Adrian G. Guggisberg

Resting state alpha-band functional connectivity and recovery after stroke

After cerebral ischemia, disruption and subsequent reorganization of functional connections occur both locally and remote to the lesion. However, the unpredictable timing and extent of sensorimotor recovery reflects a gap in understanding of these underlying neural mechanisms. We aimed to identify the plasticity of alpha-band functional neural connections within the perilesional area and the predictive value of functional connectivity with respect to motor recovery of the upper extremity after stroke. Our results show improvements in upper extremity motor recovery in relation to distributed changes in MEG-based alpha band functional connectivity, both in the perilesional area and contralesional cortex. Motor recovery was found to be predicted by increased connectivity at baseline in the ipsilesional somatosensory area, supplementary motor area, and cerebellum, contrasted with reduced connectivity of contralesional motor regions, after controlling for age, stroke onset-time and lesion size. These findings support plasticity within a widely distributed neural network and define brain regions in which the extent of network participation predicts post-stroke recovery potential.

MEG/EEG Source Reconstruction, Statistical Evaluation, and Visualization with NUTMEG

NUTMEG is a source analysis toolbox geared towards cognitive neuroscience researchers using MEG and EEG, including intracranial recordings. Evoked and unaveraged data can be imported to the toolbox for source analysis in either the time or time-frequency domains. NUTMEG offers several variants of adaptive beamformers, probabilistic reconstruction algorithms, as well as minimum-norm techniques to generate functional maps of spatiotemporal neural source activity. Lead fields can be calculated from single and overlapping sphere head models or imported from other software. Group averages and statistics can be calculated as well. In addition to data analysis tools, NUTMEG provides a unique and intuitive graphical interface for visualization of results. Source analyses can be superimposed onto a structural MRI or headshape to provide a convenient visual correspondence to anatomy. These results can also be navigated interactively, with the spatial maps and source time series or spectrogram linked accordingly. Animations can be generated to view the evolution of neural activity over time. NUTMEG can also display brain renderings and perform spatial normalization of functional maps using SPMs engine. As a MATLAB package, the end user may easily link with other toolboxes or add customized functions.

The behavioral significance of coherent resting-state oscillations after stroke

Stroke lesions induce not only loss of local neural function, but disruptions in spatially distributed areas. However, it is unknown whether they affect the synchrony of electrical oscillations in neural networks and if changes in network coherence are associated with neurological deficits. This study assessed these questions in a population of patients with subacute, unilateral, ischemic stroke. Spontaneous cortical oscillations were reconstructed from high-resolution electroencephalograms (EEG) with adaptive spatial filters. Maps of functional connectivity (FC) between brain areas were created and correlated with patient performance in motor and cognitive scores. In comparison to age matched healthy controls, stroke patients showed a selective disruption of FC in the alpha frequency range. The spatial distribution of alpha band FC reflected the pattern of motor and cognitive deficits of the individual patient: network nodes that participate normally in the affected functions showed local decreases in FC with the rest of the brain. Interregional FC in the alpha band, but not in delta, theta, or beta frequencies, was highly correlated with motor and cognitive performance. In contrast, FC between contralesional areas and the rest of the brain was negatively associated with patient performance. Alpha oscillation synchrony at rest is a unique and specific marker of network function and linearly associated with behavioral performance. Maps of alpha synchrony computed from a single resting-state EEG recording provide a robust and convenient window into the functionality and organization of cortical networks with numerous potential applications.

Why do we yawn

Yawning is a phylogenetically old behaviour that can be observed in most vertebrate species from foetal stages to old age. The origin and function of this conspicuous phenomenon have been subject to speculations for centuries. Here, we review the experimental evidence for each of these hypotheses. It is found that theories ascribing a physiological role to yawning (such as the respiratory, arousal, or thermoregulation hypotheses) lack evidence. Conversely, the notion that yawning has a communicative function involved in the transmission of drowsiness, boredom, or mild psychological stress receives increasing support from research in different fields. In humans and some other mammals, yawning is part of the action repertoire of advanced empathic and social skills.

Motor evoked potentials from masseter muscle induced by transcranial magnetic stimulation of the pyramidal tract: the importance of coil orientation.

BACKGROUNDnReliable recording of motor evoked potentials (MEPs) of the masseter muscle by transcranial magnetic stimulation (TMS) has proved more difficult than from facial or intrinsic hand muscles. Up to now it was unclear whether this difficulty was due to methodological and/or anatomical reasons.nnnMETHODSnThe mechanism of pyramidal cell activation in masseter MEPs was investigated by using magnetic and electric transcranial stimulation. Analysing the effect of magnetic coil positioning and orientation over the scalp, and scrutinizing the masseter recording technique to avoid compound motor action potential (CMAP) contamination from facial muscles, an optimized method of masseter MEPs was developed.nnnRESULTSnIn particular, an antero-lateral inducing current orientation in the stimulating coil, approximately paralleling the central sulcus, proved clearly more effective for the masseter muscles than the postero-lateral orientation (P=0.005) found optimal for intrinsic hand muscles. The thus evoked masseter MEPs by transcranial magnetic stimulation (TMS) were found to be identical in shape, amplitude and latency as those evoked by transcranial electric stimulation (TES), evidencing a direct rather than trans-synaptic activation of the pyramidal cells.nnnCONCLUSIONSnWe conclude that in TMS evoked MEPs of masseter muscles, the direct stimulation of the pyramidal tract is more easily achieved than the trans-synaptic activation, which is in contrast to the intrinsic hand muscles. We hypothesize that the presynaptic projections to pyramidal cells of the masticatory muscles are less abundant than in hand muscles, and are therefore less accessible to trans-synaptic stimulation.

Localization of cortico-peripheral coherence with electroencephalography.

BACKGROUNDnThe analysis of coherent networks from continuous recordings of neural activity with functional MRI or magnetoencephalography has provided important new insights into brain physiology and pathology. Here we assess whether valid localizations of coherent cortical networks can also be obtained from high-resolution electroencephalography (EEG) recordings.nnnMETHODSnEEG was recorded from healthy subjects and from patients with ischemic brain lesions during a tonic hand muscle contraction task and during continuous visual stimulation with an alternating checkerboard. These tasks induce oscillations in the primary hand motor area or in the primary visual cortex, respectively, which are coherent with extracerebral signals (hand muscle electromyogram or visual stimulation frequency). Cortical oscillations were reconstructed with different inverse solutions and the coherence between oscillations at each cortical voxel and the extracerebral signals was calculated. Moreover, simulations of coherent point sources were performed.nnnRESULTSnCortico-muscular coherence was correctly localized to the primary hand motor area and the steady-state visual evoked potentials to the primary visual cortex in all subjects and patients. Sophisticated head models tended to yield better localization accuracy than a single sphere model. A Minimum Variance Beamformer (MVBF) provided more accurate and focal localizations of simulated point sources than an L2 Minimum Norm (MN) inverse solution. In the real datasets, the MN maps had less localization error but were less focal than MVBF maps.nnnCONCLUSIONSnEEG can localize coherent cortical networks with sufficient accuracy.

The functional relationship between yawning and vigilance

BACKGROUNDnAlthough yawning is a ubiquitous and phylogenetically old phenomenon, its origin and purpose remain unclear. The study aimed at testing the widely held hypothesis that yawning is triggered by drowsiness and brings about a reversal or suspension of the process of falling asleep.nnnMETHODSnSubjects complaining of excessive sleepiness were spontaneously yawning while trying to stay awake in a quiet and darkened room. Changes in their electroencephalogram (EEG) and heart rate variability (HRV) associated with yawning were compared to changes associated with isolated voluntary body movements. Special care was taken to remove eye blink- and movement-artefacts from the recorded signals.nnnRESULTSnYawns were preceded and followed by a significantly greater delta activity in EEG than movements (p< or =0.008). After yawning, alpha rhythms were attenuated, decelerated, and shifted towards central brain regions (p< or =0.01), whereas after movements, they were attenuated and accelerated (p<0.02). A significant transient increase of HRV occurred after the onset of yawning and movements, which was followed by a significant slow decrease peaking 17s after onset (p<0.0001). No difference in HRV changes was found between yawns and movements.nnnCONCLUSIONSnYawning occurred during periods with increased drowsiness and sleep pressure, but was not followed by a measurable increase of the arousal level of the brain. It was neither triggered nor followed by a specific autonomic activation. Our results therefore confirm that yawns occur due to sleepiness, but do not provide evidence for an arousing effect of yawning.

Magnetoencephalographic imaging of resting-state functional connectivity predicts postsurgical neurological outcome in brain gliomas.

BACKGROUNDnThe removal of brain tumors in perieloquent or eloquent cortex risks causing new neurological deficits in patients. The assessment of the functionality of perilesional tissue is essential to avoid postoperative neurological morbidity.nnnOBJECTIVEnTo evaluate preoperative magnetoencephalography-based functional connectivity as a predictor of short- and medium-term neurological outcome after removal of gliomas in perieloquent and eloquent areas.nnnMETHODSnResting-state whole-brain magnetoencephalography recordings were obtained from 79 consecutive subjects with focal brain gliomas near or within motor, sensory, or language areas. Neural activity was estimated using adaptive spatial filtering. The mean imaginary coherence between voxels in and around brain tumors was compared with contralesional voxels and used as an index of their functional connectivity with the rest of the brain. The connectivity values of the tissue resected during surgery were correlated with the early (1 week postoperatively) and medium-term (6 months postoperatively) neurological morbidity.nnnRESULTSnPatients undergoing resection of tumors with decreased functional connectivity had a 29% rate of a new neurological deficit 1 week after surgery and a 0% rate at 6-month follow-up. Patients undergoing resection of tumors with increased functional connectivity had a 60% rate of a new deficit at 1 week and a 25% rate at 6 months.nnnCONCLUSIONnMagnetoencephalography connectivity analysis gives a valuable preoperative evaluation of the functionality of the tissue surrounding tumors in perieloquent and eloquent areas. These data may be used to optimize preoperative patient counseling and surgical strategy.

Coherent neural oscillations predict future motor and language improvement after stroke

Recent findings have demonstrated that stroke lesions affect neural communication in the entire brain. However, it is less clear whether network interactions are also relevant for plasticity and repair. This study investigated whether the coherence of neural oscillations at language or motor nodes is associated with future clinical improvement. Twenty-four stroke patients underwent high-density EEG recordings and standardized motor and language tests at 2-3 weeks (T0) and 3 months (T1) after stroke onset. In addition, EEG and motor assessments were obtained from a second population of 18 stroke patients. The graph theoretical measure of weighted node degree at language and motor areas was computed as the sum of absolute imaginary coherence with all other brain regions and compared to the amount of clinical improvement from T0 to T1. At T0, beta-band weighted node degree at the ipsilesional motor cortex was linearly correlated with better subsequent motor improvement, while beta-band weighted node degree at Brocas area was correlated with better language improvement. Clinical recovery was further associated with contralesional theta-band weighted node degree. These correlations were each specific to the corresponding brain area and independent of initial clinical severity, age, and lesion size. Findings were reproduced in the second stroke group. Conversely, later coherence increases occurring between T0 and T1 were associated with less clinical improvement. Improvement of language and motor functions after stroke is therefore associated with inter-regional synchronization of neural oscillations in the first weeks after stroke. A better understanding of network mechanisms of plasticity may lead to new prognostic biomarkers and therapeutic targets.See Ward (doi:10.1093/brain/awv265) for a scientific commentary on this article.

Forms of confabulation: Dissociations and associations

Confabulation denotes the emergence of memories of experiences and events which never took place. Whether there are distinct forms with distinct mechanisms is still debated. In this study, we explored 4 forms of confabulation and their mechanisms in 29 amnesic patients. Patients performed tests of explicit memory, executive functions, and two test of orbitofrontal reality filtering (memory selection and extinction capacity in a reversal learning task) previously shown to be strongly associated with confabulations that patients act upon and disorientation. Results indicated the following associations: (1) Intrusions in a verbal memory test (simple provoked confabulations) dissociated from all other forms of confabulation and were not associated with any specific cognitive measure. (2) Momentary confabulations, defined as confabulatory responses to questions and measured with a confabulation questionnaire, were associated with impaired mental flexibility, a tendency to fill gaps in memory, and with one measure of reality filtering. Momentary confabulations, therefore, may emanate from diverse causes. (3) Behaviourally spontaneous confabulation, characterized by confabulations that the patients act upon and disorientation, was strongly associated with failure in the two reality filtering tasks. Behaviourally spontaneous confabulation may be seen as a specific instance of momentary confabulations with a distinct mechanism. (4) A patient producing fantastic confabulations with nonsensical, illogical content had wide-spread cognitive dysfunction and failed in the reality filtering tasks. The results support the presence of truly or partially dissociable types of confabulation with different mechanisms.