Interhemispheric transfer following callosotomy in humans: role of the superior colliculus

It is now common knowledge that the total surgical section of the corpus callosum (CC) and of the other forebrain commissures prevents interhemispheric transfer (IT) of a host of mental functions. By contrast, IT of simple sensorimotor functions, although severely delayed, is not abolished, and an important question concerns the pathways subserving this residual IT. To answer this question we assessed visuomotor IT in split-brain patients using the Poffenberger paradigm (PP), that is, a behavioral paradigm in which simple reaction time (RT) to visual stimuli presented to the hemifield ipsilateral to the responding hand is compared to stimuli presented to the contralateral hemifield, a condition requiring an IT. We tested the possibility that the residual IT is mediated by the collicular commissure interconnecting the two sides of the superior colliculus (SC). To this purpose, we used short-wavelength visual stimuli, which in neurophysiological studies in non-human primates have been shown to be undetectable by collicular neurons. We found that, in both totally and partially callosotomised patients, IT was considerably longer with S-cone input than with L-cone input or with achromatic stimuli. This was not the case in healthy participants in whom IT was not affected by color. These data clearly show that the SC plays an important role in IT of sensorimotor information in the absence of the corpus callosum.     

Generation of co-speech gestures based on spatial imagery from the right-hemisphere: evidence from split-brain patients

It has been claimed that the linguistically dominant (left) hemisphere is obligatorily involved in production of spontaneous speech-accompanying gestures (Kimura, 1973a, 1973b; Lavergne and Kimura, 1987). We examined this claim for the gestures that are based on spatial imagery: iconic gestures with observer viewpoint (McNeill, 1992) and abstract deictic gestures (McNeill, et al. 1993). We observed gesture production in three patients with complete section of the corpus callosum in commissurotomy or callosotomy (two with left-hemisphere language, and one with bilaterally represented language) and nine healthy control participants. All three patients produced spatial-imagery gestures with the left-hand as well as with the right-hand. However, unlike healthy controls and the split-brain patient with bilaterally represented language, the two patients with left-hemispheric language dominance coordinated speech and spatial-imagery gestures more poorly in the left-hand than in the right-hand. It is concluded that the linguistically non-dominant (right) hemisphere alone can generate co-speech gestures based on spatial imagery, just as the left-hemisphere can.     

Sensory and motor involvement in the enhanced redundant target effect: A study comparing anterior- and totally split-brain individuals

This study investigated the redundant target effect (RTE) in partial split-brain (anterior section sparing the splenium), total split-brain, and neurologically intact individuals. All completed an RTE protocol in which targets were presented on the midline or in an inter- or intrahemispheric manner. Stimuli of different nature (luminance, equiluminant colour, and global motion) were used separately in three experiments in order to investigate the contribution of subcortical versus cortical pathways. Despite the preservation of the splenium (the portion of the corpus callosum assumed to transfer visual information), partial split-brain individuals showed an enhanced RTE pattern as compared to neurologically intact individuals. Total split-brain individuals showed a tendency toward larger RTEs with the luminance stimuli than with the colour and motion stimuli, whereas this was not the case for partial split-brain individuals, suggesting a contribution of the posterior portion of the corpus callosum in the RTE. It is therefore likely that both sensory and motor processes contribute to the enhanced RTE in split-brain individuals.     

Intraoperative subdural low-noise EEG recording of the high frequency oscillation in the somatosensory evoked potential

Objective

The detectability of high frequency oscillations (HFO, >200 Hz) in the intraoperative ECoG is restricted by their low signal-to-noise ratio (SNR). Using the somatosensory evoked HFO, we quantify how HFO detectability can benefit from a custom-made low-noise amplifier (LNA).

Synchronization clusters of interictal activity in the lateral temporal cortex of epileptic patients: intraoperative electrocorticographic analysis

OBJECTIVE: Drug-resistant temporal lobe epilepsy (TLE) can be treated by tailored surgery guided by electrocorticography (ECoG). Although its value is still controversial, ECoG activity can provide continuous information on intracortical interactions that may be useful to understand the pathophysiology of TLE. The goal of this study is to characterize local interactions in multichannel ECoG recordings of the lateral cortex of TLE patients using three synchronization measures and to link this information with surgical outcome. METHODS: Intraoperative ECoG recordings from 29 TLE patients were obtained using grids of 20 electrodes (4 x 5) covering regions T1, T2, and T3 of the lateral temporal lobe. Linear correlation, mutual information, and phase synchronization were calculated to quantify lateral intracortical interactions. Surrogate data files were generated to test results statistically. RESULTS: By distributing locally the interactions between the electrodes, we characterized the spatial patterns of ECoG activity. We found clusters of synchronized activity at specific areas of the lateral temporal cortex in most patients. Methodologically, linear correlation and phase synchronization performed better than mutual information for cluster discrimination. ROC analysis suggested that surgical removal of sharply defined synchronization clusters correlated with seizure control. CONCLUSIONS: Our results show that synchronous intraoperative ECoG activity emerges from specific cortical areas that are highly differentiated from the rest of the temporal cortex. This suggests that synchronization analysis could be used to functionally map into the temporal cortex of TLE patients. Moreover, our results suggest that these sites might be involved in the circuits that participate in clinical seizures.     

The effect of callosotomy on testicular steroidogenesis in hemiorchidectomized rats: a pituitary-independent regulatory mechanism

In recent years, increasing number of data indicate that cerebral structures exert a direct, pituitary-independent, neural regulatory action on the endocrine glands. In addition, both experimental and clinical observations indicate functional asymmetry of the control system. Therefore, the objective of the present study was to study the effect of callosotomy on testicular steroidogenesis and serum gonadotrop concentrations in rats subjected to left- or right-sided orchidectomy. In animals underwent callosotomy plus left-sided orchidectomy the basal testosterone secretion in vitro of the remaining (right) testis was significantly higher than that of intact controls, and of rats subjected to sham surgery plus left orchidectomy. In contrast, either sham operation or callosotomy plus right-sided orchidectomy did not interfere with testicular steroidogenesis. Sham surgery or callosotomy plus left orchidectomy induced a significant rise in serum follicle-stimulating hormone concentration while right orchidectomy combined either with sham surgery or callosotomy did not alter this parameter. There was no statistically significant difference between experimental groups in serum testosterone and luteinizing hormone concentrations. The results indicate the involvement of the corpus callosum in a pituitary-independent neural control of testicular steroidogenesis. The data further suggest a different response in steroidogenesis of the left and the right testis following hemicastration and callosotomy.     

Source activity in the human secondary somatosensory cortex depends on the size of corpus callosum

If corpus callosum (CC) mediates the activation of the secondary somatosensory area (SII) ipsilateral to the side of stimulation, then the peak latencies of the contra- and ipsilateral SII activity as well as the amplitude of the ipsilateral SII activity should correlate with the size of CC. Innocuous electrical stimuli of five different intensities were applied to the ventral surface of the right index finger in 15 right-handed men. EEG was recorded using 82 closely spaced electrodes. The size of CC and of seven callosal regions was measured from the mid-sagittal slice of a high-resolution anatomical MRI. The activation in the contralateral and ipsilateral SII was evaluated using spatio-temporal source analysis. At the strongest stimulus intensity, the size of the intermediate part of the callosal truncus correlated negatively with the interpeak latency of the sources in ipsi- and contralateral SII (r = -0.83, P < 0.01). Stepwise regression analysis showed that the large size of the intermediate truncus of CC was paralleled by a latency reduction of peak activity of the ipsilateral SII, whereas both contra- and ipsilateral peak latencies were positively correlated. The peak amplitude of the ipsilateral SII source correlated positively with the size of the intermediate truncus of CC, and with the peak amplitudes of sources in the primary somatosensory cortex (SI) and in the mesial frontal cortex. The results suggest that in right-handed neurologically normal men, the size of the intermediate callosal truncus contributes to the timing and amplitude of ipsilateral SII source activity.     

Changes in the electrocorticogram after implantation of intracranial electrodes in humans: The implant effect

Objective

Subacute and long-term electrocorticographic (ECoG) changes in ambulatory patients with depth and cortical strip electrodes were evaluated in order to determine the length of the implant effect.

Abnormal fronto-parietal coupling of brain rhythms in mild Alzheimer's disease: a multicentric EEG study

Cholinergic deafferentation/recovery in rats mainly impinges on the fronto‐parietal coupling of brain rhythms [D. P. Holschneider et al. (1999) Exp. Brain Res., 126 , 270–280]. Is this reflected by the functional coupling of fronto‐parietal cortical rhythms at an early stage of Alzheimer's disease (mild AD)? Resting electroencephalographic (EEG) rhythms were studied in 82 patients with mild AD and in control subjects, such as 41 normal elderly (Nold) subjects and 25 patients with vascular dementia (VaD). Patients with AD and VaD had similar mini‐mental state evaluation scores of 17–24. The functional coupling was estimated by means of the synchronization likelihood (SL) of the EEG data at electrode pairs, accounting for linear and non‐linear components of that coupling. Cortical rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha (1 8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), beta 2 (20–30 Hz) and gamma (30–40 Hz). A preliminary data analysis (Nold) showed that surface Laplacian transformation of the EEG data reduced the values of SL, possibly because of the reduction of influences due to head volume conduction. Therefore, the final analysis was performed on Laplacian‐transformed EEG data. The SL was dominant at alpha 1 band in all groups. Compared with the Nold subjects, patients with VaD and mild AD presented a marked reduction of SL at both fronto‐parietal (delta–alpha) and inter‐hemispherical (delta–beta) electrode pairs. The feature distinguishing the patients with mild AD with respect to patients with VaD groups was a more prominent reduction of fronto‐parietal alpha 1 SL. These results suggest that mild AD is characterized by an abnormal fronto‐parietal coupling of the dominant human cortical rhythm at 8–10.5 Hz.     

Drawing on mind's canvas: differences in cortical integration patterns between artists and non-artists

Our primary question was to learn whether mentally composing drawings of their own choice produce different brain electric features in artists and laymen. To this purpose, we studied multichannel electroencephalograph (EEG) signals from two broad groups (all participants were females): artists (professionally trained in visual arts) and non-artists (without any training in art). To assess the underlying synchronization, which is assumed to be the platform for general cognitive integration between different cortical regions, three measures inspired by nonlinear dynamical system theory were applied as follows: (1) index based on generalized synchronization; (2) index based on mean phase coherence; and (3) index of phase synchrony based on entropy. Results consistent over all three measures were as follows: comparing the tasks to rest, the artists showed significantly stronger short- and long-range delta band synchronization, whereas the non-artists showed enhancement in short-range beta and gamma band synchronization primarily in frontal regions; comparing the two groups during the tasks, the artists showed significantly stronger delta band synchronization and alpha band desynchronization than did the non-artists. Strong right hemispheric dominance in terms of synchronization was found in the artists. In artists, the higher synchrony in the low-frequency band is possibly due to the involvement of a more advanced long-term visual art memory and to extensive top-down processing. The results demonstrate that in artists, patterns of functional cooperation between cortical regions during mental creation of drawings were significantly different from those in non-artists.     

Acute interactive effects of MK-801 and morphine on cortical EEG and EEG power spectra in rats

The interaction between MK-801 and morphine-induced effects on cortical electroencephalography (EEG) was investigated. Rats were administered one of five MK-801 doses (IP) prior to morphine (IV). MK-801 dose-dependently increased morphine-induced global spectral power, duration of morphine-induced EEG bursts and latency to sleep onset, and decreased morphine-induced mean frequency, mobility, complexity, and edge frequency. MK-801 pretreatment shifted the relative distribution of total power to the left. Significant interaction effects were found for all spectral parameters except peak frequency. A second group of rats was administered MK-801 prior to an increasing cumulative morphine dose. MK-801 increased maximal morphine effects on all spectral parameters except peak frequency. The results are in agreement with those of recent analgesia and in vitro studies in spinal neurons, and support observations of a synergistic interaction between effects of NMDA antagonism and morphine. These data further suggest that the component of cortical EEG that is produced by mu-opioid- and NMDA-receptor interactive effects may be dominated by an inhibitory effect of morphine on NMDA receptor activity.     

Interhemispheric visuo-motor integration in humans: the effect of redundant targets

We used event-related functional magnetic resonance imaging (fMRI) to investigate the functional locus of response facilitation during parallel visuo-motor processing. In a simple reaction-time task, subjects typically respond faster to two copies of the same stimulus than to a single copy. This facilitation, called the redundant-target effect, can occur at three functional levels: perceptual, 'cognitive' or motor. Normal right handers were studied while performing a simple reaction-time task to unilateral (left or right) and bilateral light flashes. Subjects were instructed to respond with their right index finger. Reaction times were faster to bilateral light flashes than to unilateral ones, even right flashes. Greater fMRI signal for bilateral stimuli compared to unilateral ones was observed in the left precentral and postcentral gyrus, and in the right precentral gyrus. A greater fMRI signal for bilateral and for unilateral left stimuli, compared to unilateral right stimuli, was observed in an area of the right intraparietal sulcus. These results support the hypothesis that the functional locus of response facilitation during parallel visuo-motor processing is premotor.     

Bilateral coupling in learned blinking: effects of lesion aimed at callosal disconnection of the cat motor cortex

The effects of selective transection of the rostralmost portion of the corpus callosum, which contains fibers interconnecting the motor cortices of the two hemispheres, on interocular temporal coupling in the initiation of learned symmetrical blinking were examined in 5 cats trained to blink in response to a 500-ms tone paired with 100-ms airpuffs randomly delivered to either eye (alternate airpuff; 3 animals) or simultaneously directed to both eyes (bilateral airpuff; 2 animals) 400 ms after tone onset. Lesioning had no effect on ability to respond, but did cause a significant increase in the mean conditioned response (CR) latencies of both eyes in all subjects. In the intact cats, a statistically significant difference between the mean CR latencies of the two eyes (hereafter called side superiority) was found in three animals, two of which exhibited superiority of the left eye. After lesioning, it was found that the right eye proved superior to the left eye in four subjects. Both before and after lesioning, side superiority was not due to the ability of one eye to give CRs consistently shorter than those of the other eye, but it crucially depended on the higher proportion of trials in which the superior eye led. A linear correlation between CR latencies of the right and left eye was found in all animals both before and after lesioning. It is suggested that subsequent to lesioning aimed at callosal disconnection of the motor cortex, the effects on initiation of learned symmetrical blinking are the consequences of withdrawal of both bilaterally balanced modulatory influences to both eyes and lateralized modulatory influences to the left eye.     

Experimental inhibition of peroxisomal beta-oxidation in rats: influence on brain myelination

Oral administration of thioridazine, an inhibitor of peroxisomal beta-oxidation, to normal rats from weaning till day 60 causes a small increase of the very long chain fatty acid C26 in brain lipids. Myelination in the brain is decreased. In the genu of the corpus callosum the ratio of non-myelinated/myelinated axons is increased. In the commissura anterior the myelin sheaths of the axons are significantly thinner in treated than in control animals. Undernourishment caused by the drug is minimal in this experiment. Area and total DNA of glial nuclei are unaltered in both the genu and the commissura anterior of treated rats. The distribution of chromatin (texture), however, shows small differences in the corpus callosum.     

Effects of antiepileptic drugs on cortical excitability in humans: A TMS‐EMG and TMS‐EEG study

Brain responses to transcranial magnetic stimulation (TMS) recorded by electroencephalography (EEG) are emergent noninvasive markers of neuronal excitability and effective connectivity in humans. However, the underlying physiology of these TMS‐evoked EEG potentials (TEPs) is still heavily underexplored, impeding a broad application of TEPs to study pathology in neuropsychiatric disorders. Here we tested the effects of a single oral dose of three antiepileptic drugs with specific modes of action (carbamazepine, a voltage‐gated sodium channel (VGSC) blocker; brivaracetam, a ligand to the presynaptic vesicle protein VSA2; tiagabine, a gamma‐aminobutyric acid (GABA) reuptake inhibitor) on TEP amplitudes in 15 healthy adults in a double‐blinded randomized placebo‐controlled crossover design. We found that carbamazepine decreased the P25 and P180 TEP components, and brivaracetam the N100 amplitude in the nonstimulated hemisphere, while tiagabine had no effect. Findings corroborate the view that the P25 represents axonal excitability of the corticospinal system, the N100 in the nonstimulated hemisphere propagated activity suppressed by inhibition of presynaptic neurotransmitter release, and the P180 late activity particularly sensitive to VGSC blockade. Pharmaco‐physiological characterization of TEPs will facilitate utilization of TMS‐EEG in neuropsychiatric disorders with altered excitability and/or network connectivity.     

Effects of sleep deprivation on cortical excitability in patients affected by juvenile myoclonic epilepsy: a combined transcranial magnetic stimulation and EEG study

OBJECTIVE: To investigate the effect of sleep deprivation on corticospinal excitability in patients affected by juvenile myoclonic epilepsy (JME) using different transcranial magnetic stimulation (TMS) parameters. METHODS: Ten patients with JME and 10 normal subjects underwent partial sleep deprivation. Motor threshold (MT), motor evoked potential amplitude (MEP), and silent period (SP) were recorded from the thenar eminence (TE) muscles. Short latency intracortical inhibition (SICI) and short latency intracortical facilitation (SICF) were studied using paired magnetic stimulation. TMS was performed before and after sleep deprivation; EEG and TMS were performed simultaneously. RESULTS: In patients with JME, sleep deprivation induced a significant decrease in SICI and an increase in SICF, which was associated with increased paroxysmal activity. A significant decrease in the MT was observed. No significant changes in any TMS parameters were noted in normal subjects after sleep deprivation. The F wave was unchanged by sleep deprivation in both control subjects and in patients with JME. CONCLUSIONS: In patients with JME, sleep deprivation produces increases in corticospinal excitability in motor areas as measured by different TMS parameters.     

Coherence between the hippocampus and anterior thalamic nucleus as a tool to improve the effect of neurostimulation in temporal lobe epilepsy: An experimental study

BackgroundAlthough the mechanisms by which deep brain stimulation (DBS) modifies the activity of the ictal network are mostly undefined, recent studies have suggested that DBS of the anterior nucleus of the thalamus (ANT) can be an effective treatment for mesial temporal lobe epilepsy (MTLE) when resective surgery cannot be performed. In a nonhuman primate (NHP) model of MTL seizures, we showed that the ANT was actively involved during interictal and ictal periods through different patterns and that the hippocampus (HPC) and ANT synchronously oscillate in the high beta-band during seizures.ObjectiveBased on those findings, we evaluated whether the frequency of stimulation is an important parameter that interferes with seizures and how to adapt stimulation protocols to it.MethodsWe investigated the effects of low-frequency (40 Hz - determined as the ictal frequency of correlation between structures) and high-frequency (130 Hz - as commonly used in clinic) ANT stimulation in three monkeys in which MTLE seizures were initiated.ResultsLow-frequency stimulation had a strong effect on the number of seizures and the total time spent in seizure, whereas high-frequency stimulation had no effect. The coherence of oscillations between the HPC and the ANT was significantly correlated with the success of low-frequency stimulation: the greater the coherence was, the greater the antiepileptic effect of ANT-DBS.ConclusionOur results suggest that low-frequency stimulation is efficient in treating seizures in a nonhuman primate model. More importantly, the study of the coherence between the ANT and HPC during seizures can help to predict the anti-epileptic effects of ANT stimulation. Furthermore, the DBS paradigm could be customized in frequency for each patient on the basis of the coherence spectral pattern.     

Acute and long-term effects of the 5-HT2 receptor antagonist ritanserin on EEG power spectra,motor activity,and sleep: changes at the light-dark phase shift

Parallel effects of a single injection of the 5-HT(2) receptor antagonist ritanserin on EEG power spectra, sleep and motor activity were measured for a 20-h period in freely moving Sprague-Dawley rats. Ritanserin (0.3 mg/kg, i.p.), administered at light onset (passive phase), caused an immediate transient increase in the EEG power density in the low frequency range (0.25-6 Hz, mainly delta activity) and a depression in the high frequency range (27-30 Hz) accompanied by a decrease in vigilance and light slow wave sleep (SWS-1), intermediate stage of sleep and increase in deep slow wave sleep (SWS-2) compared to control treatment. All these effects were over 8 h after the injection. Twelve hours after the injection, at dark onset (active phase), there was a marked increase in vigilance and motor activity and decrease in SWS-1 and spindle frequency activity in the control animals, but all these changes were diminished by ritanserin treatment. These effects resulted in a significant relative increase in the intermediate band (peak: 12-15 Hz) of the EEG power spectra and thus, a relative increase in thalamo-cortical synchronization caused by ritanserin at dark onset. Because ritanserin is a selective 5-HT(2) receptor antagonist, we conclude that under physiological conditions serotonin increases EEG desynchronization and produces an increase in vigilance level and motor activity by tonic activation of 5-HT(2) receptors. This regulatory mechanism plays an important role in the waking process, and the appearances of its effects in the light and dark phase are markedly different.