Methods for analysis of brain connectivity: An IFCN-sponsored review

The goal of this paper is to examine existing methods to study the “Human Brain Connectome” with a specific focus on the neurophysiological ones. In recent years, a new approach has been developed to evaluate the anatomical and functional organization of the human brain: the aim of this promising multimodality effort is to identify and classify neuronal networks with a number of neurobiologically meaningful and easily computable measures to create its connectome. By defining anatomical and functional connections of brain regions on the same map through an integrated approach, comprising both modern neurophysiological and neuroimaging (i.e. flow/metabolic) brain-mapping techniques, network analysis becomes a powerful tool for exploring structural–functional connectivity mechanisms and for revealing etiological relationships that link connectivity abnormalities to neuropsychiatric disorders. Following a recent IFCN-endorsed meeting, a panel of international experts was selected to produce this current state-of-art document, which covers the available knowledge on anatomical and functional connectivity, including the most commonly used structural and functional MRI, EEG, MEG and non-invasive brain stimulation techniques and measures of local and global brain connectivity.     

In vivo assessment of interictal sarcolemmal membrane properties in hypokalaemic and hyperkalaemic periodic paralysis

ObjectiveHypokalaemic periodic paralysis (HypoPP) is caused by mutations of Ca_v1.1, and Na_v1.4 which result in an aberrant gating pore current. Hyperkalaemic periodic paralysis (HyperPP) is due to a gain-of-function mutation of the main alpha pore of Na_v1.4. This study used muscle velocity recovery cycles (MVRCs) to investigate changes in interictal muscle membrane properties in vivo.MethodsMVRCs and responses to trains of stimuli were recorded in tibialis anterior and compared in patients with HyperPP(n = 7), HypoPP (n = 10), and normal controls (n = 26).ResultsMuscle relative refractory period was increased, and early supernormality reduced in HypoPP, consistent with depolarisation of the interictal resting membrane potential. In HyperPP the mean supernormality and residual supernormality to multiple conditioning stimuli were increased, consistent with increased inward sodium current and delayed repolarisation, predisposing to spontaneous myotonic discharges.ConclusionsThe in vivo findings suggest the interictal resting membrane potential is depolarized in HypoPP, and mostly normal in HyperPP. The MVRC findings in HyperPP are consistent with presence of a window current, previously proposed on the basis of in vitro expression studies. Although clinically similar, HyperPP was electrophysiologically distinct from paramyotonia congenita.SignificanceMVRCs provide important in vivo data that complements expression studies of ion channel mutations.     

The electrically evoked long latency reflex of the biceps brachii muscle: The impact of train stimuli, preceding stimuli, and voluntary muscle contraction

Long latency reflex (LLR) responses were examined over the biceps brachii (BB) at different contraction levels after electrical single or train stimuli over the ipsilateral superficial radial nerve with an inter-stimulus interval of 3ms. Two constant motor waves were present, LLR2 with a peak latency value of 53±4ms and LLR3 with 85±10ms. LLR responses showed a significant increase (twofold) in amplitudes after train stimuli compared to up to a fourfold increase after train stimuli were combined with a weight load of 1.5kg. When LLR were investigated after subsequent (1/s) stimuli by selective averaging, a significant increase in LLR2 amplitude values was seen after the third compared with the first stimulus for trains of 3 stimuli. In the present study, 3 factors exerted an influence on LLR, namely temporal summation of synaptic potentials (by train stimuli), facilitation (with higher stimulus repetition rates), and volition (resulting in muscle contraction). The augmentation behaviour of LLR may be useful for the investigation of central nervous system diseases such as e.g. movement disorders.     

Smartphone-based tactile cueing improves motor performance in Parkinson's disease

IntroductionVisual and auditory cueing improve functional performance in Parkinson's disease (PD) patients. However, audiovisual processing shares many cognitive resources used for attention-dependent tasks such as communication, spatial orientation, and balance. Conversely, tactile cues (TC) may be processed faster, with minimal attentional demand, and may be more efficient means for modulating motor-cognitive performance. In this study we aimed to investigate the efficacy and limitations of TC for modulating simple (heel tapping) and more complex (walking) motor tasks (1) over a range of cueing intervals, (2) with/without a secondary motor task (holding tray with cups of water).MethodsTen PD patients (71 ± 9 years) and 10 healthy controls (69 ± 7 years) participated in the study. TCs was delivered through a smart phone attached to subjects' dominant arm and were controlled by a custom-developed Android application.ResultsPD patients and healthy controls were able to use TC to modulate heel tapping (F(3.8,1866.1) = 1008.1, p < 0.001), and partially modulate walking (F(3.5,1448.7) = 187.5, p < 0.001) tasks. In the walking task, PD patients modulated performance over a narrower range of cueing intervals (R² = 0.56) than healthy controls (R² = 0.84; group difference F(3.5,1448.7) = 8.6, p < 0.001). TC diminished synchronization error associated with performance of secondary motor task during walking in PD patients and healthy controls (main effect of Task (F(1,494) = 0.4; p = 0.527), Task X Group interaction (F(1,494) = 0.5; p = 0.493)).ConclusionThis study expands modalities of TC usage for movement modulation and motor-cognitive integration in PD patients. The smartphone TC application was validated as a user-friendly movement modulation aid.     

The use and limitations of the INR system

This study was undertaken to answer some practical questions physicians and medical directors of clinical laboratories face when they contemplate replacing their high international sensitivity index (ISI) thromboplastins with low ISI ones and using international normalized ratio (INR) in place of prothrombin time ratio (PTR) for monitoring warfarin therapy. To the question of whether low-ISI thromboplastins would produce a prolonged PT on normal patients, the answer is probably no. To the question of the extent of normalization of disparate PTs, determined by high and low ISI thromboplastins, of patients on oral anticoagulants upon the conversion of PTR to INR, the answer is a mixed one. For those whose PTs were 14–20 sec, conversion of PTR to INR would markedly, but not completely, normalize the PTR values. In other words, there would be a lessening of disparity of the PTR after the conversion. For patients whose PTs were >20 sec, conversion of PTR to INR could even widen the disparity seen with the PTR. Finally, when PTs were assayed on different coagulation devices with the same reagent, highly congenial results were obtained. © 1994 Wiley-Liss, Inc.     

INR comparison between the CoaguChek S and a standard laboratory method among patients with self-management of oral anticoagulation

INTRODUCTION: Portable coagulation monitors have been developed to measure International Normalised Ratio (INR) in orally anticoagulated patients using capillary whole blood from a finger stick. Because of unsatisfactory precision of some of the monitors in comparison with laboratory methods new devices are being developed. In the present study we compared INR determination with the CoaguChek S device with a standard laboratory method among patients with self-management of oral anticoagulation (OAC). METHODS: Two hundred and forty-two patients performing self-management of OAC were enrolled into this study. Parallel INR measurements were performed within one hour. Capillary INR measurements (INRcap) were done by the patients with the CoaguChek S and venous INR (INRven) by qualified medical staff using a standard laboratory method. RESULTS: We found a correlation coefficient (r(S)) of 0.85 (95% CI: 0.81-0.88) among the 242 patients between INRven and INRcap. In 84.4% of the INR parallel measurements the difference between the two values was below 0.5 INR units. In only 2 of 242 cases the difference was >1 INR unit (1.1 and 1.3). The slope of the Passing Bablok regression line was 0.91 (95% CI: 0.83-1.0) and the y-intercept 0.06 (95% CI: -0.20-0.25). Agreement between both methods was 90.5% (95% CI: 86.8-94.2) and standard-agreement even 97.1% (95% CI: 95-99.2). CONCLUSIONS: INR measurement with CoaguChek S device by trained patients revealed reliable results in comparison to the values obtained with a standard laboratory method.     

Single-unit discharges in the dorsolateral thalamus of behaving cats: ictal activity.

A new model of experimental epilepsy was designed to study in undrugged, behaving cats the involvement of the thalamus during a cortical epileptiform after-discharge (EAD). EADs were induced by electrical repetitive stimulation applied to the posterior region of an isolated suprasylvian gyrus and allowed to invade the thalamus through a pedicle of white matter connecting areas 5 and 7 of the gyrus to their thalamic target, the dorsolateral nuclei. Extracellular recordings were obtained from 49 dorsolateral cells. Projection to the thalamus of the slowly propagating cortical EAD resulted in a characteristic sequence of events in 88% of the cells. First there occurred an arrest of cellular discharges upon invasion of the anterior suprasylvian cortex (phase I). During phase II, the cell fired slow-wave sleep (SWS)-like bursts strictly timed with surface events. Later (phase III), the cell generated long trains of action potentials on a one-to-one basis with cortical waves; in most cells, partial spike inactivation was seen within each burst. A statistical study indicated that the mean intraburst interspike intervals of SWS and phase II were not significantly different. Surprisingly, a significant increase (P < 0.005) in the mean intraburst interspike interval was found between SWS (4.4 ± 0.4 ms) and phase III (6.0 ± 0.6 ms). Arguments are presented which suggest that the long intraburst interspike intervals are orthodromically generated.     

Conduction of trains of impulses in uniform myelinated fibers: Computed dependence on stimulus frequency

The conduction of trains of action potentials in myelinated fibers was studied using computer simulations based on a modification of the Hodgkin-Huxley equations. Stimulation at short but regular interstimulus intervals caused some stimuli to fail to elicit propagated action potentials.Propagated impulse trains observed close to the stimulation site, elicited by high frequency stimulus trains, took the form of ‘clusters’ of impulses, e.g. doublets or triplets. When these impulse trains were observed at distances farther from the stimulation site, interspike intervals were more uniform. For interstimulus intervals of less than 10 ms, distant intervals between impulses were relatively insensitive to the temporal patterning of impulses at the initiation zone and tended toward regular intervals corresponding to the average interstimulus intervals for propagated stimuli. This tendency toward uniform intervals between impulses was also observed for lower average frequency stimulus trains with irregular interstimulus intervals. Moreover, for the first two stimuli in a train, there was a very strong tendency toward impulse entrainment.These results indicate that intervals between impulses along unbranched myelinated axons are not fixed, but vary according to the site along the conduction pathway where they are observed. The tendency toward entrainment, and regularization of intervals, may represent a factor limiting the frequency with which interval-coded impulses are initiated.