A motor resonance mechanism in children? Evidence from subdural electrodes in a 36-month-old child.

The presence of a neural mechanism matching execution and observation of actions in the adult human brain is well established. In children, however, description of a resonance motor mechanism is still preliminary. In the present study, we recorded electroencephalographic signals from a subdural 64-contact grid electrode in a 36-month-old child with epilepsy. Spectral analysis was performed on sequences where the child drew with her right hand, watched an experimenter drawing with his right hand or was at rest. Contact sites corresponding to sensorimotor areas were discovered where absolute power was decreased during both observation and execution of hand/arm actions. These data suggest the presence of a mirror neuron system early in the developing brain.

Repetitive TMS of the motor cortex improves ipsilateral sequential simple finger movements.

BACKGROUND: Disruption of cortical function can improve behavior. Motor cortex (M1) transcallosal interactions are mainly inhibitory; after unilateral damage to M1, there is increased excitability of the unaffected M1. Repetitive transcranial magnetic stimulation (rTMS) of M1 produces a temporary reduction in cortical excitability in the same M1 that outlasts the duration of the rTMS train. The authors hypothesize that reducing cortical excitability of M1 by rTMS may improve motor performance in the ipsilateral hand by releasing the contralateral M1 from transcallosal inhibition. METHODS: Sixteen healthy volunteers participated. Using a sequential key-pressing task with the index finger, motor performance was monitored before and after rTMS (1 Hz for 10 minutes with the intensity below motor threshold) applied to the ipsilateral M1, contralateral M1, ipsilateral premotor area, or vertex (Cz). RESULTS: rTMS of M1 shortened execution time of the motor task with the ipsilateral hand without affecting performance with the contralateral hand. This effect outlasted rTMS by at least 10 minutes, was specific for M1 stimulation, and was associated with increased intracortical excitability in the unstimulated M1. CONCLUSIONS: The authors' results support the concept of an interhemispheric "rivalry." They demonstrate the utility of repetitive transcranial magnetic stimulation to explore the functional facilitation of the unstimulated counterpart motor cortex, presumably via suppression of activity in the stimulated motor cortex and transcallosal inhibition.

Studies in cognition: the problems solved and created by transcranial magnetic stimulation.

The application of transcranial magnetic stimulation (TMS) to investigate important questions in cognitive neuroscience has increased considerably in the last few years. TMS can provide substantial insights into the nature and the chronometry of the computations performed by specific cortical areas during various aspects of cognition. However, the use of TMS in cognitive studies has many potential perils and pitfalls. Although TMS can help bridge the gap between psychological models and brain-based arguments of cognitive functions, hypothesis-driven carefully designed experiments that acknowledge the current limitations of TMS are critical.

Differential effects of low-frequency rTMS at the occipital pole on visual-induced alpha desynchronization and visual-evoked potentials.

Visual-induced alpha desynchronization (VID) and visual-evoked potentials (VEPs) characterize occipital activation in response to visual stimulation but their exact relationship is unclear. Here, we tested the hypothesis that VID and VEPs reflect different aspects of cortical activation. For this purpose, we determined whether VID and VEPs are differentially modulated by low-frequency repetitive transcranial magnetic stimulation (rTMS) over the occipital pole. Scalp EEG responses to visual stimuli (flashed either to the left or to the right visual field) were recorded for 8 min in six healthy subjects (1) before, (2) immediately following, and (3) 20 min after left occipital rTMS (1 Hz, 10 min). The parameters aimed to reduce cortical excitability beyond the end of the TMS train. In addition, simple reaction times to visual stimulation were recorded (left or right hand in separate blocks). In all subjects, VID was significantly and prominently reduced by rTMS (P = 0.0001). In contrast, rTMS failed to modulate early VEP components (P1/N1). A moderate effect was found on a late VEP component close to manual response onset (P = 0.014) but this effect was in the opposite direction to the VID change. All changes were restricted to the targeted left occipital cortex. The effects were present only after right visual field stimulation when a right hand response was required, were associated with a behavioral effect, and had washed out 20 min after rTMS. We conclude that VID and early VEPs represent different aspects of cortical activation. The findings that rTMS did not change early VEPs and selectively affected VID and late VEPs in conditions where the visual input must be transferred intrahemispherically for visuomotor integration (right visual field/right hand) are suggestive of rTMS interference with higher-order visual functions beyond visual input. This is consistent with the idea that alpha desynchronization serves an integrative role through a corticocortical "gating function."

Visual pathways following cerebral hemispherectomy.

The anatomical consequences of unilateral cerebral hemispherectomy in some animal models are reviewed. We have shown that the retinogenigulate pathway undergoes severe degenerative changes in hemispherectomized monkeys, greater than those shown in cats and we proposed that remaining retinal terminals to the dorsal lateral geniculate nucleus have little potential for conveying visual information any further. All subdivisions of the pulvinar undergo severe degeneration following hemispherectomy showing that the ascending tectofugal pathway is also shut off. On the other hand, the retina subserving the blind field is not depleted of ganglion cells which still send normal appearing terminals to the midbrain pretectum and superior colliculus. Visual information from the blind hemifield can thus gain access to the brain and could potentially reach the contralateral cerebral cortex through the midbrain commissure and possibly through thalamic commissural cells.

Intracortical inhibition and facilitation in human facial motor area: difference between upper and lower facial area.

OBJECTIVE: To investigate the intracortical inhibitory and excitatory systems in the motor cortical representation of upper and lower facial muscles. METHODS: Paired-pulse transcranial magnetic stimulation (TMS) was applied to 7 healthy volunteers, with the interstimulus interval (ISI) between the conditioning stimulus (CS) and test stimulus, varied from 1 to 20 ms. CS was set at 90% of motor threshold. Muscle evoked potentials (MEPs) were recorded from first dorsal interosseus (FDI), orbicularis oculi (o. oculi) and mentalis muscles. RESULT: TMS evoked MEPs in o. oculi on both ipsi- and contralateral sides in all subjects. In the paired-pulse study, MEP amplitude in the mentalis decreased at short ISIs of 1-3 ms, followed by increases at 12-20 ms. These effects were similar to those in the FDI. O. oculi did not show a distinct inhibitory period at short ISIs and facilitation at long ISIs was detected but was significantly less than in FDI and mentalis. In o. oculi, there was no significant difference between the effects of ipsilateral and contralateral CS on the MEPs. CONCLUSION: The bi-hemispheric control of volitional movement and the modulation from brainstem projections appear to markedly influence intracortical inhibitory and excitatory systems in the motor cortical representation of o. oculi.

Enhanced visual spatial attention ipsilateral to rTMS-induced 'virtual lesions' of human parietal cortex.

The breakdown of attentional mechanisms after brain damage can have drastic behavioral consequences, as in patients suffering from spatial neglect. While much research has concentrated on impaired attention to targets contralateral to sites of brain damage, here we report the ipsilateral enhancement of visual attention after repetitive transcranial magnetic stimulation (rTMS) of parietal cortex at parameters known to reduce cortical excitability. Normal healthy subjects received rTMS (1 Hz, 10 mins) over right or left parietal cortex. Subsequently, detection of visual stimuli contralateral to the stimulated hemisphere was consistently impaired when stimuli were also present in the opposite hemifield, mirroring the extinction phenomenon commonly observed in neglect patients. Additionally, subjects' attention to ipsilateral targets improved significantly over normal levels. These results underline the potential of focal brain dysfunction to produce behavioral improvement and give experimental support to models of interhemispheric competition in the distributed brain network for spatial attention.

Increased variability of paced finger tapping accuracy following repetitive magnetic stimulation of the cerebellum in humans.

Imaging and lesion studies suggest that the cerebellum is involved in the self-generation of timed motor responses. Using repetitive transcranial magnetic stimulation (rTMS), we studied the effects of transient disruption of the lateral or medial cerebellum on a paced-finger-tapping task (PFT). Results show greater variability on the PFT task following a 5 min train of 1 Hz rTMS to the medial cerebellum. Magnetic stimulation of the lateral cerebellum or motor cortex, and sham stimulation, had no effect on performance. Expanding the results of neuroimaging studies, these data show the causal link between activity in the medial cerebellum and the production of timed movements. This is the first demonstration of the feasibility of transiently disrupting the cerebellum by rTMS and inducing behavioral effects. This method of 'virtual lesions' can expand the study of the role of the cerebellum in motor control and cognition.

Anatomical sparing in the superior colliculus of hemispherectomized monkeys.

Using the monkey as a model for human hemispherectomy, the effects of early removal of a whole cerebral hemisphere on the cytoarchitecture and cytochrome oxidase histochemistry of the superior colliculus (SC) were evaluated. Results show that the SC ipsilateral to the cortical lesion suffers a 29.9% average volume reduction and a 32.7% total loss of neurons compared to the contralateral SC. Neuronal densities and metabolic activity are similar in normal and hemispherectomized monkeys. Furthermore, the ipsi- and contralesional SC receive retinal inputs as revealed with intraocular injections of tritiated proline. These data suggest that the superior colliculus retains functional capabilities following hemispherectomy in monkey.

Quantitative analysis of the retinal ganglion cell layer in the ostrich, Struthio camelus.

The total number, distribution and peak density of ganglion cells were evaluated in the Nissl-stained retina of the ostrich (Struthio camelus). The mean (n = 4) total number of retinal ganglion cells (RGC) was estimated at 2,274,128 (s.d. = 273, 152). The ostrich retina exhibited a prominent horizontal visual streak along which a central area located nasal to the pecten had a peak density of 9,500 cells/mm2. A high concentration of cells with a peak density of 2,646 cells/mm2 was also observed in the temporal retina, slightly dorsal to the visual streak. The results further showed that the ostrich eye has a 15-mm pupil entrance diameter, its mean axial length is 39.81 mm, the estimated retinal magnification factor is 0.4075 mm/deg and the maximum visual acuity along the well-defined visual streak was estimated to be 19.32 cycles/deg. The latter component of the retina might subserve vision along the horizon while the temporal region mediates binocular processing. The data also showed that the degree of retinal illumination in this bird could be comparable to that noted in some nocturnal species. The findings in this study suggest that the ostrich might not be restricted to diurnal activity.

Retinal projections to the pregeniculate nucleus in the hemispherectomized monkey.

Intraocular injections of tritiated proline were used to test the hypothesis that unilateral removal of all visual cortical areas results in increased distribution of retinal terminals in the pregeniculate nucleus (PGN) of the thalamus in monkeys. Following hemispherectomy, retinal input to the ipsilateral PGN was reduced by an average of 18.5% when compared to its contralateral homologue, which corresponded to the reduction in nuclear volume (19.3%). Our results show that removal of cortical afferents to the external layer of the PGN does not induce invasion of retinal projections into this region of the nucleus.

Retinogeniculate projections following early cerebral hemispherectomy in the vervet monkey.

The effects of early, unilateral cerebral hemispherectomy on retinogeniculate projections were studied in the vervet monkey (Cercopithecus aethiops sabeus). Hemispherectomy eliminates all geniculocortical pathways and thus removes cortical factors involved in the survival of retinogeniculate projections. Complete removal of the left cerebral cortex was performed in two monkeys at 6 months and 8 months of age. After a post-surgical survival period of 50 months (SHG3) and 45 months (SHG4), both animals and a normal adult monkey received intraocular injections of [3H]proline (5 mCi) in the left eye and WGA-HRP (100 microliters, 5%) in the right eye. The dorsal lateral geniculate nucleuseuron (LGNd) ipsilateral to the hemispherectomy was on average 73% smaller than the contralateral LGNd. The magno- and parvocellular layers ipsilateral to the cortical ablation in both hemispherectomized subjects received a layered, eye-specific pattern of retinal input. This suggests that retinogeniculate projections could be sustained in the absence of geniculate relay cells.

Stereological evaluation of substantia nigra cell number in normal and hemispherectomized monkeys.

The assessment of the anatomical consequences of cortical lesions on subcortical visual relays is necessary to further understand residual visual capacities. Unbiased stereological techniques were used to evaluate cell numbers in the substantia nigra (SN), a structure involved in the control of saccadic eye movements. Cell numbers were very similar in the ipsi- and contralateral SN of the hemispherectomized animal (329,926 vs. 310,248). These numbers are close to what was observed in the normal monkey (300,130 and 320, 859). In one case, part of the striatum was lesioned in addition to the cerebral hemisphere. Noticeable effects were observed in the SN ipsilateral to the cortical lesion: volume was reduced by 30.5% while the number of neurons, compared to the contralateral side, dropped by 43.2% (186,644 vs. 328,757). These results suggest that due to its anatomical sparing following hemispherectomy the SN, in addition to other subcortical structures, is in a prime position to modulate the spared saccadic behaviors seen after massive cortical injuries.

Transneuronal degeneration of retinal ganglion cells in early hemispherectomized monkeys.

Transneuronal retrograde cell changes in the retina of the primate have been well documented after lesions to striate cortex, but little is known about the effects of hemispherectomy, a surgical procedure used in humans for the treatment of intractable epilepsy. In order to follow the time course of this degenerative process, we examined the retinae of six monkeys who underwent a total hemispherectomy at various postnatal ages with a survival period of 4 years. We demonstrate that transneuronal retrograde degeneration in the retina following hemispherectomy is inversely correlated with age at the time of the lesion. This degeneration is maximal when the lesion is induced within the first 4-6 months of life and less pronounced from 8 months to adulthood.

Transneuronal retrograde degeneration of retinal ganglion cells following cerebral hemispherectomy in cats.

We have assessed the extent of transneuronal retrograde degeneration of retinal ganglion cells (RGCs) following the removal of a whole cerebral hemisphere at postnatal age 16 and 25 days. In the P16 animal, the nasal retina contralateral to the lesion suffered a 41% cell loss, whereas cell loss in the temporal retina ipsilateral to the lesion was 33%. Cell loss was greater in nasal retina and mainly included medium sized cells (200-600 microns2). In the P25 animal overall there was no evidence for ganglion cell loss.