Differentiation of specific ripple patterns helps to identify epileptogenic areas for surgical procedures

ObjectiveHigh frequency oscillations (HFOs) at 80–500 Hz are promising markers of epileptic areas. Several retrospective studies reported that surgical removal of areas generating HFOs was associated with a good seizure outcome. Recent reports suggested that ripple (80–200 Hz) HFO patterns co-existed with different background EEG activities. We hypothesized that the coexisting background EEG pattern may distinguish physiological from epileptic ripples.MethodsRates of HFOs were analyzed in intracranial EEG recordings of 22 patients. Additionally, ripple patterns were classified for each channel depending either as coexisting with a flat or oscillatory background activity. A multi-variate analysis was performed to determine whether removal of areas showing the above EEG markers correlated with seizure outcome.ResultsRemoval of areas generating high rates of ‘fast ripples (>200 Hz)’ and ‘ripples on a flat background activity’ showed a significant correlation with a seizure-free outcome. In contrast, removal of high rates of ‘ripples’ or ‘ripple patterns in a continuously oscillating background’ was not significantly associated with seizure outcome.ConclusionRipples occurring in an oscillatory background activity may be suggestive of physiological activity, while those on a flat background reflect epileptic activity.SignificanceConsideration of coexisting background patterns may improve the delineation of the epileptogenic areas using ripple oscillations.     

High frequency oscillations in intra-operative electrocorticography before and after epilepsy surgery

ObjectiveRemoval of brain tissue showing high frequency oscillations (HFOs; ripples: 80–250 Hz and fast ripples: 250–500 Hz) in preresection electrocorticography (preECoG) in epilepsy patients seems a predictor of good surgical outcome. We analyzed occurrence and localization of HFOs in intra-operative preECoG and postresection electrocorticography (postECoG).MethodsHFOs were automatically detected in one-minute epochs of intra-operative ECoG sampled at 2048 Hz of fourteen patients. Ripple, fast ripple, spike, ripples on a spike (RoS) and not on a spike (RnoS) rates were analyzed in pre- and postECoG for resected and nonresected electrodes.ResultsRipple, spike and fast ripple rates decreased after resection. RnoS decreased less than RoS (74% vs. 83%; p = 0.01). Most fast ripples in preECoG were located in resected tissue. PostECoG fast ripples occurred in one patient with poor outcome. Patients with good outcome had relatively high postECoG RnoS rates, specifically in the sensorimotor cortex.ConclusionsOur observations show that fast ripples in intra-operative ECoG, compared to ripples, may be a better biomarker for epileptogenicity. Further studies have to determine the relation between resection of epileptogenic tissue and physiological ripples generated by the sensorimotor cortex.SignificanceFast ripples in intra-operative ECoG can help identify the epileptogenic zone, while ripples might also be physiological.     

Influence of contact size on the detection of HFOs in human intracerebral EEG recordings

ObjectiveHigh frequency oscillations (HFOs) are brief electroencephalographic events associated with epileptic activity, and likely representing biological markers of the epileptogenic zone. HFOs are usually detected with intracranial EEG and detection is influenced by contact size. The size of commercially available intracerebral electrodes varies widely. This study assesses HFO detection rates from adjacent electrode contacts in human intracerebral recordings.MethodsIntracerebral recordings were collected from 11 patients undergoing stereoelectroencephalographic investigation using hybrid depth electrodes containing adjacent large (0.8 or 5 mm²) and small (0.2 or 0.3 mm²) contacts. HFOs were marked manually during 5-min tracings in 131 pairs of adjacent large and small contacts. HFO rates per minute and mean event durations were compared between adjacent contacts.ResultsA minimal but statistically significant advantage in ripple detection was found in a subgroup of large contacts. Otherwise, HFO rates and mean event durations were not statistically different between groups.ConclusionThe size of clinical contacts within the studied range did not influence HFO detection in a clinically relevant manner. Larger contacts provide a minimal advantage for ripple detection.SignificanceOur findings suggest that commercially available intracerebral electrodes with contacts between 0.2 and 5 mm² likely possess similar HFO detection abilities.     

Cognitive changes in people with temporal lobe epilepsy over a 13-year period

ObjectivesThe aims of our study were to evaluate cognitive decline in people with temporal lobe epilepsy over a period of 13 years and to determine what clinical and treatment characteristics may have been associated with these.Materials and methodsThirty-three individuals with temporal lobe epilepsy underwent the same neuropsychological assessment of verbal and nonverbal memory, attention, and executive functions using the same cognitive test battery as one used 13 years ago. Long-term verbal and nonverbal memory was tested four weeks later. Results were compared with those carried out 13 years earlier.ResultsThere was no significant change in verbal and verbal–logical memory tests; however, nonverbal memory worsened significantly. Long-term verbal memory declined for 21.9% of participants, long-term verbal–logical memory for 34.4%, and long-term nonverbal memory for 56.3%. Worsening of working verbal and verbal–logical memory was associated with longer epilepsy duration and lower levels of patients' education; worsening of verbal delayed recall and long-term verbal–logical memory was associated with higher seizure frequency. Decline in long-term nonverbal memory had significant association with a longer duration of epilepsy. The worsening of reaction and attention inversely correlated with the symptoms of depression.ConclusionOver a 13-year period, cognitive functions did not change significantly. Good seizure control and reduced symptoms of depression in this sample of people with temporal lobe epilepsy were associated with better cognitive functioning. The predictors of change of cognitive functions could be complex and require further study.     

Improving the identification of High Frequency Oscillations

ObjectiveHigh Frequency Oscillations (HFOs), including Ripples (80–250 Hz) and Fast Ripples (250–500 Hz), can be recorded from intracranial macroelectrodes in patients with intractable epilepsy. We implemented a procedure to establish the duration for which a stable measurement of rate of HFOs is achieved.MethodsTo determine concordance, Kappa coefficient was computed. The information gained when increasing the duration was analyzed in terms of HFO rates and ranking of channels with respect to HFO and spike rates.ResultsIn a group of 30 patients, Kappa was 0.7 for ripples, 0.7 for fast ripples and 0.67 for spikes. Five minutes provided the same information as 10 min in terms of rates in 9/10 patients and with respect to ranking of channels in 8/10 patients; 5/30 patients did not achieve stable measurements of HFOs or spikes and needed marking for 10 min.ConclusionWe propose that 5 min provides in most cases the same information as a longer interval when identifying HFOs and spikes in slow wave sleep, and present methods to identify when this is not the case.SignificanceThis procedure is useful to control for consistency between readers and to evaluate if the selected interval provides stable information, for automatic and visual identification of events.     

Auditory verbal memory and psychosocial symptoms are related in children with idiopathic epilepsy

ObjectiveIdiopathic epilepsies are considered to have relatively good prognoses and normal or near normal developmental outcomes. Nevertheless, accumulating studies demonstrate memory and psychosocial deficits in this population, and the prevalence, severity and relationships between these domains are still not well defined. We aimed to assess memory, psychosocial function, and the relationships between these two domains among children with idiopathic epilepsy syndromes using an extended neuropsychological battery and psychosocial questionnaires.MethodsCognitive abilities, neuropsychological performance, and socioemotional behavior of 33 early adolescent children, diagnosed with idiopathic epilepsy, ages 9–14 years, were assessed and compared with 27 age- and education-matched healthy controls.ResultsCompared to controls, patients with stabilized idiopathic epilepsy exhibited higher risks for short-term memory deficits (auditory verbal and visual) (p < 0.0001), working memory deficits (p < 0.003), auditory verbal long-term memory deficits (p < 0.0021), and more frequent psychosocial symptoms (p < 0.0001). The severity of auditory verbal memory deficits was related to severity of psychosocial symptoms among the children with epilepsy but not in the healthy controls.SignificanceResults suggest that deficient auditory verbal memory may be compromising psychosocial functioning in children with idiopathic epilepsy, possibly underscoring that cognitive variables, such as auditory verbal memory, should be assessed and treated in this population to prevent secondary symptoms.     

Impaired sleep-related consolidation of declarative memories in idiopathic focal epilepsies of childhood

ObjectiveDeclarative memory is consolidated during sleep in healthy children. We tested the hypothesis that consolidation processes are impaired in idiopathic focal epilepsies (IFE) of childhood in association with frequent interictal epileptiform discharges (IEDs) during sleep.MethodsA verbal (word-pair association) and a nonverbal (2D object location) declarative memory task were administrated to 15 children with IFEs and 8 control children 6–12 years of age. Patients had either centrotemporal (11 patients) or occipital (4 patients) IEDs. All but 3 patients had a history of unprovoked seizures, and 6 of them were treated with valproate (VPA). The learning procedure (location of object pairs presented on a grid; association of word pairs) was executed in the evening. Retrieval was tested immediately after learning and on the next morning after a night of sleep. Participants were tested twice, once in natural home conditions and one month later in the unfamiliar conditions of the sleep unit under EEG monitoring.ResultsOvernight recall performance was lower in children with IFE than in control children on both tasks (ps < 0.05). Performance in home conditions was similar to that in hospital conditions. Higher spike–wave index (SWI) during nonrapid eye movement (NREM) sleep was associated with poorer performance in the nonverbal task (p < 0.05). Valproate treatment was not associated with overnight recall performance for both tasks (ps > 0.05).ConclusionMemory consolidation is impaired in IFE of childhood. The association between higher SWI during NREM sleep and poorer nonverbal declarative memory consolidation supports the hypothesis that interictal epileptic activity could disrupt sleep memory consolidation.     

Automatic 80-250Hz "ripple" high frequency oscillation detection in invasive subdural grid and strip recordings in epilepsy by a radial basis function neural network

ObjectiveRecent studies give evidence that high frequency oscillations (HFOs) in the range between 80 Hz and 500 Hz in invasive recordings of epilepsy patients have the potential to serve as reliable markers of epileptogenicity. This study presents an algorithm for automatic HFO detection.MethodsThe presented HFO detector uses a radial basis function neural network. Input features of the detector were energy, line length and instantaneous frequency. Visual marked “ripple” HFOs (80–250 Hz) of 3 patients were used to train the neural network, and a further 8 patients served for the detector evaluation.ResultsDetector sensitivity and specificity were 49.1% and 36.3%. The linear and rank correlation between visual and automatic marked “ripple” HFO counts over the channels were significant for all recordings. A reference detector based on the line length achieved a sensitivity of 35.4% and a specificity of 46.8%.ConclusionsAutomatic detections corresponded only partly to visual markings for single events but the relative distribution of brain regions displaying “ripple” HFO activity is reflected by the automated system.SignificanceThe detector allows the automatic evaluation of brain areas with high HFO frequency, which is of high relevance for the demarcation of the epileptogenic zone.     

Functional substrate for memory function differences between patients with left and right mesial temporal lobe epilepsy associated with hippocampal sclerosis

ObjectiveLittle is known about the functional substrate for memory function differences in patients with left or right mesial temporal lobe epilepsy (mTLE) associated with hippocampal sclerosis (HS) from an electrophysiological perspective. To characterize these differences, we hypothesized that hippocampal theta connectivity in the resting-state might be different between patients with left and right mTLE with HS and be correlated with memory performance.MethodsResting-state hippocampal theta connectivity, identified via whole-brain magnetoencephalography, was evaluated. Connectivity and memory function in 41 patients with mTLE with HS (left mTLE = 22; right mTLE = 19) were compared with those in 46 age-matched healthy controls and 28 patients with focal cortical dysplasia (FCD) but without HS.ResultsConnectivity between the right hippocampus and the left middle frontal gyrus was significantly stronger in patients with right mTLE than in patients with left mTLE. Moreover, this connectivity was positively correlated with delayed verbal recall and recognition scores in patients with mTLE. Patients with left mTLE had greater delayed recall impairment than patients with right mTLE and FCD. Similarly, delayed recognition performance was worse in patients with left mTLE than in patients with right mTLE and FCD. No significant differences in memory function between patients with right mTLE and FCD were detected. Patients with right mTLE showed significantly stronger hippocampal theta connectivity between the right hippocampus and left middle frontal gyrus than patients with FCD and left mTLE.ConclusionOur results suggest that right hippocampal–left middle frontal theta connectivity could be a functional substrate that can account for differences in memory function between patients with left and right mTLE. This functional substrate might be related to different compensatory mechanisms against the structural hippocampal lesions in left and right mTLE groups. Given the positive correlation between connectivity and delayed verbal memory function, hemispheric-specific hippocampal–frontal theta connectivity assessment could be useful as an electrophysiological indicator of delayed verbal memory function in patients with mTLE with HS.     

Impact of hippocampal subfield histopathology in episodic memory impairment in mesial temporal lobe epilepsy and hippocampal sclerosis

ObjectiveThe objective of the study was to analyze preoperative visual and verbal episodic memories in a homogeneous series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) submitted to corticoamygdalohippocampectomy and its association with neuronal cell density of each hippocampal subfield.MethodsThe hippocampi of 72 right-handed patients were collected and prepared for histopathological examination. Hippocampal sclerosis patterns were determined, and neuronal cell density was calculated. Preoperatively, two verbal and two visual memory tests (immediate and delayed recalls) were applied, and patients were divided into two groups, left and right MTLE (36/36).ResultsThere were no statistical differences between groups regarding demographic and clinical data. Cornu Ammonis 4 (CA4) neuronal density was significantly lower in the right hippocampus compared with the left (p = 0.048). The groups with HS presented different memory performance — the right HS were worse in visual memory test [Complex Rey Figure, immediate (p = 0.001) and delayed (p = 0.009)], but better in one verbal task [RAVLT delayed (p = 0.005)]. Multiple regression analysis suggested that the verbal memory performance of the group with left HS was explained by CA1 neuronal density since both tasks were significantly influenced by CA1 [Logical Memory immediate recall (p = 0.050) and Logical Memory and RAVLT delayed recalls (p = 0.004 and p = 0.001, respectively)]. For patients with right HS, both CA1 subfield integrity (p = 0.006) and epilepsy duration (p = 0.012) explained Complex Rey Figure immediate recall performance. Ultimately, epilepsy duration also explained the performance in the Complex Rey Figure delayed recall (p < 0.001).SignificanceCornu Ammonis 1 (CA1) hippocampal subfield was related to immediate and delayed recalls of verbal memory tests in left HS, while CA1 and epilepsy duration were associated with visual memory performance in patients with right HS.     

Theory of own mind and autobiographical memory in adults with ASD

While there is solid evidence of other-related theory of mind (ToM) deficits in autism, there is less research addressing self-related ToM impairments. To date, relations between self-related ToM and other cognitive skills related to representing own mental states such as autobiographical memory have scarcely been investigated. Thus, the purpose of this study was to investigate the differential relations of self-and other-related theory of mind skills and autobiographical memory in n = 20 adults with Autism Spectrum Disorder and n = 20 matched controls using standardized measures. The overall results indicated a specific relation between recalled episodic autobiographical memories on the episodic and semantic autobiographical memory interview and the performance on the mind-mindedness for oneself task in adults with ASD, which proved to be largely independent of verbal and nonverbal IQ.     

Decreased processing speed might account for working memory span deficit in schizophrenia,and might mediate the associations between working memory span and clinical symptoms

ObjectiveVerbal working memory span is decreased in patients with schizophrenia, and this might contribute to impairment in higher cognitive functions as well as to the formation of certain clinical symptoms. Processing speed has been identified as a crucial factor in cognitive efficiency in this population. We tested the hypothesis that decreased processing speed underlies the verbal working memory deficit in patients and mediates the associations between working memory span and clinical symptoms.MethodForty-nine schizophrenia inpatients recruited from units for chronic and acute patients, and forty-five healthy participants, were involved in the study. Verbal working memory span was assessed by means of the letter-number span. The Digit Copy test was used to assess motor speed, and the Digit Symbol Substitution Test to assess cognitive speed.ResultsThe working memory span was significantly impaired in patients (F(1,90) = 4.6, P < 0.05). However, the group difference was eliminated when either the motor or the cognitive speed measure was controlled (F(1,89) = 0.03, P = 0.86, and F(1,89) = 0.03, P = 0.88). In the patient group, working memory span was significantly correlated with negative symptoms (r = –0.52, P < 0.0001) and thought disorganisation (r = –0.34, P < 0.025) scores. Regression analyses showed that the association with negative symptoms was no longer significant when the motor speed measure was controlled (β = –0.12, P = 0.20), while the association with thought disorganisation was no longer significant when the cognitive speed measure was controlled (β = –0.10, P = 0.26).ConclusionsDecrement in motor and cognitive speed plays a significant role in both the verbal working memory impairment observed in patients and the associations between verbal working memory impairment and clinical symptoms.     

Accelerated Long Term Forgetting in patients with focal seizures: Incidence rate and contributing factors

BackgroundAccelerated Long Term Forgetting (ALF) is usually defined as a memory impairment that is seen only at long delays (e.g., after days or weeks) and not at shorter delays (e.g., 30 min) typically used in clinical settings. Research indicates that ALF occurs in some patients with epilepsy, but the incidence rates and underlying causes have not been established. In this study, we considered these issues.MethodsForty-four patients with a history of focal seizures were tested at 30 min and 7 day delays for material from the Rey Auditory Verbal Learning Test (RAVLT) and Aggie Figures Test. Recently published norms from a matched group of 60 control subjects (Miller et al., 2015 ) were used to determine whether patients demonstrated ALF, impairment at 30 min or intact memory performance.ResultsThe incidence of ALF in the epilepsy patients (18%) was > 3 times higher than normal on the RAVLT, but no different (7%) from the incidence in normal subjects on the Aggie Figures. A different, but again significantly high, proportion of patients (36%) showed shorter-term memory deficits on at least one task. ALF was found mainly in patients with temporal-lobe epilepsy, but also occurred in one patient with an extratemporal seizure focus. Presence of a hippocampal lesion was the main predicting factor of ALF.ConclusionsMany patients with a focal seizure disorder show memory deficits after longer delays that are not evident on standard assessment. The present study explored the factors associated with this ALF memory profile. These new findings will enhance clinical practice, particularly the management of patients with memory complaints.     

High-frequency oscillations recorded with surface EEG in neonates with seizures

ObjectiveNeonatal seizures are often the first symptom of perinatal brain injury. High-frequency oscillations (HFOs) are promising new biomarkers for epileptogenic tissue and can be found in intracranial and surface EEG. To date, we cannot reliably predict which neonates with seizures will develop childhood epilepsy. We questioned whether epileptic HFOs can be generated by the neonatal brain and potentially predict epilepsy.MethodsWe selected 24 surface EEGs sampled at 2048 Hz with 175 seizures from 16 neonates and visually reviewed them for HFOs. Interictal epochs were also reviewed.ResultsWe found HFOs in thirteen seizures (7%) from four neonates (25%). 5025 ictal ripples (rate 10 to 1311/min; mean frequency 135 Hz; mean duration 66 ms) and 1427 fast ripples (rate 8 to 356/min; mean frequency 298 Hz; mean duration 25 ms) were marked. Two neonates (13%) showed interictal HFOs (285 ripples and 25 fast ripples). Almost all HFOs co-occurred with sharp transients. We could not find a relationship between neonatal HFOs and outcome yet.ConclusionsNeonatal HFOs co-occur with ictal and interictal sharp transients.SignificanceThe neonatal brain can generate epileptic ripples and fast ripples, particularly during seizures, though their occurrence is not common and potential clinical value not evident yet.     

Validation of Chinese version of the Morisky Medication Adherence Scale in patients with epilepsy

PurposeThis study aimed to validate a Chinese version of the Morisky Medication Adherence Scale (MMAS-8) in patients with epilepsy. The relationships between adherence, seizure frequency, and adverse effects were assessed using this method.MethodsData from patients diagnosed with epilepsy at the Department of Neurology of Huashan Hospital were collected between January and June 2013. To validate the MMAS-8, internal consistency, test–retest reliability, and factor analysis were calculated. Relationships between adherence, seizure frequency, and adverse effects were assessed using Pearson's correlation.ResultsOne hundred and eleven patients were recruited. The MMAS-8 had moderate internal consistency (Cronbach's α = 0.556) and good test–retest reliability (intraclass correlation coefficient = 0.729). The MMAS-8 adherence rate was 79.2%. MMAS-8 adherence was negatively correlated with seizure frequency and adverse effects (r = –0.708, p < 0.001; r = –0.484, p < 0.001).ConclusionThe MMAS-8 scale can be used as a tool to assess medication adherence in Chinese patients with epilepsy. Better seizure control and lower rates of adverse effects were significantly correlated with higher adherence scores.     

Patterns of verbal learning and memory in children with intractable temporal lobe or frontal lobe epilepsy

PurposeThe objective of this study was to provide a better understanding of the verbal learning and memory (VLM) patterns that might differentiate children with frontal lobe epilepsy (FLE) from children with temporal lobe epilepsy (TLE) and to examine the impact of variables thought to influence outcomes (seizure laterality, age at seizure onset, age at assessment, epilepsy duration, number of antiepileptic drugs).MethodsRetrospective analyses were carried out for children with intractable unilateral TLE (n = 100) and FLE (n = 27) who completed standardized measures of VLM entailing lists of single words or lists of word pairs.ResultsMean intelligent quotients and VLM scores on single words fell within the average range for both groups, whereas scores fell within the low average to borderline range on word pairs. No significant overall differences in VLM were found between the group with TLE and the group with FLE.Older age at assessment and older age at seizure onset were generally associated with better VLM in both groups but were related to better performance in a number of indices in the group with TLE and only fewer intrusions in the group with FLE.ConclusionsThe VLM profiles of children with TLE and FLE are generally similar. Older age at assessment and older age at seizure onset have a favorable impact on both groups but are related to better encoding, retrieval, and monitoring processes for the group with TLE and improved memory monitoring (i.e., as indicated by fewer intrusions) in the group with FLE.     

Etomidate activates epileptic high frequency oscillations

ObjectiveThe short acting anesthetic etomidate has been shown to provoke epileptic spikes and rarely seizures. Influence of etomidate on the occurrence of epileptic HFO (high frequency oscillations) however is unknown. An HFO inducing effect of etomidate would allow further validation of the substance as a provocation measure in presurgical evaluation as well as provide insights into the common mechanisms of HFO, spike and seizure generation.MethodsWe retrospectively analyzed EEG data from four patients who underwent etomidate activation during invasive video-EEG monitoring with subdural strip electrodes. Spikes were manually selected in raw data, HFO in band pass filtered data (80–250 Hz). Rate and spatial distribution of HFO and spikes in three segments were compared: immediately after etomidate administration, as well as during slow wave sleep and while awake.ResultsRates of HFO and spikes increased significantly after etomidate administration: Overall average rates of spikes were 9.7/min during sleep, 10/min while awake and 61.4/min after etomidate. Average HFO rates were 9.5/min during sleep, 8.3/min while awake and 24.4/min after etomidate (p < 0.001, non-parametric ANOVA). Spatial distributions of HFO and spikes after administration of etomidate were consistent with the seizure onset zone (SOZ) and area of resection when available (SOZ: two patients; resection: one patient; no information: one patient). Except for spurious events, no additional HFO and spike foci were seen with activation.ConclusionsEtomidate administration activates spikes and HFO. Spatial distributions do not extend beyond electrodes showing spikes and HFO without Etomidate and seem consistent with the epileptic network.SignificanceEtomidate activation is a safe procedure to provoke not only epileptic spikes but also HFO, which were shown to have a high specificity for the SOZ.     

An investigation of self-injurious behaviors in adults with severe intellectual disabilities

Self-injurious behavior (SIB) is commonly observed among individuals with intellectual disability (ID) living in state-run supports and services centers. Specific examples of SIB include poking oneself in the eye; harming oneself by hitting, scratching, or pinching; and pica (i.e., swallowing objects causing bodily harm). Previous research has focused on SIB in individuals with ID more generally without focusing on specific levels of ID or taking into account other important personal variables. This study examined 45 adults with severe ID living in two large state-run facilities in the Southeastern United States who were separated into groups for comparison (ASD and non ASD; verbal and nonverbal). Data was collected on the presence of SIB using the Autism Spectrum Disorder-Problem Behavior Adult Version (ASD-PBA). A two-way analysis of variance (ANOVA) was conducted to determine if there were significant differences between groups on rates of SIB. Individuals with ID and ASD exhibited significantly higher rates of SIB than individuals with only ID, F (1,43) = 50.84, p < 0.05. Furthermore, verbal individuals had significantly higher rates of SIB than nonverbal individuals, F (1,43) = 57.612, p < 0.05. There was a significant interaction between the effects of ASD diagnosis and verbal ability on rates of SIB, F (1,43) = 50.84, p < 0.05. The implications of these findings in the context of other research on ID, ASD, SIB, and verbal abilities are discussed.     

Pitfalls of high-pass filtering for detecting epileptic oscillations: A technical note on “false” ripples

ObjectivesTo analyze interictal High frequency oscillations (HFOs) as observed in the medial temporal lobe of epileptic patients and animals (ripples, 80–200 Hz and fast ripples, 250–600 Hz). To show that the identification of interictal HFOs raises some methodological issues, as the filtering of sharp transients (e.g., epileptic spikes or artefacts) or signals with harmonics can result in “false” ripples. To illustrate and quantify the occurrence of false ripples on filtered EEG traces.MethodsWe have performed high-pass filtering on both simulated and real data. We have also used two alternate methods: time-frequency analysis and matching pursuit.ResultsTwo types of events were shown to produce oscillations after filtering that could be confounded with actual oscillatory activity: sharp transients and harmonics of non-sinusoidal signals.ConclusionsHigh-pass filtering of EEG traces for detection of oscillatory activity should be performed with great care. Filtered traces should be compared to original traces for verification of presence of transients. Additional techniques such as time-frequency transforms or sparse decompositions are highly beneficial.SignificanceOur study draws the attention on an issue of great importance in the marking of HFOs on EEG traces. We illustrate complementary methods that can help both researchers and clinicians.     

Effects of the noncompetitive AMPA receptor antagonist perampanel on thalamo-cortical excitability: A study of high-frequency oscillations in somatosensory evoked potentials

ObjectiveWe designed a longitudinal cohort study on People with Epilepsy (PwE) with the aim of assessing the effect of Perampanel (PER) on cortico-subcortical networks, as measured by high-frequency oscillations of somatosensory evoked potentials (SEP-HFOs). SEP-HFOs measure the excitability of both thalamo-cortical projections (early HFOs) and intracortical GABAergic synapses (late HFOs), thus they could be used to study the anti-glutamatergic action of PER, a selective antagonist of the AMPA receptor.Methods15 PwE eligible for PER add-on therapy, were enrolled prospectively. Subjects underwent SEPs recording from the dominant hand at two times: PwE_T0 (baseline, before PER titration) and PwE_T1 (therapeutic dose of 4 mg). HFOs were obtained by filtering N20 scalp response in the 400–800 Hz range. Patients were compared with a normative population of 15 healthy controls (HC) matched for age and sex.ResultsWe found a significant reduction of Total HFOs and mostly early HFOs area between PwE_T0 and PwE_T1 (p = 0.05 and p = 0.045 respectively) and between HC and PwE_T1 (p = 0.01). Furthermore, we found a significant reduction of P24/N24 Amplitude between PwE_T0 and HC and between PwE_T0 and PwE_T1 (p = 0.006 and p = 0.032, respectively).ConclusionsIntroduction of PER as add-on therapy reduced the area of total HFOs, acting mainly on the early burst, related to thalamo-cortical pathways. Furthermore P24/N24 amplitude, which seems to reflect a form of cortico-subcortical integration, resulted increased in PwE at T0 and normalized at T1.SignificanceOur findings suggest that PER acts on cortico-subcortical excitability. This could explain the broad spectrum of PER and its success in forms of epilepsy characterized by thalamo-cortical hyperexcitability.