Interhemispheric Transmission Time Research Articles

Differential impairment of interhemispheric transmission in bipolar disease

There is abundant evidence that the cerebral white matter and in particular the corpus callosum show several structural abnormalities in both schizophrenia (SCZ) and bipolar disease (BD). However, which cognitive functions are impaired as a result of these anomalies is still unclear. Previous behavioural tests of interhemispheric crosstalk have shown a differential impairment in SCZ with interhemispheric transmission time, as tested with the Poffenberger paradigm, essentially normal but with an abnormally enhanced interhemispheric summation effect, as tested with the redundant signal effect. The present study was inspired by this discrepancy and by the more general question of a possible overlap between the pathophysiology of SCZ and BD. We tested both SCZ and BD patients in the Poffenberger paradigm and redundant signal effect and found a similar dissociation, namely a normal interhemispheric transfer time and an abnormal redundant signal effect. The only difference between the two groups was a selective slowing of speed of response of the dominant right hand in the SCZ group suggesting an impairment of left hemisphere functions. These results cast further light on the question of common and differential impairments of basic psychological functions in the two diseases.

Data-driven approach to the estimation of connectivity and time delays in the coupling of interacting neuronal subsystems

One of the challenges in neuroscience is the detection of directionality between signals reflecting neural activity. To reveal the directionality of coupling and time delays between interacting multi-scale signals, we use a combination of a data-driven technique called empirical mode decomposition (EMD) and partial directed coherence (PDC) together with the instantaneous causality test (ICT). EMD is used to separate multiple processes associated with different frequency bands, while PDC and ICT allow to explore directionality and characteristic time delays, respectively. We computationally validate our approach for the cases of both stochastic and chaotic oscillatory systems with different types of coupling. Moreover, we apply our approach to the analysis of the connectivity in different frequency bands between local field potentials (LFPs) bilaterally recorded from the left and right of subthalamic nucleus (STN) in patients with Parkinson’s disease (PD). We reveal a bidirectional coupling between the left and right STN in the beta-band (10–30 Hz) for an akinetic PD patient and in the tremor band (3–5 Hz) for a tremor-dominant PD patient. We detect a short time delay, most probably reflecting the inter-hemispheric transmission time. Additionally, in both patients we observe a long time delay of approximately a mean period of the beta-band activity in the akinetic PD patient or the tremor band activity in the tremor-dominant PD patient. These long delays may emerge in subcortico-thalamic loops or longer pathways, comprising reflex loops, respectively. We show that the replacement of EMD by conventional bandpass filtering complicates the detection of directionality and leads to a spurious detection of time delays.

Interhemispheric transmission time in persons with Down syndrome

The study of cerebral specialization in persons with Down syndrome (DS) has revealed an anomalous pattern of organization. Specifically, persons with DS elicit a right cerebral hemisphere lateralization for receptive language and a left cerebral hemisphere lateralization for the production of simple and complex movements: a pattern quite different from the left hemisphere lateralization typically characterizing the aforementioned processes in the non-DS population. It is thought that the putative separation between speech perception and movement planning systems as well as the cost of interhemispheric integration impedes verbal-motor behaviours in persons with DS. Moreover, morphological anomalies of callosal structure may further amplify between-hemisphere communication difficulties in the DS population. In the present investigation, we employed a behavioural technique (i.e. the Poffenberger paradigm; Poffenberger) to determine whether global anomalies of callosal structure further amplify deficits in interhemispheric communication. Fourteen individuals with DS and 25 chronological age-matched and gender-equated participants without intellectual disability performed a visuomotor reaction time (RT) test with their left or right hand to visual stimuli appearing left or right of visual fixation. Typically it is reported that responses to visual stimuli appearing ipsilateral to the responding hand (i.e. the uncrossed condition) are faster than responses wherein visual stimuli and responding hand are contralaterally mapped (i.e. the crossed condition). The increased RT associated with the crossed condition is reported on the order of 4 ms and has been interpreted to reflect the physiological result of interhemispheric transmission. Not surprisingly persons with DS exhibited slower and more variable RTs relative to control counterparts. In addition, a reliable RT advantage favouring the uncrossed conditions was observed among control participants but not persons with DS. In keeping with the extant literature, RT performance of the DS group was slower and more variable than control counterparts. This finding has been interpreted to reflect an 'adaptive reaction' wherein the perceptual-motor abilities of persons with DS are not optimized to respond to externally paced stimuli. In terms of evaluating interhemispheric transmission via the Poffenberger paradigm, our results show the finite measures of explicit brain-behaviour relations characterizing so-called healthy controls are not always tenable in the DS population. Indeed, we believe such a finding underpins the aforementioned 'adaptive reaction' exemplifying preferred movement control in persons with DS.

Long distance communication in the human brain: timing constraints for inter-hemispheric synchrony and the origin of brain lateralization.

Analysis of corpus callosum fiber composition reveals that inter-hemispheric transmission time may put constraints on the development of inter-hemispheric synchronic ensembles, especially in species with large brains like humans. In order to overcome this limitation, a subset of large-diameter callosal fibers are specialized for fast inter-hemispheric transmission, particularly in large-brained species. Nevertheless, the constraints on fast inter-hemispheric communication in large-brained species can somehow contribute to the development of ipsilateral, intrahemispheric networks, which might promote the development of brain lateralization.

Interhemispheric transmission of visuomotor information in humans: fMRI evidence.

Normal human subjects underwent functional magnetic resonance imaging (fMRI) while performing a simple visual manual reaction-time (RT) task with lateralized brief stimuli, the so-called Poffenberger's paradigm. This paradigm was employed to measure interhemispheric transmission (IT) time by subtracting mean RT for the uncrossed hemifield-hand conditions, that is, those conditions not requiring an IT, from the crossed hemifield-hand conditions, that is, those conditions requiring an IT to relay visual information from the hemisphere of entry to the hemisphere subserving the response. The obtained difference is widely believed to reflect callosal conduction time, but so far there is no direct physiological evidence in humans. The aim of our experiment was twofold: first, to test the hypothesis that IT of visuomotor information requires the corpus callosum and to identify the cortical areas specifically activated during IT. Second, we sought to discover whether IT occurs mainly at premotor or perceptual stages of information processing. We found significant activations in a number of frontal, parietal, and temporal cortical areas and in the genu of the corpus callosum. These activations were present only in the crossed conditions and therefore were specifically related to IT. No selective activation was present in the uncrossed conditions. The location of the activated callosal and cortical areas suggests that IT occurs mainly, but not exclusively, at premotor level. These results provide clear cut evidence in favor of the hypothesis that the crossed-uncrossed difference in the Poffenberger paradigm depends on IT rather than on a differential hemispheric activation.

Reduced interhemispheric transmission in schizophrenia patients: evidence from event-related potentials

Interhemispheric transfer was investigated in 14 schizophrenia patients and 15 age- and sex-matched healthy controls in a lateralized lexical decision task. Words and pseudowords were tachistoscopically presented either to the left or to the right visual hemifield. Event-related potentials were determined from a 65-channel electroencephalogram. Information transfer between hemispheres was assessed by the interhemispheric transmission time (IHTT), the N1-latency difference between ipsilateral and contralateral hemisphere. Controls, but not schizophrenia patients showed significantly faster IHTT from the right to the left hemisphere for words, while IHTT from the left to the right hemisphere did not differ between groups and stimuli. These findings are interpreted in terms of a deficit in schizophrenia to transfer verbal information from the right to the left hemisphere via the corpus callosum.

CRT screens may give rise to biased estimates of interhemispheric transmission time in the Poffenberger paradigm.

It has been shown that computer video-display units do not emit luminance uniformly over the entire screen, but emit more light on the right hand side than on the left hand side. The present study investigates whether this luminance asymmetry has implications for the manual and vocal estimates of interhemispheric transmission time (IHTT) in the Poffenberger paradigm. In particular, it is shown that previous reports of right visual-field advantages for vocal responses are an artifact of the luminance asymmetry of computer screens and that this asymmetry also has implications for estimates of differences in transmission time from the right to the left hemisphere in manual responses. In addition, we examined the impact of stimulus intensity and dark adaptation to the IHTT estimates and found that neither had an effect. This is in line with previous evidence that interhemispheric transfer in the Poffenberger paradigm does not depend on the transfer of visual information.

Visuo-spatial neural response interactions in early cortical processing during a simple reaction time task: a high-density electrical mapping study

The timecourse and scalp topography of interactions between neural responses to stimuli in different visual quadrants, straddling either the vertical or horizontal meridian, were studied in 15 subjects. Visual evoked potentials (VEPs) were recorded from 64 electrodes during a simple reaction time (RT) task. VEPs to single stimuli displayed in different quadrants were summed (‘sum’) and compared to the VEP response from simultaneous stimulation of the same two quadrants (‘pair’). These responses would be equivalent if the neural responses to the single stimuli were independent. Divergence between the ‘pair’ and ‘sum’ VEPs indicates a neural response interaction. In each visual field, interactions occurred within 72–86 ms post-stimulus over parieto-occipital brain regions. Independent of visual quadrant, RTs were faster for stimulus pairs than single stimuli. This replicates the redundant target effect (RTE) observed for bilateral stimulus pairs and generalizes the RTE to unilateral stimulus pairs. Using Miller's ‘race’ model inequality (Miller J. Divided attention: evidence for coactivation with redundant signals, Cognitive Psychology 1982;14:247–79), we found that probability summation could fully account for the RTE in each visual field. Although measurements from voltage waveforms replicated the observation of earlier peak P1 latencies for the ‘pair’ versus ‘sum’ comparison (Miniussi C, Girelli M, Marzi CA. Neural site of the redundant target effect: electrophysiological evidence. Journal of Cognitive Neuroscience 1998;10:216–30), this did not hold with measurements taken from second derivative (scalp current density) waveforms. Since interaction effects for bilateral stimulus pairs occurred within 86 ms and require interhemispheric transfer, transcallosal volleys must arrive within 86 ms, which is earlier than previously calculated. Interaction effects for bilateral conditions were delayed by ≈10 ms versus unilateral conditions, consistent with current estimates of interhemispheric transmission time. Interaction effects place an upper limit on the time required for neuronal ensembles to combine inputs from different quadrants of visual space (≈72 ms for unilateral and ≈82 ms for bilateral conditions).

Normal Development of Bilateral Field Advantage and Evoked Potential Interhemispheric Transmission Time

Implications of the developmental progression of myelination of the corpus callosum were studied using evoked potential interhemispheric transmission time (EP-IHTT) and the bilateral field advantage (BFA) in letter matching. Forty-two normal children aged 7 to 17 years were asked to respond regarding whether 2 letters matched when presented either unilaterally (both in the same visual field) or bilaterally (1 letter in each field). Evoked potentials were recorded with bilateral midparietal electrodes during unilateral presentations of the letter-matching task. Age-related changes were found for both EP-IHTT and BFA. BFA in reaction time in the visual letter-matching task increased significantly with age. Decreasing EP-IHTT with age was also evident (although only in a statistical trend). These findings lend support to the hypothesis that increased callosal myelination during late childhood has functional significance. Callosal maturation appears to result in faster interhemispheric transfer and increasing ability to integrate information across the midline.

The crossed-uncrossed difference in simple reaction times to lateralized auditory stimuli is not a measure of interhemispheric transmission time: evidence from the split brain.

In a complete commissurotomy patient, the difference in simple (detection) reaction times between responses to contralateral and ipsilateral auditory stimuli was found to be small (less than 5 ms) and not reliable, whereas the difference between contralateral and ipsilateral responses to lateralized visual stimuli was found to be large (ranging from 25 ms to 45 ms in different previous studies) and always reliable. This suggests that the reaction times difference in detecting lateralized auditory stimuli is not a valid estimate of interhemispheric transmission time.

Bilateral field interactions, hemispheric specialization and evoked potential interhemispheric transmission time

The interrelationship between bilateral visual field processing, hemispheric specialization and interhemispheric transmission time (IHTT) was examined in two experiments in order to test two theories regarding callosal function and lateralized visual processing. Contrary to both theoretical speculations [Braun, Neuropsychology Review, Vol. 3, pp.321–365, 1992] and a recent report [Nowicka et al. Neuropsychologia, Vol. 34, pp. 147–151, 1996], the directional asymmetry in evoked potential measures of IHTT did not vary with task differences in indices of hemispheric specialization. IHTT was faster from right to left hemispheres regardless of visual field advantage for the task. Similarly, patterns of correlation between IHTT and bilateral field advantage did not change between verbal and spatial matching tasks, despite differences in visual field advantage. Since the latter data did not consistently support the Brown and Jeeves [ Neuropsychologia, Vol. 31. pp. 1267–1281, 1993] hypothesis, an alternative hypothesis involving hemispheric asymmetries in attention rather than processing specialization was proposed.

Nasotemporal overlap investigated in a case of agenesis of the corpus callosum

In primates fibres from nasal retinae project contralaterally and those from temporal retinae ipsilaterally. At the border between these two regions an area of overlap where ipsi- and contralaterally projecting ganglion cells intermingle has been demonstrated in monkeys and cats. However, behavioural studies have failed to provide confirmatory evidence in humans. In this experiment simple reaction times to lateralized light flashes at four points of eccentricity (1/2, 1, 2 and 4 degrees) were recorded in an acallosal female. Responses made by the directly stimulated hemisphere were subtracted from those made by the indirectly stimulated hemisphere to arrive at estimates of interhemispheric transmission time. If present, a region of overlap should result in information being available to both hemispheres and consequently alleviate the need for any interhemispheric crossing. However, a large transmission time was found, even with stimuli presented close to fixation, thereby providing no evidence for the existence of such a region in humans.

Temporal Integration of Events Within and Between the Cerebral Hemispheres

The effect of interhemispheric transmission time (IHTT) on temporal perception was investigated by comparing simultaneity thresholds under unimanual and bimanual stimulation conditions. In the unimanual conditions the tactile stimuli were delivered to the same hand and were received by the same hemisphere, but in bimanual conditions, where stimuli were delivered to different hands, interhemispheric communication was necessary in order to compare the timing of the two stimuli. Randomised order of stimulating the fingers of the hands was compared with consistent stimulation of each hand. Previous studies have used only consistent stimulation. Thirty-two undergraduate university students (16 males and 16 females) were tested. Bimanual simultaneity thresholds were significantly higher than unimanual. Previous research showing an absence of laterality effects for simultaneity judgements was confirmed, supporting a hemispheric equivalence model of temporal processing. Simultaneity thresholds were not affected by randomisation of stimulus location, indicating that expectancy effects were not responsible for the difference between bimanual and unimanual thresholds. The implication of these findings is that temporal perceptions are affected by the process of interhemispheric transmission.

Interhemispheric transmission of information and functional asymmetry of the human brain

The study investigated directional differences in interhemispheric transmission time using the VEPs method. Specificially we were interested in whether there exists an asymmetry in the transmission of information to and from the hemisphere specialized in its processing. Two type of stimuli, specific for the left and right hemisphere, were presented in the left and right visual fields. The latency differences between visual evoked potential components registered in the hemispheres ipsilateral and contralateral to the stimulated hemifield were compared. Interhemispheric transmission time was shorter when the information was transferred from the hemisphere non-specialized for its processing to the specialized one than in the opposite direction. The results suggest the existence of a physiological mechanism that ensures fast transmission of information to that hemisphere which is more efficient in its processing.

Channels of the corpus callosum. Evidence from simple reaction times to lateralized flashes in the normal and the split brain.

We studied 75 normal subjects and three commissurotomized patients using unimanual simple reaction times to lateralized flashes as a behavioural estimate of interhemispheric transmission time. Three different versions of the paradigm were performed: (i) the basic task; (ii) a motor task, with an increased complexity of the motor response; and (iii) a visual task, with an increased complexity of the visual stimulus presentation. We tested two hypotheses. First, that the new versions of the simple reaction time task result in shifts in hemispheric specialization for processing motor output (indicated by a main effect of response hand) or visual input (indicated by a main effect of visual field) alone, without affecting callosal transmission. In that case normals and split brain patients would show no significant task by response hand by visual field interaction and no significant task by crossed-uncrossed difference interaction. Secondly, that the new versions of the task affect callosal transfer. In that case, normals, but not split brain patients, would show a significant task by response hand by visual field interaction and a significant task by crossed-uncrossed difference interaction. Results are consistent with the latter hypothesis, showing that the motor task significantly changed the response hand by visual field interaction and the crossed-uncrossed difference, but only in normal subjects, perhaps producing a switch in the callosal channel subserving the interhemispheric transfer.

Is interhemispheric transfer time related to age? A developmental study

In simple visuomotor reaction time tasks, the difference between reaction time (RT) in the uncrossed hand/hemifield condition from RT in the crossed hand/hemifield, known as CUD (crossed-uncrossed difference), has been interpreted as reflecting interhemispheric transmission time (IHTT). Several studies in normal adults have found a CUD of a few milliseconds (3–4), while an abnormally long CUD has been reported in patients who underwent a surgical section of the corpus callosum or in congential acallosal subjects. The corpus callosum, which is the most important structure for interhemispheric transfer of information, completes its myelination approximately by age ten. It has been hypothesized that the functional maturity of the corpus callosum concides with the termination of the myelination cycle. No developmental study has focused on the development of IHTT, in relation to callosal maturation. The purpose of our study has been to investigate the development of interhemispheric transfer of visuomotor information in children aged seven to eleven, using a simple RT task with lateralized visual stimuli. The results indicate an age-related decrease of CUD, which we interpret as reflecting the maturation of the corpus callosum during childhood years.

Laterality effects in normal subjects: evidence for interhemispheric interactions.

In this review we describe three methods of research that have been used to study relationships between the cerebral hemispheres in normal human subjects. We briefly mention reaction-time studies, which have been used to measure interhemispheric transmission time; more pertinent to laterality effects, however, are lateralized visual field studies, in which stimuli can be presented either unilaterally or to both visual fields simultaneously, and dichotic listening studies, wherein different stimuli are presented to the two ears simultaneously. Recent examples from the literature of experiments employing these techniques are discussed as they pertain to an understanding of interhemispheric interaction. Some suggestions are offered concerning appropriate procedures for studying interhemispheric interactions in normal human subjects.

Behavioral estimates of interhemispheric transmission time and the signal detection method: a reappraisal.

On the basis of a review of the literature, Bashore (1981) concluded that only simple reaction time experiments with manual responses yielded consistent behavioral estimates of interhemispheric transmission time. A closer look at the data, however, revealed that these experiments were the only ones in which large numbers of observations were invariably obtained from many subjects. To investigate whether the methodological flaw was the origin of Bashore's conclusion, two experiments were run in which subjects had to react to lateralized light flashes. The first experiment dealt with manual reactions, the second with verbal reactions. Each experiment included a condition without catch trials (i.e., simple reaction time) and two conditions with catch trials. Catch trials were trials in which no stimulus was given and in which the response was to be withheld. Both experiments returned consistent estimates of interhemispheric transmission time in the range of 2-3 msec. No differences were found between the simple reaction time condition and the signal detection conditions with catch trials. Data were analyzed according to the variable criterion theory. This showed that the effect of catch trials, as well as the effect of interhemispheric transmission, was situated at the height of the detection criterion, and not in the rate of the information transmission.

Human strabismus: Evaluation of the interhemispheric transmission time and hemiretinal differences using a reaction time task

Experimentally induced strabismus in visually immature cats leads to abnormal development of the posterior corpus callosum. This, in turn, should lead to abnormal interhemispheric integration of unilaterally presented visual information. To test whether strabismus produces deficits in the human commissural visual system, the interhemispheric transmission time (ITT) was compared in strabismic and normal subjects. Simple unimanual reaction times (RT) were tested in 30 subjects in response to a lateralized target presented monocularly at 4° and 35° nasally and temporally from the fovea along the horizontal meridian. This method was also used to examine the effect of strabismus on the central and peripheral portions of each hemiretina. The results showed that in strabismic subjects with or without amblyopia, the ITT did not differ significantly from normals at both eccentricities. In non-amblyopic strabismic patients, RTs in the central and peripheral portions of hemiretina were comparable to normals. However, a reduced speed of response was found in the central visual field (4°) in the amblyopic eye. Our results suggest that the ITT is normal in strabismic subjects and that the longer RTs in the central portion of the nasal and temporal hemiretina of the amblyopic eye may be associated with the severe amblyopic condition.

Directional asymmetries in interhemispheric transmission time: Evidence from visual evoked potentials

The hypothesis was tested that interhemispheric transfer time (IHTT), as measured in the latency of bilaterally recorded visual evoked potentials, is directionally asymmetric, i.e. that an IHTT is faster for transmission from right-to-left hemisphere, than from left-to-right. A meta-analysis of 18 experiments within the published literature reporting visual evoked potential IHTTs indicates a significant experiment-wise predominance of faster right-to-left IHTTs. A new experiment is also reported in which significantly faster right-to-left IHTT was found in visual evoked potentials recorded from parietal electrodes to lateral visual field presentations while subjects performed a task requiring complex stimulus recognition and analysis, and a choice response.