Determining Surgical Candidacy in Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy that is amenable to surgical treatment. In the carefully selected patient, excellent seizure outcome can be achieved with minimal or no side effects from surgery. This may result in improved psychosocial functioning, achieving higher education, and maintaining or gaining employment. The objective of this paper is to discuss the surgical selection process of a patient with TLE. We define what constitutes a patient that has medically refractory TLE, describe the typical history and physical examination, and distinguish between mesial TLE and neocortical TLE. We then review the role of routine (ambulatory/sleep-deprived electroencephalography (EEG), video EEG, magnetic resonance imaging (MRI), neuropsychological testing, and Wada testing) and ancillary preoperative testing (positron emission tomography, single-photon emission computed tomography (SPECT), subtraction ictal SPECT correlated to MRI (SISCOM), magnetoencephalography, magnetic resonance spectroscopy, and functional MRI) in selecting surgical candidates. We describe the surgical options for resective epilepsy surgery in TLE and its commonly associated risks while highlighting some of the controversies. Lastly, we present teaching cases to illustrate the presurgical workup of patients with medically refractory TLE

Distinctive biophysical features of human cell-types: insights from studies of neurosurgically resected brain tissue

Electrophysiological characterization of live human tissue from epilepsy patients has been performed for many decades. Although initially these studies sought to understand the biophysical and synaptic changes associated with human epilepsy, recently, it has become the mainstay for exploring the distinctive biophysical and synaptic features of human cell-types. Both epochs of these human cellular electrophysiological explorations have faced criticism. Early studies revealed that cortical pyramidal neurons obtained from individuals with epilepsy appeared to function “normally” in comparison to neurons from non-epilepsy controls or neurons from other species and thus there was little to gain from the study of human neurons from epilepsy patients. On the other hand, contemporary studies are often questioned for the “normalcy” of the recorded neurons since they are derived from epilepsy patients. In this review, we discuss our current understanding of the distinct biophysical features of human cortical neurons and glia obtained from tissue removed from patients with epilepsy and tumors. We then explore the concept of within cell-type diversity and its loss (i.e., “neural homogenization”). We introduce neural homogenization to help reconcile the epileptogenicity of seemingly “normal” human cortical cells and circuits. We propose that there should be continued efforts to study cortical tissue from epilepsy patients in the quest to understand what makes human cell-types “human”

A Wireless Neuroprosthesis for Patients with Drug-refractory Epilepsy:A Proof-of-Concept Study

Objective Acute or protracted cortical recording may be necessary for patients with drug-refractory epilepsy to identify the ictogenic regions before undergoing resection. Currently, these invasive recording techniques present certain limitations, one of which is the need for cables connecting the recording electrodes placed in the intracranial space with external devices displaying the recorded electrocorticographic signals. This equates to a direct connection between the sterile intracranial space with the non-sterile environment. Due to the increasing likelihood of infections with time, subdural grids are typically removed a few days after implantation, a limiting factor in localizing the epileptogenic zone if seizures are not frequent enough to be captured within this time-frame. Furthermore, patients are bound to stay in the hospital, connected by the wires to the recording device, thus increasing substantially the treatment costs. To address some of the current shortcomings of invasive monitoring, we developed a neuroprosthesis made of a subdural silicone grid connected to a wireless transmitter allowing prolonged electrocorticografic recording and direct cortical stimulation. This device consists of a silicone grid with 128-platinum/iridium contacts, connected to an implantable case providing wireless recording and stimulation. The case also houses a wirelessly rechargeable battery for chronic long-term implants. We report the results of the first human proof-of-concept trial for wireless transmission of electrocorticographic recordings using a device suited for long-term implantation in three patients with drug-refractory epilepsy. Methods Three patients with medically refractory epilepsy underwent the temporary intraoperative placement of the subdural grid connected to the wireless device for recording and transmission of electrocorticographic signals for a duration of five minutes before the conventional recording electrodes were placed or the ictal foci were resected. Results Wireless transmission of brain signals was successfully achieved. The wireless electrocorticographic signal was judged of excellent quality by a blinded neurophysiologist. Conclusions This preliminary experience reports the first successful placement of a wireless electrocorticographic recording device in humans. Long-term placement for prolonged wireless electrocorticographic recording in epilepsy patients will be the next step

Closed-Loop Interruption of Hippocampal Ripples through Fornix Stimulation in the Non-Human Primate

AbstractBackgroundHippocampal sharp-wave ripples (SWRs) arising from synchronous bursting in CA3 pyramidal cells and propagating to CA1 are thought to facilitate memory consolidation. Stimulation of the CA3 axon collaterals comprising the hippocampal commissure in rats interrupts sharp-wave ripples and leads to memory impairment. In primates, however, these commissural collaterals are limited. Other hippocampal fiber pathways, like the fornix, may be potential targets for modulating ongoing hippocampal activity, with the short latencies necessary to interrupt ripples.ObjectiveThe aim of this study is to determine the efficacy of closed-loop stimulation adjacent to the fornix for interrupting hippocampal ripples.MethodStimulating electrodes were implanted bilaterally alongside the fornix in the macaque, together with microelectrodes targeting the hippocampus for recording SWRs. We first verified that fornix stimulation reliably and selectively evoked a response in the hippocampus. We then implemented online detection and stimulation as hippocampal ripples occurred.ResultsThe closed-loop interruption method was effective in interrupting ripples as well as the associated hippocampal multi-unit activity, demonstrating the feasibility of ripple interruption using fornix stimulation in primates.ConclusionAnalogous to murine research, such an approach will likely be useful in understanding the role of SWRs in memory formation in macaques and other primates sharing these pathways, such as humans. More generally, closed-loop stimulation of the fornix may prove effective in interrogating hippocampal-dependent memory processes. Finally, this rapid, contingent-DBS approach may be a means for modifying pathological high-frequency events within the hippocampus, and potentially throughout the extended hippocampal circuit

Neurocognitive and Seizure Outcomes of Selective Amygdalohippocampectomy versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy.

Objective. To report our institutional seizure and neuropsychological outcomes for a series of patients with mesial temporal lobe epilepsy (mTLE) undergoing anterior temporal lobectomy (ATL) or selective amygdalohippocampectomy (SelAH) between 2004 and 2011. Methods. A retrospective study of patients with mTLE was conducted. Seizure outcome was reported using time-to-event analysis. Cognitive outcome was reported using the change principal in component factor scores, one each, for intellectual abilities, visuospatial memory, and verbal memory. The Boston Naming Test was used for naming assessment. Language dominant and nondominant resections were compared separately. Student's t-test was used to assess statistical significance. Results. Ninety-six patients (75 ATL, 21 SelAH) were included; fifty-four had complete neuropsychological follow-up. Median follow-up was 40.5 months. There was no statistically significant difference in seizure freedom or any of the neuropsychological outcomes, although there was a trend toward greater postoperative decline in naming in the dominant hemisphere group following ATL. Conclusion. Seizure and neuropsychological outcomes did not differ for the two surgical approaches which is similar to most prior studies. Given the theoretical possibility of SelAH sparing language function in patients with epilepsy secondary to mesial temporal sclerosis and the limited high-quality evidence creating equipoise, a multicenter randomized clinical trial is warranted

Addressing the Language Binding Problem With Dynamic Functional Connectivity During Meaningful Spoken Language Comprehension

During speech, how does the brain integrate information processed on different timescales and in separate brain areas so we can understand what is said? This is the language binding problem. Dynamic functional connectivity (brief periods of synchronization in the phase of EEG oscillations) may provide some answers. Here we investigate time and frequency characteristics of oscillatory power and phase synchrony (dynamic functional connectivity) during speech comprehension. Twenty adults listened to meaningful English sentences and non-sensical “Jabberwocky” sentences in which pseudo-words replaced all content words, while EEG was recorded. Results showed greater oscillatory power and global connectivity strength (mean phase lag index) in the gamma frequency range (30–80 Hz) for English compared to Jabberwocky. Increased power and connectivity relative to baseline was also seen in the theta frequency range (4–7 Hz), but was similar for English and Jabberwocky. High-frequency gamma oscillations may reflect a mechanism by which the brain transfers and integrates linguistic information so we can extract meaning and understand what is said. Slower frequency theta oscillations may support domain-general processing of the rhythmic features of speech. Our findings suggest that constructing a meaningful representation of speech involves dynamic interactions among distributed brain regions that communicate through frequency-specific functional networks

Cognitive boundary signals in the human medial temporal lobe shape episodic memory representation

While experience unfolds continuously, memories are organized as a set of discrete events that bind together the “where”, “when”, and “what” of episodic memory. This segmentation of continuous experience is thought to be facilitated by the detection of salient environmental or cognitive events. However, the underlying neural mechanisms and how such segmentation shapes episodic memory representations remain unclear. We recorded from single neurons in the human medial temporal lobe while subjects watched videos with different types of embedded boundaries and were subsequently evaluated for memories of the video contents. Here we show neurons that signal the presence of cognitive boundaries between subevents from the same episode and neurons that detect the abstract separation between different episodes. The firing rate and spike timing of these boundary-responsive neurons were predictive of later memory retrieval accuracy. At the population level, abrupt neural state changes following boundaries predicted enhanced memory strength but impaired order memory, capturing the behavioral tradeoff subjects exhibited when recalling episodic content versus temporal order. Successful retrieval was associated with reinstatement of the neural state present following boundaries, indicating that boundaries structure memory search. These findings reveal a neuronal substrate for detecting cognitive boundaries and show that cognitive boundary signals facilitate the mnemonic organization of continuous experience as a set of discrete episodic events

Dynamic functional brain network connectivity during pseudoword processing relates to children’s reading skill

Learning to read requires children to link print (orthography) with its corresponding speech sounds (phonology). Yet, most EEG studies of reading development focus on emerging functional specialization (e.g., developing increasingly refined orthographic representations), rather than directly measuring the functional connectivity that links orthography and phonology in real time. In this proof-of-concept study we relate children's reading skill to both orthographic specialization for print (via the N170, also called the N1, event related potential, ERP) and orthographic-phonological integration (via dynamic/event-related EEG phase synchronization – an index of functional brain network connectivity). Typically developing English speaking children (n = 24; 4–14 years) and control adults (n = 20; 18–35 years) viewed pseudowords, consonants and unfamiliar false fonts during a 1-back memory task while 64-channel EEG was recorded. Orthographic specialization (larger N170 for pseudowords vs. false fonts) became more left-lateralized with age, but not with reading skill. Conversely, children's reading skill correlated with functional brain network connectivity during pseudoword processing that requires orthography-phonology linking. This was seen during two periods of simultaneous low frequency synchronization/high frequency desynchronization of posterior-occipital brain network activity. Specifically, in stronger readers, left posterior-occipital activity showed more delta (1–3Hz) synchronization around 300–500 ms (simultaneous with gamma 30–80 Hz desynchronization) and more gamma desynchronization around 600–1000 ms (simultaneous with theta 3–7Hz synchronization) during pseudoword vs. false font processing. These effects were significant even when controlling for age (moderate – large effect sizes). Dynamic functional brain network connectivity measures the brain's real-time sound-print linking. It may offer an under-explored, yet sensitive, index of the neural plasticity associated with reading development. Reading requires us to link visual print with speech sound processing. Yet, most EEG reading research explores functional specialization not integration. While children's age relates to ERPs (N170) associated with print specialization. Children's reading skill relates to real-time functional brain network connectivity. EEG phase synchrony = sensitive index of functional integration during reading