Flexible head-casts for high spatial precision MEG.

BACKGROUND: In combination with magnetoencephalographic (MEG) data, accurate knowledge of the brain's structure and location provide a principled way of reconstructing neural activity with high temporal resolution. However, measuring the brain's location is compromised by head movement during scanning, and by fiducial-based co-registration with magnetic resonance imaging (MRI) data. The uncertainty from these two factors introduces errors into the forward model and limit the spatial resolution of the data. NEW METHOD: We present a method for stabilizing and reliably repositioning the head during scanning, and for co-registering MRI and MEG data with low error. RESULTS: Using this new flexible and comfortable subject-specific head-cast prototype, we find within-session movements of <0.25mm and between-session repositioning errors around 1mm. COMPARISON WITH EXISTING METHOD(S): This method is an improvement over existing methods for stabilizing the head or correcting for location shifts on- or off-line, which still introduce approximately 5mm of uncertainty at best (Adjamian et al., 2004; Stolk et al., 2013; Whalen et al., 2008). Further, the head-cast design presented here is more comfortable, safer, and easier to use than the earlier 3D printed prototype, and give slightly lower co-registration errors (Troebinger et al., 2014b). CONCLUSIONS: We provide an empirical example of how these head-casts impact on source level reproducibility. Employment of the individual flexible head-casts for MEG recordings provide a reliable method of safely stabilizing the head during MEG recordings, and for co-registering MRI anatomical images to MEG functional data.

Analysis of simultaneous MEG and intracranial LFP recordings during Deep Brain Stimulation: a protocol and experimental validation.

BACKGROUND: Deep Brain Stimulation (DBS) is an effective treatment for several neurological and psychiatric disorders. In order to gain insights into the therapeutic mechanisms of DBS and to advance future therapies a better understanding of the effects of DBS on large-scale brain networks is required. NEW METHOD: In this paper, we describe an experimental protocol and analysis pipeline for simultaneously performing DBS and intracranial local field potential (LFP) recordings at a target brain region during concurrent magnetoencephalography (MEG) measurement. Firstly we describe a phantom setup that allowed us to precisely characterise the MEG artefacts that occurred during DBS at clinical settings. RESULTS: Using the phantom recordings we demonstrate that with MEG beamforming it is possible to recover oscillatory activity synchronised to a reference channel, despite the presence of high amplitude artefacts evoked by DBS. Finally, we highlight the applicability of these methods by illustrating in a single patient with Parkinson's disease (PD), that changes in cortical-subthalamic nucleus coupling can be induced by DBS. COMPARISON WITH EXISTING APPROACHES: To our knowledge this paper provides the first technical description of a recording and analysis pipeline for combining simultaneous cortical recordings using MEG, with intracranial LFP recordings of a target brain nucleus during DBS.

Cortical mechanisms of mirror therapy after stroke.

BACKGROUND AND OBJECTIVE: Mirror therapy is a new form of stroke rehabilitation that uses the mirror reflection of the unaffected hand in place of the affected hand to augment movement training. The mechanism of mirror therapy is not known but is thought to involve changes in cerebral organization. We used magnetoencephalography (MEG) to measure changes in cortical activity during mirror training after stroke. In particular, we examined movement-related changes in the power of cortical oscillations in the beta (15-30 Hz) frequency range, known to be involved in movement. METHODS: Ten stroke patients with upper limb paresis and 13 healthy controls were recorded using MEG while performing bimanual hand movements in 2 different conditions. In one, subjects looked directly at their affected hand (or dominant hand in controls), and in the other, they looked at a mirror reflection of their unaffected hand in place of their affected hand. The movement-related beta desynchronization was calculated in both primary motor cortices. RESULTS: Movement-related beta desynchronization was symmetrical during bilateral movement and unaltered by the mirror condition in controls. In the patients, movement-related beta desynchronization was generally smaller than in controls, but greater in contralesional compared to ipsilesional motor cortex. This initial asymmetry in movement-related beta desynchronization between hemispheres was made more symmetrical by the presence of the mirror. CONCLUSIONS: Mirror therapy could potentially aid stroke rehabilitation by normalizing an asymmetrical pattern of movement-related beta desynchronization in primary motor cortices during bilateral movement.

Between thought and expression, a magnetoencephalography study of the "tip-of-the-tongue" phenomenon.

"Tip-of-the-tongue" (TOT) is the phenomenon associated with the inaccessibility of a known word from memory. It is universally experienced, increases in frequency with age, and is most common for proper nouns. It is a good model for the symptom of anomia experienced much more frequently by some aphasic patients following brain injury. Here, we induced the TOT state in older participants while they underwent brain scanning with magnetoencephalography to investigate the changes in oscillatory brain activity associated with failed retrieval of known words. Using confrontation naming of pictures of celebrities, we successfully induced the TOT state in 29% of trials and contrasted it with two other states: "Know" where the participants both correctly recognized the celebrity's face and retrieved their name and "Don't Know" when the participants did not recognize the celebrity. We wished to test Levelt's influential model of speech output by carrying out two analyses, one epoching the data to the point in time when the picture was displayed and the other looking back in time from when the participants first articulated their responses. Our main findings supported the components of Levelt's model, but not their serial activation over time as both semantic and motor areas were identified in both analyses. We also found enduring decreases in the alpha frequency band in the left ventral temporal region during the TOT state, suggesting ongoing semantic search. Finally, we identified reduced beta power in classical peri-sylvian language areas for the TOT condition, suggesting that brain regions that encode linguistic memories are also involved in their attempted retrieval.

High precision anatomy for MEG.

Precise MEG estimates of neuronal current flow are undermined by uncertain knowledge of the head location with respect to the MEG sensors. This is either due to head movements within the scanning session or systematic errors in co-registration to anatomy. Here we show how such errors can be minimized using subject-specific head-casts produced using 3D printing technology. The casts fit the scalp of the subject internally and the inside of the MEG dewar externally, reducing within session and between session head movements. Systematic errors in matching to MRI coordinate system are also reduced through the use of MRI-visible fiducial markers placed on the same cast. Bootstrap estimates of absolute co-registration error were of the order of 1mm. Estimates of relative co-registration error were <1.5mm between sessions. We corroborated these scalp based estimates by looking at the MEG data recorded over a 6month period. We found that the between session sensor variability of the subject's evoked response was of the order of the within session noise, showing no appreciable noise due to between-session movement. Simulations suggest that the between-session sensor level amplitude SNR improved by a factor of 5 over conventional strategies. We show that at this level of coregistration accuracy there is strong evidence for anatomical models based on the individual rather than canonical anatomy; but that this advantage disappears for errors of greater than 5mm. This work paves the way for source reconstruction methods which can exploit very high SNR signals and accurate anatomical models; and also significantly increases the sensitivity of longitudinal studies with MEG.

Cholinergic enhancement of visual attention and neural oscillations in the human brain.

Cognitive processes such as visual perception and selective attention induce specific patterns of brain oscillations. The neurochemical bases of these spectral changes in neural activity are largely unknown, but neuromodulators are thought to regulate processing. The cholinergic system is linked to attentional function in vivo, whereas separate in vitro studies show that cholinergic agonists induce high-frequency oscillations in slice preparations. This has led to theoretical proposals that cholinergic enhancement of visual attention might operate via gamma oscillations in visual cortex, although low-frequency alpha/beta modulation may also play a key role. Here we used MEG to record cortical oscillations in the context of administration of a cholinergic agonist (physostigmine) during a spatial visual attention task in humans. This cholinergic agonist enhanced spatial attention effects on low-frequency alpha/beta oscillations in visual cortex, an effect correlating with a drug-induced speeding of performance. By contrast, the cholinergic agonist did not alter high-frequency gamma oscillations in visual cortex. Thus, our findings show that cholinergic neuromodulation enhances attentional selection via an impact on oscillatory synchrony in visual cortex, for low rather than high frequencies. We discuss this dissociation between high- and low-frequency oscillations in relation to proposals that lower-frequency oscillations are generated by feedback pathways within visual cortex.

Method for simultaneous voxel-based morphometry of the brain and cervical spinal cord area measurements using 3D-MDEFT.

PURPOSE: To investigate whether a 3D-modified driven equilibrium Fourier transform (MDEFT)-based acquisition protocol established for brain morphometry also yields reliable information about the cross-sectional spinal cord area (SCA). MATERIALS AND METHODS: Images of brain and cervical cord of 10 controls and eight subjects with spinal cord injury (SCI) were acquired with the 3D-MDEFT-based imaging protocol and an 8-channel receive head coil. The new protocol was validated by two observers 1) comparing the SCA measured with the standard acquisition protocol (3D magnetization-prepared rapid acquisition gradient echo [MPRAGE] and dedicated spine coil) and the new protocol; and 2) determining the scan-rescan reproducibility of the new protocol. RESULTS: Scan-rescan reproducibility of SCA measurements with the MDEFT approach showed a similar precision for both observers with standard deviation (SD) <4.5 mm(2) and coefficient of variation (CV) ≤5.1%. Analysis of variance (ANOVA) revealed a main effect of observer and interaction between observer and scan protocol that could be primarily attributed to a small observer bias for MPRAGE (difference in SCA <2.1 mm(2)). No bias was observed for 3D-MDEFT vs. 3D-MPRAGE. CONCLUSION: The 3D-MDEFT method allows for robust unbiased assessment of SCA in addition to brain morphology.

A cortical potential reflecting cardiac function.

Emotional trauma and psychological stress can precipitate cardiac arrhythmia and sudden death through arrhythmogenic effects of efferent sympathetic drive. Patients with preexisting heart disease are particularly at risk. Moreover, generation of proarrhythmic activity patterns within cerebral autonomic centers may be amplified by afferent feedback from a dysfunctional myocardium. An electrocortical potential reflecting afferent cardiac information has been described, reflecting individual differences in interoceptive sensitivity (awareness of one's own heartbeats). To inform our understanding of mechanisms underlying arrhythmogenesis, we extended this approach, identifying electrocortical potentials corresponding to the cortical expression of afferent information about the integrity of myocardial function during stress. We measured changes in cardiac response simultaneously with electroencephalography in patients with established ventricular dysfunction. Experimentally induced mental stress enhanced cardiovascular indices of sympathetic activity (systolic blood pressure, heart rate, ventricular ejection fraction, and skin conductance) across all patients. However, the functional response of the myocardium varied; some patients increased, whereas others decreased, cardiac output during stress. Across patients, heartbeat-evoked potential amplitude at left temporal and lateral frontal electrode locations correlated with stress-induced changes in cardiac output, consistent with an afferent cortical representation of myocardial function during stress. Moreover, the amplitude of the heartbeat-evoked potential in the left temporal region reflected the proarrhythmic status of the heart (inhomogeneity of left ventricular repolarization). These observations delineate a cortical representation of cardiac function predictive of proarrhythmic abnormalities in cardiac repolarization. Our findings highlight the dynamic interaction of heart and brain in stress-induced cardiovascular morbidity.

Etomidate for procedural sedation in emergency medicine.

STUDY OBJECTIVE: We describe and analyze the effectiveness and safety of etomidate for procedural sedation and evaluate the patient's perspective on effectiveness, side effects, and satisfaction. METHODS: We conducted an observational retrospective study of all patients who received etomidate for procedural sedation over 2 years in 3 affiliated suburban emergency departments of a large group-model health maintenance organization. Data were abstracted from the ED records. Additionally, a patient questionnaire was prospectively administered by telephone. RESULTS: Etomidate was used for sedation in 134 patients between 6 and 93 years of age during 150 procedures. The mean cumulative dose was 0.20 mg/kg. Adjunctive medication was used in 36 (23%) procedures. Moderate sedation with verbal arousability was induced in 48 (32%) patients, and deep sedation with verbal unresponsiveness was induced in 102 (68%) patients. Full recovery to the preprocedural level of alertness was achieved within 30 minutes in 142 (95%) of procedures. Mean changes in systolic blood pressure, pulse rate, and oxygen saturation were clinically insignificant. There were 7 (4.7%; 95% confidence interval [CI] 1.9% to 9.4%) adverse events, including 5 (3.3%; 95% CI 1.1% to 7.6%) cases of oxygen desaturation below 94% in older patients (>55 years of age) who received slightly higher mean doses of etomidate (0.23 mg/kg). Four of these patients received brief assisted bag-valve-mask ventilation and recovered uneventfully; none required endotracheal intubation. The questionnaire was completed by 120 (90%) of 134 patients and involved 136 procedures. During 127 (93%) of these, etomidate was believed to be extremely effective in causing sleep, and for 127 (93%) it induced complete procedural amnesia. Only 5 (4%) patients experienced nausea or vomiting. Regarding willingness to receive etomidate for their next procedure, the patients' responses were favorable: extremely, 95%; moderately, 2%; slightly, 3%; and not at all, 1%. CONCLUSION: Etomidate is a useful agent for carefully conducted procedural sedation because it provides effective, brief, deep sedation with little hemodynamic compromise. Its safety may be jeopardized by the occurrence of respiratory depression in older patients receiving higher doses. Patients report a high degree of satisfaction with etomidate.