Interactive data exploration websites for large-scale electrophysiology.

Methodological advances in neuroscience have enabled the collection of massive datasets which demand innovative approaches for scientific communication. Existing platforms for data storage lack intuitive tools for data exploration, limiting our ability to interact effectively with these brain-wide datasets. We introduce two public websites: (Data and Atlas) developed for the International Brain Laboratory which provide access to millions of behavioral trials and hundreds of thousands of individual neurons. These interfaces allow users to discover both the raw and processed brain-wide data released by the IBL at the scale of the whole brain, individual sessions, trials, and neurons. By hosting these data interfaces as websites they are available cross-platform with no installation. By releasing each site's code as a modular open-source framework, other researchers can easily develop their own web interfaces and explore their own data. As neuroscience datasets continue to expand, customizable web interfaces offer a glimpse into a future of streamlined data exploration and act as blueprints for future tools.

A modular architecture for organizing, processing and sharing neurophysiology data.

We describe an architecture for organizing, integrating and sharing neurophysiology data within a single laboratory or across a group of collaborators. It comprises a database linking data files to metadata and electronic laboratory notes; a module collecting data from multiple laboratories into one location; a protocol for searching and sharing data and a module for automatic analyses that populates a website. These modules can be used together or individually, by single laboratories or worldwide collaborations.

Accurate Localization of Linear Probe Electrode Arrays across Multiple Brains.

Recently developed probes for extracellular electrophysiological recordings have large numbers of electrodes on long linear shanks. Linear electrode arrays, such as Neuropixels probes, have hundreds of recording electrodes distributed over linear shanks that span several millimeters. Because of the length of the probes, linear probe recordings in rodents usually cover multiple brain areas. Typical studies collate recordings across several recording sessions and animals. Neurons recorded in different sessions and animals thus have to be aligned to each other and to a standardized brain coordinate system. Here, we evaluate two typical workflows for localization of individual electrodes in standardized coordinates. These workflows rely on imaging brains with fluorescent probe tracks and warping 3D image stacks to standardized brain atlases. One workflow is based on tissue clearing and selective plane illumination microscopy (SPIM), whereas the other workflow is based on serial block-face two-photon (SBF2P) microscopy. In both cases electrophysiological features are then used to anchor particular electrodes along the reconstructed tracks to specific locations in the brain atlas and therefore to specific brain structures. We performed groundtruth experiments, in which motor cortex outputs are labeled with ChR2 and a fluorescence protein. Light-evoked electrical activity and fluorescence can be independently localized. Recordings from brain regions targeted by the motor cortex reveal better than 0.1-mm accuracy for electrode localization, independent of workflow used.

Standardized and reproducible measurement of decision-making in mice.

Progress in science requires standardized assays whose results can be readily shared, compared, and reproduced across laboratories. Reproducibility, however, has been a concern in neuroscience, particularly for measurements of mouse behavior. Here, we show that a standardized task to probe decision-making in mice produces reproducible results across multiple laboratories. We adopted a task for head-fixed mice that assays perceptual and value-based decision making, and we standardized training protocol and experimental hardware, software, and procedures. We trained 140 mice across seven laboratories in three countries, and we collected 5 million mouse choices into a publicly available database. Learning speed was variable across mice and laboratories, but once training was complete there were no significant differences in behavior across laboratories. Mice in different laboratories adopted similar reliance on visual stimuli, on past successes and failures, and on estimates of stimulus prior probability to guide their choices. These results reveal that a complex mouse behavior can be reproduced across multiple laboratories. They establish a standard for reproducible rodent behavior, and provide an unprecedented dataset and open-access tools to study decision-making in mice. More generally, they indicate a path toward achieving reproducibility in neuroscience through collaborative open-science approaches.

In science, it is of vital importance that multiple studies corroborate the same result. Researchers therefore need to know all the details of previous experiments in order to implement the procedures as exactly as possible. However, this is becoming a major problem in neuroscience, as animal studies of behavior have proven to be hard to reproduce, and most experiments are never replicated by other laboratories. Mice are increasingly being used to study the neural mechanisms of decision making, taking advantage of the genetic, imaging and physiological tools that are available for mouse brains. Yet, the lack of standardized behavioral assays is leading to inconsistent results between laboratories. This makes it challenging to carry out large-scale collaborations which have led to massive breakthroughs in other fields such as physics and genetics. To help make these studies more reproducible, the International Brain Laboratory (a collaborative research group) et al. developed a standardized approach for investigating decision making in mice that incorporates every step of the process; from the training protocol to the software used to analyze the data. In the experiment, mice were shown images with different contrast and had to indicate, using a steering wheel, whether it appeared on their right or left. The mice then received a drop of sugar water for every correction decision. When the image contrast was high, mice could rely on their vision. However, when the image contrast was very low or zero, they needed to consider the information of previous trials and choose the side that had recently appeared more frequently. This method was used to train 140 mice in seven laboratories from three different countries. The results showed that learning speed was different across mice and laboratories, but once training was complete the mice behaved consistently, relying on visual stimuli or experiences to guide their choices in a similar way. These results show that complex behaviors in mice can be reproduced across multiple laboratories, providing an unprecedented dataset and open-access tools for studying decision making. This work could serve as a foundation for other groups, paving the way to a more collaborative approach in the field of neuroscience that could help to tackle complex research challenges.

Imaging slow brain activity during neocortical and hippocampal epileptiform events with electrical impedance tomography.

OBJECTIVE: Electrical impedance tomography (EIT) is an imaging technique that produces tomographic images of internal impedance changes within an object using surface electrodes. It can be used to image the slow increase in cerebral tissue impedance that occurs over seconds during epileptic seizures, which is attributed to cell swelling due to disturbances in ion homeostasis following hypersynchronous neuronal firing and its associated metabolic demands. In this study, we characterised and imaged this slow impedance response during neocortical and hippocampal epileptiform events in the rat brain and evaluated its relationship to the underlying neural activity. APPROACH: Neocortical or hippocampal seizures, comprising repeatable series of high-amplitude ictal spikes, were induced by electrically stimulating the sensorimotor cortex or perforant path of rats anaesthetised with fentanyl-isoflurane. Transfer impedances were measured during ≥30 consecutive seizures, by applying a sinusoidal current through independent electrode pairs on an epicortical array, and combined to generate an EIT image of slow activity. MAIN RESULTS: The slow impedance responses were consistently time-matched to the end of seizures and EIT images of this activity were reconstructed reproducibly in all animals (p < 0.03125, N = 5). These displayed foci of activity that were spatially confined to the facial somatosensory cortex and dentate gyrus for neocortical and hippocampal seizures, respectively, and encompassed a larger volume as the seizure progressed. Centre-of-mass analysis of reconstructions revealed that this activity corresponded to the true location of the epileptogenic zone, as determined by EEG recordings and fast neural EIT measurements which were obtained simultaneously. SIGNIFICANCE: These findings suggest that the slow impedance response presents a reliable marker of hypersynchronous neuronal activity during epileptic seizures and can thus be utilised for investigating the mechanisms of epileptogenesis in vivo and for aiding localisation of the epileptogenic zone during presurgical evaluation of patients with refractory epilepsies.

Optimised induction of on-demand focal hippocampal and neocortical seizures by electrical stimulation.

BACKGROUND: Epilepsy is a common neurological disorder affecting over 60 million people globally, approximately a third of whom are refractory to pharmacotherapy. Surgical resection of the epileptogenic zone is frequently unsuitable or ineffective, particularly for individuals with focal neocortical or mesial temporal lobe epilepsy. Therefore, there is a need to develop animal models for elucidating the mechanisms of focal epilepsies and evaluating novel treatment strategies. NEW METHOD: We present two adapted in vivo seizure models, the neocortical and hippocampal epileptic afterdischarge models, that enable stereotyped seizures to be induced on demand by electrical stimulation in anaesthetised, neurologically intact rats. The stimulation parameters and anaesthetic were optimised to generate electrographically reproducible, self-sustaining seizures with a well-defined focal origin. RESULTS: Neocortical or hippocampal seizures were consistently generated under fentanyl-isoflurane anaesthesia by stimulating the sensorimotor cortex or perforant path, respectively, with 100 Hz trains of biphasic square-wave pulses. The induced seizures were suppressed by propofol, an established antiseizure anaesthetic, thus validating the clinical responsiveness of the developed models. COMPARISON WITH EXISTING METHODS: The high degree of reproducibility in seizure presentation, predictable seizure induction and ability to operate in anaesthetised animals renders these models overall less laborious and more cost-effective than most conventionally used seizure models. CONCLUSIONS: The proposed models provide an efficient method for the high-throughput screening of novel antiseizure therapies, including closed-loop stimulation paradigms, and are well-suited to in vivo investigations that require tight regulation of seizure timing under anaesthetised conditions, particularly neuroimaging studies aimed at understanding the development of epileptogenic networks.

In vivo imaging of deep neural activity from the cortical surface during hippocampal epileptiform events in the rat brain using electrical impedance tomography.

Electrical impedance tomography (EIT) is a medical imaging technique which reconstructs images of the internal impedance changes within an object using non-penetrating surface electrodes. To date, EIT has been used to image fast neural impedance changes during somatosensory evoked potentials and epileptiform discharges through the rat cerebral cortex with a resolution of 2 â€‹ms and <300 â€‹µm. However, imaging of neural activity in subcortical structures has never been achieved with this technique. Here, we evaluated the feasibility of using EIT to image epileptiform activity in the rat hippocampus using non-penetrating electrodes implanted on the cortical surface. Hippocampal epileptiform events, comprising repetitive 30-50 â€‹Hz ictal spikes, were induced by electrically stimulating the perforant path of rats anaesthetised with fentanyl-isoflurane. For each of ≥30 seizures, impedance measurements were obtained by applying 100 â€‹µA current at 1.4 â€‹kHz through an independent pair of electrodes on a 54-electrode planar epicortical array and recording boundary voltages on all remaining electrodes. EIT images of averaged ictal spikes were reconstructed using impedance recordings from all seizures in each animal. These revealed a focus of neural activity localised to the dentate gyrus which was spatially and temporally aligned to local field potential (LFP) recordings and could be reconstructed reproducibly in all animals with a localisation accuracy of ≤400 â€‹µm (p â€‹< â€‹0.03125, N â€‹= â€‹5). These findings represent the first experimental evidence of the ability of EIT to image neural activity in subcortical structures from the surface of the cortex with high spatiotemporal resolution and suggest that this method may be used for improving understanding of functional connectivity between cortico-hippocampal networks in both physiological and pathophysiological states.

Investigating the safety of fast neural electrical impedance tomography in the rat brain.

OBJECTIVE: Electrical impedance tomography (EIT) can be used to image impedance changes which arise due to fast electrical activity during neuronal depolarisation and so holds therapeutic potential for improving the localisation of epileptic seizure foci in patients with treatment-resistant epilepsy to aid surgical resection of epileptogenic tissue. Prolonged cortical stimulation may, however, induce neural injury through excitotoxicity and electrochemical reactions at the tissue-electrode interface. The purpose of this work was to assess whether current levels used in fast neural EIT studies induce histologically detectable tissue damage when applied continuously to the rat cerebral cortex. APPROACH: A 57-electrode epicortical array was placed on one or both hemispheres of adult Sprague Dawley rats anaesthetised with isoflurane. In an initial series of experiments, current was injected simultaneously at 10, 25, 50, 75 and 100 µA for 1 h at 1.725 kHz through five electrodes across two epicortical arrays to provide a preliminary indication of the safety of these current levels. Since no obvious cortical damage was observed in these rats, the current level chosen for further investigation was 100 µA, the upper-bound of the range of interest. In a separate series of experiments, 100 µA was applied through a single electrode for 1 h at 1.725 kHz to verify its safety. Following termination of stimulation, brain samples were fixed in formalin and histologically processed with Haematoxylin and Eosin (H&E) and Nissl stains. MAIN RESULTS: Histological analysis revealed that continuous injection of 100 µA current, equating to a current density of 354 Am-2, into the rat cortex at 1.725 kHz does not cause cortical tissue damage or any alterations to neuronal morphology. SIGNIFICANCE: The safety of current injections during typical EIT protocols for imaging fast neural activity have been validated. The current density established to be safe for continuous application to the cortex, 354 Am-2, exceeds the present safety limit of 250 Am-2 which has been complied with to date, and thus encourages the application of more intensified fast neural EIT protocols. These findings will aid protocol design for future clinical and in vivo EIT investigations aimed at imaging fast neural activity, particularly in situations where the signal-to-noise ratio is considerably reduced.

Simultaneous EIT and EEG using frequency division multiplexing.

OBJECTIVE: Methods have previously been reported for simultaneous EIT and EEG recording, but these have relied on post-hoc signal processing to remove switching artefacts from the EEG signal and require dedicated hardware filters and the use of separate EEG and EIT electrodes. This work aims to demonstrate that an uncorrupted EEG signal can be collected simultaneously with EIT data by using frequency division multiplexing (FDM), and to show that the EIT data provides useful information when compared to EEG source localisation. APPROACH: A custom FDM EIT current source was created and evaluated in resistor phantom and neonatal head tank experiments, where a static and dynamic perturbation was imaged. EEG and EIT source localisation were compared when an EEG dipole was placed in the tank. EEG and EIT data were collected simultaneously in a human volunteer, using both a standard EEG and a visual evoked potential (VEP) paradigms. MAIN RESULTS: Differences in EEG and VEP collected with and without simultaneous EIT stimulation showed no significant differences in amplitude, latency or PSD (p-values >0.3 in all cases). Compared with EEG source localisation, EIT reconstructions were more accurately able to reconstruct both the centre of mass and volume of a perturbation. SIGNIFICANCE: The reported method is suitable for collecting EIT in a clinical setting, without disrupting the clinical EEG or requiring additional measurement electrodes, which lowers the barrier to entry for data collection. EIT collection can be integrated with existing clinical workflows in EEG/ECoG, with minimal disruption to the patient or clinical team.

Imaging fast electrical activity in the brain during ictal epileptiform discharges with electrical impedance tomography.

Electrical Impedance Tomography (EIT) is an emerging medical imaging technique which can produce tomographic images of internal impedance changes within an object using non-penetrating surface electrodes. It has previously been used to image impedance changes due to neuronal depolarisation during evoked potentials in the rat somatosensory cortex with a resolution of 2 ms and <200 µm, using an epicortical electrode array. The purpose of this work was to use this technique to elucidate the intracortical spatiotemporal trajectory of ictal spike-and-wave discharges (SWDs), induced by electrical stimulation in an acute rat model of epilepsy, throughout the cerebral cortex. Seizures lasting 16.5 ±â€¯5.3 s with repetitive 2-5 Hz SWDs were induced in five rats anaesthetised with fentanyl-isoflurane. Transfer impedance measurements were obtained during each seizure with a 57-electrode epicortical array by applying 50 µA current at 1.7 kHz to two electrodes and recording voltages from all remaining electrodes. Images were reconstructed from averaged SWD-related impedance traces obtained from EIT measurements in successive seizures. We report the occurrence of reproducible impedance changes during the initial spike phase, which had an early onset in the whisker barrel cortex and spread posteriorly, laterally and ventrally over 20 ms (p < 0.03125, N = 5). These findings, which confirm and extend knowledge of SWD initiation and expression, suggest that EIT is a valuable neuroimaging tool for improving understanding of neural circuits implicated in epileptic phenomena.

Frequency-dependent characterisation of impedance changes during epileptiform activity in a rat model of epilepsy.

OBJECTIVE: Electrical impedance tomography (EIT) can be used to image impedance changes associated with epileptiform activity and so holds therapeutic potential for improving presurgical localisation of the ictal onset zone in patients with treatment-resistant epilepsy. There are two principal impedance changes which occur during seizures that may be imaged with EIT: (a) a fast, transient impedance decrease over milliseconds due to hypersynchronous neuronal depolarisation in individual ictal discharges; and (b) a larger, slow impedance increase caused by cell swelling over the course of the seizure. The magnitude of these signals is highly dependent on the carrier frequency of applied current used for obtaining impedance measurements. The purpose of this work was to characterise the frequency response of the fast and slow impedance changes during epileptiform activity. APPROACH: Seizures were induced in anaesthetised rats by electrically stimulating the cerebral cortex. During each seizure, impedance measurements were obtained by delivering 50 µA, through two electrodes on an epicortical array, at one of 20 frequencies in the 1-10 kHz range. Recordings were demodulated to determine the magnitude of fast and slow impedance responses at each frequency. MAIN RESULTS: The fast impedance change during averaged ictal discharges reached a maximal amplitude and signal-to-noise ratio (SNR) of -0.36% ± 0.05% and 50.2 ± 11.3, respectively, at 1355 Hz. At this frequency, the slow impedance change had an amplitude of 4.61% ± 1.32% and an SNR of 545 ± 125, which did not significantly change across frequency (p > 0.01). SIGNIFICANCE: We conclude that the optimal frequency for imaging epileptiform activity is 1355 Hz, which maximises the SNR of fast neural changes whilst enabling simultaneous measurement of slow changes. These findings will inform future investigations aimed at imaging epilepsy in subcortical brain structures, where SNR is considerably reduced, and those using parallel, multi-frequency EIT.

Feasibility of imaging evoked activity throughout the rat brain using electrical impedance tomography.

Electrical Impedance Tomography (EIT) is an emerging technique which has been used to image evoked activity during whisker displacement in the cortex of an anaesthetised rat with a spatiotemporal resolution of 200 µm and 2 ms. The aim of this work was to extend EIT to image not only from the cortex but also from deeper structures active in somatosensory processing, specifically the ventral posterolateral (VPL) nucleus of the thalamus. The direct response in the cortex and VPL following 2 Hz forepaw stimulation were quantified using a 57-channel epicortical electrode array and a 16-channel depth electrode. Impedance changes of -0.16 ±â€¯0.08% at 12.9 ±â€¯1.4 ms and -0.41 ±â€¯0.14% at 8.8±1.9 ms were recorded from the cortex and VPL respectively. For imaging purposes, two 57-channel epicortical electrode arrays were used with one placed on each hemisphere of the rat brain. Despite using parameters optimised toward measuring thalamic activity and undertaking extensive averaging, reconstructed activity was constrained to the cortical somatosensory forepaw region and no significant activity at a depth greater than 1.6 mm below the surface of the cortex could be reconstructed. An evaluation of the depth sensitivity of EIT was investigated in simulations using estimates of the conductivity change and noise levels derived from experiments. These indicate that EIT imaging with epicortical electrodes is limited to activity occurring 2.5 mm below the surface of the cortex. This depth includes the hippocampus and so EIT has the potential to image activity, such as epilepsy, originating from this structure. To image deeper activity, however, alternative methods such as the additional implementation of depth electrodes will be required to gain the necessary depth resolution.

Feasibility of imaging epileptic seizure onset with EIT and depth electrodes.

Imaging ictal and interictal activity with Electrical Impedance Tomography (EIT) using intracranial electrode mats has been demonstrated in animal models of epilepsy. In human epilepsy subjects undergoing presurgical evaluation, depth electrodes are often preferred. The purpose of this work was to evaluate the feasibility of using EIT to localise epileptogenic areas with intracranial electrodes in humans. The accuracy of localisation of the ictal onset zone was evaluated in computer simulations using 9M element FEM models derived from three subjects. 5 mm radius perturbations imitating a single seizure onset event were placed in several locations forming two groups: under depth electrode coverage and in the contralateral hemisphere. Simulations were made for impedance changes of 1% expected for neuronal depolarisation over milliseconds and 10% for cell swelling over seconds. Reconstructions were compared with EEG source modelling for a radially orientated dipole with respect to the closest EEG recording contact. The best accuracy of EIT was obtained using all depth and 32 scalp electrodes, greater than the equivalent accuracy with EEG inverse source modelling. The localisation error was 5.2 ±â€¯1.8, 4.3 ±â€¯0 and 46.2 ±â€¯25.8 mm for perturbations within the volume enclosed by depth electrodes and 29.6 ±â€¯38.7, 26.1 ±â€¯36.2, 54.0 ±â€¯26.2 mm for those without (EIT 1%, 10% change, EEG source modelling, n = 15 in 3 subjects, p < 0.01). As EIT was insensitive to source dipole orientation, all 15 perturbations within the volume enclosed by depth electrodes were localised, whereas the standard clinical method of visual inspection of EEG voltages, only localised 8 out of 15 cases. This suggests that adding EIT to SEEG measurements could be beneficial in localising the onset of seizures.

Characterising the frequency response of impedance changes during evoked physiological activity in the rat brain.

OBJECTIVE: Electrical impedance tomography (EIT) can image impedance changes associated with evoked physiological activity in the cerebral cortex using an array of epicortical electrodes. An impedance change is observed as the externally applied current, normally confined to the extracellular space is admitted into the conducting intracellular space during neuronal depolarisation. The response is largest at DC and decreases at higher frequencies due to capacitative transfer of current across the membrane. Biophysical modelling has shown that this effect becomes significant above 100 Hz. Recordings at DC, however, are contaminated by physiological endogenous evoked potentials. By moving to 1.7 kHz, images of somatosensory evoked responses have been produced down to 2 mm with a resolution of 2 ms and 200 µm. Hardware limitations have so far restricted impedance measurements to frequencies <2 kHz. The purpose of this work was to establish the optimal frequency for extending EIT to image throughout the brain and to characterise the response at frequencies >2 kHz using improved hardware. APPROACH: Impedance changes were recorded during forepaw somatosensory stimulation in both cerebral cortex and the VPL nucleus of the thalamus in anaesthetised rats using applied currents of 1 kHz to 10 kHz. MAIN RESULTS: In the cortex, impedance changed by -0.04 ± 0.02 % at 1 kHz, reached a peak of -0.13 ± 0.05 % at 1475 Hz and decreased to -0.05 ± 0.02 % at 10 kHz. At these frequencies, changes in the thalamus were -0.26 ± 0.1%, -0.4 ± 0.15 % and -0.08 ± 0.03 % respectively. The signal-to-noise ratio was also highest at 1475 Hz with values of -29.5 ± 8 and -31.6 ±10 recorded from the cortex and thalamus respectively. Signficance: This indicates that the optimal frequency for imaging cortical and thalamic evoked activity using fast neural EIT is 1475 Hz.

Optimisation of current injection protocol based on a region of interest.

OBJECTIVE: Electrical impedance tomography has the potential to image fast neural activity associated with physiological or epileptic activity throughout the brain. These applications pose a particular challenge as expected voltage changes on the electrodes are less than 1% and geometrical constraints of the body under investigation mean that electrodes can not be evenly distributed around its boundary. Unlike other applications, however, information regarding the location of expected activity is typically available. An informative method for choosing current paths that maximise sensitivity to specific regions is desirable. APPROACH: Two electrode addressing protocol generation methods based on current density vectors concentrated in a region of interest have been proposed. One focuses solely on maximising its magnitude while the other considers its distribution. The quality of reconstructed images using these protocols was assessed in a simulation study conducted in a human and rat mesh and compared to the protocol that maximises distance between injecting electrodes. MAIN RESULTS: When implementing the protocol that focused on maximising magnitude, the current density concentrated in a region of interest increased by up to a factor of 3. When the distribution of the current was maximised, the spread of current density vectors increased by up to fivefold. For the small conductivity changes expected in the applications explored, image quality was best when implementing the protocol that maximised current density. The average image error when using this protocol was 7% better than when employing other protocols. SIGNIFICANCE: We conclude that for fast neural EIT applications, the protocol that maximises current density is the best protocol to implement.

A Versatile and Reproducible Multi-Frequency Electrical Impedance Tomography System.

A highly versatile Electrical Impedance Tomography (EIT) system, nicknamed the ScouseTom, has been developed. The system allows control over current amplitude, frequency, number of electrodes, injection protocol and data processing. Current is injected using a Keithley 6221 current source, and voltages are recorded with a 24-bit EEG system with minimum bandwidth of 3.2 kHz. Custom PCBs interface with a PC to control the measurement process, electrode addressing and triggering of external stimuli. The performance of the system was characterised using resistor phantoms to represent human scalp recordings, with an SNR of 77.5 dB, stable across a four hour recording and 20 Hz to 20 kHz. In studies of both haeomorrhage using scalp electrodes, and evoked activity using epicortical electrode mats in rats, it was possible to reconstruct images matching established literature at known areas of onset. Data collected using scalp electrode in humans matched known tissue impedance spectra and was stable over frequency. The experimental procedure is software controlled and is readily adaptable to new paradigms. Where possible, commercial or open-source components were used, to minimise the complexity in reproduction. The hardware designs and software for the system have been released under an open source licence, encouraging contributions and allowing for rapid replication.

Are patient specific meshes required for EIT head imaging?

Head imaging with electrical impedance tomography (EIT) is usually done with time-differential measurements, to reduce time-invariant modelling errors. Previous research suggested that more accurate head models improved image quality, but no thorough analysis has been done on the required accuracy. We propose a novel pipeline for creation of precise head meshes from magnetic resonance imaging and computed tomography scans, which was applied to four different heads. Voltages were simulated on all four heads for perturbations of different magnitude, haemorrhage and ischaemia, in five different positions and for three levels of instrumentation noise. Statistical analysis showed that reconstructions on the correct mesh were on average 25% better than on the other meshes. However, the stroke detection rates were not improved. We conclude that a generic head mesh is sufficient for monitoring patients for secondary strokes following head trauma.