Reduced spatial frequency differentiation and sex-related specificities in fearful face detection in autism: Insights from EEG and the predictive brain model.

Face processing relies on predictive processes driven by low spatial frequencies (LSF) that convey coarse information prior to fine information conveyed by high spatial frequencies. However, autistic individuals might have atypical predictive processes, contributing to facial processing difficulties. This may be more normalized in autistic females, who often exhibit better socio-communicational abilities than males. We hypothesized that autistic females would display a more typical coarse-to-fine processing for socio-emotional stimuli compared to autistic males. To test this hypothesis, we asked adult participants (44 autistic, 51 non-autistic) to detect fearful faces among neutral faces, filtered in two orders: from coarse-to-fine (CtF) and from fine-to-coarse (FtC). Results show lower d' values and longer reaction times for fearful detection in autism compared to non-autistic (NA) individuals, regardless of the filtering order. Both groups presented shorter P100 latency after CtF compared to FtC, and larger amplitude for N170 after FtC compared to CtF. However, autistic participants presented a reduced difference in source activity between CtF and FtC in the fusiform. There was also a more spatially spread activation pattern in autistic females compared to NA females. Finally, females had faster P100 and N170 latencies, as well as larger occipital activation for FtC sequences than males, irrespective of the group. Overall, the results do not suggest impaired predictive processes from LSF in autism despite behavioral differences in fear detection. However, they do indicate reduced brain modulation by spatial frequency in autism. In addition, the findings highlight sex differences that warrant consideration in understanding autistic females.

The epileptic blip syndrome.

We report on the case of an adolescent with juvenile myoclonic epilepsy exhibiting compulsory sporadic voluntary movement. These movements entailed the deliberate act of touching her forehead with her hand and were triggered by a short and indefinable cephalic sensation. Upon inquiry regarding the nature of this movement, the patient reported a sudden perception of a peculiar event localized "inside her head". In the course of a prolonged video-electroencephalographic recording, it appeared that the movements consistently followed the occurrence of diffuse Generalized Spike-and-Wave Bursts (GSWBs), lasting one to three seconds. This observation suggests that the impact of the GSWBs on the patient's stream of consciousness could be detected by the patient herself, who attributed it to an internal sensation, like a "blip on a screen". This clinical observation echoes the "blip syndrome", as described by the neurologist James W. Lance thirty years ago. These findings give some support that "blips" could be of an epileptic origin and lend weight to the notion that some patients could perceive their own EEG discharges. Moreover, this observation should be added to the perennial debate on the cognitive impact of intercritical discharges.

Sex modulation of faces prediction error in the autistic brain.

Recent research suggests that autistic females may have superior socio-cognitive abilities compared to autistic males, potentially contributing to underdiagnosis in females. However, it remains unclear whether these differences arise from distinct neurophysiological functioning in autistic males and females. This study addresses this question by presenting 41 autistic and 48 non-autistic adults with a spatially filtered faces oddball paradigm. Analysis of event-related potentials from scalp electroencephalography reveal a neurophysiological profile in autistic females that fell between those of autistic males and non-autistic females, highlighting sex differences in autism from the initial stages of face processing. This finding underscores the urgent need to explore neurophysiological sex differences in autism and encourages efforts toward a better comprehension of compensation mechanism and a clearer definition of what is meant by camouflaging.

From one to many: Hypertonia in schizophrenia spectrum psychosis an integrative review and adversarial collaboration report.

Different types of resistance to passive movement, i.e. hypertonia, were described in schizophrenia spectrum disorders (SSD) long before the introduction of antipsychotics. While these have been rediscovered in antipsychotic-naïve patients and their non-affected relatives, the existence of intrinsic hypertonia vs drug-induced parkinsonism (DIP) in treated SSD remains controversial. This integrative review seeks to develop a commonly accepted framework to specify the putative clinical phenomena, highlight conflicting issues and discuss ways to challenge each hypothesis and model through adversarial collaboration. The authors agreed on a common framework inspired from systems neuroscience. Specification of DIP, locomotor paratonia (LMP) and psychomotor paratonia (PMP) identified points of disagreement. Some viewed parkinsonian rigidity to be sufficient for diagnosing DIP, while others viewed DIP as a syndrome that should include bradykinesia. Sensitivity of DIP to anticholinergic drugs and the nature of LPM and PMP were the most debated issues. It was agreed that treated SSD should be investigated first. Clinical features of the phenomena at issue could be confirmed by torque, EMG and joint angle measures that could help in challenging the selectivity of DIP to anticholinergics. LMP was modeled as the release of the reticular formation from the control of the supplementary motor area (SMA), which could be challenged by the tonic vibration reflex or acoustic startle. PMP was modeled as the release of primary motor cortex from the control of the SMA and may be informed by subclinical echopraxia. If these challenges are not met, this would put new constraints on the models and have clinical and therapeutic implications.

Long-term analgesic effect of trans-spinal direct current stimulation compared to non-invasive motor cortex stimulation in complex regional pain syndrome.

The aim of the present study was to compare the analgesic effect of motor cortex stimulation using high-frequency repetitive transcranial magnetic stimulation or transcranial direct current stimulation and transcutaneous spinal direct current stimulation in patients with complex regional pain syndrome. Thirty-three patients with complex regional pain syndrome were randomized to one of the three treatment groups (repetitive transcranial magnetic stimulation, n = 11; transcranial direct current stimulation, n = 10; transcutaneous spinal direct current stimulation, n = 12) and received a series of 12 sessions of stimulation for 3 weeks (induction phase) and 11 sessions for 4 months (maintenance therapy). The primary end-point was the mean pain intensity assessed weekly with a visual numerical scale during the month prior to treatment (baseline), the 5-month stimulation period and 1 month after the treatment. The weekly visual numerical scale pain score was significantly reduced at all time points compared to baseline in the transcutaneous spinal direct current stimulation group, at the last two time points in the repetitive transcranial magnetic stimulation group (end of the 5-month stimulation period and 1 month later), but at no time point in the transcranial direct current stimulation group. A significant pain relief was observed at the end of induction phase using transcutaneous spinal direct current stimulation compared to repetitive transcranial magnetic stimulation (P = 0.008) and to transcranial direct current stimulation (P = 0.003). In this trial, transcutaneous spinal direct current stimulation was more efficient to relieve pain in patients with complex regional pain syndrome compared to motor cortex stimulation techniques (repetitive transcranial magnetic stimulation, transcranial direct current stimulation). This efficacy was found during the induction phase and was maintained thereafter. This study warrants further investigation to confirm the potentiality of transcutaneous spinal direct current stimulation as a therapeutic option in complex regional pain syndrome.

How valid are proxy assessment of mental health and sleep comorbidities of patients with epilepsy using standardized questionnaires?

BACKGROUND: The study aimed to determine the level of agreement between patients with epilepsy and their proxies when assessing psychiatric comorbidities, sleep disorders, and medication adherence using standardized questionnaires. METHODS: This agreement study is an ancillary analysis of the PRERIES study, a matched case-control study exploring SUDEP risk factors. Controls aged 15 years and older, with active epilepsy or in remission for less than 5 years were recruited between 01/01/2011 and 03/31/2019. An interview was carried out by a trained psychologist on both the patient and a proxy-respondent. During these independent interviews, the following comorbidities were explored: psychiatric comorbidities using the MINI, the STAI- Y2 and NDDI-E scales, sleep disorders with the SDQ-SA and Epworth scales and medication adherence. Level of agreement between patient and their proxy was estimated using Gwet's AC1&2. RESULTS: Among the 107 patient-proxy dyads recruited, proxy respondents were mainly family members (65.4%) or spouses (30.8%). Exploration of present major depression showed excellent agreement at 0.81 [0.65;0.97], as well as exploration of dysthymia at 0.96 [0.61;1]. Suicidal risk evaluation had a lesser agreement at 0.77 [0.60;0.94]. Agreement on anxiety was moderate 0.5 [0.38;0.62]. For sleep disorder, SDQ-SA presented a better agreement than the Epworth questionnaire with respectively 0.73 [0.51;0.95] and 0.45 [0.26;0.63]. For medication adherence, the overall agreement rate was excellent (0.90 [0.78;1]). CONCLUSION: Exploration of potential risk factors through families can give valuable and relatively robust information, especially if the respondent lives with the patient, and should be retrieved, when possible, in usual clinical setting.

The natural history of terms describing functional (neurological) disorders in the medical literature of the last 60 years.

BACKGROUND: Functional neurological disorders (FND), a subtype of functional disorders (FD), are a frequent motive for neurology referrals. The various presentations and the unknown physiopathology of FD have led to the multiplication of terms describing these disorders over the years. METHODS: We examined the FD-related articles published from 1960 to 2020 in PubMed and PsycINFO databases. We searched for: psychogenic, somatization, somatoform, medically unexplained symptoms, hysteria, conversion disorder, dissociative, functional neurological disorder, and functional disorder. Use rates in the title, abstract, keyword, or MeSH fields were collected over successive 5-year periods. After correcting for off-topic results, we examined proportional distribution over time, term associations, and disciplinary fields (neurology and psychiatry). Term impact was estimated via H-index and number of citations. RESULTS: We found that none of the terms is prevailing in the recent medical literature. We observed three trends in the use rates: stability, increase, and decrease of use over time. While most of the terms were present in a stable proportion of the publications, hysteria and psychogenic lost popularity over time. We found a differential preference for terminology between disciplines. Functional neurological disorder showed the highest citation impact, yielding 10% of highly cited publications. CONCLUSION: We found a dynamic and evolving use of the different terms describing FD in the last 60 years. Despite the tendency to use the term functional in the recent highly cited publications, its low prevalence and coexistence with several other terms suggest that a precise, explanatory and non-offensive term remains yet to be found.

Stratifying sudden death risk in adults with drug-resistant focal epilepsy: The SUDEP-CARE score.

BACKGROUND AND PURPOSE: A clinical risk score for sudden unexpected death in epilepsy (SUDEP) in patients with drug-resistant focal epilepsy could help improve prevention. METHODS: A case-control study was conducted including (i) definite or probable SUDEP cases collected by the French National Sentinel Mortality Epilepsy Network and (ii) control patients from the French national research database of epilepsy monitoring units. Patients with drug-resistant focal epilepsy were eligible. Multiple logistic regressions were performed. After sensitivity analysis and internal validation, a simplified risk score was developed from the selected variables. RESULTS: Sixty-two SUDEP cases and 620 controls were included. Of 21 potential predictors explored, seven were ultimately selected, including generalized seizure frequency (>1/month vs. <1/year: adjusted odds ratio [AOR] 2.6, 95% confidence interval [CI] 1.25-5.41), nocturnal or sleep-related seizures (AOR 4.49, 95% CI 2.68-7.53), current or past depression (AOR 2.0, 95% CI 1.19-3.34) or the ability to alert someone of an oncoming seizure (AOR 0.57, 95% CI 0.33-0.98). After internal validation, a clinically usable score ranging from -1 to 8 was developed, with high discrimination capabilities (area under the receiver operating curve 0.85, 95% CI 0.80-0.90). The threshold of 3 has good sensitivity (82.3%, 95% CI 72.7-91.8), whilst keeping a good specificity (82.7%, 95% CI 79.8-85.7). CONCLUSIONS: These results outline the importance of generalized and nocturnal seizures on the occurrence of SUDEP, and show a protective role in the ability to alert someone of an oncoming seizure. The SUDEP-CARE score is promising and will need external validation. Further work, including paraclinical explorations, could improve this risk score.

Parakinesia: A Delphi consensus report.

Abnormal movements are intrinsic to some forms of endogenous psychoses. Spontaneous dyskinesias are observed in drug-naïve first-episode patients and at-risk subjects. However, recent descriptions of spontaneous dyskinesias may actually represent the rediscovery of a more complex phenomenon, 'parakinesia' which was described and documented in extensive cinematographic recordings and long-term observations by German and French neuropsychiatrists decades before the introduction of antipsychotics. With the emergence of drug induced movement disorders, the description of parakinesia has been refined to emphasize the features enabling differential diagnosis with tardive dyskinesia. Unfortunately, parakinesia was largely neglected by mainstream psychiatry to the point of being almost absent from the English-language literature. With the renewed interest in motor phenomena intrinsic to SSD, it was timely not only to raise awareness of parakinesia, but also to propose a scientifically usable definition for this phenomenon. Therefore, we conducted a Delphi consensus exercise with clinicians familiar with the concept of parakinesia. The original concept was separated into hyperkinetic parakinesia (HPk) as dyskinetic-like expressive movements and parakinetic psychomotricity (PPM), i.e., patient's departing from the patient's normal motion style. HPk prevails on the upper part of the face and body, resembling expressive and reactive gestures that not only occur inappropriately but also appear distorted. Abnormal movements vary in intensity depending on the level of psychomotor arousal and are thus abated by antipsychotics. HPk frequently co-occurs with PPM, in which gestures and mimics lose their naturalness and become awkward, disharmonious, stiff, mannered, and bizarre. Patients are never spontaneously aware of HPk or PPM, and the movements are never experienced as self-dystonic or self-alien. HPk and PPM are highly specific to endogenous psychoses, in which they are acquired and progressive, giving them prognostic value. Their differential diagnoses and correspondences with current international concepts are discussed.

The Predictive Role of Low Spatial Frequencies in Automatic Face Processing: A Visual Mismatch Negativity Investigation.

Visual processing is thought to function in a coarse-to-fine manner. Low spatial frequencies (LSF), conveying coarse information, would be processed early to generate predictions. These LSF-based predictions would facilitate the further integration of high spatial frequencies (HSF), conveying fine details. The predictive role of LSF might be crucial in automatic face processing, where high performance could be explained by an accurate selection of clues in early processing. In the present study, we used a visual Mismatch Negativity (vMMN) paradigm by presenting an unfiltered face as standard stimulus, and the same face filtered in LSF or HSF as deviant, to investigate the predictive role of LSF vs. HSF during automatic face processing. If LSF are critical for predictions, we hypothesize that LSF deviants would elicit less prediction error (i.e., reduced mismatch responses) than HSF deviants. Results show that both LSF and HSF deviants elicited a mismatch response compared with their equivalent in an equiprobable sequence. However, in line with our hypothesis, LSF deviants evoke significantly reduced mismatch responses compared to HSF deviants, particularly at later stages. The difference in mismatch between HSF and LSF conditions involves posterior areas and right fusiform gyrus. Overall, our findings suggest a predictive role of LSF during automatic face processing and a critical involvement of HSF in the fusiform during the conscious detection of changes in faces.

Long-term prophylactic efficacy of transcranial direct current stimulation in chronic migraine. A randomised, patient-assessor blinded, sham-controlled trial.

OBJECTIVE: To assess the prophylactic effect of anodal tDCS of the left motor cortex in patients with resistant chronic migraine (CM) and its long-term maintenance. METHODS: In a patient-assessor blinded, sham-controlled trial, 36 patients were randomized to receive anodal tDCS (active group, n = 18) or sham tDCS (sham group, n = 18). The studied population was characterized by a previous failure of at least 3 classes of preventive drugs and a mean duration of migraine history of 26 years. The tDCS procedure consisted of an induction phase of 5 consecutive daily sessions (week 1) followed by a maintenance phase of 1 weekly session during the next 4 weeks and two bimonthly sessions in the next month, for a total of 11 sessions during 2 months. Anodal tDCS was delivered at 2 mA intensity for 20 min over the left motor cortex. The primary endpoint was the reduction in the monthly number of migraine attacks from baseline to each period of follow-up (months 1, 2, 3, 5) between the active and sham groups. RESULTS: The monthly number of migraine attacks expressed as the percentage of reduction from baseline was significantly reduced in the active versus the sham group, from the end of first month (-21% ± 22 vs. -2% ±25, p = 0.019) to the end of follow-up (3-month post-treatment) (-32% ± 33 vs. -6% ±39, p = 0.011). At this time, the rate of responders, defined as a reduction of the monthly number of migraine attacks ≥30% from baseline, was significantly higher in the active group than in the sham group (50% vs. 14%, p = 0.043). CONCLUSION: Our results show a marked prophylactic effect of anodal tDCS of the left motor cortex in resistant CM extending several months after the stimulation period, and suggest that this neuromodulatory approach may be part of the prophylactic alternatives available for CM.

Adult phenotype of KCNQ2 encephalopathy.

BACKGROUND: Pathogenic KCNQ2 variants are a frequent cause of developmental and epileptic encephalopathy. METHODS: We recruited 13 adults (between 18 years and 45 years of age) with KCNQ2 encephalopathy and reviewed their clinical, EEG, neuroimaging and treatment history. RESULTS: While most patients had daily seizures at seizure onset, seizure frequency declined or remitted during childhood and adulthood. The most common seizure type was tonic seizures (early) infancy, and tonic-clonic and focal impaired awareness seizures later in life. Ten individuals (77%) were seizure-free at last follow-up. In 38% of the individuals, earlier periods of seizure freedom lasting a minimum of 2 years followed by seizure recurrence had occurred. Of the 10 seizure-free patients, 4 were receiving a single antiseizure medication (ASM, carbamazepine, lamotrigine or levetiracetam), and 2 had stopped taking ASM. Intellectual disability (ID) ranged from mild to profound, with the majority (54%) of individuals in the severe category. At last contact, six individuals (46%) remained unable to walk independently, six (46%) had limb spasticity and four (31%) tetraparesis/tetraplegia. Six (46%) remained non-verbal, 10 (77%) had autistic features/autism, 4 (31%) exhibited aggressive behaviour and 4 (31%) destructive behaviour with self-injury. Four patients had visual problems, thought to be related to prematurity in one. Sleep problems were seen in six (46%) individuals. CONCLUSION: Seizure frequency declines over the years and most patients are seizure-free in adulthood. Longer seizure-free periods followed by seizure recurrence are common during childhood and adolescence. Most adult patients have severe ID. Motor, language and behavioural problems are an issue of continuous concern.

Successful Treatment of a Paroxysmal Kinesigenic Dyskinesia Patient with Carbamazepine-Induced Stevens-Johnson Syndrome Using Oxcarbazepine Monotherapy: A Case Report.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare condition characterized by abnormal involuntary movements that are precipitated by a sudden movement. PKD is often misdiagnosed with psychogenic movement disorders. Carbamazepine is usually the first choice of medication due to its well-established evidence but could induce Stevens-Johnson syndrome. We report a 21-year-old male patient with PKD referred to our movement disorders clinic after being misdiagnosed with conversion syndrome. PRRT2 gene testing using next-generation sequencing revealed a mutation in c.649dupC p. (Arg217fs). The patient responded well to carbamazepine but had to withdraw the treatment due to carbamazepine-induced Stevens-Johnson syndrome after 3 weeks of medication. Our patient did not respond to trials of levetiracetam and phenytoin but finally responded well to oxcarbazepine. The patient was followed up for 4 years, during which he had no attacks and no side effects. Here, we present a PKD case with carbamazepine-induced Stevens-Johnson syndrome successfully treated with oxcarbazepine despite the risk of cross-reactive skin eruption between these antiepileptics. Careful history taking and examining patient's attacks are crucial to accurate diagnosis and treatment in PKD patients.

A 12-month pilot study outcomes of vagus nerve stimulation in Crohn's disease.

BACKGROUND: The vagus nerve has anti-inflammatory properties. We aimed to investigate vagus nerve stimulation (VNS) as a new therapeutic strategy targeting an intrinsic anti-inflammatory pathway in a pilot study in Crohn's disease patients. The main objectives addressed the questions of long-term safety, tolerability, and anti-inflammatory effects of this therapy. This study is the continuation of previous reported findings at 6 months. METHODS: Nine patients with moderate active disease underwent VNS. An electrode wrapped around the left cervical vagus nerve was continuously stimulated over 1 year. Clinical, biological, endoscopic parameters, cytokines (plasma, gut), and mucosal metabolites were followed-up. KEY RESULTS: After 1 year of VNS, five patients were in clinical remission and six in endoscopic remission. C-reactive protein (CRP) and fecal calprotectin decreased in six and five patients, respectively. Seven patients restored their vagal tone and decreased their digestive pain score. The patients' cytokinergic profile evolved toward a more "healthy profile": Interleukins 6, 23, 12, tumor necrosis factor α, and transforming growth factorß1 were the most impacted cytokines. Correlations were observed between CRP and tumor necrosis factor α, and some gut mucosa metabolites as taurine, lactate, alanine, and beta-hydroxybutyrate. VNS was well tolerated. CONCLUSION & INFERENCES: Vagus nerve stimulation appears as an innovative and well-tolerated treatment in moderate Crohn's disease. After 12 months, VNS has restored a homeostatic vagal tone and reduced the inflammatory state of the patients. VNS has probably a global modulatory effect on the immune system along with gut metabolic regulations. This pilot study needs replication in a larger randomized double-blinded control study.

Emergency room diagnoses of psychogenic nonepileptic seizures with psychogenic status and functional (psychogenic) symptoms: Whopping.

Collecting 130 electronic medical records and diagnoses from emergency room stays of eleven patients with confirmed psychogenic nonepileptic seizure (PNES) over a 17-year period (2001-2018), 48 different diagnostic terms were retrieved. This emphasized the need for a consensual terminology encompassing not only PNES but also all functional transient (paroxysmal) events, including episodes of motor or sensory deficits, and cognitive symptoms. Rather than defining what it is not (PNES, stroke mimicks…), it would be more accurate to define what it is: a paroxysmal functional event.

PNESSE 1: Psychogenic status and status epilepticus: Could they be distinguished retrospectively? A survey among neurologists.

OBJECTIVE: The aim of this study was to evaluate neurologists' reliability in recognizing retrospectively a diagnosis of psychogenic status and status epilepticus (SE) based solely on clinical semiology, as reported in medical charts. METHODS: This is a retrospective analysis of medical records of patients with suspected SE, diagnosed with psychogenic status and SE, proven by video-electroencephalography (EEG) monitoring, over a two-year period, from January 1st 2012 to December 31st 2013. Eight additional patients outside this time frame were included in this series because they had video-EEG proven psychogenic status, and they met all the inclusion criteria. The group with SE was divided into symptomatic SE (SSE) if a precipitating factor was identified, and undetermined SE (USE) if none were identified. Twenty-two neurologists from the CHU de Grenoble-Alpes were asked to fill out a survey where they were asked to score, for each patient, their agreement, using Likert scales, for the respective diagnoses of psychogenic status and SE. Their opinions were based on a provided written sheet summarizing the clinical description of the event and patients' clinical context. Neurologists were blinded to video-EEG monitoring results and final diagnosis. The level of agreement, disagreement, and the homogeneity of neurologist's responses according to the final diagnosis were then calculated. Finally, clinical data, as provided in the event's clinical description and context, considered as highly relevant by neurologists to establish an accurate diagnosis were gathered. RESULTS: Eighteen neurologists completed the survey for 48 patients, including 11 diagnosed with psychogenic status and 37 with SE (30 with SSE and 7 with USE). For patients diagnosed with SE, the presence of a precipitating factor increased the likelihood and the homogeneity among neurologists of a diagnosis of SE (77%), with a specificity (Sp) of 96% and a positive predictive value of 95%. The lack of a precipitating factor significantly decreased the diagnosis likelihood of SE (55%) with a predictive value of 82%. For patients diagnosed with psychogenic status, most of neurologists agreed with the diagnosis of psychogenic status (69%) with a predictive value of 82%, although heterogeneity in the diagnosis was found. According to neurologists participating in this study, most significant terms, found in the medical charts, helping to distinguish SE from psychogenic status were "stereotypical movements", "limb myoclonus", "epilepsy", and "vigilance alteration". To differentiate psychogenic status from SE, most relevant terms used by neurologists were "resistance to eyes opening", "anarchic movements", "prolonged motor manifestations", "limb tremor" and "opisthotonus". However, analysis of the distribution of the terms among the different groups (SSE, USE, and psychogenic status) showed no significant difference. SIGNIFICANCE: This study is in line with previous literature highlighting the difficulty in retrospectively differentiating SE from psychogenic status based on clinical events description recorded in the medical chart.

A Case of Peripherally Induced Task-Specific "Lipstick Dystonic Tremor".

Background: Peripherally induced movement disorders (PIMDs) represent a rare and debated complication of peripheral trauma. Phenomenology Shown: We report a case of task-specific "lipstick" jerky dystonic tremor as a consequence of traumatic shoulder injury, successfully treated with EMG-guided botulinum toxin injections. Educational Value: This case expands the phenotypic spectrum of PIMDs, with a visual example of a task-specific dystonic tremor after peripheral trauma, and the efficacy of EMG-guided botulinum toxin treatment in the setting of posttraumatic dystonic tremor.

Temporal Dynamics of Natural Static Emotional Facial Expressions Decoding: A Study Using Event- and Eye Fixation-Related Potentials.

This study aims at examining the precise temporal dynamics of the emotional facial decoding as it unfolds in the brain, according to the emotions displayed. To characterize this processing as it occurs in ecological settings, we focused on unconstrained visual explorations of natural emotional faces (i.e., free eye movements). The General Linear Model (GLM; Smith and Kutas, 2015a,b; Kristensen et al., 2017a) enables such a depiction. It allows deconvolving adjacent overlapping responses of the eye fixation-related potentials (EFRPs) elicited by the subsequent fixations and the event-related potentials (ERPs) elicited at the stimuli onset. Nineteen participants were displayed with spontaneous static facial expressions of emotions (Neutral, Disgust, Surprise, and Happiness) from the DynEmo database (Tcherkassof et al., 2013). Behavioral results on participants' eye movements show that the usual diagnostic features in emotional decoding (eyes for negative facial displays and mouth for positive ones) are consistent with the literature. The impact of emotional category on both the ERPs and the EFRPs elicited by the free exploration of the emotional faces is observed upon the temporal dynamics of the emotional facial expression processing. Regarding the ERP at stimulus onset, there is a significant emotion-dependent modulation of the P2-P3 complex and LPP components' amplitude at the left frontal site for the ERPs computed by averaging. Yet, the GLM reveals the impact of subsequent fixations on the ERPs time-locked on stimulus onset. Results are also in line with the valence hypothesis. The observed differences between the two estimation methods (Average vs. GLM) suggest the predominance of the right hemisphere at the stimulus onset and the implication of the left hemisphere in the processing of the information encoded by subsequent fixations. Concerning the first EFRP, the Lambda response and the P2 component are modulated by the emotion of surprise compared to the neutral emotion, suggesting an impact of high-level factors, in parieto-occipital sites. Moreover, no difference is observed on the second and subsequent EFRP. Taken together, the results stress the significant gain obtained in analyzing the EFRPs using the GLM method and pave the way toward efficient ecological emotional dynamic stimuli analyses.