Effects of propofol on cortico-cortical evoked potentials in the dorsal language white matter pathway

ObjectiveIn order to evaluate the clinical utility even under general anesthesia, the present study aimed to clarify the effect of anesthesia on the cortico–cortical evoked potentials (CCEPs).MethodsWe analyzed 14 patients’ data in monitoring the integrity of the dorsal language pathway by using CCEPs both under general anesthesia with propofol and remifentanil and awake condition, with the main aim of clarifying the effect of anesthesia on the distribution and waveform of CCEPs.ResultsThe distribution of larger CCEP response sites, including the locus of the maximum CCEP response site, was marginally affected by anesthesia. With regard to similarity of waveforms, the mean waveform correlation coefficient indicated a strong agreement. CCEP N1 amplitude increased by an average of 25.8% from general anesthesia to waking, except three patients. CCEP N1 latencies had no correlation in changes between the two conditions.ConclusionsWe demonstrated that the distribution of larger CCEP responses was marginally affected by anesthesia and that the CCEP N1 amplitude had tendency to increase from general anesthesia to the awake condition.SignificanceThe CCEP method provides the efficiency of intraoperative monitoring for dorsal language white matter pathway even under general anesthesia.     

Epileptogenic network of focal epilepsies mapped with cortico-cortical evoked potentials

ObjectiveThe goal of this study was to investigate the spatial extent and functional organization of the epileptogenic network through cortico-cortical evoked potentials (CCEPs) in patients being evaluated with intracranial stereoelectroencephalography.MethodsWe retrospectively included 25 patients. We divided the recorded sites into three regions: epileptogenic zone (EZ); propagation zone (PZ); and noninvolved zone (NIZ). The root mean square of the amplitudes was calculated to reconstruct effective connectivity network. We also analyzed the N1/N2 amplitudes to explore the responsiveness influenced by epileptogenicity. Prognostic analysis was performed by comparing intra-region and inter-region connectivity between seizure-free and non-seizure-free groups.ResultsOur results confirmed that stimulation of the EZ caused the strongest responses on other sites within and outside the EZ. Moreover, we found a hierarchical connectivity pattern showing the highest connectivity strength within EZ, and decreasing connectivity gradient from EZ, PZ to NIZ. Prognostic analysis indicated a stronger intra-EZ connection in the seizure-free group.ConclusionThe EZ showed highest excitability and dominantly influenced other regions. Quantitative CCEPs can be useful in mapping epileptic networks and predicting surgical outcome.SignificanceThe generated computational connectivity model may enhance our understanding of epileptogenic networks and provide useful information for surgical planning and prognosis prediction.     

Recording cortico-cortical evoked potentials of the human arcuate fasciculus under general anaesthesia

ObjectiveWe examined the feasibility of using cortico-cortical evoked potentials (CCEPs) to monitor the major cortical white matter tract involved in language, the arcuate fasciculus (AF), during surgery under general anaesthesia.MethodsWe prospectively recruited nine patients undergoing surgery for lesions in the left peri-sylvian cortex, for whom awake surgery was not indicated. High angular resolution diffusion imaging (HARDI) tractography was used to localise frontal and temporal AF terminations, which guided intraoperative cortical strip placement.ResultsCCEPs were successfully evoked in 5/9 patients, showing a positive potential (P1) at 12 ms and a negative component (N1) at 21 ms when stimulating from the frontal lobe and recording in the temporal lobe. CCEP responses peaked in the posterior middle temporal gyrus. No CCEPs were evoked when stimulating temporal sites and recording from frontal contacts.ConclusionFor the first time, we show that CCEPs can be evoked from the peri-sylvian cortices also in adult patients who are not candidates for awake procedures. Our results are akin to those described in the awake setting and suggest the recorded activity is conveyed by the arcuate fasciculus.SignificanceThis intraoperative approach may have promising implications in reducing deficits in patients that require surgery in language areas under general anesthesia.     

Delayed neonatal visual evoked potentials are associated to asymmetric growth pattern in twins

ObjectivesTo study the association between intrauterine growth and visual pathways maturation by neonatal visual evoked potentials (VEPs) in twins, in view of a possible prognostic role.MethodsSeventy-four twin neonates from 37 pregnancies were selected based on gestational age of more than 30 weeks and uneventful perinatal clinical course. Flash VEPs were recorded at the same postmenstrual age in each twin pair. The association between P2 latency and anthropometric variables at birth was analyzed by comparison within each twin pair and regarding each variable as ordered difference between the two twins.ResultsAnalysis of differences within each twin pair highlighted that inter-twin difference in P2 latency was significantly related to difference in ponderal index (PI) (p = 0.048).Expressing the difference in latency as a categorical binary variable, the correlation was significant for both difference in PI, (median difference = −0.36, 95% CI −0.54 to −0.14, p = 0.001) and difference in body mass index (BMI), (median difference = −1.06, 95% CI −1.74 to −0.29, p = 0.006).ConclusionsLower values of PI and BMI differences are associated to delayed VEP latency in twin pairs.SignificanceVEP latency suggests reduced myelination of visual pathways when difference in growth pattern occurs in twins.     

Effects of stimulation intensity on intracranial cortico-cortical evoked potentials: A titration study

ObjectiveThe aim of the present study was to investigate the optimal stimulation parameters for eliciting cortico-cortical evoked potentials (CCEPs) for mapping functional and epileptogenic networks.MethodsWe studied 13 patients with refractory epilepsy undergoing intracranial EEG monitoring. We systematically titrated the intensity of single-pulse electrical stimulation at multiple sites to assess the effect of increasing current on salient features of CCEPs such as N1 potential magnitude, signal to noise ratio, waveform similarity, and spatial distribution of responses. Responses at each incremental stimulation setting were compared to each other and to a final set of responses at the maximum intensity used in each patient (3.5–10 mA, median 6 mA).ResultsWe found that with a biphasic 0.15 ms/phase pulse at least 2–4 mA is needed to differentiate between non-responsive and responsive sites, and that stimulation currents of 6–7 mA are needed to maximize amplitude and spatial distribution of N1 responses and stabilize waveform morphology.ConclusionsWe determined a minimum stimulation threshold necessary for eliciting CCEPs, as well as a point at which the current-dependent relationship of several response metrics all saturate.SignificanceThis titration study provides practical, immediate guidance on optimal stimulation parameters to study specific features of CCEPs, which have been increasingly used to map both functional and epileptic brain networks in humans.     

Inter-ictal network of focal epilepsy and effects of clinical factors on network activity

ObjectiveAim of the study was to explore the inter-ictal, resting-state EEG network in patients with focal epilepsy (FE) and to specify clinical factors that influence network activity.MethodsFunctional EEG connectivity (EEGfC) differences were computed between 232 FE patients (FE group) and 77 healthy controls. EEGfC was computed among 23 cortical regions within each hemisphere, for 25 very narrow bands from 1 to 25 Hz. We computed independent effects for six clinical factors on EEGfC in the FE group, by ANOVA and post-hoc t-statistics, corrected for multiple comparisons by false discovery rate method.ResultsRobust, statistically significant EEGfC differences emerged between the FE and the healthy control groups. Etiology, seizure type, duration of the illness and antiepileptic treatment were independent factors that influenced EEGfC. Statistically significant results occurred selectively in one or a few very narrow bands and outlined networks. Most abnormal EEGfC findings occurred at frequencies that mediate integrative and motor activities.ConclusionsFE patients have abnormal resting-state EEGfC network activity. Clinical factors significantly modify EEGfC.SignificanceDelineation of the FE network and modifying factors can open the way for targeted investigations and introduction of EEGfC into epilepsy research and practice.     

Fixation-related potentials in naming speed: A combined EEG and eye-tracking study on children with dyslexia

ObjectiveWe combined electroencephalography (EEG) and eye-tracking recordings to examine the underlying factors elicited during the serial Rapid-Automatized Naming (RAN) task that may differentiate between children with dyslexia (DYS) and chronological age controls (CAC).MethodsThirty children with DYS and 30 CAC (M_age = 9.79 years; age range 7.6 through 12.1 years) performed a set of serial RAN tasks. We extracted fixation-related potentials (FRPs) under phonologically similar (rime-confound) or visually similar (resembling lowercase letters) and dissimilar (non-confounding and discrete uppercase letters, respectively) control tasks.ResultsResults revealed significant differences in FRP amplitudes between DYS and CAC groups under the phonologically similar and phonologically non-confounding conditions. No differences were observed in the case of the visual conditions. Moreover, regression analysis showed that the average amplitude of the extracted components significantly predicted RAN performance.ConclusionFRPs capture neural components during the serial RAN task informative of differences between DYS and CAC and establish a relationship between neurocognitive processes during serial RAN and dyslexia.SignificanceWe suggest our approach as a methodological model for the concurrent analysis of neurophysiological and eye-gaze data to decipher the role of RAN in reading.     

A prewarning sign for hearing loss by brainstem auditory evoked potentials during microvascular decompression surgery for hemifacial spasm

ObjectiveWe aimed to define the prewarning sign of brainstem auditory evoked potentials (BAEPs) associated with cerebellar retraction (CR) during microvascular decompression surgery for hemifacial spasm.MethodsA total of 241 patients with a latency prolongation of 1 ms or an amplitude decrement of 50% of wave V were analyzed. According to BAEPs before significant changes during CR, patients were classified into Groups A (latency prolongation of wave I [≥0.5 ms] without prolongation of the I–III interpeak interval [<0.5 ms]) and B (no latency prolongation of wave I [<0.5 ms] with prolongation of the I–III interpeak interval [≥0.5 ms]). BAEPs and postoperative hearing loss (HL) were compared between the two groups.ResultsGroup B comprised 160 (66.4%) patients. With maximal changes in wave V, latency prolongation (≥1 ms) with amplitude decrement (≥50%) was more common in Group B (p < 0.018). At the end of the operation, wave V loss was observed in 11 patients, including 10 patients from Group B. Five patients developed postoperative HL; all were from Group B.ConclusionsLatency prolongation of wave III during CR was associated with serious BAEPs changes and postoperative HL.SignificanceLatency prolongation of wave III is a significant prewarning sign.     

High-gamma modulation language mapping with stereo-EEG: A novel analytic approach and diagnostic validation

ObjectiveA novel analytic approach for task-related high-gamma modulation (HGM) in stereo-electroencephalography (SEEG) was developed and evaluated for language mapping.MethodsSEEG signals, acquired from drug-resistant epilepsy patients during a visual naming task, were analyzed to find clusters of 50–150 Hz power modulations in time–frequency domain. Classifier models to identify electrode contacts within the reference neuroanatomy and electrical stimulation mapping (ESM) speech/language sites were developed and validated.ResultsIn 21 patients (9 females), aged 4.8–21.2 years, SEEG HGM model predicted electrode locations within Neurosynth language parcels with high diagnostic odds ratio (DOR 10.9, p < 0.0001), high specificity (0.85), and fair sensitivity (0.66). Another SEEG HGM model classified ESM speech/language sites with significant DOR (5.0, p < 0.0001), high specificity (0.74), but insufficient sensitivity. Time to largest power change reliably localized electrodes within Neurosynth language parcels, while, time to center-of-mass power change identified ESM sites.ConclusionsSEEG HGM mapping can accurately localize neuroanatomic and ESM language sites.SignificancePredictive modelling incorporating time, frequency, and magnitude of power change is a useful methodology for task-related HGM, which offers insights into discrepancies between HGM language maps and neuroanatomy or ESM.     

Contribution of different somatosensory afferent input to subcortical somatosensory evoked potentials in humans

ObjectivesTo investigate the subcortical somatosensory evoked potentials (SEPs) to electrical stimulation of either muscle or cutaneous afferents.MethodsSEPs were recorded in 6 patients suffering from Parkinson’s disease (PD) who underwent electrode implantation in the pedunculopontine (PPTg) nucleus area. We compared SEPs recorded from the scalp and from the intracranial electrode contacts to electrical stimuli applied to: 1) median nerve at the wrist, 2) abductor pollicis brevis motor point, and 3) distal phalanx of the thumb. Also the high-frequency oscillations (HFOs) were analysed.ResultsAfter median nerve and pure cutaneous (distant phalanx of the thumb) stimulation, a P1-N1 complex was recorded by the intracranial lead, while the scalp electrodes recorded the short-latency far-field responses (P14 and N18). On the contrary, motor point stimulation did not evoke any low-frequency component in the PPTg traces, nor the N18 potential on the scalp. HFOs were recorded to stimulation of all modalities by the PPTg electrode contacts.ConclusionsStimulus processing within the cuneate nucleus depends on modality, since only the cutaneous input activates the complex intranuclear network possibly generating the scalp N18 potential.SignificanceOur results shed light on the subcortical processing of the somatosensory input of different modalities.     

Long-term impact of prenatal exposure to chemotherapy on executive functioning: An ERP study

ObjectiveThis study examines the long-term impact of prenatal exposure to chemotherapy on executive functioning and the contribution of late-prematurity to this effect, using event-related potentials.MethodsMothers of the prenatal-exposed children (n = 20) were diagnosed with cancer and received chemotherapeutic treatment during pregnancy. We recruited healthy controls (n = 20) who were matched on a 1:1 ratio regarding prematurity, age and sex.We assessed executive functioning at the age of nine, using two event-related potential paradigms: a Go/Nogo paradigm to investigate processes of response inhibition and conflict monitoring, as well as a Posner paradigm to investigate spatial attention.ResultsLower potentials were found in prenatal-exposed children compared to controls in the Go/Nogo P3 and Posner positive slow wave. Moreover, prenatal-exposed children responded slower on the Posner paradigm compared to controls (p < .033), with more incorrect responses (p = .023). In the control group, the N2 Go/Nogo wave was more pronounced in children born after a longer gestation.ConclusionsThis is the first study that demonstrates an effect of prenatal exposure to chemotherapy on the development of executive functioning, not limited to the effect of late-prematurity.SignificanceThis study emphasizes the necessity of a long-term follow-up of prenatal-exposed children to re-inform clinical practice on the costs and benefits of late-premature induction over treatment during pregnancy.     

Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Acute effects of spaced cathodal transcranial direct current stimulation in drug resistant focal epilepsies

ObjectiveTo evaluate the safety and temporal dynamic of the antiepileptic effect of spaced transcranial direct current stimulation (tDCS) in different focal epilepsies.MethodsCathodal tDCS with individual electrode placement was performed in 15 adults with drug resistant focal epilepsy. An amplitude of 2 mA was applied twice for 9 minutes, with an interstimulation interval of 20 minutes. Tolerability was assessed via the Comfort Rating Questionnaire and the frequency of interictal epileptiform discharges (IEDs) was sequentially compared between the 24 hours before and after tDCS.ResultsTDCS led to a significant reduction in the total number of IEDs/24 h by up to 68% (mean ± SD: −30.4 ± 21.1%, p = 0.001) as well as in seizure frequency (p = 0.041). The maximum IED reduction was observed between the 3rd and 21st hour after stimulation. Favorable clinical response was associated with structural etiology and clearly circumscribed epileptogenic foci but did not differ between frontal and temporal epilepsies. Overall, the tDCS treatment was well tolerated and did not lead to severe adverse events.ConclusionsThe spaced stimulation approach proved to be safe and well-tolerated in patients with drug-resistant unifocal epilepsies, leading to sustained IED and seizure frequency reduction.SignificanceSpaced tDCS induces mediate antiepileptic effects with promising therapeutic potential.     

The role of substance P in acupuncture signal transduction and effects

BackgroundAcupuncture has been used to treat a wide variety of diseases, disorders, and conditions for more than 2500 years. While the anatomical structures of acupuncture points (or acupoints) are largely unknown, our previous studies have suggested that many acupoints can be identified as cutaneous neurogenic inflammatory spots (neurogenic spots or Neuro-Sps), arising from the release of neuropeptides from activated small diameter sensory afferents at topographically distinct body surfaces due to the convergence of visceral and somatic afferents. In turn, the neuropeptides released during neurogenic inflammation may play important roles in the effects of acupuncture as well as the formation of active acupoints. Thus, the present study has focused on the role of substance P (SP) in acupuncture signal transduction and effects.MethodsNeuro-Sps were detected by using in vivo fluorescence imaging after intravenous injection of Evans blue dye (EBD) and compared with traditional acupoints. Stimulatory effects of the Neuro-Sps were examined in a rat model of immobilization-induced hypertension (IMH). The roles of increased SP in Neuro-Sps were also investigated by using immunohistochemistry, in vivo single-fiber peripheral nerve recordings, and in vivo midbrain extracellular recordings.ResultsNeurogenic inflammation quickly appeared at acupoints on the wrist and was fully developed within 15 min in IMH model. The Neuro-Sps showed an increased release of SP from afferent nerve terminals. Mechanical stimulation of these Neuro-Sps increased cell excitability in the midbrain (rostral ventrolateral medulla) and alleviated the development of hypertension, which was blocked by the local injection of the SP receptor antagonist CP-99994 into Neuro-Sps prior to acupuncture and mimicked by the local injection of capsaicin. Single fiber recordings of peripheral nerves showed that increased SP into the Neuro-Sps elevated the sensitivity of A- and C-fibers in response to acupuncture stimulation. In addition, the discharge rates of spinal wide dynamic response (WDR) neurons significantly increased following SP or acupuncture treatment in Neuro-Sps in normal rats, but decreased following the injection of CP-99994 into Neuro-Sps in IMH rats.ConclusionsOur findings suggest that SP released during neurogenic inflammation enhances the responses of sensory afferents to the needling of acupoints and triggers acupuncture signaling to generate acupuncture effects.     

Transitions between repetitive tapping and upper limb freezing show impaired movement-related beta band modulation

ObjectiveFreezing phenomena in idiopathic Parkinson’s disease (PD) constitute an important unaddressed therapeutic need. Changes in cortical neurophysiological signatures may precede a single freezing episode and indicate the evolution of abnormal motor network processes. Here, we hypothesize that the movement-related power modulation in the beta-band observed during regular finger tapping, deteriorates in the transition period before upper limb freezing (ULF).MethodsWe analyzed a 36-channel EEG of 13 patients with PD during self-paced repetitive tapping of the right index finger. In offline analysis, we compared the transition period immediately before ULF (‘transition’) with regular tapping regarding movement-related power modulation and interregional phase synchronization.ResultsFrom time-frequency analyses, we observed that the tap cycle related beta-band power modulation over the left sensorimotor area was diminished in the transition period before ULF. Furthermore, increased beta-band power was observed in the transition period compared to regular tapping centered over the left centro-parietal and right frontal areas. Phase synchronization between the left fronto-parietal areas and the left sensorimotor area was elevated during transition compared to regular tapping.ConclusionTogether, these results indicate that diminished beta band power modulation and increased phase synchronization precede ULF.SignificanceWe demonstrate that pathological cortical motor processing is present in the transition phase from regular tapping to an ULF episode.     

Measuring the effects of first antiepileptic medication in Temporal Lobe Epilepsy: Predictive value of quantitative-EEG analysis

ObjectiveTo determine the quantitative EEG responses in a population of drug-naïve patients with Temporal Lobe Epilepsy (TLE) after Levetiracetam (LEV) initiation as first antiepileptic drug (AED). We hypothesized that the outcome of AED treatment can be predicted from EEG data in patients with TLE.MethodsTwenty-three patients with TLE and twenty-five healthy controls were examined. Clinical outcome was dichotomized into seizure-free (SF) and non-seizure-free (NSF) after two years of LEV. EEG parameters were compared between healthy controls and patients with TLE at baseline (EEG^pre) and after three months of AED therapy (EEG^pre-post) and between SF and NSF patients. Receiver Operating Characteristic curves models were built to test whether EEG parameters predicted outcome.ResultsAED therapy induces an increase in EEG power for Alpha (p = 0.06) and a decrease in Theta (p < 0.05). Connectivity values were lower in SF compared to NSF patients (p < 0.001). Quantitative EEG predicted outcome after LEV treatment with an estimated accuracy varying from 65.2% to 91.3% (area under the curve [AUC] = 0.56–0.93) for EEG^pre and from 69.9% to 86.9% (AUC = 0.69–0.94) for EEG^pre-post.ConclusionsAED therapy induces EEG modifications in TLE patients, and such modifications are predictive of clinical outcome.SignificanceQuantitative EEG may help understanding the effect of AEDs in the central nervous system and offer new prognostic biomarkers for patients with epilepsy.     

Differentiating neurodegenerative parkinsonian syndromes using vestibular evoked myogenic potentials and balance assessment

ObjectiveVestibular evoked myogenic potentials (VEMP) were investigated to differentiate between parkinsonian syndromes. We correlated balance and VEMP parameters to investigate the VEMP brainstem circuits as possible origin for postural instability.MethodsWe assessed clinical status, ocular and cervical VEMP (oVEMP, cVEMP) and conducted a balance assessment (posturography, Activities-specific Balance Confidence Scale, Berg Balance Scale, modified Barthel Index) in 76 subjects: 30 with Parkinson’s disease (PD), 16 with atypical parkinsonism (AP) and 30 healthy controls. VEMP were elicited by using a mini-shaker on the forehead.ResultsPatients with PD had a prolonged oVEMP n10 in comparison to controls and prolonged p15 compared to controls and AP. Patients with AP showed reduced oVEMP amplitudes compared to PD and controls. CVEMP did not differ between groups. Postural impairment was higher in AP compared to controls and PD, particularly in the rating scales. No correlations between VEMP and posturography were found. A support vector machine classifier was able to automatically classify controls and patient subgroups with moderate to good accuracy based on oVEMP latencies and balance questionnaires.ConclusionsBoth oVEMP and posturography, but not cVEMP, may be differentially affected in PD and AP. We did not find evidence that impairment of the cVEMP or oVEMP pathways is directly related to postural impairment.SignificanceOVEMP and balance assessment could be implemented in the differential diagnostic work-up of parkinsonian syndromes.     

Vestibular evoked myogenic potentials and their clinical utility in patients with amyotrophic lateral sclerosis

ObjectiveTo evaluate the diagnostic value of vestibular evoked myogenic potentials (VEMPs) in the assessment of brainstem function integrity in patients with amyotrophic lateral sclerosis (ALS).MethodsThis was a prospective case-control study including 30 definite or probable ALS patients divided into two groups (with or without brainstem involvement) and 30 healthy controls. Cervical (c-), masseter (m-) and ocular VEMP (o-VEMP) measurements were obtained for all the participants.ResultsThe c-VEMP mean p13 and n23 were significantly prolonged in the ALS patients. The interside peak differences in p13 and n23 of c-VEMP and in n10 and p15 of o-VEMP were significantly prolonged. The rates of alteration in c-VEMP, m-VEMP and o-VEMP in the ALS patients were 67%, 40%, and 45%, respectively. The ALS patients with brainstem involvement had a significantly higher percentage of VEMP abnormalities than did those without brainstem involvement (p = 0.027).Conclusionsc-VEMP is a sensitive tool to detect lower levels of brainstem involvement. Impairments in o-VEMP and m-VEMP indicate involvement of the upper brainstem. The use of combined VEMPs may provide useful insights into the pathophysiological mechanism of ALS.SignificanceVEMPs may be useful in the evaluation of brainstem dysfunction in ALS patients.     

The role of G protein-coupled estrogen receptor 1 on neurological disorders

G protein-coupled estrogen receptor 1 (GPER) is a membrane-associated estrogen receptor (ER) associated with rapid estrogen-mediated effects. Over recent years GPER emerged has a potential therapeutic target to induce neuroprotection, avoiding the side effects elicited by the activation of classical ERs. The putative neuroprotection triggered by GPER selective activation was demonstrated in mood disorders, Alzheimer’s disease or Parkinson’s disease of male and female in vivo rodent models. In others, like ischemic stroke, the results are contradictory and currently there is no consensus on the role played by this receptor. However, it seems clear that sex is a biological variable that may impact the results. The major objective of this review is to provide an overview about the physiological effects of GPER in the brain and its putative contribution in neurodegenerative disorders, discussing the data about the signaling pathways involved, as well as, the diverse effects observed.