and acute medication intake considerably at T1 and T2 (all p < 0.05). The nociceptive blink reflex area under the curve was considerably lower at T1 and T2 than at baseline without changing the habituation slope. At T2, there was a significant increase in the delayed somatosensory evoked potentials amplitude reduction (habituation) but not in the initial cortical activation. Our findings showed that erenumab, in addition to its well-known peripheral effects, can induce central effects earlier in the brainstem and later in the cortex. We cannot rule out whether these results are due to a direct effect of erenumab on the central nervous system or an indirect effect secondary to peripheral drug modulation.

Acoustic change complex using short duration stimuli in normal hearing children: temporal resolution and frequency discrimination

Objective Acoustic Change Complex (ACC) is a cortical auditory evoked potential elicited in response to a change in an ongoing sound. Since it is supposed to reflect auditory discrimination at the cortical level, recording of this potential has recently gained much attention. From a technical standpoint, the stimulus used should be long enough to accommodate the needed change. This research addresses the development and standardization of short duration tonal stimuli which can be implemented in most of the Evoked Potential (EP) equipment used in regular Audiology clinics. Methods Short duration tonal stimuli (500 msec.) were generated and edited using Audacity software. Temporal change was done using gap-in-tones stimuli (6, 10, 30 and 50 msec. in 1000 Hz tone). Frequency change was represented by frequency pairs (2%, 4%, 10% and 25% change from 1000 Hz base frequency). The developed stimuli were then used to generate ACC potential in 41 normal hearing children ranging in age from 2 to 10 years. A comparison was held between ACC response recorded using the different stimuli in reference to percent identifiability, morphology, latency and amplitude measures. Results Gap-in-tones at 10 msec. and 4% frequency change could elicit ACC response in 100% of subjects. ACC had the same morphology of the onset response in the majority of subjects, with longer latency and smaller amplitude. ACC amplitude was consistently affected by magnitude of change. Conclusion ACC was successfully recorded in 100% of normal hearing children using the developed short duration tonal stimuli for temporal change (10 msec.) and frequency change (4%). These stimuli can be uploaded in clinical EP equipment. ACC amplitude could be a better indicator of cortical discrimination compared to latency.

Cortical beta burst dynamics are altered in Parkinson's disease but normalized by deep brain stimulation

Exaggerated subthalamic beta oscillatory activity and increased beta range cortico-subthalamic synchrony have crystallized as the electrophysiological hallmarks of Parkinson's disease. Beta oscillatory activity is not tonic but occurs in ‘bursts’ of transient amplitude increases. In Parkinson's disease, the characteristics of these bursts are altered especially in the basal ganglia. However, beta oscillatory dynamics at the cortical level and how they compare with healthy brain activity is less well studied. We used magnetoencephalography (MEG) to study sensorimotor cortical beta bursting and its modulation by subthalamic deep brain stimulation in Parkinson's disease patients and age-matched healthy controls. We show that the changes in beta bursting amplitude and duration typical of Parkinson's disease can also be observed in the sensorimotor cortex, and that they are modulated by chronic subthalamic deep brain stimulation, which, in turn, is reflected in improved motor function at the behavioural level. In addition to the changes in individual beta bursts, their timing relative to each other was altered in patients compared to controls: bursts were more clustered in untreated Parkinson's disease, occurring in ‘bursts of bursts’, and re-burst probability was higher for longer compared to shorter bursts. During active deep brain stimulation, the beta bursting in patients resembled healthy controls’ data. In summary, both individual bursts’ characteristics and burst patterning are affected in Parkinson's disease, and subthalamic deep brain stimulation normalizes some of these changes to resemble healthy controls’ beta bursting activity, suggesting a non-invasive biomarker for patient and treatment follow-up.

Real-Time Neuropsychological Testing of Sensorimotor Cognition During Awake Surgery in Precentral and Postsomatosensory Areas

For patients undergoing brain surgery, once primary motor and sensory areas are identified by direct electrical stimulation, resection can be performed in the precentral and postsomatosensory areas while monitoringcognition. For this purpose, we developed a real-time neuropsychological testing (RTNT) protocol tappingsensorimotor cognition. We retrospectively reviewed a consecutive series of 57 adult patients with tumors in the precentral and postsomatosensory areas who performed the RTNT sequence. The testing protocol used continuously throughout resection for excisions comprised action verbs, mental rotation of body parts, action imagery, action semantics, ideomotor praxis, and short-term memory. The patients' median performance on RTNT tests was significantly lower for mental rotation and action imagery (χ2 (2) = 55.98, P < 0.001), as well as their minimumvalue of patients' performance (χ2 (2) = 85.048, P< 0.001) and their delta calculated between the patients' performance at the first versus the last RTNT run (χ2(2)=14.33, P < 0.05). Patients showing such decreases in performance on action imagery had lesions overlapping on the right precentral and postcentral gyrus, the supplementary motor area, and the superior and inferior parietal lobe. For the mental rotation task, their maximum lesion overlay included the right cingulum/supplementary motor area and left superior and inferior parietal lobe and medial precuneus. The mean resection extent was 91.15% ± 17.45 and correlated with the number of motor-related positive sites found by the direct electrical stimulation at cortical (r= -0.279, P = 0.020) and white matter (r = -0.417, P= 0.001) level. The sensory-motor RTNT is performed to assist surgery in the precentral and postsomatosensory areas.

Electroencephalographic Measurement on Post-stroke Sensory Deficiency in Response to Non-painful Cold Stimulation.

BackgroundReduced elementary somatosensation is common after stroke. However, the measurement of elementary sensation is frequently overlooked in traditional clinical assessments, and has not been evaluated objectively at the cortical level. This study designed a new configuration for the measurement of post-stroke elementary thermal sensation by non-painful cold stimulation (NPCS). The post-stroke cortical responses were then investigated during elementary NPCS on sensory deficiency via electroencephalography (EEG) when compared with unimpaired persons.MethodTwelve individuals with chronic stroke and fifteen unimpaired controls were recruited. A 64-channel EEG system was used to investigate the post-stroke cortical responses objectively during the NPCS. A subjective questionnaire of cold sensory intensity was also administered via a numeric visual analog scale (VAS). Three water samples with different temperatures (i.e., 25, 10, and 0°C) were applied to the skin surface of the ventral forearm for 3 s via glass beaker, with a randomized sequence on either the left or right forearm of a participant. EEG relative spectral power (RSP) and topography were used to evaluate the neural responses toward NPCS with respect to the independent factors of stimulation side and temperature.ResultsFor unimpaired controls, NPCS initiated significant RSP variations, mainly located in the theta band with the highest discriminative resolution on the different temperatures (P < 0.001). For stroke participants, the distribution of significant RSP spread across all EEG frequency bands and the temperature discrimination was lower than that observed in unimpaired participants (P < 0.05). EEG topography showed that the NPCS could activate extensive and bilateral sensory cortical areas after stroke. Significant group differences on RSP intensities were obtained in each EEG band (P < 0.05). Meanwhile, significant asymmetry cortical responses in RSP toward different upper limbs were observed during the NPCS in both unimpaired controls and participants with stroke (P < 0.05). No difference was found between the groups in the VAS ratings of the different temperatures (P > 0.05).ConclusionThe post-stroke cortical responses during NPCS on sensory deficiency were characterized by the wide distribution of representative RSP bands, lowered resolution toward different temperatures, and extensive activated sensory cortical areas.

FC027: Uric Acid Stimulates Cytoskeleton Pathways in Vascular Smooth Muscle Cells Through F-ACTIN Polymerization and Atrogin, Αsma and SM22 up Regulation

Abstract BACKGROUND AND AIMS Hyperuricaemia (HU) has been identified as a risk factor for hypertension and renal disease. The most widely documented pathogenetic mechanisms for the uric acid (UA) mediated vascular and renal damage are vascular inflammation and remodeling. Vascular smooth muscle cells (VSMCs) possess a distinctive property of plasticity that allows the phenotypic transition and contributes to vascular remodeling. The aim of this study was to investigate UA effects on VSMC cell line, focusing on phenotypic transition and searching for possible signals involved in this process. METHOD MOVAS, a mouse VSMC cell line, was exposed for short (0–6 h) or long time (24–48 h) to 0 (No Treated cells: NT), 6, 9 and 12 mg/dL of UA, respectively. We evaluated cell viability by MTT test, migration property in a 48-well microchemotaxis chamber (using an 8 μm pore size, polycarbonate polyvinylpyrrolidone-free filters) and by phalloidin staining. Changes in cytoskeleton proteins [Smoothelin (SMT), alpha-Smooth Muscle Actin (αSMA), Smooth Muscle 22 Alpha (SM 22α)] were detected by real time polymerase chain reaction (rt-PCR) and Western blot. In addition, we evaluated angiotensin receptor 1 (AT1) and atrogin 1 expression by rt-PCR and Map kinase activation (Erk 1,2) by western blot. Lastly, we tested the UA effects on cellular changes through a prior treatment with angiotensin receptor blockers, Valsartan (V) and Losartan (L) 10 µmol. RESULTS A small increment in cell proliferation was observed at 24 h (+11%–15%; P &amp;lt; 0.05). UA promoted an increased migratory rate in UA treated VSMCs at 24 and 48 h respect to untreated cells (P &amp;lt; 0.001). These results were confirmed by F-actin intracellular distribution: the AlexaFluor 594-conjugate-phalloidin staining revealed a compact polymerization of F-actin in stress fibers along the major cell axis in untreated cells, while a re-arrangement in thinner and poorly oriented fibers localized at cortical level were found in UA treated cells (Fig. 1). When we evaluated cytoskeleton components, we found out that 24 h UA exposition rose up, SMT (2.5–3.4-fold; P &amp;lt; 0.05), αSMA (1.3–1.5-fold; P &amp;lt; 0.05) and SM 22α levels (1.3–2.5-fold P &amp;lt; 0.05). Conversely, we found a 48 h UA treatment caused them to drop (SMT = –20%–40%, P &amp;lt; 0.05; αSMA = –20%–40%, P &amp;lt; 0.05; SM 22α = –30%–43%, P &amp;lt; 0.05). Atrogin-1 was 2-fold up regulated at 48 h in UA treated VMSCs compared with NT (P = 0.04), suggesting a possible role for UA in cytoskeleton remodeling (Fig. 2). Furthermore, we observed a significant increase in VSMC area (+30%; P &amp;lt; 0.001) regardless of UA concentration and time exposition. Supposing a key role of Angiotensin involvement in UA induced VSMCs changes, AT1 expression was assessed. We found AT1 was up regulated in UA treated VSMCs compared with NT (P = 0.04). As expected, V and L had inhibitory effects on AT1 upregulation. Moreover, the two angiotensin receptors blockers inhibited all the phenotypic changes induced by UA. Lastly, UA induced a time dependent Erk 1, 2 phosphorylation (1.5–2.5-fold versus T0; P &amp;lt; 0.05–0.01), which was reversed by both L and V. CONCLUSION The results of this study show for the first time as UA-induced cytoskeletal changes involve polymerization of F-actin, Atrogin, αSMA and up-regulation of SM22.These results reveal the pathways by which UA induces an increase in VSMC area and in migratory rate, suggesting UA as a key player in vascular remodeling.

Color Compensatory Mechanism of Chromatic Adaptation at the Cortical Level.

Reportedly, some chromatic adaptations have extremely short temporal properties, while others have rather long ones. We aimed to dynamically measure the transition of a neutral point as an aftereffect during chromatic adaptation to understand the temporal characteristics of chromatic adaptation. The peripheral retina was exposed to a yellow light to progress color adaptation, while the transition of a neutral point was measured at the fovea. In Experiment 1, the aftereffect had initially progressed but subsequently recovered despite ongoing chromatic adaptation and regardless of the retinal exposure size, suggesting that the adaptation mechanism at the cortical level continues to readjust the color appearance based on daylight conditions. Experiment 2 was similar to Experiment 1, except that it included participants of varying ages. Older eyes behaved in a homologous manner with younger eyes in Experiment 2, albeit quantitative differences. Regardless of age, similar recalibration of neutral points shifted by color adaptation suggests the color compensation function in older eyes may not change due to long-term chromatic adaptation by optical yellowing. In conclusion, the chromatic adaptation mechanism at the cortical level readjusts color perception, even in younger eyes, according to the daylight neutral point. This daylight information may be stored in the neural mechanism of color vision.

Don't Stop Me Now: Neural Underpinnings of Increased Impulsivity to Temporally Predictable Events.

Although the benefit of temporal predictability for behavior is long-established, recent studies provide evidence that knowing when an important event will occur comes at the cost of greater impulsivity. Here, we investigated the neural basis of inhibiting actions to temporally predictable targets using an EEG-EMG method. In our temporally cued version of the stop-signal paradigm (two-choice task), participants used temporal information delivered by a symbolic cue to speed their responses to the target. In a quarter of the trials, an auditory signal indicated that participants had to inhibit their actions. Behavioral results showed that although temporal cues speeded RTs, they also impaired the ability to stop actions as indexed by longer stop-signal reaction time. In line with behavioral benefits of temporal predictability, EEG data demonstrated that acting at temporally predictable moments facilitated response selection at the cortical level (reduced frontocentral negativity just before the response). Likewise, activity of the motor cortex involved in suppression of incorrect response hand was stronger for temporally predictable events. Thus, by keeping an incorrect response in check, temporal predictability likely enabled faster implementation of the correct response. Importantly, there was no effect of temporal cues on the EMG-derived index of online, within-trial inhibition of subthreshold impulses. This result shows that although participants were more prone to execute a fast response to temporally predictable targets, their inhibitory control was, in fact, unaffected by temporal cues. Altogether, our results demonstrate that greater impulsivity when responding to temporally predictable events is paralleled by enhanced neural motor processes involved in response selection and implementation rather than impaired inhibitory control.