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Hippocampal theta oscillations have been implicated in spatial memory function in both rodents and humans. What is less clear is how hippocampal theta interacts with higher frequency oscillations to support long‐term memory. Here we asked 10 presurgical epilepsy patients undergoing intracranial EEG recording to perform a long‐term spatial memory task in desktop virtual reality and found that increased theta power in two discrete bands (“low” 2‐5 Hz and “high” 6‐11 Hz) during cued retrieval was associated with improved task performance. Similarly, increased coupling between “low” theta phase and gamma amplitude during the same period was associated with improved task performance. Finally, low and high gamma amplitude appeared to peak at different phases of the theta cycle; providing a novel connection between human hippocampal function and rodent data. These results help to elucidate the role of theta oscillations and theta‐gamma phase‐amplitude coupling in human long‐term memory.

Our aim was to demonstrate the first use of Optically Pumped Magnetoencephalography (OP-MEG) in an epilepsy patient with unrestricted head movement. Current clinical MEG uses a traditional SQUID system for recording MEG signal, where sensors are cryogenically cooled and housed in a helmet in which the patient’s head is fixed. Here we use a different type of sensor (OPM), which operates at room temperature and can be placed directly on the patient’s scalp, permitting free head movement. We performed two 30 minute OP-MEG recording sessions in a patient with refractory focal epilepsy and compared these with clinical scalp EEG performed earlier. OP-MEG was able to identify analogous interictal activity to scalp EEG, and source localise this activity to an appropriate brain region. This is the first application of OP-MEG in human epilepsy. Future directions include simultaneous EEG/OP-MEG recording and prolonged OP-MEG telemetry.

Reflex epilepsies have been demonstrated to exploit specific networks that subserve normal physiological function. It is unclear whether more common forms of epilepsy share this particular feature. By measuring interictal spikes in patients with a range of epilepsies, we show that 2 tasks known to specifically engage the hippocampus and temporal neocortex promoted increased interictal spiking within these regions, whereas a nonhippocampal dependent task did not. This indicates that interictal spike frequency may reflect the processing demands being placed on specific functional-anatomical networks in epilepsy. ANN NEUROL 2019;86:304-309.

Introduction Respiratory failure is one of the most common causes of mortality in myotonic dystrophy type 1 (DM1). The variation in the DM1 phenotype causes difficulty in clinically predicting the severity of respiratory involvement, and variables such as daytime somnolence are insensitive for identifying patients who require continuous or bilevel nocturnal positive airway pressure (NPAP). Methods We retrospectively analyzed a cohort of 126 adult onset patients with DM1 at the point of their first respiratory assessment to identify significant factors in predicting ventilator requirement. Results Triplet repeat years score and Muscle Impairment Rating Scale were significantly linearly related to NPAP and, thus, formed the model. Discussion We devised a simple model to aid clinicians in predicting at first visit those patients with DM1 who are likely to require NPAP. We also describe the causes of failure to tolerate NPAP in DM1. Muscle Nerve 59:683-687, 2019.

Both magnetoencephalography and stereo-electroencephalography are used in presurgical epilepsy assessment, with contrasting advantages and limitations. It is not known whether simultaneous stereo-electroencephalography–magnetoencephalography recording confers an advantage over both individual modalities, in particular whether magnetoencephalography can provide spatial context to epileptiform activity seen on stereo-electroencephalography. Twenty-four adult and paediatric patients who underwent stereo-electroencephalography study for pre-surgical evaluation of drug-resistant focal epilepsy, were recorded using simultaneous stereo-electroencephalography–magnetoencephalography, of which 14 had abnormal interictal activity during recording. The 14 patients were divided into two groups; those with detected superficial (n = 7) and deep (n = 7) brain interictal activity. Interictal spikes were independently identified in stereo-electroencephalography and magnetoencephalography. Magnetoencephalography dipoles were derived using a distributed inverse method. There was no significant difference between stereo-electroencephalography and magnetoencephalography in detecting superficial spikes (P = 0.135) and stereo-electroencephalography was significantly better at detecting deep spikes (P = 0.002). Mean distance across patients between stereo-electroencephalography channel with highest average spike amplitude and magnetoencephalography dipole was 20.7 ± 4.4 mm. for superficial sources, and 17.8 ± 3.7 mm. for deep sources, even though for some of the latter (n = 4) no magnetoencephalography spikes were detected and magnetoencephalography dipole was fitted to a stereo-electroencephalography interictal activity triggered average. Removal of magnetoencephalography dipole was associated with 1 year seizure freedom in 6/7 patients with superficial source, and 5/6 patients with deep source. Although stereo-electroencephalography has greater sensitivity in identifying interictal activity from deeper sources, a magnetoencephalography source can be localized using stereo-electroencephalography information, thereby providing useful whole brain context to stereo-electroencephalography and potential role in epilepsy surgery planning., In the largest case series to date, Vivekananda et al. perform simultaneous magnetoencephalography and stereo-electroencephalography in refractory focal epilepsy patients. They demonstrate that for deep brain epileptogenic foci, magnetoencephalography dipoles could be derived from average stereo-electroencephalography data, thereby overcoming a traditional limitation of magnetoencephalography of reduced sensitivity for deep sources.

Highlights • We applied Hidden Markov Model (HMM) to concurrent MEG and intracranial EEG (iEEG). • Epilepsy cohort HMM analysis yielded states similar to those of healthy subjects. • iEEG power correlated with the time course of HMM states. • Functional clusters of iEEG electrodes agreed with those based on spatial location. • Our pipeline can be used for group analysis of concurrent MEG and invasive data., Background Intracranial electroencephalography (iEEG) recordings are used for clinical evaluation prior to surgical resection of the focus of epileptic seizures and also provide a window into normal brain function. A major difficulty with interpreting iEEG results at the group level is inconsistent placement of electrodes between subjects making it difficult to select contacts that correspond to the same functional areas. Recent work using time delay embedded hidden Markov model (HMM) applied to magnetoencephalography (MEG) resting data revealed a distinct set of brain states with each state engaging a specific set of cortical regions. Here we use a rare group dataset with simultaneously acquired resting iEEG and MEG to test whether there is correspondence between HMM states and iEEG power changes that would allow classifying iEEG contacts into functional clusters. Methods Simultaneous MEG-iEEG recordings were performed at rest on 11 patients with epilepsy whose intracranial electrodes were implanted for pre-surgical evaluation. Pre-processed MEG sensor data was projected to source space. Time delay embedded HMM was then applied to MEG time series. At the same time, iEEG time series were analyzed with time-frequency decomposition to obtain spectral power changes with time. To relate MEG and iEEG results, correlations were computed between HMM probability time courses of state activation and iEEG power time course from the mid contact pair for each electrode in equally spaced frequency bins and presented as correlation spectra for the respective states and iEEG channels. Association of iEEG electrodes with HMM states based on significant correlations was compared to that based on the distance to peaks in subject-specific state topographies. Results Five HMM states were inferred from MEG. Two of them corresponded to the left and the right temporal activations and had a spectral signature primarily in the theta/alpha frequency band. All the electrodes had significant correlations with at least one of the states (p

Highlights • Primary neuronal cultures from cryopreserved tissue retain functional neuronal properties. • Cryopreservation of brain tissue allows long-distance collaborations. • Exchange of cryopreserved tissue can reduce the need to maintain multiple colonies of mutant mice., Background Dissociated primary neuronal cultures are widely used as a model system to investigate the cellular and molecular properties of diverse neuronal populations and mechanisms of action potential generation and synaptic transmission. Typically, rodent primary neuronal cultures are obtained from freshly-dissociated embryonic or postnatal brain tissue, which often requires intense animal husbandry. This can strain resources when working with genetically modified mice. New method Here we describe an experimental protocol for frozen storage of mouse hippocampi, which allows fully functional dissociated primary neuronal cultures to be prepared from cryopreserved tissue. Results We show that thawed hippocampal neurons have functional properties similar to those of freshly dissociated neurons, including neuronal morphology, excitability, action potential waveform and synaptic neurotransmitter release, even after cryopreservation for several years. Comparison to the existing methods In contrast to the existing methods, the protocol described here allows for efficient long-term storage of samples, allowing researchers to perform functional experiments on neuronal cultures from brain tissue collected in other laboratories. Conclusions We anticipate that this method will facilitate collaborations among laboratories based at distant locations and will thus optimise the use of genetically modified mouse models, in line with the 3Rs (Replacement, Reduction and Refinement) recommended for scientific use of animals in research.

Hippocampal theta oscillations have been implicated in spatial memory function in both rodents and humans. What is less clear is how hippocampal theta interacts with higher frequency oscillations during spatial memory function, and how this relates to subsequent behaviour. Here we asked ten human epilepsy patients undergoing intracranial EEG recording to perform a desk-top virtual reality spatial memory task, and found that increased theta power in two discrete bands (‘low’ 2-5Hz and ‘high’ 6-9Hz) during cued retrieval was associated with improved task performance. Similarly, increased coupling between ‘low’ theta phase and gamma amplitude during the same period was associated with improved task performance. These results support a role of theta oscillations and theta-gamma phase-amplitude coupling in human spatial memory function.

Hyperammonaemia is often encountered in acute neurology and can be the cause of acute or chronic neurological symptoms. Patients with hyperammonaemia may present with seizures or encephalopathy, or may be entirely asymptomatic. The underlying causes are diverse but often straightforward to diagnose, although sometimes require specialist investigations. Haemodialysis or haemo(dia)filtration is the first-line treatment for acute severe hyperammonaemia (of any cause) in an adult. Here we discuss our approach to adult patients with hyperammonaemia identified by a neurologist.

Although action potentials propagate along axons in an all-or-none manner, subthreshold membrane potential fluctuations at the soma affect neurotransmitter release from synaptic boutons. An important mechanism underlying analog–digital modulation is depolarization-mediated inactivation of presynaptic Kv1-family potassium channels, leading to action potential broadening and increased calcium influx. Previous studies have relied heavily on recordings from blebs formed after axon transection, which may exaggerate the passive propagation of somatic depolarization. We recorded instead from small boutons supplied by intact axons identified with scanning ion conductance microscopy in primary hippocampal cultures and asked how distinct potassium channels interact in determining the basal spike width and its modulation by subthreshold somatic depolarization. Pharmacological or genetic deletion of Kv1.1 broadened presynaptic spikes without preventing further prolongation by brief depolarizing somatic prepulses. A heterozygous mouse model of episodic ataxia type 1 harboring a dominant Kv1.1 mutation had a similar broadening effect on basal spike shape as deletion of Kv1.1; however, spike modulation by somatic prepulses was abolished. These results argue that the Kv1.1 subunit is not necessary for subthreshold modulation of spike width. However, a disease-associated mutant subunit prevents the interplay of analog and digital transmission, possibly by disrupting the normal stoichiometry of presynaptic potassium channels.

Summary Direct electrical access to presynaptic ion channels has hitherto been limited to large specialized terminals such as the calyx of Held or hippocampal mossy fiber bouton. The electrophysiology and ion-channel complement of far more abundant small synaptic terminals (≤1 μm) remain poorly understood. Here we report a method based on superresolution scanning ion conductance imaging of small synapses in culture at approximately 100–150 nm 3D resolution, which allows presynaptic patch-clamp recordings in all four configurations (cell-attached, inside-out, outside-out, and whole-cell). Using this technique, we report presynaptic recordings of K+, Na+, Cl−, and Ca2+ channels. This semiautomated approach allows direct investigation of the distribution and properties of presynaptic ion channels at small central synapses. Video Abstract, Highlights • Topographic imaging of live synaptic boutons at nanoscale resolution • Cell-attached patch-clamp recordings of ion channels in small central synapses • Whole-cell small presynaptic bouton recordings, Novak and colleagues have developed a method for nanoscale-targeted patch-clamp presynaptic recordings in submicrometer central synapses identified using superresolution scanning ion conductance microscopy. This semiautomated approach opens a new window on the physiology of small presynaptic terminals.