Lars Buentjen

Radiofrequency lesioning for epileptogenic periventricular nodular heterotopia: a rational approach.

Periventricular nodular heterotopias (PNHs) are frequently associated with pharmacoresistant epilepsy. They are considered part of a dysfunctional network, connected to the overlying cortex. Therefore, removal of the PNHs and additional cortectomy or lobectomy seem to be essential for significant and long‐lasting seizure reduction. These procedures, however, can have considerable limitations, especially in patients with functional eloquent cortex adjacent to the PNH. Alternatively, stereotactic neurosurgery can reduce the surgical trauma. Presented is a 56‐year‐old man who became seizure‐free after stereotactically guided radiofrequency lesioning of a solitary PNH.

Corticothalamic phase synchrony and cross-frequency coupling predict human memory formation

The anterior thalamic nucleus (ATN) is thought to play an important role in a brain network involving the hippocampus and neocortex, which enables human memories to be formed. However, its small size and location deep within the brain have impeded direct investigation in humans with non-invasive techniques. Here we provide direct evidence for a functional role for the ATN in memory formation from rare simultaneous human intrathalamic and scalp electroencephalogram (EEG) recordings from eight volunteering patients receiving intrathalamic electrodes implanted for the treatment of epilepsy, demonstrating real-time communication between neocortex and ATN during successful memory encoding. Neocortical-ATN theta oscillatory phase synchrony of local field potentials and neocortical-theta-to-ATN-gamma cross-frequency coupling during presentation of complex photographic scenes predicted later memory for the scenes, demonstrating a key role for the ATN in human memory encoding. DOI:http://dx.doi.org/10.7554/eLife.05352.001

Direct Targeting of the Thalamic Anteroventral Nucleus for Deep Brain Stimulation by T1-Weighted Magnetic Resonance Imaging at 3 T

Background: The thalamic anteroventral nucleus (AV) is a promising target structure for deep brain stimulation (DBS) in patients suffering from refractory epilepsy. Direct visualization of the AV would improve spatial accuracy in functional stereotactic neurosurgery for treatment of this disease. Methods: On 3-tesla magnetic resonance imaging (MRI), acquisition parameters were adjusted for optimal demarcation of the AV in 1 healthy subject. Reliability of AV visualization was then evaluated in 5 healthy individuals and 3 patients with refractory epilepsy. Results: In all individuals, an adjusted T1-weighted sequence allowed for demarcation of the AV. It was clearly distinguishable from hyperintense myelin-rich lamellae surrounding it ventrally and laterally and appeared hypo-intense compared to the adjacent thalamic nuclei. Image resolution and contrast facilitated direct stereotactic targeting of the AV prior to DBS surgery in all 3 patients. Conclusions: Direct targeting of the AV can be achieved, which has immediate implications for the accuracy of MRI-guided DBS in patients with refractory epilepsy.

Thalamic theta phase alignment predicts human memory formation and anterior thalamic cross-frequency coupling

Previously we reported electrophysiological evidence for a role for the anterior thalamic nucleus (ATN) in human memory formation (Sweeney-Reed et al., 2014). Theta-gamma cross-frequency coupling (CFC) predicted successful memory formation, with the involvement of gamma oscillations suggesting memory-relevant local processing in the ATN. The importance of the theta frequency range in memory processing is well-established, and phase alignment of oscillations is considered to be necessary for synaptic plasticity. We hypothesized that theta phase alignment in the ATN would be necessary for memory encoding. Further analysis of the electrophysiological data reveal that phase alignment in the theta rhythm was greater during successful compared with unsuccessful encoding, and that this alignment was correlated with the CFC. These findings support an active processing role for the ATN during memory formation. DOI: http://dx.doi.org/10.7554/eLife.07578.001

Direct Visualization of Anatomic Subfields within the Superior Aspect of the Human Lateral Thalamus by MRI at 7T

BACKGROUND AND PURPOSE: The morphology of the human thalamus shows high interindividual variability. Therefore, direct visualization of landmarks within the thalamus is essential for an improved definition of electrode positions for deep brain stimulation. The aim of this study was to provide anatomic detail in the thalamus by using inversion recovery TSE imaging at 7T. MATERIALS AND METHODS: The MR imaging protocol was optimized on 1 healthy subject to segment thalamic nuclei from one another. Final images, acquired with 0.52-mm2 in-plane resolution and 3-mm section thickness, were compared with stereotactic brain atlases to assign visualized details to known anatomy. The robustness of the visualization of thalamic nuclei was assessed with 4 healthy subjects at lower image resolution. RESULTS: Thalamic subfields were successfully delineated in the dorsal aspect of the lateral thalamus. T1-weighting was essential. MR images had an appearance very similar to that of myelin-stained sections seen in brain atlases. Visualized intrathalamic structures were, among others, the lamella medialis, the external medullary lamina, the reticulatum thalami, the nucleus centre médian, the boundary between the nuclei dorso-oralis internus and externus, and the boundary between the nuclei dorso-oralis internus and zentrolateralis intermedius internus. CONCLUSIONS: Inversion recovery–prepared TSE imaging at 7T has a high potential to reveal fine anatomic detail in the thalamus, which may be helpful in enhancing the planning of stereotactic neurosurgery in the future.

Pre-stimulus thalamic theta power predicts human memory formation

Pre-stimulus theta (4-8Hz) power in the hippocampus and neocortex predicts whether a memory for a subsequent event will be formed. Anatomical studies reveal thalamus-hippocampal connectivity, and lesion, neuroimaging, and electrophysiological studies show that memory processing involves the dorsomedial (DMTN) and anterior thalamic nuclei (ATN). The small size and deep location of these nuclei have limited real-time study of their activity, however, and it is unknown whether pre-stimulus theta power predictive of successful memory formation is also found in these subcortical structures. We recorded human electrophysiological data from the DMTN and ATN of 7 patients receiving deep brain stimulation for refractory epilepsy. We found that greater pre-stimulus theta power in the right DMTN was associated with successful memory encoding, predicting both behavioral outcome and post-stimulus correlates of successful memory formation. In particular, significant correlations were observed between right DMTN theta power and both frontal theta and right ATN gamma (32-50Hz) phase alignment, and frontal-ATN theta-gamma cross-frequency coupling. We draw the following primary conclusions. Our results provide direct electrophysiological evidence in humans of a role for the DMTN as well as the ATN in memory formation. Furthermore, prediction of subsequent memory performance by pre-stimulus thalamic oscillations provides evidence that post-stimulus differences in thalamic activity that index successful and unsuccessful encoding reflect brain processes specifically underpinning memory formation. Finally, the findings broaden the understanding of brain states that facilitate memory encoding to include subcortical as well as cortical structures.

Anterior Thalamic High Frequency Band Activity Is Coupled with Theta Oscillations at Rest

Cross-frequency coupling (CFC) between slow and fast brain rhythms, in the form of phase–amplitude coupling (PAC), is proposed to enable the coordination of neural oscillatory activity required for cognitive processing. PAC has been identified in the neocortex and mesial temporal regions, varying according to the cognitive task being performed and also at rest. PAC has also been observed in the anterior thalamic nucleus (ATN) during memory processing. The thalamus is active during the resting state and has been proposed to be involved in switching between task-free cognitive states such as rest, in which attention is internally-focused, and externally-focused cognitive states, in which an individual engages with environmental stimuli. It is unknown whether PAC is an ongoing phenomenon during the resting state in the ATN, which is modulated during different cognitive states, or whether it only arises during the performance of specific tasks. We analyzed electrophysiological recordings of ATN activity during rest from seven patients who received thalamic electrodes implanted for treatment of pharmacoresistant focal epilepsy. PAC was identified between theta (4–6 Hz) phase and high frequency band (80–150 Hz) amplitude during rest in all seven patients, which diminished during engagement in tasks involving an external focus of attention. The findings are consistent with the proposal that theta–gamma coupling in the ATN is an ongoing phenomenon, which is modulated by task performance.

Case report: practicability of functionally based tractography of the optic radiation during presurgical epilepsy work up.

Pre-operative tractography of the optic radiation (OR) has been advised to assess the risk for postoperative visual field deficit (VFD) in certain candidates for resective epilepsy surgery. Diffusion tensor imaging (DTI) tractography relies on a precise anatomical determination of start and target regions of interest (ROIs), such as the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). The post-chiasmal visual pathway and V1 show considerable inter-individual variability, and in epilepsy patients parenchymatous lesions might further complicate this matter. A functionally based tractography (FBT) seems beneficial for precise OR identification. We assessed practicability of FBT for OR identification in a patient with occipital lobe epilepsy due to a temporo-occipital maldevelopmental tumor. The MRI protocol at 3T included a T1-weighted sagittal 3D scan, a T2-weighted axial 2D scan and a DTI scan using an echo planar spin echo sequence. ROIs for fiber tracking of OR (LGN & V1) were determined with T2*-weighted fMRI-based retinotopic assessment. After DTI pre-processing and fiber tracking, paths with similar properties were combined in clusters for visual presentation and OR localization. Retinotopic phase maps allowed for the identification of V1 and LGN for a precise DTI-based reconstruction of OR, which was distant to the patients tumor. Location and structure of ORs were comparable in each hemisphere. FBT could thus influence the human research of the extrastriate visual pathway and the risk management of post-operative VFD in epilepsy surgery.

Active prosthesis dependent functional cortical reorganization following stroke

The present study investigated the neural correlates associated with gait improvements triggered by an active prosthesis in patients with drop-foot following stroke during the chronic stage. Eleven patients took part in the study. MEG recordings in conjunction with somatosensory stimulation of the left and right hand as well as gait analyses were performed shortly before or after prosthesis implantation surgery and 3–4 months later. Plastic changes of the sensorimotor cortex of the ipsi- and contralesional hemisphere were revealed. Gait analysis indicated that all patients improved their gait with the active prosthesis. Patients with larger plastic changes within the lesioned hemisphere maintained their improved gait performance even when the prosthesis was turned off. Patients with larger contralesional changes also improved their gait with the active prosthesis. However, their gait measures decreased when the prosthesis was turned off. The current data provide the neural basis of gait improvement triggered by an active prosthesis and has important implications with respect to the choice of the type of active prosthesis (implantable vs removable) and to the selection procedure of the patients (length of testing period).

Clinical, neuropsychological, and pre-stimulus dorsomedial thalamic nucleus electrophysiological data in deep brain stimulation patients

The data presented here comprise clinical, neuropsychological, and intrathalamic electrophysiological data from 7 patients with pharmacoresistant focal epilepsy and are related to the article “Pre-stimulus thalamic theta power predicts human memory formation” C.M. Sweeney-Reed, T. Zaehle, J. Voges, F.C. Schmitt, L. Buentjen, K. Kopitzki, et al. (2016) [1]. The patients participated in a memory paradigm after receiving electrodes implanted in the DMTN due to the surgical approach taken in electrode insertion for deep brain stimulation of the anterior thalamic nucleus. Epilepsy duration and pre-operative neuropsychological tests provide an indication of the profile of patients receiving intrathalamic electrode implantation and the memory capabilities in such a patient group. The electrophysiological data were recorded from the right DMTN preceding stimulus presentation during intentional memory encoding. The patients viewed a series of photographic scenes, which they judged as indoors or outdoors. The 900 ms epochs prior to stimulus presentation were labeled as preceding successful or unsuccessful subsequent memory formation according to a subsequent memory test for the items. The difference between theta power preceding successful versus unsuccessful subsequent memory formation is shown against time for each patient individually.