Dopamine and deep brain stimulation accelerate the neural dynamics of volitional action in Parkinson's disease.

The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is whether dopamine and DBS facilitate de novo build-up of neural dynamics for motor execution or accelerate existing cortical movement initiation signals through shared modulatory circuit effects. Answering these questions can provide the foundation for new closed-loop neurotherapies with adaptive DBS, but the objectification of neural processing delays prior to performance of volitional action remains a significant challenge. To overcome this challenge, we studied readiness potentials and trained brain signal decoders on invasive neurophysiology signals in 25 DBS patients (12 female) with Parkinson's disease during performance of self-initiated movements. Combined sensorimotor cortex electrocorticography (ECoG) and subthalamic local field potential (LFP) recordings were performed OFF therapy (N = 22), ON dopaminergic medication (N = 18) and ON subthalamic deep brain stimulation (N = 8). This allowed us to compare their therapeutic effects on neural latencies between the earliest cortical representation of movement intention as decoded by linear discriminant analysis classifiers and onset of muscle activation recorded with electromyography (EMG). In the hypodopaminergic OFF state, we observed long latencies between motor intention and motor execution for readiness potentials and machine learning classifications. Both, dopamine and DBS significantly shortened these latencies, hinting towards a shared therapeutic mechanism for alleviation of akinesia. To investigate this further, we analysed directional cortico-subthalamic oscillatory communication with multivariate granger causality. Strikingly, we found that both therapies independently shifted cortico-subthalamic oscillatory information flow from antikinetic beta (13-35 Hz) to prokinetic theta (4-10 Hz) rhythms, which was correlated with latencies in motor execution. Our study reveals a shared brain network modulation pattern of dopamine and DBS that may underlie the acceleration of neural dynamics for augmentation of movement initiation in Parkinson's disease. Instead of producing or increasing preparatory brain signals, both therapies modulate oscillatory communication. These insights provide a link between the pathophysiology of akinesia and its' therapeutic alleviation with oscillatory network changes in other non-motor and motor domains, e.g. related to hyperkinesia or effort and reward perception. In the future, our study may inspire the development of clinical brain computer interfaces based on brain signal decoders to provide temporally precise support for action initiation in patients with brain disorders.

Two stages of speech envelope tracking in human auditory cortex modulated by speech intelligibility.

The envelope is essential for speech perception. Recent studies have shown that cortical activity can track the acoustic envelope. However, whether the tracking strength reflects the extent of speech intelligibility processing remains controversial. Here, using stereo-electroencephalogram technology, we directly recorded the activity in human auditory cortex while subjects listened to either natural or noise-vocoded speech. These 2 stimuli have approximately identical envelopes, but the noise-vocoded speech does not have speech intelligibility. According to the tracking lags, we revealed 2 stages of envelope tracking: an early high-γ (60-140 Hz) power stage that preferred the noise-vocoded speech and a late θ (4-8 Hz) phase stage that preferred the natural speech. Furthermore, the decoding performance of high-γ power was better in primary auditory cortex than in nonprimary auditory cortex, consistent with its short tracking delay, while θ phase showed better decoding performance in right auditory cortex. In addition, high-γ responses with sustained temporal profiles in nonprimary auditory cortex were dominant in both envelope tracking and decoding. In sum, we suggested a functional dissociation between high-γ power and θ phase: the former reflects fast and automatic processing of brief acoustic features, while the latter correlates to slow build-up processing facilitated by speech intelligibility.

Temporal order of signal propagation within and across intrinsic brain networks.

We studied the temporal dynamics of activity within and across functional MRI (fMRI)-derived nodes of intrinsic resting-state networks of the human brain using intracranial electroencephalography (iEEG) and repeated single-pulse electrical stimulation (SPES) in neurosurgical subjects implanted with intracranial electrodes. We stimulated and recorded from 2,133 and 2,372 sites, respectively, in 29 subjects. We found that N1 and N2 segments of the evoked responses are associated with intra- and internetwork communications, respectively. In a separate cognitive experiment, evoked electrophysiological responses to visual target stimuli occurred with less temporal separation across pairs of electrodes that were located within the same fMRI-defined resting-state networks compared with those located across different resting-state networks. Our results suggest intranetwork prior to internetwork information processing at the subsecond timescale.

Does seizure propagate within or across intrinsic brain networks? An intracranial EEG study.

BACKGROUND: Understanding the spatiotemporal propagation profiles of seizures is crucial for the preoperative assessment of epilepsy patients. The present study aimed to investigate whether seizures exhibit propagation patterns that align with intrinsic networks (INs). METHODS: A quantitative analysis was conducted to examine ictal fast activity (IFA). The Epileptogenicity Index (EI) was employed to assess the epileptogenicity, spectral features, and temporal characteristics of IFA. Intra-network and inter-network comparisons were made regarding the IFA-related metrics. Additionally, the metrics were correlated with Euclidean distance. Network connection maps were generated to visualize seizures originating from different INs, allowing for comparisons between distinct groups. RESULTS: Data for 81 seizures in 43 subjects were captured using stereoelectroencephalography implantation. Three metrics were compared: EI, time involvement (TI), and energy ratio index (ERI). Intra-network channels exhibited higher EI, earlier involvement of IFA, and stronger high-frequency energy. These findings were further validated through subgroup analyses stratified by neuropathology, seizure type, and seizure origination lobe. Correlation analyses revealed a negative association between distance and both EI and ERI, while distance exhibited a positive correlation with TI. Seizures originating from different INs exhibited varying propagation characteristics. CONCLUSIONS: The study findings highlight the dominant role of intra-network dynamics over inter-network during seizure propagation. These results contribute to our understanding of seizure dynamics and their relationship with INs.

Pallidal activities during sleep and sleep decoding in dystonia, Huntington's, and Parkinson's disease.

BACKGROUND: Sleep disturbances are highly prevalent in movement disorders, potentially due to the malfunctioning of basal ganglia structures. Pallidal deep brain stimulation (DBS) has been widely used for multiple movement disorders and been reported to improve sleep. We aimed to investigate the oscillatory pattern of pallidum during sleep and explore whether pallidal activities can be utilized to differentiate sleep stages, which could pave the way for sleep-aware adaptive DBS. METHODS: We directly recorded over 500 h of pallidal local field potentials during sleep from 39 subjects with movement disorders (20 dystonia, 8 Huntington's disease, and 11 Parkinson's disease). Pallidal spectrum and cortical-pallidal coherence were computed and compared across sleep stages. Machine learning approaches were utilized to build sleep decoders for different diseases to classify sleep stages through pallidal oscillatory features. Decoding accuracy was further associated with the spatial localization of the pallidum. RESULTS: Pallidal power spectra and cortical-pallidal coherence were significantly modulated by sleep-stage transitions in three movement disorders. Differences in sleep-related activities between diseases were identified in non-rapid eye movement (NREM) and REM sleep. Machine learning models using pallidal oscillatory features can decode sleep-wake states with over 90% accuracy. Decoding accuracies were higher in recording sites within the internus-pallidum than the external-pallidum, and can be precited using structural (P < 0.0001) and functional (P < 0.0001) whole-brain neuroimaging connectomics. CONCLUSION: Our findings revealed strong sleep-stage dependent distinctions in pallidal oscillations in multiple movement disorders. Pallidal oscillatory features were sufficient for sleep stage decoding. These data may facilitate the development of adaptive DBS systems targeting sleep problems that have broad translational prospects.

Interictal HFO and FDG-PET correlation predicts surgical outcome following SEEG.

OBJECTIVE: This study aimed to investigate the quantitative relationship between interictal 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) and interictal high-frequency oscillations (HFOs) from stereo-electroencephalography (SEEG) recordings in patients with refractory epilepsy. METHODS: We retrospectively included 32 patients. FDG-PET data were quantified through statistical parametric mapping (SPM) t test modeling with normal controls. Interictal SEEG segments with four, 10-min segments were selected randomly. HFO detection and classification procedures were automatically performed. Channel-based HFOs separating ripple (80-250 Hz) and fast ripple (FR; 250-500 Hz) counts were correlated with the surrounding metabolism T score at the individual and group level, respectively. The association was further validated across anatomic seizure origins and sleep vs wake states. We built a joint feature FR × T reflecting the FR and hypometabolism concordance to predict surgical outcomes in 28 patients who underwent surgery. RESULTS: We found a negative correlation between interictal FDG-PET and HFOs through the linear mixed-effects model (R2  = .346 and .457 for ripples and FRs, respectively, p < .001); these correlations were generalizable to different epileptogenic-zone lobar localizations and vigilance states. The FR × T inside the resection volume could be used as a predictor for surgical outcomes with an area under the curve of 0.81. SIGNIFICANCE: The degree of hypometabolism is associated with HFO generation rate, especially for FRs. This relationship would be meaningful for selection of SEEG candidates and for optimizing SEEG scheme planning. The concordance between FRs and hypometabolism inside the resection volume could provide prognostic information regarding surgical outcome.

Cortical phase-amplitude coupling is key to the occurrence and treatment of freezing of gait.

Freezing of gait is a debilitating symptom in advanced Parkinson's disease and responds heterogeneously to treatments such as deep brain stimulation. Recent studies indicated that cortical dysfunction is involved in the development of freezing, while evidence depicting the specific role of the primary motor cortex in the multi-circuit pathology of freezing is lacking. Since abnormal beta-gamma phase-amplitude coupling recorded from the primary motor cortex in patients with Parkinson's disease indicates parkinsonian state and responses to therapeutic deep brain stimulation, we hypothesized this metric might reveal unique information on understanding and improving therapy for freezing of gait. Here, we directly recorded potentials in the primary motor cortex using subdural electrocorticography and synchronously captured gait freezing using optoelectronic motion-tracking systems in 16 freely-walking patients with Parkinson's disease who received subthalamic nucleus deep brain stimulation surgery. Overall, we recorded 451 timed up-and-go walking trials and quantified 7073 s of stable walking and 3384 s of gait freezing in conditions of on/off-stimulation and with/without dual-tasking. We found that (i) high beta-gamma phase-amplitude coupling in the primary motor cortex was detected in freezing trials (i.e. walking trials that contained freezing), but not non-freezing trials, and the high coupling in freezing trials was not caused by dual-tasking or the lack of movement; (ii) non-freezing episodes within freezing trials also demonstrated abnormally high couplings, which predicted freezing severity; (iii) deep brain stimulation of subthalamic nucleus reduced these abnormal couplings and simultaneously improved freezing; and (iv) in trials that were at similar coupling levels, stimulation trials still demonstrated lower freezing severity than no-stimulation trials. These findings suggest that elevated phase-amplitude coupling in the primary motor cortex indicates higher probabilities of freezing. Therapeutic deep brain stimulation alleviates freezing by both decoupling cortical oscillations and enhancing cortical resistance to abnormal coupling. We formalized these findings to a novel 'bandwidth model,' which specifies the role of cortical dysfunction, cognitive burden and therapeutic stimulation on the emergence of freezing. By targeting key elements in the model, we may develop next-generation deep brain stimulation approaches for freezing of gait.

Intracranial Electroencephalography Reveals Selective Responses to Cognitive Stimuli in the Periventricular Heterotopias.

Our recent work suggests that non-lesional epileptic brain tissue is capable of generating normal neurophysiological responses during cognitive tasks, which are then seized by ongoing pathologic epileptic activity. Here, we aim to extend the scope of our work to epileptic periventricular heterotopias (PVH) and examine whether the PVH tissue also exhibits normal neurophysiological responses and network-level integration with other non-lesional cortical regions. As part of routine clinical assessment, three adult patients with PVH underwent implantation of intracranial electrodes and participated in experimental cognitive tasks. We obtained simultaneous recordings from PVH and remote cortical sites during rest as well as controlled experimental conditions. In all three subjects (two females), cognitive experimental conditions evoked significant electrophysiological responses in discrete locations within the PVH tissue that were correlated with responses seen in non-epileptic cortical sites. Moreover, the responsive PVH sites exhibited correlated electrophysiological activity with responsive, non-lesional cortical sites during rest conditions. Taken together, our work clearly demonstrates that the PVH tissue may be functionally organized and it may be functionally integrated within cognitively engaged cortical networks despite its anatomic displacement during neurodevelopment.SIGNIFICANCE STATEMENT Periventricular heterotopias (PVH) are developmentally abnormal brain tissues that frequently cause epileptic seizures. In a rare opportunity to obtain direct electrophysiological recordings from PVH, we were able to show that, contrary to common assumptions, PVH functional activity is similar to healthy cortical sites during a well-established cognitive task and exhibits clear resting state connectivity with the responsive cortical regions.

Low-frequency oscillations link frontal and parietal cortex with subthalamic nucleus in conflicts.

Low-frequency oscillations (LFOs, 28 Hz) in the subthalamic nucleus(STN) are known to reflect cognitive conflict. However, it is unclear if LFOs mediate communication and functional interactions among regions implicated in conflict processing, such as the motor cortex (M1), premotor cortex (PMC), and superior parietal lobule (SPL). To investigate the potential contribution of LFOs to cognitive conflict mediation, we recorded M1, PMC, and SPL activities by right subdural electrocorticography (ECoG) simultaneously with bilateral STN local field potentials (LFPs) by deep brain stimulation electrodes in 13 patients with Parkinson's disease who performed the arrow version of the Eriksen flanker task. Elevated cue-related LFO activity was observed across patients during task trials, with the earliest onset in PMC and SPL. At cue onset, LFO power exhibited a significantly greater increase or a trend of a greater increase in the PMC, M1, and STN, and less increase in the SPL during high-conflict (incongruent) trials than in low-conflict (congruent) trials. The local LFO power increases in PMC, SPL, and right STN were correlated with response time, supporting the notion that these structures are critical hubs for cognitive conflict processing. This power increase was accompanied by increased functional connectivity between the PMC and right STN, which was correlated with response time across subjects. Finally, ipsilateral PMC-STN Granger causality was enhanced during high-conflict trials, with direction from STN to PMC. Our study indicates that LFOs link the frontal and parietal cortex with STN during conflicts, and the ipsilateral PMC-STN connection is specifically involved in this cognitive conflict processing.

Neural underpinnings of default mode network on empathy revealed by intracranial stereoelectroencephalography.

BACKGROUND: Empathy is the ability to understand and share the feelings of others. It is fundamental to emotional intelligence and social iterations. Neuroimaging studies have demonstrated that empathy activates brain regions associated with the social cognition network. AIM: To explore the neural underpinnings of empathy revealed by stereoelectroencephalography utilizing recurrence quantification analysis (RQA). METHODS: This retrospective cohort included 38 epilepsy patients with stereoelectroencephalography implantation. RQA metrics were applied to parameterize the network organization of default mode network (DMN) brain regions. The relationships between DMN, seizure burden activity, and empathy, as measured using the Interpersonal Reactivity Index, were examined using partial least-square regression and mediation analysis. RESULTS: RQA metrics with DMN (R2  = 0.75, PBonferroni  < 0.001) and its subsystems (medial temporal subsystem: R2  = 0.53, PBonferroni  < 0.001; core subsystem: R2  = 0.70, PBonferroni  < 0.001; dorsal medial subsystem: R2  = 0.48, PBonferroni  < 0.001) were positively correlated with empathy scores. Of 13 RQA metrics, the mean diagonal line length, entropy of the diagonal line lengths, trapping time, maximal vertical line length, and recurrence time of second type were found to be statistically higher in patient cohorts with reportedly high empathy. Furthermore, DMN characteristics (b path: F = 3.69, P = 0.04), rather than seizure burdens (direct effect: t = 0.33, P = 0.74, c' = - 0.007), mediated empathy status. CONCLUSION: The present study used various RQA metrics to parameterize the network organization of DMN and determine the neural underpinning of DMN for empathy modulation.

Local field potentials in Parkinson's disease: A frequency-based review.

Deep brain stimulation (DBS) surgery offers a unique opportunity to record local field potentials (LFPs), the electrophysiological population activity of neurons surrounding the depth electrode in the target area. With direct access to the subcortical activity, LFP research has provided valuable insight into disease mechanisms and cognitive processes and inspired the advent of adaptive DBS for Parkinson's disease (PD). A frequency-based framework is usually employed to interpret the implications of LFP signatures in LFP studies on PD. This approach standardizes the methodology, simplifies the interpretation of LFP patterns, and makes the results comparable across studies. Importantly, previous works have found that activity patterns do not represent disease-specific activity but rather symptom-specific or task-specific neuronal signatures that relate to the current motor, cognitive or emotional state of the patient and the underlying disease. In the present review, we aim to highlight distinguishing features of frequency-specific activities, mainly within the motor domain, recorded from DBS electrodes in patients with PD. Associations of the commonly reported frequency bands (delta, theta, alpha, beta, gamma, and high-frequency oscillations) to motor signs are discussed with respect to band-related phenomena such as individual tremor and high/low beta frequency activity, as well as dynamic transients of beta bursts. We provide an overview on how electrophysiology research in DBS patients has revealed and will continuously reveal new information about pathophysiology, symptoms, and behavior, e.g., when combining deep LFP and surface electrocorticography recordings.

Neuroimaging Phenotyping and Assessment of Structural-Metabolic-Electrophysiological Alterations in the Temporal Neocortex of Focal Cortical Dysplasia IIIa.

BACKGROUND: Focal cortical dysplasia IIIa (FCD IIIa) is a common histopathological finding in temporal lobe epilepsy. However, subtle alterations in the temporal neocortex of FCD IIIa renders presurgical diagnosis and definition of the resective range challenging. PURPOSE: To explore neuroimaging phenotyping and structural-metabolic-electrophysiological alterations in FCD IIIa. STUDY TYPE: Retrospective. SUBJECTS: One hundred and sixty-seven subjects aged 4-39 years, including 64 FCD IIIa patients, 89 healthy controls and 14 FCD I patients as disease controls. FIELD STRENGTH/SEQUENCE: 3 T, fast-spin-echo T2 -weighted fluid-attenuated inversion recovery (FLAIR), synthetic T1 -weighted magnetization prepared rapid acquisition gradient echo (MPRAGE). ASSESSMENT: Surface-based linear model was applied to reveal neuroimaging phenotyping in FCD IIIa and assess its relationship with clinical variables. Logistic regression was implemented to identify FCD IIIa patients. Epileptogenicity mapping (EM) was conducted to explore the structural-metabolic-electrophysiological alterations in temporal neocortex of FCD IIIa. STATISTICAL TESTS: Student's t-test was applied to determine the significance of paired differences. Calibration curves were plotted to assess the goodness-of-fit (GOF) of the models, combined with the Hosmer-Lemeshow test. RESULTS: FCD IIIa exhibited widespread hyperintensities in temporal neocortex, and these alterations correlated with disease duration (Puncorrected < 0.01). Machine learning model accurately identified 84.4% of FCD IIIa patients, 92.1% of healthy controls and 92.9% of FCD I patients. Cross-modality analysis showed a significant negative correlation between FLAIR hyperintensity and positron emission tomography hypometabolism P < 0.01). Furthermore, epileptogenic cortices were located predominantly in brain regions with FLAIR hyperintensity and hypometabolism. DATA CONCLUSION: FCD IIIa exhibited widespread temporal neocortex FLAIR hyperintensity. Automated machine learning of neuroimaging patterns is conducive for accurate identification of FCD IIIa. The degree and distribution of morphological alterations related to the extent of metabolic and epileptogenic abnormalities, lending support to its potential value for reduction of the radiative and invasive approaches during presurgical workup. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

The Rolandic operculum generates different semiologies in insulo-opercular and temporal lobe epilepsies.

PURPOSE: The role of the Rolandic operculum in in mesial temporal lobe epilepsy (MTLE) is to produce oroalimentary automatisms (OAAs). In insulo-opercular epilepsy (IOE), the Rolandic operculum may produce perioral muscle clonic or tonic movements or contractions. This paper aims to confirm the symptomatogenic zone of facial symptoms in IOE and to explain this phenomenon. METHODS: A total of 45 IOE patients and 15 MTLE patients were analyzed. The patients with IOE were divided into facial (+) and (-) groups according to the facial symptoms. The interictal positron emission tomography (PET) data were compared among groups. Furthermore, electroclinical correlation, functional connectivity and energy ratio (ER) were analyzed with stereo-electroencephalography (SEEG). RESULTS: Intergroup PET differences were observed mainly in the Rolandic operculum. Electroclinical correlation showed that the Rolandic operculum was the only brain area showing any correlations. Compared with the facial (-) group, the facial (+) group showed stronger functional connectivity and a higher ER in the alpha 1, alpha 2 and beta sub-bands. In the Rolandic operculum, compared with those of the MTLE group, the h2 and ER of the facial (+) group were higher in the high frequency sub-bands. Intergroup comparison of the ER in the seizure onset zones (SOZ) showed no significant difference. SIGNIFICANCE: The symptomatogenic zone of facial symptoms in IOE is the Rolandic operculum. Seizure propagation to the Rolandic operculum generates different semiologies because of the different synchronization frequencies and energies of the sub-bands depending on the site of seizure origin. This may be due to the complex spreading pathway from the SOZ to the symptomatogenic zone.

Effective connectivity among the hippocampus, amygdala, and temporal neocortex in epilepsy patients: A cortico-cortical evoked potential study.

OBJECTIVE: Mesial temporal lobe epilepsy (MTLE) is one of the most common types of intractable epilepsy. The hippocampus and amygdala are two crucial structures of the mesial temporal lobe and play important roles in the epileptogenic network of MTLE. This study aimed to explore the effective connectivity among the hippocampus, amygdala, and temporal neocortex and to determine whether differences in effective connectivity exist between MTLE patients and non-MTLE patients. METHODS: This study recruited 20 patients from a large cohort of drug-resistant epilepsy patients, of whom 14 were MTLE patients. Single-pulse electrical stimulation (SPES) was performed to acquire cortico-cortical evoked potentials (CCEPs). The root mean square (RMS) was used as the metric of the magnitude of CCEP to represent the effective connectivity. We then conducted paired and independent sample t-tests to assess the directionality of the effective connectivity. RESULTS: In both MTLE patients and non-MTLE patients, the directional connectivity from the amygdala to the hippocampus was stronger than that from the hippocampus to the amygdala (P < 0.01); the outward connectivity from the amygdala to the cortex was stronger than the inward connectivity from the cortex to the amygdala (P < 0.01); the amygdala had stronger connectivity to the neocortex than the hippocampus (P < 0.01). In MTLE patients, the neocortex had stronger connectivity to the hippocampus than to the amygdala (P < 0.01). No significant differences in directional connectivity were noted between the two groups. CONCLUSIONS: A unique effective connectivity pattern among the hippocampus, amygdala, and temporal neocortex was identified through CCEPs analysis. This study may aid in our understanding of physiological and pathological networks in the brain and inspire neurostimulation protocols for neurological and psychiatric disorders.

Neural networks underlying hyperkinetic seizures: A quantitative PET and SEEG study.

OBJECTIVE: Hyperkinetic seizures (HKS) are characterized by complex movements that commonly occur during seizures arising from diverse cortical structures. A common semiology network may exist and analyzing the anatomo-electrical mechanisms would facilitate presurgical evaluation. Here, quantitative positron emission tomography (PET) and stereoelectroencephalography (SEEG) analysis was used to explore the underlying mechanism of HKS. METHODS: We retrospectively collected patients with epilepsy with HKS between 2014 and 2019. The interictal PET data of patients with epilepsy with HKS were compared with those of 25 healthy subjects using statistical parametric mapping to identify regions with significant hypometabolism. Then, regions of interest (ROI) for SEEG analysis were identified based on the results of PET analysis. Patients in which the ROIs were covered by intracerebral electrodes were selected for further analysis. Stereoelectroencephalography -clinical correlations with latency measurements were analyzed, and we also performed coherence analysis among ROIs both before and during HKS. RESULTS: Based on the inclusion criteria, 27 patients were analyzed. In the PET analysis, significant hypometabolism was observed in the ipsilateral dorsoanterior insular lobe, bilateral mesial frontal lobes (supplementary motor area/middle cingulate cortex, SMA/MCC), and the bilateral heads of the caudate nuclei in patients with HKS compared with the control group (p < 0.001). We selected dorsoanterior insula and SMA/MCC as ROIs for SEEG analysis. Eight patients with 23 HKS events were selected for further analysis. There was a linear correlation between the ictal involvement of both the dorsoanterior insula and SMA/MCC with the onset of HKS. Stereoelectroencephalography analysis indicated alpha range activity seemed more often associated with dorsoanterior insula and SMA/MCC involvement during HKS. CONCLUSIONS: The dorsoanterior insular lobe, mesial frontal lobes (SMA/MCC), and the bilateral heads of the caudate nuclei were probably involved in the generation of HKS. The SEEG analysis further indicated that the occurrence of HKS might be partly associated with synchronized rhythmical alpha activity between dorsoanterior insula and SMA/MCC.

The electroclinical features and surgical outcomes of inferior perisylvian epilepsy.

OBJECTIVE: To summarize the clinical and electrophysiological observations of epilepsy originating from the inferior perisylvian cortex, and analyze the potential epileptic networks underlying the semiological manifestations. METHODS: We retrospectively analyzed patients with refractory inferior perisylvian epilepsy (IPE) who had undergone resective surgery, and then reviewed the demographic, clinical, neuroelectrophysiological, neuroimaging, surgical, histopathological, and follow-up data of the patients from the respective medical records. The selected patients were then categorized in accordance with the results of semiological analysis. Quantitative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) analysis was performed to investigate the underlying neural network. RESULTS: Of the 18 IPE patients assessed in this study, ipsilateral frontotemporal epileptic discharges or its onsets were the dominant interictal or ictal scalp EEG observations. In addition, oroalimentary or manual automatism was the most frequently documented manifestation, followed by facial tonic or clonic movements. Moreover, the semiological analysis identified and classified the patients into 2 patterns, and the PET statistical analyses conducted on these 2 groups revealed differences in the neural network between them. CONCLUSION: Inferior perisylvian epilepsy possesses semiological manifestations similar to those of mesial temporal lobe epilepsy or rolandic opercular epilepsy, hence these conditions should be carefully differentiated. Performing lesionectomy or cortectomy, sparing the mesial temporal structures, was found to be an effective and safe treatment modality for IPE.

Symptomatogenic zone and network of oroalimentary automatisms in mesial temporal lobe epilepsy.

OBJECTIVE: Oroalimentary automatisms (OAAs) are common clinical manifestations of medial temporal lobe epilepsy. Nevertheless, the location of the symptomatogenic zone of OAAs remains unclear. The generation mechanism of OAAs also has not been clarified. We attempt to explain these problems by analyzing interictal [18 F]-fluorodeoxyglucose positron emission tomography (18 FDG-PET) imaging and ictal stereo-electroencephalography (SEEG) recordings in patients with medial temporal lobe epilepsy. METHODS: Fifty-seven patients with mesial temporal lobe epilepsy were analyzed retrospectively. All underwent anterior temporal lobectomy (ATL) and were seizure-free. The patients were divided into OAA (+) and OAA (-) groups according to the occurrence of consistent stereotyped OAAs. The interictal PET data were compared with those of 18 healthy controls and were then compared between groups using statistical parametric mapping (SPM). Functional connectivity using linear regression analysis was performed between the target brain regions. To clarify the network of OAAs, ictal epileptogenicity index (EI) values, and the nonlinear correlation method h2 were performed with SEEG on patients. RESULTS: Compared to OAAs (-), the rolandic operculum was the only area with significant differences. Hippocampus and rolandic operculum showed significant correlations in the OAA (+) group (y = 0.758x+0.470, R2  = 0.456, P = 0.000). No correlation was found in the OAA (-) group (P = 0.486). The EI values of the OAA (+) group (median 0.20) were significantly higher (P < 0.0001) than those of the OAA (-) group (median 0). The h2 in the OAA (+) group (h2  = 0.23 ± 0.13) showed stronger functional connectivity (t = 6.166, P < 0.0001) than that of the OAA (-) group (h2  = 0.08 ± 0.05). SIGNIFICANCE: The rolandic operculum is most likely to be the symptomatogenic zone of OAAs. In medial temporal lobe epilepsy, unilateral functional connection from the hippocampus to the rolandic operculum during seizure onset is the basis for the generation of OAAs.

Automated detection of hippocampal sclerosis using clinically empirical and radiomics features.

OBJECTIVE: Temporal lobe epilepsy is a common form of epilepsy that might be amenable to surgery. However, magnetic resonance imaging (MRI)-negative hippocampal sclerosis (HS) can hamper early diagnosis and surgical intervention for patients in clinical practice, resulting in disease progression. Our aim was to automatically detect and evaluate the structural alterations of HS. METHODS: Eighty patients with pharmacoresistant epilepsy and histologically proven HS and 80 healthy controls were included in the study. Two automated classifiers relying on clinically empirical and radiomics features were developed to detect HS. Cross-validation was implemented on all participants, and specificity was assessed in the 80 controls. The performance, robustness, and clinical utility of the model were also evaluated. Structural analysis was performed to investigate the morphological abnormalities of HS. RESULTS: The computational model based on clinical empirical features showed excellent performance, with an area under the curve (AUC) of 0.981 in the primary cohort and 0.993 in the validation cohort. One of the features, gray-white matter boundary blurring in the temporal pole, exhibited the highest weight in model performance. Another model based on radiomics features also showed satisfactory performance, with AUC of 0.997 in the primary cohort and 0.978 in the validation cohort. In particular, the model improved the detection rate of MRI-negative HS to 96.0%. The novel feature of cortical folding complexity of the temporal pole not only played a crucial role in the classifier but also had significant correlation with disease duration. SIGNIFICANCE: Machine learning with quantitative clinical and radiomics features is shown to improve HS detection. HS-related structural alterations were similar in the MRI-positive and MRI-negative HS patient groups, indicating that misdiagnosis originates mainly from empirical interpretation. The cortical folding complexity of the temporal pole is a potentially valuable feature for exploring the nature of HS.

Motor cortex stimulation: a systematic literature-based analysis of effectiveness and case series experience.

BACKGROUND: Aim to quantitatively analyze the clinical effectiveness for motor cortex stimulation (MCS) to refractory pain. METHODS: The literatures were systematically searched in database of Cocharane library, Embase and PubMed, using relevant strategies. Data were extracted from eligible articles and pooled as mean with standard deviation (SD). Comparative analysis was measured by non-parametric t test and linear regression model. RESULTS: The pooled effect estimate from 12 trials (n = 198) elucidated that MCS shown the positive effect on refractory pain, and the total percentage improvement was 35.2% in post-stroke pain and 46.5% in trigeminal neuropathic pain. There is no statistical differences between stroke involved thalamus or non-thalamus. The improvement of plexus avulsion (29.8%) and phantom pain (34.1%) was similar. The highest improvement rate was seen in post-radicular plexopathy (65.1%) and MCS may aggravate the pain induced by spinal cord injury, confirmed by small sample size. Concurrently, Both the duration of disease (r = 0.233, p = 0.019*) and the time of follow-up (r = 0.196, p = 0.016*) had small predicative value, while age (p = 0.125) had no correlation to post-operative pain relief. CONCLUSIONS: MCS is conducive to the patients with refractory pain. The duration of disease and the time of follow-up can be regarded as predictive factor. Meanwhile, further studies are needed to reveal the mechanism of MCS and to reevaluate the cost-benefit aspect with better-designed clinical trials.

Value of stereo-electroencephalogram in reoperation of patients with pharmacoresistant epilepsy: a single center, retrospective study.

PURPOSE: To systematically elucidate the value of stereo-electroencephalogram (SEEG) in the reoperation of patients with pharmacoresistant epilepsy. METHODS: Epilepsy patients who had previously undergone a failed operation and agreed to a reoperation were included in this study. The single center retrospective study evaluated the value of SEEG in epileptogenic zones (EZ) lateralization and localization as well as the complications related to the implantation. RESULTS: In total, fourteen patients met the inclusion criteria and received reoperation after implantation of SEEG. The average number of electrodes in each patient is 7.9. At the last available follow-up, nine (64.3%) patients were completely seizure-free according to the International League Against Epilepsy (ILAE) criteria. No significant complications were found in the cohort, two patients' electrodes were loosened and removed because of the seizure. No significant predictors of seizure-free status were identified in the present study, including the result of presurgical MRI, pathology and surgical strategy. CONCLUSIONS: Based on the comprehensive presurgical assessment data and careful discussion of multidisciplinary team, failed epileptic surgery deserves a second chance. Moreover, SEEG is an effective and safe methodology to determine the location of the EZ with the goal of performing reoperation.