Xueyuan Wang

Assessment of Age-Related Morphometric Changes of Subcortical Structures in Healthy People Using Ultra-High Field 7 Tesla Magnetic Resonance Imaging

Objective: To assess the age-related morphometric changes of subcortical structures in healthy people. Materials and Methods: Ultra-high field 7 tesla magnetic resonance (MR) imaging in humans was used to visualize the subcortical structures of healthy young, middle-aged and elderly participants. Using the magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) sequence, we assessed the visibility of the margins of the thalamus and white matter in the thalamus, as well as the anterior commissure (AC) and posterior commissure (PC) length, the maximal height of the thalamus, the half width of the third ventricle and the distance between the AC and the center of the mammillothalamic tract (MTT) at the level of the AC-PC plane. All quantitative data were statistically evaluated. Results: The AC-PC length did not differ significantly among the three groups. The maximal height of the thalamus decreased with age (rs(53) = −0.719, p < 0.001). The half width of the third ventricle (rs(53) = 0.705, p < 0.001) and the distance between the AC and the center of the MTT (rs(53) = 0.485, p < 0.001) increased with age. The distance between the AC and the center of the MTT of the young and the elderly participants differed significantly (p = 0.007). Conclusion: The AC-PC length is not a good candidate for proportional correction during atlas-to-patient registration. The maximal height of the thalamus and the half width of the third ventricle correlated strongly with age, and the MTT position in relation to the AC shifted posteriorly as age increased. These age-related morphometric changes of subcortical structures should be considered in targeting for functional neurosurgery.

High-frequency stimulation of anterior nucleus of thalamus desynchronizes epileptic network in humans

Epilepsy has been classically seen as a brain disorder resulting from abnormally enhanced neuronal excitability and synchronization. Although it has been described since antiquity, there are still significant challenges achieving the therapeutic goal of seizure freedom. Deep brain stimulation of the anterior nucleus of the thalamus has emerged as a promising therapy for focal drug-resistant epilepsy; the basic mechanism of action, however, remains unclear. Here, we show that desynchronization is a potential mechanism of deep brain stimulation of the anterior nucleus of the thalamus by studying local field potentials recordings from the cortex during high-frequency stimulation (130 Hz) of the anterior nucleus of the thalamus in nine patients with drug-resistant focal epilepsy. We demonstrate that high-frequency stimulation applied to the anterior nucleus of the thalamus desynchronizes ipsilateral hippocampal background electrical activity over a broad frequency range, and reduces pathological epileptic discharges including interictal spikes and high-frequency oscillations. Furthermore, high-frequency stimulation of the anterior nucleus of the thalamus is capable of decoupling large-scale neural activity involving the hippocampus and distributed cortical areas. We found that stimulation frequencies ranging from 15 to 45 Hz were associated with synchronization of hippocampal local field potentials, whereas higher frequencies (>45 Hz) promoted desynchronization of ipsilateral hippocampal activity. Moreover, reciprocal effective connectivity between the anterior nucleus of the thalamus and the hippocampus was demonstrated by hippocampal-thalamic evoked potentials and thalamic-hippocampal evoked potentials. In summary, high-frequency stimulation of the anterior nucleus of the thalamus is shown to desynchronize focal and large-scale epileptic networks, and here is proposed as the mechanism for reducing seizure generation and propagation. Our data also demonstrate position-specific correlation between deep brain stimulation applied to the anterior nucleus of the thalamus and patients with temporal lobe epilepsy and seizure onset zone within the Papaz circuit or limbic system. Our observation may prove useful for guiding electrode implantation to increase clinical efficacy.

Properties of afterdischarges from electrical stimulation in patients with epilepsy

OBJECTIVE To investigate the properties of afterdischarges (ADs) from intracerebral electrical stimulation (ES) in patients with epilepsy who underwent stereotactic electroencephalography (SEEG) and determine the relationship between epileptogenic zone (EZ) or irritative zone (IZ) and ADs. METHODS We retrospectively analyzed 10 patients with intractable epilepsy who underwent SEEG. ESs were delivered following the given parameters: bipolar, biphasic, 50Hz, 0.2ms pulse duration, 0.5-10mA. The properties of ADs were documented, including their incidence, location, threshold, morphology and evolution. RESULTS A total of 213 ADs (5%) were elicited by 4701 trains of ES. Stimulation through contacts implanted in the hippocampus (59%) generally evoked more ADs than contacts elsewhere (19%). AD thresholds for hippocampal stimulation were significantly lower than those for stimulation in grey matter. Polyspikes (58%) were the most common AD morphology. Evolution occurred more commonly with sequential spikes (47%) than with other AD morphologies (14%). There was no significant correlation between the location of ADs and EZ. However, ADs were significantly more frequently localized to IZ than areas outside IZ (P<0.05). CONCLUSIONS There seemed to be a lack of correlation between the location of ADs and EZ. However, ADs were more likely to be elicited in IZ.

Continuous behavioral tracing-based online functional brain mapping with intracranial electroencephalography

Intracranial electroencephalography (iEEG) has proven to be a reliable tool in clinical functional brain mapping. While iEEG signals are believed to be highly informative, making online or real-time functional mapping possible, the utilization of corresponding behavioral information in traditional trial-based paradigms is typically low. This imbalance has limited the efficiency and effectiveness in current iEEG-based functional mapping approaches. OBJECTIVE In the current study, we were to investigate whether using more dedicate behavioral information can improve iEEG-based functional mapping. APPROACH We continuously monitored behavioral outputs of patients during iEEG recording, transformed them into regressors, and assessed their correlations with iEEG signals. MAIN RESULTS Functional cortical sites identified in preliminary test using the proposed method showed considerable consistency with the results from electrical cortical stimulation (ECS) as well as a trial-based method. Continuous behavioral tracing yielded more dependency to neural signals than sole event markers-derived regressor. Based on this, we successfully performed online functional brain mapping during five neurosurgery operations, which yielded satisfactory results. SIGNIFICANCE In the present study, we showed the utilization of continuous behavioral tracing can improve the efficiency of iEEG-based functional brain mapping. We then demonstrated this approach is adequate for multi-session intraoperative functional assessment within short time span, which is of considerable clinical value.

Out-of-body experience in the anterior insular cortex during the intracranial electrodes stimulation in an epileptic child

The authors present a case of an out-of- body experience (OBE) that occurred in a child with intractable epilepsy when stimulating the anterior insular cortex (AIC) by intracranial electrodes. After destroying several sites precisely located at the left AIC by radiofrequency thermocoagulation, the patients seizures disappeared, and the OBE could not be reproduced when repeatedly stimulating these sites. To our knowledge, it has never been reported that an OBE occurred in the AIC. We analyze the mechanism of an OBE mostly appearing in temporo-parietal junction (TPJ) and propose two perspectives for a possible mechanism involving the AIC causing the OBE.

Determining the quantitative threshold of high-frequency oscillation distribution to delineate the epileptogenic zone by automated detection

Objective: We proposed an improved automated high frequency oscillations (HFOs) detector that could not only be applied to various intracranial electrodes, but also automatically remove false HFOs caused by high-pass filtering. We proposed a continuous resection ratio of high order HFO channels and compared this ratio with each patients post-surgical outcome, to determine the quantitative threshold of HFO distribution to delineate the epileptogenic zone (EZ). Methods: We enrolled a total of 43 patients diagnosed with refractory epilepsy. The patients were used to optimize the parameters for SEEG electrodes, to test the algorithm for identifying false HFOs, and to calculate the continuous resection ratio of high order HFO channels. The ratio can be used to determine a quantitative threshold to locate the epileptogenic zone. Results: Following optimization, the sensitivity, and specificity of our detector were 66.84 and 73.20% (ripples) and 69.76 and 66.13% (fast ripples, FRs), respectively. The sensitivity and specificity of our algorithm for removing false HFOs were 76.82 and 94.54% (ripples) and 72.55 and 94.87% (FRs), respectively. The median of the continuous resection ratio of high order HFO channels in patients with good surgical outcomes, was significantly higher than in patients with poor outcome, for both ripples and FRs (P < 0.05 ripples and P < 0.001 FRs). Conclusions: Our automated detector has the advantage of not only applying to various intracranial electrodes but also removing false HFOs. Based on the continuous resection ratio of high order HFO channels, we can set the quantitative threshold for locating epileptogenic zones.

Electrical stimulation of the insulo-opercular region: visual phenomena and altered body-ownership symptoms

PURPOSE Using direct intracerebral electrical stimulation (ES) in epileptic patients to evoke symptoms to help identify the functional neuroanatomy of the insular lobe and opercula. METHODS We selected 43 patients who had at least 1 electrode inserted into the insula or opercula via an oblique approach among 135 patients with intractable epilepsy. Bipolar stimulation was chosen, and the stimulation parameters of the biphasic waves included a pulse width of 0.2 ms, a frequency of 50 Hz, a duration of 3 s, and an intensity gradually increasing from 0.5 to 4 mA. RESULTS In total, 93 electrodes were implanted into the insula or insular opercula, and 169 of 281 contacts (60.1%) evoked 212 responses by ES of the insula. 142 responses were induced by stimulating the insular opercula in 126 of 343 sites (36.7%). Usual responses, such as somatosensory, visceral sensory, speech, auditory, and motor responses, were evoked. In addition, rarely reported responses, including cardiovascular symptoms (tachycardia), visual symptoms evoked by ES of the parietal and temporal opercula, and vestibular symptoms (like the loss of ownership of the body) evoked following stimulation of the posterior insula and parietal operculum, were also induced in our study. CONCLUSIONS The insula and opercula perform various and complicated functions. The posterior insula and parietal operculum could play important roles in body-ownership symptoms. The complicated visual phenomena were partially related to the temporal operculum.

The surgical outcome of patients with bilateral temporal lobe epilepsy

OBJECTIVES The purpose of this study is to explore the surgical outcome of unilateral anterior temporal lobectomy (ATL) for patients with bilateral temporal lobe epilepsy (BTLE). METHODS We retrospectively reviewed the data of patients who were diagnosed with BTLE by scalp electroencephalogram (EEG) and underwent ATL from 2001 to 2015. In addition, 80 patients were randomly selected as a control group. RESULTS One hundred seventeen patients were included in this study and were divided into four groups by intracranial recordings as follows: 78 patients with unilateral seizure onset (Group 1), 13 patients with lateralizable dominant seizure onset (Group 2), 14 patients with lateralizable neuroimaging abnormalities (Group 3), and 12 patients without lateralizable dominant seizure onset or neuroimaging abnormalities (Group 4). The 12 patients in Group 4 declined surgical resection, whereas the remaining 105 patients received ATL, and 93 of them were followed up for more than 1 year after surgery. At the 1-, 2-, and 3-year follow-ups the percentage of patients who were seizure free was 52.9%, 56.5%, and 58.9%, respectively. For the mean postoperative efficacy, there was a statistical difference in patients who were seizure free either between Group 1 + Group 2 + Group 3 and the control group (44.1% vs. 67.5%, p = 0.002), or between Group 1 and the control group (48.5% vs. 67.5%, p = 0.019), or between Group 2 + Group 3 and the control group (32.0% vs. 67.5%, p = 0.002). However, the difference was significant only at the first year follow-up, and there was no significant difference afterward. SIGNIFICANCE Although the surgical outcome of patients with BTLE is not as good as that of patients with unilateral TLE in short-term follow-up, quite a portion of these patients could benefit from unilateral temporal lobe resection in the long term.

Correlation between extreme fear and focal cortical dysplasia in anterior cingulate gyrus: Evidence from a surgical case of refractory epilepsy

Localizing the semiology of ictal fear and seizure onset in epilepsy patients is commonly challenging due to limited value of routine electroencephalography (EEG) and very few surgical attempts. Here we reported a case of refractory epilepsy characterized by aura of extreme fear and hypermotor seizures, in which the left (dominant hemisphere) anterior cingulate gyrus (ACG) was determined to be the epileptogenic zone (EZ) through multiple modalities of presurgical evaluation including analysis of high frequency oscillation on intracranial EEG. Tailored resection of EZ was thus performed and pathological examination revealed focal cortical dysplasia (FCD) type IIb. The patient has been seizure free during an 18-month follow-up. The report has provided novel anatomical, electrophysiological and surgical evidences suggesting the critical role of ACG in ictal fear and possibility of surgical management of fear-manifesting refractory epilepsy.