Interhemispheric Delay Research Articles

White-matter degradation and dynamical compensation support age-related functional alterations in human brain.

Structural connectivity of the brain at different ages is analyzed using diffusion-weighted magnetic resonance imaging (MRI) data. The largest decrease of streamlines is found in frontal regions and for long inter-hemispheric links. The average length of the tracts also decreases, but the clustering is unaffected. From functional MRI we identify age-related changes of dynamic functional connectivity (dFC) and spatial covariation features of functional connectivity (FC) links captured by metaconnectivity. They indicate more stable dFC, but wider range and variance of MC, whereas static features of FC did not show any significant differences with age. We implement individual connectivity in whole-brain models and test several hypotheses for the mechanisms of operation among underlying neural system. We demonstrate that age-related functional fingerprints are only supported if the model accounts for: (i) compensation of the individual brains for the overall loss of structural connectivity and (ii) decrease of propagation velocity due to the loss of myelination. We also show that with these 2 conditions, it is sufficient to decompose the time-delays as bimodal distribution that only distinguishes between intra- and inter-hemispheric delays, and that the same working point also captures the static FC the best, and produces the largest variability at slow time-scales.

Symmetry of ictal slow waves may predict the outcomes of corpus callosotomy for epileptic spasms

We aimed to analyse the ictal electrographic changes on scalp electroencephalography (EEG), focusing on high-voltage slow waves (HVSs) in children with epileptic spasms (ES) and tonic spasms (TS) and then identified factors associated with corpus callosotomy (CC) outcomes. We enrolled 17 patients with ES/TS who underwent CC before 20 years of age. Post-CC Engel’s classification was as follows: I in 7 patients, II in 2, III in 4, and IV in 4. Welch’s t-test was used to analyse the correlation between ictal HVSs and CC outcomes based on the following three symmetrical indices: (1) negative peak delay: interhemispheric delay between negative peaks; (2) amplitude ratio: interhemispheric ratio of amplitude values for the highest positive peaks; and (3) duration ratio: interhemispheric ratio of slow wave duration. Ages at CC ranged from 17–237 months. Four to 15 ictal EEGs were analysed for each patient. The negative peak delay, amplitude ratio and duration ratio ranged from 0–530 ms, 1.00–7.40 and 1.00–2.74, respectively. The negative peak delay, amplitude ratio and duration ratio were significantly higher in the seizure residual group (p = 0.017, <0.001, <0.001, respectively). Symmetry of ictal HVSs may predict favourable outcomes following CC for ES/TS.

65. Intracortical and interhemispheric changes induced by Transcutaneous spinal Direct Current Stimulation (tsDCS)

Transcutaneous spinal Direct Current Stimulation (tsDCS) is a new and safe technique for modulating spinal cord excitability. We evaluated the effects of supraspinal and cortical stimulation in healthy subjects before (T0) and at different intervals (T1, T2) after anodal, cathodal and sham tsDCS (20′, 2.0 mA) applied over the thoracic spinal cord (T10–T12). We studied the effects of tsDCS on cortical Silent Period (cSP), paired-pulse short intracortical inhibition (SICI, interstimulus interval = 3 ms), intracortical facilitation (ICF, ISI = 10 ms), interhemispheric motor connectivity and visual processing (ipsilateral Silent Period, iSP; Transcallosal Conduction Time, TCT; hemifield Visual Evoked Potentials, hVEPs). Cathodal tsDCS (c-tsDCS) decreased SICI, while anodal one elicited opposite effects (FDI: p = 0.0023; TA: p = 0.0004); conversely, tsDCS left ICF and cSP duration unchanged. Moreover, anodal tsDCS increased TCT (p < 0.001) and the interhemispheric delay for both the main VEP components (N1: p = 0.0003; P1: p < 0.0001), dampening at the same time iSP duration (APB: p < 0.0001; AH: p = 0.0005; deltoid: p < 0.0001), while cathodal stimulation had opposite effects (p < 0.0001). tsDCS a useful approach, complementary to either SCS or non-invasive brain stimulation techniques, to restore spinal drive through supra-spinal modulating mechanisms; tsDCS could also represent an early rehabilitation strategy in patients with sub-acute brain lesions, when transcranial stimulation is avoided due to safety concerns.

114. An unexpected target of Spinal Direct Current Stimulation: Interhemispheric connectivity in humans

Transcutaneous spinal Direct Current Stimulation (tsDCS) is a noninvasive technique based on the application of weak currents over spinal cord. We studied the effects of tsDCS on interhemispheric connectivity and visual processing by evaluating changes in ipsilateral Silent Period (iSP), Transcallosal Conduction Time (TCT) and hemifield Visual Evoked Potentials (hVEPs), before and at different intervals following sham, anodal and cathodal tsDCS (T10–T12 level, 2.0 mA, 20′). Motor Evoked Potentials (MEPs) were recorded from abductor pollicis brevis (APB), abductor hallucis (AH) and deltoid muscles. hVEPs were recorded bilaterally by reversal of a horizontal square wave grating. Anodal tsDCS increased TCT (p < 0.001) and the interhemispheric delay for both the main VEP components (N1: p = 0.0003; P1: p < 0.0001), dampening iSP duration (APB: p < 0.0001; AH: p = 0.0005; deltoid: p < 0.0001), while cathodal stimulation elicited opposite effects (p < 0.0001). tsDCS would be a promising therapeutic tool in managing a number of human diseases characterized by an impaired interhemispheric processing, with anodal stimulation leading to a functional disconnection between hemispheres. It could also be helpful as an early rehabilitation strategy in patients with acute brain lesions, when other non-invasive brain stimulation techniques are not indicated due to safety concerns.

Characterization of ictal slow waves in epileptic spasms.

We characterized the clinico-neurophysiological features of epileptic spasms, particularly focusing on high-voltage slow waves during ictal EEG. We studied 22 patients with epileptic spasms recorded during digital video-scalp EEG, including five individuals who still had persistent spasms after callosotomy. We analysed the duration, amplitude, latency to onset of electromyographic bursts, and distribution of the highest positive and negative peaks of slow waves in 352 spasms. High-voltage positive slow waves preceded the identifiable muscle contractions of spasms. The mean duration of these positive waves was 569±228m, and the mean latency to electromyographic onset was 182±127m. These parameters varied markedly even within a patient. The highest peak of the positive component was distributed in variable regions, which was not consistent with the location of lesions on MRI. The peak of the negative component following the positivity was distributed in the neighbouring or opposite areas of the positive peak distribution. No changes were evident in the pre- or post-surgical distributions of the positive peak, or in the interhemispheric delay between both hemispheres, in individuals with callosotomy. Our data imply that ictal positive slow waves are the most common EEG changes during spasms associated with a massive motor component. Plausible explanations for these widespread positive slow waves include the notion that EEG changes possibly reflect involvement of both cortical and subcortical structures.

An unexpected target of spinal direct current stimulation: Interhemispheric connectivity in humans

BackgroundTranscutaneous spinal Direct Current Stimulation (tsDCS) is a noninvasive technique based on the application of weak electrical currents over spinal cord. New methodWe studied the effects of tsDCS on interhemispheric motor connectivity and visual processing by evaluating changes in ipsilateral Silent Period (iSP), Transcallosal Conduction Time (TCT) and hemifield Visual Evoked Potentials (hVEPs), before (T0) and at a different intervals following sham, anodal and cathodal tsDCS (T9-T11 level, 2.0mA, 20′). Motor Evoked Potentials (MEPs) were recorded from abductor pollicis brevis (APB), abductor hallucis (AH) and deltoid muscles. hVEPs were recorded bilaterally by reversal of a horizontal square wave grating with the display positioned in the right hemifield. ResultsAnodal tsDCS increased TCT (p<0.001) and the interhemispheric delay for both the main VEP components (N1: p=0.0003; P1: p<0.0001), dampening at the same time iSP duration (APB: p<0.0001; AH: p=0.0005; deltoid: p<0.0001), while cathodal stimulation elicited opposite effects (p<0.0001). DiscussiontsDCS modulates interhemispheric processing in a polarity-specific manner, with anodal stimulation leading to a functional disconnection between hemispheres. tsDCS would be a new promising therapeutic tool in managing a number of human diseases characterized by an impaired interhemispheric balance, or an early rehabilitation strategy in patients with acute brain lesions, when other non-invasive brain stimulation techniques (NIBS) are not indicated due to safety concerns.

Layer-specific interhemispheric functional connectivity in the somatosensory cortex of rats: resting state electrophysiology and fMRI studies.

The spontaneous cerebral hemodynamic fluctuations observed during the resting state have been frequently visualized using functional magnetic resonance imaging (rsfMRI). However, the neuronal populations and neuroelectric characteristics underlying the functional connectivity of cerebrohemodynamic activities are poorly understood. We investigated the characteristics of bi-hemispheric functional connectivity via electrophysiology and rsfMRI in the primary sensory cortex of rats anesthetized by α-chloralose. Unlike the evoked responses, the spontaneous electrophysiological activity was concentrated in the infragranular layers and could be classified into subtypes with distinctive current sources and sinks. Both neuroelectric and rsfMRI signals were interhemispherically correlated in a layer-specific manner, suggesting that there are independent neural inputs to infragranular and granular/supragranular layers. The majority of spontaneous electrophysiological activities were bilaterally paired with delays of up to ~50ms between each pair. The variable interhemispheric delay implies the involvement of indirect, multi-neural pathways. Our findings demonstrated the diverse activity patterns of layer-specific electrophysiological substrates and suggest the recruitment of multiple, non-specific brain regions in construction of interhemispheric functional connectivity.

Cortical representation of different motor rhythms during bimanual movements

The cortical control of bimanual and unimanual movements involves complex facilitatory and inhibitory interhemispheric interactions. We analysed the part of the cortical network directly related to the motor output by corticomuscular (64 channel EEG-EMG) and cortico-cortical (EEG-EEG) coherence and delays at the frequency of a voluntarily maintained unimanual and bimanual rhythm and in the 15-30-Hz band during isometric contractions. Voluntary rhythms of each hand showed coherence with lateral cortical areas in both hemispheres and occasionally in the frontal midline region (60-80% of the recordings and 10-30%, respectively). They were always coherent between both hands, and this coherence was positively correlated with the interhemispheric coherence (p<0.01). Unilateral movements were represented mainly in the contralateral cortex (60-80 vs. 10-30% ipsilateral, p<0.01). Ipsilateral coherence was more common in left-hand movements, paralleled by more left-right muscle coherence. Partial corticomuscular coherence most often disappeared (p<0.05) when the contralateral cortex was the predictor, indicating a mainly indirect connection of ipsilateral/frontomesial representations with the muscle via contralateral cortex. Interhemispheric delays had a bimodal distribution (1-10 and 15-30ms) indicating direct and subcortical routes. Corticomuscular delays (mainly 12-25ms) indicated fast corticospinal projections and musculocortical feedback. The 15-30-Hz corticomuscular coherence during isometric contractions (60-70% of recordings) was strictly contralaterally represented without any peripheral left-right coherence. Thus, bilateral cortical areas generate voluntary unimanual and bimanual rhythmic movements. Interhemispheric interactions as detected by EEG-EEG coherence contribute to bimanual synchronization. This is distinct from the unilateral cortical representation of the 15-30-Hz motor rhythm during isometric movements.

Cerebral Haemodynamic Disturbances in Patients with Moderate Carotid Artery Stenosis

Objective Dynamic MR perfusion imaging can detect cerebral perfusion deficits resulting from severe internal carotid artery (ICA) stenosis. It is unknown, however, whether moderate ICA stenosis (50–69%) also causes haemodynamic disturbance. We investigated whether cerebral perfusion deficits were detectable in patients with moderate ICA stenosis. Methods Eighteen patients underwent T 2* weighted cerebral MR perfusion imaging with a gadolinium based contrast agent. Differences in mean time to peak (mTTP) and relative cerebral blood volume (rCBV) between cerebral hemispheres were calculated for middle cerebral artery territory regions by a reader blinded to the angiographic and clinical findings. Results There were significant differences in mTTP between cerebral hemispheres in 15 patients with a mean inter-hemispheric delay in mTTP of 0.49 s (95% confidence intervals, 0.25 and 0.72 s) which was statistically significant ( p<0.001). In 1 patient with bilateral moderate stenosis there was no difference in mTTP. Conclusions Moderate ICA stenosis results in significant ipsilateral cerebral perfusion delays detectable by dynamic susceptibility MRI. Follow-up studies might reveal whether these delays improve following carotid endarterectomy.

Is a cortical spike discharge "transferred" to the contralateral cortex via the corpus callosum?: An intraoperative observation of electrocorticogram and callosal compound action potentials.

By means of the intraoperative electrophysiologic observation, we reevaluated the "transfer" theory that a transcallosal volley invoked by a cortical spike discharge in one hemisphere directly causes its contralateral counterpart via the corpus callosum (CC). Twenty-six patients who underwent corpus callosotomy were the subjects of this study. Intraoperatively, electrocorticograms from both hemispheres were simultaneously monitored with callosal compound action potentials (CCAPs) from the CC. Analysis was conducted on (a) the interhemispheric delay of bilaterally synchronous spike-and-wave discharges (BSSWs), and (b) the chronological relation between BSSWs and CCAPs. The side of prior spike discharges was never fixed but was occasionally reversed. Interhemispheric delays between the BSSWs were not constant, regardless of direction, and fluctuated in all patients. Most of the interhemispheric delays were distributed within 20 ms with a mode of 0 ms. The waveform of the CCAP was characterized by slow-rising negative potential change that attained its peak after a cortical spike discharge. These findings were identical in all the patients regardless of whether the BSSWs were changed or unchanged after callosotomy. If the "transfer" role of the CC is true, interhemispheric delays between BSSWs must be longer than interhemispheric axonal conduction time (about 20 ms), and a preceding cortical spike discharge must produce a CCAP and then a contralateral one in order of time. However, this hypothesis was not confirmed in the present study. We propose the interhemispheric recruitment of the epileptogenic state as a different role of the CC on epileptogenesis.

A biologically motivated and analytically soluble model of collective oscillations in the cortex. II. Application to binding and pattern segmentation.

Feature linking and pattern separation are shown to be performed as simultaneous processes by a highly connected auto-associative network of spiking neurons (spike response model). In principle, many (e.g., with nine) patterns can be separated, but with a biological set of parameters the number is limited to four. The patterns have been learned by an asymmetric hebbian rule that can handle a low activity which may vary from pattern to pattern (in a range between 4% and 7%). Spikes are generated by a threshold process and--with some delay--transmitted to postsynaptic neurons. There they evoke an excitatory or inhibitory postsynaptic potential (EPSP or IPSP). Spike emission is followed by an absolute refractory period (1 ms) and activates an inhibitory delay loop that prevents continuous firing. Three different network topologies are discussed, i.e., a structureless fully connected system, a network composed of two 'hemispheres', and finally a hierarchical network with four subsystems that represent different 'functions' and interact via feedforward and feedback connections. Functional feedback turns out to be essential for context-sensitive binding. The coherence between the two hemispheres is dependent on the interhemispheric delays. If these are on average too large, the two hemispheres oscillate coherently by themselves but phase-shifted by half a period with respect to each other.

Time Is of the Essence: A Conjecture that Hemispheric Specialization Arises from Interhemispheric Conduction Delay

Tomasch (1954) and Aboitiz et al. (1992) found the majority of the fibers of the human corpus callosum are under 1 micron in diameter. Electron microscopic studies of Swadlow et al. (1980) and the detailed study of LaMantia and Rakic (1990a) on macaques show the average size of the myelinated callosal axons also to be less than 1 micron. In man, the average-sized myelinated fiber interconnecting the temporal lobes would have a one-way, interhemispheric delay of over 25 msec. Thus, finely detailed, time-critical neuronal computations (i.e., tasks that strain the capacity of the callosum and hence could not be handled by just the larger fibers) would be performed more quickly via shorter and faster intrahemispheric circuits. While one transit across the commissural system might yield tolerable delays, multiple passes as in a system involving "setting" would seem prohibitively slow. We suggest that these temporal limits will be avoided if the neural apparatus necessary to perform each high-resolution, time-critical task is gathered in one hemisphere. If the, presumably overlapping, neural assemblies needed to handle overlapping tasks are clustered together, this would lead to hemispheric specialization. The prediction follows that the large brains of mammals such as elephants and cetaceans will also manifest a high degree of hemispheric specialization.

Interhemispheric communication following unilateral cerebrovascular lesions

39 patients with a single small cerebrovascular lesion (20 in the right, 19 in the left hemisphere) were subjected to a simple reaction time (RT) task with visual stimuli flashed to the visual field either ipsilateral or contralateral to the cerebral lesion. The subject responded always with the ipsilateral hand. The crossed-uncrossed difference (CUD), i.e. the RT when both stimulus and response occur on the same side minus the RT when stimulus and response occur on opposite sides, is assumed to assess the transit time of information through callosal fibers, and in normal people is about 3-5 msec. In our patients the mean CUD, expressed as the difference between contralateral and ipsilateral responses, was 20 msec. Patients with parietal lesions had still longer CUDs, 37 msec on the average. There was no statistical difference in CUDs between right and left brain-damaged patients. The CUD in brain-damaged patients was of the same order of magnitude as that found in acallosal or split-brain patients. Nonetheless, the present findings are interpreted as reflecting the intrahemispheric rather than the interhemispheric delay in information transmission, with the possible additive effect of an asymmetrical orienting of attention.

INTRAHEMISPHERIC AND INTERHEMISPHERIC SPREAD OF CEREBRAL CORTICAL MYOCLONIC ACTIVITY AND ITS RELEVANCE TO EPILEPSY

Nine patients with cortical myoclonus (due to various pathologies), in whom movement of one limb induced bilateral limb jerks, were investigated. Three of these patients also had bilateral cortical reflex myoclonus when one limb was subjected to an electrical stimulus. The relative latencies to onset of electromyogram (EMG) activity in various ipsilateral and contralateral muscles in action and reflex jerks were studied. Bilateral reflex and action jerks induced by unilateral electrical stimuli or limb movement were not synchronous. EMG activity was usually recorded in the muscles of the stimulated or moved limb, before being recorded in the homologous muscles of the contralateral limb. It is proposed that this difference in relative latency between homologous muscles represents the interhemispheric delay due to the transcallosal spread of excitation from one sensorimotor cortex to the opposite cerebral cortex. The relative latencies of muscles on the same side of the body reflected not only the differences in efferent delays from the motor cortex via spinal cord and peripheral nerves, but also delays due to the spread of myoclonic activity within the sensorimotor cortex itself. This intrahemispheric spread followed a grossly somatotopic pattern. It is suggested that this spread involves cortico-cortical pathways. The additional delay due to spread of activity from hand to leg area of the sensorimotor cortex was about 10 ms in the first active hemisphere, in both generalized reflex and action jerks. The delays due to somatotopic spread of activity in the opposite later activated hemisphere were shorter. The tendency for spread of excitation through callosal and cortico-cortical pathways is an additional pathophysiological abnormality in some patients with cortical myoclonus, and may be important in the generalization of seizures seen in these patients.

Visual evoked potentials in a patient with prosopagnosia

Visual evoked potentials (VEPs) were recorded from a 53-year-old man with prosopagnosia during presentation of slides of known and unknown faces and under two control conditions. ANOVA comparisons with a normal male group showed no differences in P100 amplitude, P300 amplitude or P300 latency. There were no significant evoked potential differences between the patient and controls specifically related to the face conditions. There was, however, a significant delay in the latency of P100 from both hemispheres during all types of stimuli. This prolonged latency was asymmetrical, showing a right sided emphasis with the control conditions: pattern reversal and slides of geometric designs. This finding, of a dissociation in the interhemispheric delay, provides physiological evidence of stimulus-specific organisation at an early, sensory level. The fact that the P100 component showed a marked delay, yet P300 fell within normal limits for amplitude and latency, suggests that this patient's problem lies at a perceptual level.

An electroretinal and visual evoked potential study in Friedreich's ataxia.

We made an electroretinographic (ERG) and visual evoked potential (VEP) study of 12 patients with Friedreich's ataxia whose diagnosis was established using the Quebec diagnostic criteria. ERGs and VEPs were elicited to the same stimulating conditions. Flash evoked luminance changes and pattern-specific evoked potentials to check and diamond stimuli were used. Statistical analysis of the data was made using independent sample t-tests. Significant VEP delays were present under all test conditions. The presence of significant interocular and interhemispheric delays as well as evidence of abnormal temporal dispersion of the VEP response suggest there to be both diffuse anterior visual system disease and retrochiasmal involvement in Friedreich's ataxia. The implicit times of the ERG b-waves were statistically within normal limits but the waveforms were of low amplitude and deformed and there were significant interocular implicit time differences. These ERG results suggest there are retinal conduction abnormalities in Friedreich's ataxia which possibly play a role in the genesis of the abnormal VEPs.