Electrophysiological Differences Research Articles

Sex-related differences in incidence, phenotype and risk of sudden cardiac death in inherited arrhythmia syndromes.

Inherited Arrhythmia Syndromes (IAS) including long QT and Brugada Syndrome, are characterized by life-threatening arrhythmias in the absence of apparent structural heart disease and are caused by pathogenic variants in genes encoding cardiac ion channels or associated proteins. Studies of large pedigrees of families affected by IAS have demonstrated incomplete penetrance and variable expressivity. Biological sex is one of several factors that have been recognized to modulate disease severity in IAS. There is a growing body of evidence linking sex hormones to the susceptibility to arrhythmias, yet, many sex-specific disease aspects remain underrecognized as female sex and women with IAS are underinvestigated and findings from male-predominant cohorts are often generalized to both sexes with minimal to no consideration of relevant sex-associated differences in prevalence, disease manifestations and outcome. In this review, we highlight current knowledge of sex-related biological differences in normal cardiac electrophysiology and sex-associated factors that influence IAS phenotypes.

The effect of sex and age on ex vivo cardiac electrophysiology: insight from a guinea pig model.

Highlighting the importance of sex as a biological variable, we recently reported sex differences in guinea pig in vivo electrocardiogram (ECG) measurements. However, substantial inconsistencies exist in this animal model, with conflicting reports of sex-specific differences in cardiac electrophysiology observed in vivo and in vitro. Herein, we evaluated whether sexual dimorphism persists in ex vivo preparations, using an isolated intact heart preparation. Pseudo-ECG recordings were collected in conjunction with dual optical mapping of transmembrane voltage and intracellular calcium from Langendorff-perfused hearts. In contrast to our in vivo results, we did not observe sex-specific differences in ECG parameters collected from isolated hearts. Furthermore, we observed significant age-specific differences in action potential duration (APD) and Ca2+ transient duration (CaD) during both normal sinus rhythm (NSR) and in response to dynamic pacing but only a modest sex-specific difference in CaD30. Similarly, the alternans fluctuation coefficient, conduction velocity during sinus rhythm or in response to pacing, and electrophysiology parameters (atrioventricular nodal effective refractory period, Wenckebach cycle length) were comparable between males and females. Results of our study suggest that the observed sex-specific differences in in vivo ECG parameters from guinea pigs are diminished in ex vivo isolated heart preparations, although age-specific patterns are prevalent. To assess sex as a biological variable in cardiac electrophysiology, a comprehensive approach may be necessary using both in vitro measurements from cardiomyocyte or intact heart preparations with secondary follow-up in vivo studies.NEW & NOTEWORTHY We evaluated whether the guinea pig heart has intrinsic sex-specific differences in cardiac electrophysiology. Although we observed sex-specific differences in in vivo ECGs, these differences did not persist ex vivo. Using a whole heart model, we observed similar APD, CaD, conduction velocity, and alternans susceptibility in males and females. We conclude that sex-specific differences in guinea pig cardiac electrophysiology are likely influenced by the in vivo environment and less dependent on the intrinsic electrical properties of the heart.

Noninvasive electrophysiological differences between women and men: differences in body size not an explanation.

There are numerous sex-related differences in cardiac electrophysiology and arrhythmia propensity but very little knowledge about the reasons. Difference in body size has been proposed as one reason and was tested in this study of >20 cardiac electrophysiology parameters in 319 (158 women) apparently healthy 50- to 64-yr-old subjects from a randomly enrolled population sample, the pilot SCAPIS (Swedish Cardiopulmonary Bioimaging Study), using Frank vectorcardiography. We studied conventional conduction intervals, parameters reflecting electrical heterogeneity (dispersion) in the ventricles, QRS- and T-vector directions, spatial QRS-T angles, and T-vector loop morphology. Body surface area (BSA; 2 methods) and lean body mass (LBM), both estimated from body weight and height, were used as body size parameters. According to multivariable linear regression analysis adjusted for sex, there was no association between electrophysiological parameters and body size apart from QRS duration and QRSarea. In conclusion, most electrophysiological parameters assessed completely noninvasively and showing statistically significant differences between women and men on the group level show no association with BSA or LBM. Scaling (indexing) the electrophysiological parameters for body size parameters is therefore not an option. Consequently, the explanation for the sex-related electrophysiological differences should be sought along other lines.NEW & NOTEWORTHY We sought explanations for sex-related differences in >20 cardiac electrophysiology parameters including conventional conduction intervals in 319 (158 women) apparently healthy 50- to 64-yr-old subjects using Frank vectorcardiography, a novelty. Our hypothesis that body size was partly explanatory for such differences had to be refuted apart from QRS duration and QRSarea. Scaling (indexing) electrophysiological parameters for body size is therefore not an option and explanations for electrophysiological sex-related differences are to be sought elsewhere.

Sex differences in cardiac electrophysiology: does body size matter?

Sex differences in cardiac electrophysiology: does body size matter?

Feasibility of Measuring the Behavioral and Electrophysiological Masking-Level Difference with Nonsense-Syllable Stimuli.

The masking-level difference (MLD) can be measured via voluntary behavioral responses (voluntary behavioral MLD [vMLD]) and/or via electrophysiological cortical auditory evoked potentials (CAEPs; electrophysiological MLD [eMLD]). It may be possible to enhance the ecologic validity of the MLD by using nonsense-syllable speech stimuli. The aim of this study is to determine the feasibility of measuring both the vMLD and eMLD with speech stimuli. The study also investigates whether certain nonsense-syllable stimuli (/α/, /dα/, /di/, /tα/, /wα/) may be more useful than others in measuring both the vMLD and eMLD. This is a descriptive feasibility pilot study. Seventeen young adults (age range 19-26 years; 15 women) with hearing thresholds of 0.25-8.0 kHz ≤ 25 dB HL, bilaterally, were recruited. Behavioral and electrophysiological MLDs were measured with similar methods. The MLD was defined as SoNo - SπNo thresholds. Stimuli were natural-sounding nonsense syllables (/α/, /dα/, /di/, /tα/, /wα/), which were presented in 65 dB HL continuous speech-weighted noise. The eMLD was measured with the CAEP P2. Group means, standard deviations, and distributions were presented. The feasibility of using nonsense syllables was evaluated by considering whether measurable vMLDs and eMLDs were produced. Useful nonsense syllables produced vMLDs and eMLDs with (1) comparatively large mean magnitudes, (2) few negligible MLDs, and (3) distributions with adequate spread and few extreme values. The stimuli /α/ (6.0 [1.9]) and /wα/ (7.5 [1.3]) produced vMLDs with the highest average magnitudes, with no vMLDs of 0 dB and with adequate spread. The stimulus /α/ produced eMLDs with the highest average magnitude (9.6 [2.8]), no eMLDs of 0 dB and adequate spread, whereas the stimulus /wα/ produced eMLDs with an adequate magnitude (6.9 [3.9]), no MLDs of 0 dB, but with a right-skewed distribution and an extreme value. The other stimuli produced vMLDs with low mean magnitudes and several vMLDs of 0 dB. These pilot data support the feasibility of using nonsense syllables to record vMLDs and eMLDs. The stimulus /α/ appeared most useful for both behavioral and electrophysiological modalities. Differences in MLDs across modalities may be attributed to low-level audibility of some high-frequency components of the stimuli.

A positive allosteric modulator of mGlu4 receptors restores striatal plasticity in an animal model of l-Dopa-induced dyskinesia

By decreasing glutamate transmission, mGlu4 receptor positive allosteric modulators (mGlu4-PAM), in combination with levodopa (l-DOPA) may restore the synergy between glutamatergic and dopaminergic transmissions, thus maximizing the improvement of motor function in Parkinson's disease (PD). This study aimed to clarify the effects of foliglurax, a selective mGlu4-PAM, on the loss of bidirectional synaptic plasticity associated with l-DOPA-induced dyskinesia (LID). Behavioral assessments compared dyskinesia intensity in 6-hydroxydopamine (6-OHDA)-lesioned rats treated with l-DOPA or l-DOPA plus foliglurax. In slices from the same rats, patch-clamp techniques were used to examine electrophysiological differences in glutamatergic synapses, evaluating the EPSCs mediated by NMDA and AMPA receptors in striatal spiny projection neurons. High-frequency stimulation of corticostriatal fibers was used as long-term potentiation (LTP)-inducing protocol. Conversely, 15 min of low-frequency stimulation was applied to depotentiate LTP. The density of dendritic spines was measured in striatal slices in the same experimental conditions. Our results show that, in corticostriatal slices, foliglurax decreased spontaneous glutamatergic transmission in both sham-operated and 6-OHDA lesioned rats. When co-administered with l-DOPA in 6-OHDA-lesioned rats, foliglurax fully restored dendritic spine density in a dose-dependent manner. Moreover, this co-treatment rescued striatal bidirectional plasticity and attenuated the intensity of l-DOPA-induced dyskinesia. This is the first demonstration in an animal model of PD and dyskinesia that a mGlu4 PAM can restore striatal synaptic plasticity.

Single-neuron models linking electrophysiology, morphology, and transcriptomics across cortical cell types.

Which cell types constitute brain circuits is a fundamental question, but establishing the correspondence across cellular data modalities is challenging. Bio-realistic models allow probing cause-and-effect and linking seemingly disparate modalities. Here, we introduce a computational optimization workflow to generate 9,200 single-neuron models with active conductances. These models are based on 230 invitro electrophysiological experiments followed by morphological reconstruction from the mouse visual cortex. We show that, in contrast to current belief, the generated models are robust representations of individual experiments and cortical cell types as defined via cellular electrophysiology or transcriptomics. Next, we show that differences in specific conductances predicted from the models reflect differences in gene expression supported by single-cell transcriptomics. The differences in model conductances, in turn, explain electrophysiological differences observed between the cortical subclasses. Our computational effort reconciles single-cell modalities that define cell types and enables causal relationships to be examined.

Effects of fibroblast on electromechanical dynamics of human atrial tissue-insights from a 2D discrete element model.

Roughly 75% of normal myocardial tissue volume is comprised of myocytes, however, fibroblasts by number are the most predominant cells in cardiac tissue. Previous studies have shown distinctive differences in cellular electrophysiology and excitability between myocytes and fibroblasts. However, it is still unclear how the electrical coupling between the two and the increased population of fibroblasts affects the electromechanical dynamics of cardiac tissue. This paper focuses on investigating effects of fibroblast-myocyte electrical coupling (FMEC) and fibroblast population on atrial electrical conduction and mechanical contractility by using a two-dimensional Discrete Element Method (DEM) model of cardiac tissue that is different to finite element method (FEM). In the model, the electro-mechanics of atrial cells are modelled by a biophysically detailed model for atrial electrical action potentials and myofilament kinetics, and the atrial fibroblasts are modelled by an active model that considers four active membrane ionic channel currents. Our simulation results show that the FMEC impairs myocytes’ electrical action potential and mechanical contractibility, manifested by reduced upstroke velocity, amplitude and duration of action potentials, as well as cell length shortening. At the tissue level, the FMEC slows down the conduction of excitation waves, and reduces strain of the tissue produced during a contraction course. These findings provide new insights into understandings of how FMEC impairs cardiac electrical and mechanical dynamics of the heart.

Electrophysiological differences in distinct hearing threshold level individuals with and without tinnitus distress.

Tinnitus is the perception of sound when no actual external noise is present. Tinnitus is highly prevalent, with more than 1 in 7 adults in the EU having tinnitus, and it causes negative effects on quality of life for many individuals. However, there is currently no cure for tinnitus and its pathophysiology and genesis are unknown. Auditory evoked potentials (AEPs) provide a non-invasive means by which the electrical signals evoked by the brain can be recorded, and constitute a useful indicator for the evaluation of auditory disorders such as tinnitus and hearing loss. The present study analyzed a total of 98 auditory middle evoked potential (AMLR) waveforms, a subtype of AEPs, from 49 participants with subjective tinnitus, attempting to identify differences in AMLR parameters between sufferers with and without tinnitus distress. The waveforms were divided into three categories according to the ear's hearing level, and comparisons were made between sufferers in the same hearing level category. The results of the analysis indicated some statistically significant differences in AMLR latencies and amplitudes between the compared groups. Clinical Relevance- Identification of the electro-physiological profile of subjective tinnitus sufferers based on the distress manifested by tinnitus using AMLRs.

Large-scale Multimodal Recordings on a High-density Neurochip: Olfactory Bulb and Hippocampal Networks.

A striking example of the brain's complexity and continued plasticity is the addition of new neuronal components to a circuit in a process called neurogenesis. Two brain regions exhibit profound circuit remodeling through this process - the olfactory bulb and hippocampus. However, how local network changes in both regions influence global circuit rewiring and dynamic network features remain largely unexplored due to the lack of spatiotemporal resolution technology and large-scale electrophysiological activity recordings. Here, we demonstrate large-scale recordings using a high-density neurochip to reveal multimodal circuit-wide electrophysiological properties and layer-specific functional connectivity in the olfactory bulb and hippocampal networks. Our findings illustrate simultaneous recordings from the entire network, which allows us to quantify synchronous electrophysiological parameter differences and layer-specific waveform markers. Examining pairwise cross-covariance between active electrode pairs reveals individual neuronal ensemble contributions to synchronous activation between layers and hub microcircuits, demonstrating network-wide rewiring. Our study suggests a novel tool to address the computational implications of large-scale activity patterns in functional multimodal neurogenic circuits.

Cortical VIP+ Interneurons in the Upper and Deeper Layers Are Transcriptionally Distinct.

Different interneuron classes have distinct laminar distribution patterns which contribute to the layer-specific organization of cortical microcircuits. However, laminar differences within the same interneuron classes are not well recognized. Despite systematic efforts towards neuron cell-type taxonomy in the neocortex by single-cell transcriptomics, less attention has been driven towards laminar differences in interneurons compared to projection neurons. VIP+ interneurons are the major interneuron class that mostly populate superficial layers and mediate disinhibition. A few reports noted the morphological and electrophysiological differences between VIP+ interneurons residing in layers I-III (upper layer) and layers IV-VI (deeper layer), but little is known about their molecular differences. Here, we delineated the laminar difference in their transcriptome employing single-cell RNA sequencing (scRNAseq) data from public databases. Analysis of 1175 high-quality VIP+ interneurons in the primary visual cortex (VISp) showed that the upper layer and deeper layer VIP+ interneurons are transcriptionally distinct distinguished by genes implicated in synapse organization and regulation of membrane potential. Similar differences are also observed in the anterior lateral motor cortex (ALM) and primary motor cortex (MOp). Cross-comparing between the top 10 differentially expressed genes (DEGs) with Allen Mouse Brain in situ hybridization database, we identified Tac2 and CxCl14 as potential marker genes of upper layer VIP+ interneurons across most cortical regions. Importantly, such expression patterns are conserved in the human brain. Together, we revealed significant laminar differences in transcriptomic profiles within VIP+ interneurons, which provided new insight into their molecular heterogeneity that may contribute to their functional diversity.

The Personality Traits and P300 of Offspring of Parents With Alcohol Dependence Differ Depending on Current Risky Drinking: A Preliminary Case-Control Study.

AimsThe aim of this study was to investigate the personality traits, and P300 component in the offspring of parents with alcohol dependence (OPAD) currently engaged in risky drinking and those not engaged in risky drinking, and to further explore the correlates of problematic alcohol use.MethodsA case-control study was conducted according to the cutoff of the Alcohol Use Disorder Identification Test (AUDIT). The frequency of the TaqIA polymorphism of the dopamine receptor D2 gene associated with alcohol dependence was compared between the two OPAD groups. Tridimensional Personality Questionnaire (TPQ), The Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and the MINI-International Neuropsychiatric Interview (M.I.N.I.) were measured or interviewed in OPAD not engaged in risky drinking (resilient; n = 35) and those currently engaged in risky drinking (vulnerable; n = 20). P300 was measured to test the possible electrophysiological differences. The correlates of alcohol use were analyzed.ResultsVulnerable OPAD showed higher novelty seeking subscale scores (NS4; 4.45 ± 2.012 vs. 3.31 ± 1.728, P < 0.05) and harm avoidance subscale scores (HA4; 5.3 ± 2.319 vs. 3.66 ± 2.461, P < 0.05) than resilient OPAD, while the total scores of each dimension showed no significant difference. OPAD engaged in risky drinking showed more tobacco use than OPAD resistant to risky drinking. OPAD with risky drinking showed a shorter P300 latency than resilient OPAD on Fz electrodes. AUDIT scores of OPAD were correlated with P300 latency.ConclusionsP300 differed between OPAD with and without risky drinking and alcohol use was associated with P300 latency, indicating that P300 may be used in the early detection of vulnerable OPAD and early intervention in the future.

P.112 Clinical and Electrophysiological characteristics of anti-nodal/paranodal antibodies in chronic inflammatory demyelinating polyradiculoneuropathy patients

Background: CIDP is an autoimmune polyneuropathy. Antibodies against the Node of Ranvier have been described, NF155,NF140/186 and contactin-1. Methods: A retrospective review of patients with CIDP who tested positive for antinodal/paranodal antibodies via Western blot were evaluated. We have included 20 sero-negative CIDP patients. All patients met definite or probable EFNS criteria. clinical, electrophysiological data and response to treatment were obtained. Results: Forty-five patients tested positive for the antibodies. Sixteen were positive for NF155,11 for NF140, 5 for CNTN1,11 were double positive for NF155 and NF140, and 3 were triple positive for NF155, NF140 and CNTN. Age of onset was similar in both seronegative (53.9 ± 3.1 yrs.) versus seropositive(52.3 ± 2.4 yrs.).Chronic presentation manifested in 85% of seronegative, 80% of seropositivepatients.Intrestingly,all triple-positive patients presented with a more acute presentation(i.e,&lt;8 wks.)7/20 seronegative (35%),1/16 NF155, 6/11 NF140,1/5 contactin, 2/11 of doublepositive, 3/3 of triple-positive (28%,13/46) responded to IVIg. Conclusions: No major clinical or electrophysiological differences between groups. triple-positive patients showed 100% response to IVIg.These results cast doubt on the specificity of the Western blot as a clinico-electrophysiologic discriminator. Future testing with cellbased assays will likely provide a robust measure that will guide treatment decision.

Electrophysiological differences of deep sedation with dexmedetomidine versus propofol

Abstract Funding Acknowledgements Type of funding sources: None. Background Dexmedetomidine and propofol are commonly used drugs for deep sedation during cardiovascular interventions. Patients undergoing these interventions often have impaired sinus node function or atrioventricular (AV) conduction disease. Anesthetics used for deep sedation may further compromise sinus node function and AV nodal conduction, and thereby interfere with the intervention. Purpose To compare the electrophysiological effects of dexmedetomidine and propofol on the function of the sinus node and AV conduction. Methods We randomized patients undergoing first atrial fibrilation ablation 1:1 to deep sedation by dexmedetomidine (DEX group) versus propofol (PRO group), according to a standardized protocol. At the end of the ablation procedure with the patients still deeply sedated and hemodynamically stable, we conducted a standard electrophysiological study and assessed sinus node function, properties of AV conduction and atrial refractoriness. Results Of 160 patients (65±11 years old; 32% female) included into the study, 80 patients were randomized to the DEX and PRO group each. Procedure duration (128±59 minutes) and sedation depth, as assessed by the "Modified Observer’s Assessment of Alertness/Sedation" score (median 3; interquartile range 2, 3), was not different among groups. DEX group patients received a mean of 231±111 mcg of dexmedetomidine and PRO group patients a mean of 657±356 mg of propofol. The table shows the results of the electrophysiological study. DEX group patients had lower sinus rate and longer unadjusted sinus node recovery time (SNRT) at pacing cycle lengths of 600, 500 and 400 ms. However, both corrected (SNRT-RR) and normalized (SNRT/RR) SNRT did not differ among groups. Compared to PRO group patients, AV nodal conduction was slower in DEX group patients as evidenced by longer PR and AH intervals, and a higher Wenckebach cycle length and AV node effective refractory period (ERP) was observed. Conduction properties in the His-Purkinje system were not different among groups, as QRS width and HV interval were similar. An arrhythmia, mainly atrial fibrillation, was induced in 33 patients (21%) during the electrophysiological study, without differences among groups. Conclusions Sinus rate and AV conduction are slower during deep sedation with dexmedetomidine compared to propofol. These differences in electrophysiological effects need to be taken into account when using these anesthetics during cardiovascular interventions.

The electrophysiological masking level difference: effects of age and mediation of hearing and cognition

Objective Evaluate the conceptual framework that age effects on the electrophysiological binaural masking level difference (MLD) are partially mediated by age-related hearing loss and/or global cognitive function via mediation analysis. Design Participants underwent a series of audiometric tests. The MLD was measured via cortical auditory evoked potentials using a speech stimulus (/ɑ/) in speech-weighted background noise. We used mediation analyses to determine the total effect, natural direct effects, and natural indirect effects, which are displayed as regression coefficients ([95% CI]; p value). Study sample Twenty-eight individuals aged 19–87 years (mean [SD]: 53.3 [25.2]), recruited from the community. Results Older age had a significant total effect on the MLD (-0.69 [95% CI: −0.96, −0.45]; p < 0.01). Neither pure tone average (-0.11 [95% CI: −0.43, 0.24; p = 0.54] nor global cognitive function (-0.02 [95% CI: −0.13, 0.02]; p = 0.55) mediated the relationship of age and the MLD and effect sizes were small. Results were insensitive to use of alternative hearing measures or inclusion of interaction terms. Conclusions The electrophysiological MLD may be an age-sensitive measure of binaural temporal processing that is minimally affected by age-related hearing loss and global cognitive function.

Effect of Obesity on Arithmetic Processing in Preteens With High and Low Math Skills: An Event-Related Potentials Study.

Preadolescence is an important period for the consolidation of certain arithmetic facts, and the development of problem-solving strategies. Obese subjects seem to have poorer academic performance in math than their normal-weight peers, suggesting a negative effect of obesity on math skills in critical developmental periods. To test this hypothesis, event-related potentials (ERPs) were collected during a delayed-verification math task using simple addition and subtraction problems in obese [above 95th body mass index (BMI) percentile] and non-obese (between 5th and 90th BMI percentile) preteens with different levels of math skill; thirty-one with low math skills (14 obese, mean BMI = 26.40, 9.79 years old; 17 non-obese, BMI = 17.45, 9.76 years old) and thirty-one with high math skills (15 obese, BMI = 26.90, 9.60 years old; 16 non-obese, BMI = 17.13, 9.63 years old). No significant differences between weight groups were observed in task accuracy regardless of their mathematical skill level. For ERPs, electrophysiological differences were found only in the subtraction condition; participants with obesity showed an electrophysiologic pattern associated with a reduced ability to allocate attention resources regardless of their math skill level, these differences were characterized by longer P300 latency than their normal-weight peers. Moreover, the participants with obesity with high math skills displayed hypoactivity in left superior parietal lobule compared with their normal-weight peers. Additionally, obese preteens with low math skills displayed smaller arithmetic N400 amplitude than non-obese participants, reflecting difficulties in retrieving visual, semantic, and lexical information about numbers. We conclude that participants with obesity are less able than their normal-weight peers to deploy their attention regardless of their behavioral performance, which seems to have a greater effect on obese participants with low math skills because they also show problems in the retrieval of solutions from working memory, resulting in a delay in the development of mathematical skills.

328 Induced Spreading Depolarizations Produce Exaggerated Electrophysiologic Pathology in a Rat Model of Traumatic Brain Injury

INTRODUCTION: Spreading depolarizations (SDs) are waves of cortical depolarization that cause loss of ion homeostasis, brain silencing, and are prognostic of worse functional outcome in traumatic brain injury (TBI) patients. SDs occur in ∼50% of surgical TBI patients and have potential to spread from areas of injured brain into less-injured or “uninjured” cortex. Understanding differences in how injured versus uninjured cortex responds to SD waves can provide insight for therapeutic targets. METHODS: Adult Long Evans rats were subjected to either a moderate lateral fluid percussion injury (LFPI) or a sham injury. Beginning 103.4 ± 28.4 minutes after injury or sham, an electrode was placed at the site of injury (or sham) and electrocorticographic activity was recorded for two hours. SDs were induced every 15 minutes using 1M potassium chloride (KCl) soaked cotton balls placed on a frontal craniectomy separate from the recording site. Saline soaked cotton balls were used as a control. RESULTS: A total of 37 SDs were induced in the uninjured group and 32 SDs were induced in the injured group. No SDs were recorded in saline controls. There was no difference in the average time from KCl application to the start of the SD between groups (sham = 136.2, LFPI = 113.9, p = 0.4219). There was also no difference in average amplitude of the direct current (DC) shift (sham = 10.33, LFPI = 13.26, p = 0.1402). However, the injured group had longer average duration of DC shifts (sham = 53.54, LFPI = 99.22, p &lt; 0.0001), longer average depression durations (sham = 206.6, LFPI = 265.8, p = 0.001), and larger average depth of depression (sham = 0.6824, LFPI = 0.8399, p = 0.0018). CONCLUSION: Our study revealed electrophysiologic differences between SDs induced in injured versus uninjured animals. Further studies are needed to determine the impact of these differences on neuronal damage and functional outcome.

Reconfiguration of response rule is more difficult than that of task goal: Behavior and electrophysiological evidence

Previous studies have investigated the neural mechanisms underlying cognitive control by using the task-switching paradigm, but differentiation from response rule switching (RR-switch) remains poorly explored. In this study, a partial voluntary task-switching (VTS) paradigm was used to explore the electrophysiological differences between task switching (T-switch) and RR-switching. Participants were sequentially presented with Arabic numerals colored red or green. If the color in the current trial was the same as that in the previous trial, the participants had to perform the same task following the same response rule. Otherwise, they had to voluntarily switch tasks (e.g., from parity task to magnitude task) or switch response rules (e.g., from “pressing F for odd and J for even number” to “pressing J for odd and F for even number”). The behavioral results indicated that RR-switch was infrequently selected, and the performance was less efficient than that of the T-switch. Event-related potential results showed that both T- and RR-switches elicited a larger switch-positivity in the P2 and P3 time windows than that in the repeat condition. Switch-positivity was larger for RR-switch than for T-switch over the frontal sites, suggesting that more attention and cognitive resources were required to update information for the RR-switch than for the T-switch. These findings suggest that in the VTS, the hierarchical relationship between task goals and response rules is relatively loose, resulting in the neural disassociation of task reconfiguration and response change.

Differential gene expression in layer 3 pyramidal neurons across 3 regions of the human cortical visual spatial working memory network.

Visual spatial working memory (vsWM) is mediated by a distributed cortical network composed of multiple nodes, including primary visual (V1), posterior parietal (PPC), and dorsolateral prefrontal (DLPFC) cortices. Feedforward and feedback information is transferred among these nodes via projections furnished by pyramidal neurons (PNs) located primarily in cortical layer 3. Morphological and electrophysiological differences among layer 3 PNs across these nodes have been reported; however, the transcriptional signatures underlying these differences have not been examined in the human brain. Here we interrogated the transcriptomes of layer 3 PNs from 39 neurotypical human subjects across 3 critical nodes of the vsWM network. Over 8,000 differentially expressed genes were detected, with more than 6,000 transcriptional differences present between layer 3 PNs in V1 and those in PPC and DLPFC. Additionally, over 600 other genes differed in expression along the rostral-to-caudal hierarchy formed by these 3 nodes. Moreover, pathway analysis revealed enrichment of genes in V1 related to circadian rhythms and in DLPFC of genes involved in synaptic plasticity. Overall, these results show robust regional differences in the transcriptome of layer 3 PNs, which likely contribute to regional specialization in their morphological and physiological features and thus in their functional contributions to vsWM.

EEG Correlates of Active Stopping and Preparation for Stopping in Chronic Tic Disorder

Motor inhibition is an important cognitive process involved in tic suppression. As the right frontal lobe contains important inhibitory network nodes, we characterized right superior, middle, and inferior frontal gyral (RSFG, RMFG, RIFG) event-related oscillations during motor inhibition in youth with chronic tic disorders (CTD) versus controls. Fourteen children with CTD and 13 controls (10–17 years old) completed an anticipated-response stop signal task while dense-array electroencephalography was recorded. Between-group differences in spectral power changes (3–50 Hz) were explored after source localization and multiple comparisons correction. Two epochs within the stop signal task were studied: (1) preparatory phase early in the trial before motor execution/inhibition and (2) active inhibition phase after stop signal presentation. Correlation analyses between electrophysiologic data and clinical rating scales for tic, obsessive-compulsive symptoms, and inattention/hyperactivity were performed. There were no behavioral or electrophysiological differences during active stopping. During stop preparation, CTD participants showed greater event-related desynchronization (ERD) in the RSFG (γ-band), RMFG (β, γ-bands), and RIFG (θ, α, β, γ-bands). Higher RSFG γ-ERD correlated with lower tic severity (r = 0.66, p = 0.04). Our findings suggest RSFG γ-ERD may represent a mechanism that allows CTD patients to keep tics under control and achieve behavioral performance similar to peers.