Using fMRI to localize target regions for implanted brain-computer interfaces in locked-in syndrome.

OBJECTIVE: Electrocorticography (ECoG)-based brain-computer interface (BCI) systems have the potential to improve quality of life of people with locked-in syndrome (LIS) by restoring their ability to communicate independently. Before implantation of such a system, it is important to localize ECoG electrode target regions. Here, we assessed the predictive value of functional magnetic resonance imaging (fMRI) for the localization of suitable target regions on the sensorimotor cortex for ECoG-based BCI in people with locked-in syndrome. METHODS: Three people with locked-in syndrome were implanted with a chronic, fully implantable ECoG-BCI system. We compared pre-surgical fMRI activity with post-implantation ECoG activity from areas known to be active and inactive during attempted hand movement (sensorimotor hand region and dorsolateral prefrontal cortex, respectively). RESULTS: Results showed a spatial match between fMRI activity and changes in ECoG low and high frequency band power (10 - 30 and 65 - 95 Hz, respectively) during attempted movement. Also, we found that fMRI can be used to select a sub-set of electrodes that show strong task-related signal changes that are therefore likely to generate adequate BCI control. CONCLUSIONS: Our findings indicate that fMRI is a useful non-invasive tool for the pre-surgical workup of BCI implant candidates. SIGNIFICANCE: If these results are confirmed in more BCI studies, fMRI might be used for more efficient surgical BCI procedures with focused cortical coverage and lower participant burden.

High frequency oscillations associate with neuroinflammation in low-grade epilepsy associated tumors.

OBJECTIVE: High frequency oscillations (HFOs) in intraoperative electrocorticography (ioECoG) are thought to be generated by hyperexcitable neurons. Inflammation may promote neuronal hyperexcitability. We investigated the relation between HFOs and inflammation in tumor-related epilepsy. METHODS: We identified HFOs (ripples 80-250 Hz, fast ripples 250-500 Hz) in the preresection ioECoG of 32 patients with low-grade tumors. Localization of recorded HFOs was classified based on magnetic resonance imaging reconstructions: in tumor, in resected non-tumorous area and outside the resected area. We tested if the following inflammatory markers in the tumor or peritumoral tissue were related to HFOs: activated microglia, cluster of differentiation 3 (CD3)-positive T-cells, interleukin 1-beta (IL1ß), toll-like receptor 4 (TLR4) and high mobility group box 1 protein (HMGB1). RESULTS: Tumors that generated ripples were infiltrated by more CD3-positive cells than tumors without ripples. Ripple rate outside the resected area was positively correlated with IL1ß/TLR4/HMGB1 pathway activity in peritumoral area. These two areas did not directly overlap. CONCLUSIONS: Ripple rates may be associated with inflammatory processes. SIGNIFICANCE: Our findings support that ripple generation and spread might be associated with synchronized fast firing of hyperexcitable neurons due to certain inflammatory processes. This pilot study provides arguments for further investigations in HFOs and inflammation.

Residual fast ripples in the intraoperative corticogram predict epilepsy surgery outcome.

OBJECTIVE: We studied whether residual high-frequency oscillations (80-500 Hz; ripples, 80-250 Hz), especially fast ripples (FRs, 250-500 Hz), in post-resection intraoperative electrocorticography (ECoG) predicted seizure recurrence in comparison to residual interictal spikes and ictiform spike patterns. METHODS: We studied, retrospectively, ECoG recorded at 2,048 Hz after resection in a cohort of patients with refractory focal epilepsy. We analyzed occurrence and number of residual FRs, ripples, interictal spikes, and ictiform spike patterns within the last minute of each recording and compared these to seizure recurrence. RESULTS: We included 54 patients (median age 15.5 years) with 25 months median follow-up. Twenty-four patients had recurrent seizures. We found residual FRs, ripples, spikes, and ictiform spike patterns in 12, 51, 38, and 9 patients. Nine out of 12 patients with residual FRs had recurrent seizures (p = 0.016, positive predictive value 75%). Other ECoG events did not predict seizure recurrence. Patients with seizures had higher FR rates than seizure-free patients (p = 0.022). FRs near the resection and in distant pathologic areas could have changed the resection in 8 patients without harming functionally eloquent areas. One seizure-free patient had FRs in distant functionally eloquent areas. CONCLUSIONS: Residual FRs in post-resection ECoG are prognostic markers for seizure recurrence, especially if their number is high. Tailoring could rely on FRs, but requires careful assessment of the ECoG, as FRs in functionally eloquent areas might not be pathologic.

Safety of a dedicated brain MRI protocol in patients with a vagus nerve stimulator.

Although implanted metallic devices constitute a relative contraindication to magnetic resonance imaging (MRI) scanning, the safety of brain imaging in a patient with a vagus nerve stimulator (VNS) is classified as "conditional," provided that specific manufacturer guidelines are followed when a transmit and receive head coil is used at 1.5 or 3.0 Tesla. The aim of this study was to evaluate the safety of performing brain MRI scans in patients with the VNS. From September 2009 until November 2011, 101 scans were requested in 73 patients with the VNS in The Netherlands. Patients were scanned according to the manufacturer's guidelines. No patient reported any side effect, discomfort, or pain during or after the MRI scan. In one patient, a lead break was detected based on device diagnostics after the MRI-scan. However, because no system diagnostics had been performed prior to MR scanning in this patient, it is unclear whether MR scanning was responsible for the lead break. The indication for most scans was epilepsy related. Twenty-six scans (26%) were part of a (new) presurgical evaluation and could probably better have been performed prior to VNS implantation. Performing brain MRI scans in patients with an implanted VNS is safe when a modified MRI protocol is followed.

Is cold paresis related to axonal depolarization?

Cold paresis may occur in multifocal motor neuropathy and lower motor neuron disease. It was proposed to reflect nerve lesions where axons are depolarized due to loss of Na/K-pump activity. In those circumstances, a further decrease in pump activity by cooling may induce extra depolarization, conduction block, and weakness. Evidence for this hypothesis is incomplete because it is unknown if cold induces depolarization in human motor axons and other factors may contribute to the symptoms. To solve these questions, we examined 10 normal subjects. At 37, 25, 20, and 15°C we assessed: excitability in the median nerve, decrement on 3-Hz stimulation, pulsed Doppler of a wrist artery, and thenar muscle strength. Cooling induced: (1) findings compatible with axonal depolarization on excitability testing (fanning-in of threshold electrotonus, steepened current threshold relation, increased refractory period, decreased super- and subexcitability), (2) decreased Doppler peak systolic velocity without causing ischemia, (3) decreased muscle strength and impaired muscle relaxation. Decrement tests and compound muscle action potential amplitude remained normal. The excitability findings induced by cooling were best explained by axonal depolarization due to the effect of temperature on Na/K-pump activity. The induced weakness may be explained not only by this mechanism but also by impaired muscle contraction.

Detection of subclinical electroencephalographic seizure patterns with multichannel amplitude-integrated EEG in full-term neonates.

OBJECTIVE: To compare the seizure pattern detection rate of single-channel and multichannel amplitude-integrated EEG (aEEG), using conventional EEG (cEEG) as a gold standard, in full-term neonates with hypoxic-ischemic encephalopathy. The optimal electrode derivation for seizure detection with single-channel aEEG was also investigated. METHODS: Twelve infants with cEEG seizure patterns (10s) were investigated. cEEG signals were transformed into aEEG signals. Seizure patterns and the number of patients identified with 1 seizure patterns were calculated for single- and multichannel aEEG. RESULTS: On cEEG, 121 seizure patterns with a mean duration of 58s were identified, 68% of which occurred over the centrotemporal region. The sensitivity of aEEG for the detection of seizure patterns was 30% (C.I.: 0.22-0.38) for single-channel aEEG and 39% (C.I.: 0.31-0.48) for multichannel aEEG. Multichannel aEEG identified all patients with 1 seizure pattern (C.I.: 0.75-1.00), whereas single-channel aEEG (with C4-C3 as the optimal electrode derivation) identified all but one of the patients (C.I.: 0.66-0.99). CONCLUSIONS: Seizure pattern detection rate is slightly better with multichannel aEEG compared with single-channel (C4-C3) aEEG. Multichannel aEEG identified correctly all patients with 1 seizure pattern in this small selection of patients. SIGNIFICANCE: Single-channel aEEG may detect most patients (in a selected group) with severe neonatal seizures patterns; patient identification can be improved using multichannel recordings.