Cerebral dominance for action in the human brain: the selection of actions.

PET was used to study cerebral dominance for the selection of action. In one condition the subjects moved one of two fingers depending on the cue presented (choice reaction time), and in another they moved the same finger whatever the cue (simple reaction time). There was also a baseline condition in which cues were shown but no movements were made. A conjunction analysis was performed to reveal those areas which were more activated for the choice versus simple reaction time, irrespective of whether the right or left hand was used. The activations were in prefrontal, premotor and intraparietal areas, and they were all in the left hemisphere. Thus, while there were activations in the right hemisphere for the choice versus simple reaction time task when the subjects used their left (contralateral) hand, there were activations in left prefrontal, premotor and parietal areas whether the right (contralateral) or left (ipsilateral) hands were used. It is argued that the results suggest that the left hemisphere is dominant not only for speech but also for action in general.

Signal-, set-, and movement-related activity in the human premotor cortex.

Single unit recording studies in non-human premotor cortex have revealed neurons with motor-related activity. Other neurons, however, seem to be involved in prior movement selection and preparation processes, and have activity related to visual instruction signals or movement preparation ('set'). We have used single pulse transcranial magnetic stimulation (TMS) to identify similar processes in human subjects. In Experiment 1 subjects performed a cued movement task while being stimulated with TMS over three sites: sensorimotor cortex, posterior premotor cortex and anterior premotor cortex. TMS slowed movements when applied at 140 ms after the visual cue over the anterior premotor site, at 180 ms after the visual cue over the posterior premotor site, and at 220 ms and later after the visual cue over the sensorimotor cortex. The results are consistent with a change from signal to movement-related processing when moving from premotor to motor cortex. In Experiment 2 there was a preparatory set period between the instruction signal that informed subjects which movement to make and the 'go' signal that informed them when to actually make the movement. TMS was applied over the anterior premotor site and the sensorimotor site during the set period. At both sites TMS had similar effects on slowing subsequent movements. The results suggest set activity in both premotor and motor cortices in human subjects.

Signal-, set- and movement-related activity in the human brain: an event-related fMRI study.

Electrophysiological studies on monkeys have been able to distinguish sensory and motor signals close in time by pseudorandomly delaying the cue that instructs the movement from the stimulus that triggers the movement. We have used a similar experimental design in functional magnetic resonance imaging (fMRI), scanning subjects while they performed a visuomotor conditional task with instructed delays. One of four shapes was presented briefly. Two shapes instructed the subjects to flex the index finger; the other two shapes coded the flexion of the middle finger. The subjects were told to perform the movement after a tone. We have exploited a novel use of event-related fMRI. By systematically varying the interval between the visual and acoustic stimuli, it has been possible to estimate the significance of the evoked haemodynamic response (EHR) to each of the stimuli, despite their temporal proximity in relation to the time constant of the EHR. Furthermore, by varying the phase between events and image acquisition, we have been able to achieve high temporal resolution while scanning the whole brain. We dissociated sensory and motor components of the sensorimotor transformations elicited by the task, and assessed sustained activity during the instructed delays. In calcarine and occipitotemporal cortex, the responses were exclusively associated with the visual instruction cues. In temporal auditory cortex and in primary motor cortex, they were exclusively associated with the auditory trigger stimulus. In ventral prefrontal cortex there were movement-related responses preceded by preparatory activity and by signal-related activity. Finally, responses associated with the instruction cue and with sustained activity during the delay period were observed in the dorsal premotor cortex and in the dorsal posterior parietal cortex. Where the association between a visual cue and the appropriate movement is arbitrary, the underlying visuomotor transformations are not achieved exclusively through frontoparietal interactions. Rather, these processes seem to rely on the ventral visual stream, the ventral prefrontal cortex and the anterior part of the dorsal premotor cortex.

Temporary interference in human lateral premotor cortex suggests dominance for the selection of movements. A study using transcranial magnetic stimulation.

It is known that damage to the left hemisphere can lead to movement deficits, and that patients with apraxia have difficulty in selecting movements. Neurophysiological recording studies and lesion studies have shown that the premotor cortex is important for the selection of movements in monkeys. In this study we used transcranial magnetic stimulation (TMS) to disrupt the processing in human premotor cortex. We applied TMS to normal healthy volunteers over the premotor and primary motor areas while they carried out choice reaction time and simple reaction-time tasks. We measured response times of either hand as subjects were stimulated over the left and right hemisphere separately. We found that we were able to delay responses by stimulating at short cue-stimulus intervals (100-140 ms) over premotor cortex and at longer cue-stimulus intervals (300-340 ms) over primary motor cortex while subjects performed the choice reaction-time task with the contralateral hand. We were also able to delay responses with the ipsilateral hand while stimulating over the left premotor cortex, but not while stimulating over the right premotor cortex or either sensorimotor cortex. Premotor cortex stimulation alone disrupts an early stage of movement selection; motor cortex stimulation disrupts the movements at a later stage of execution. There was no distinguishing short cue-stimulus interval effect when premotor cortex was stimulated in the simple reaction time paradigm, where the movement selection demands of the task are kept to a minimum. We conclude that the premotor cortex is important for selecting movements after a visual cue and that the left hemisphere is dominant for the rapid selection of action.

How do visual instructions influence the motor system?

The paper distinguishes the use of visual cues to guide reaching and grasping, and the ability to learn to associate arbitrary sensory cues with movements. Using positron emission tomography (PET), we have shown that the arbitrary association of visual cues and movements involves the ventral visual system (prestriate, inferotemporal and ventral prefrontal cortex), the basal ganglia and the dorsal premotor cortex. Using functional magnetic resonance imaging (fMRI), we have shown that the evoked haemodynamic responses in the ventral visual system are time-locked to the presentation of the visual cues, that the response in the motor cortex is locked to the time of response, and that the response in the dorsal premotor cortex shows cuerelated, movement-related and set-related components. Using PET we have shown that there are learning-related changes in activation in both the ventral prestriate cortex and the basal ganglia (globus pallidus) when subjects learn a visuomotor associative task. We argue that the basal ganglia may act as a flexible system for learning the association of sensory cues and movements.

Philanthotoxins block glutamatergic transmission in rat hippocampus--I. Reduction of high affinity glutamate uptake demonstrated by light microscopy surface autoradiography.

1. Effects of structural philanthotoxin (PTX) analogues on the high affinity uptake of [3H]-L-glutamate by slices of the rat hippocampus were studied using light microscopy surface autoradiography. 2. Considering the various effects of the PTX-analogues it can be concluded that the presence of an aromatic nucleus in the molecule is an important moiety, while the number and distribution of positive charges in the polyamine chain seems to be of a still not understood importancy.

Philanthotoxins block glutamatergic transmission in rat hippocampus--II. Inhibition of synaptic transmission in the CA1 region.

1. Philanthotoxins decrease the amplitude of the population spike (PS), the field excitatory postsynaptic potential (f-EPSP), and the presynaptic volley (PV), as evoked by Shaffer-collateral-commisural inputs to the CA1 pyramidal cells in the rat hippocampus slice. 2. The effects are slow and often not completely reversible. 3. Dideaza-philanthotoxin-12 is, in all experiments, the most active antagonist showing a very poor recovery. 4. Using a twin pulse the percentual decreases of f-EPSP and PV amplitudes are almost identical for the first and second response. However, the first PS is much more affected than the second one, indicating a possible effect on the inhibiting circuit. 5. Philanthotoxins cause a non-competitive inhibition. 6. Besides a possible postsynaptic block and a distinct presynaptic effect (preceding paper) a non-postsynaptic effect (on the PV) is described.

Effects of polyamines on synaptic transmission, with special attention to the glutamatergic system.

Effects of synthetic philanthotoxin-4.3.3 (PTX-4.3.3) and of its eleven structural analogues on glutamatergic transmission in the insect muscle, nicotinic transmission in the insect CNS and glutamatergic transmission in the mammalian CNS, are described. Compared with the insect muscle, the insect CNS is about 100 times less sensitive for most of these toxins and the mammalian CNS about 1000 times less reactive. In general, the relative activities of the analogues are comparable except for one toxin: dideaza-PTX-12, which is hardly active in insects and is the most active blocker of synaptic transmission from the Schaffer collaterals to pyramidal cells in the rat hippocampal slices. Dideaza-PTX-12 is also the most active inhibitor of glutamate uptake. It is concluded that the latter compound may be a prototype of a new class of neuroactive drugs affecting the glutamatergic transmission in the mammalian CNS.

Discharge induction in molluscan peptidergic cells requires a specific set of autoexcitatory neuropeptides.

The peptidergic caudodorsal cells of the pond snail Lymnaea stagnalis generate long lasting discharges of synchronous spiking activity to release their products. During caudodorsal cell discharges a peptide factor is released which induces similar discharges in silent caudodorsal cells [Ter Maat A. et al. (1988) Brain Res. 438, 77-82]. To identify this factor, the electrophysiological effects of putative caudodorsal cell gene products, calfluxin, caudodorsal cell hormone, four alpha caudodorsal cell peptides and three beta caudodorsal cell peptides, were tested individually and in various combinations. Calfluxin, alpha caudodorsal cell peptide and beta 1 caudodorsal cell peptide each had no effect on membrane potential or excitability of the caudodorsal cells. All other caudodorsal cell peptides caused excitatory responses, but did not induce discharges. Instead, only a specific combination of four caudodorsal cell peptides, caudodorsal cell hormone and alpha caudodorsal cell peptide (1-11, 3-11 and 3-10), evoked caudodorsal cell discharges with similar characteristics to electrically evoked discharges. Incomplete versions of this combination failed to cause a discharge. In addition, antibodies to caudodorsal cell hormone or alpha caudodorsal cell peptide reduced caudodorsal cell excitability and prevented the generation of discharges by electrical stimulation. These results suggest that excitatory autotransmission caused by four caudodorsal cell peptides provides a means to amplify excitatory inputs, thus leading to the generation of the all-or-nothing caudodorsal cell discharge.

In the snail Helix aspersa the gonadotropic hormone-producing dorsal bodies are under inhibitory nervous control of putative growth hormone-producing neuroendocrine cells.

In many Stylommatophora, dorsal bodies (DB) consist of cell groups dispersed in the connective tissue surrounding the cerebral ganglia. It has previously been shown that in these animals the DB cells are under inhibitory nervous control. In the present tissue culture experiment on Helix aspersa it is shown that the axons innervating the DB cells originate from the peptidergic cerebral green cells (CeGC). It is argued that the observed morphological relationship between the CeGC and the DB--the CeGc produce a growth hormone, the DB a female gonadotropic hormone--reflects the antagonism between growth and reproduction which has often been reported for pulmonate snails.

Vasopressin neuron survival in neonatal Brattleboro rats; critical factors in graft development and innervation of the host brain.

Previously it was found that grafts of supraoptic plus paraventricular areas from 19-day-old foetal normal rats survived in the third ventricle of the brain of 4- to 6-day-old, vasopressin-deficient Brattleboro pups, but could not alleviate their polyuria. In the present series, factors important in graft development were analysed. Again using day-19 fetuses as donors, anterohypothalamus grafts as well as grafts placed near a crushed median eminence survived relatively poorly, but showed the presence of vasopressin neurons immunocytochemically one month post-grafting. Homotopic grafting in the supraoptic nucleus, however, even failed to show surviving vasopressin neurons. Graft survival was improved by the use of donor tissue of fetuses younger than day 19. Parvocellular vasopressin cells were frequently seen, organized into clusters resembling the normal suprachiasmatic nucleus. However, magnocellular neurons, as normally seen in supraoptic and paraventricular nuclei, only survived grafting when taken between days 11 and 15 of fetal age. It was concluded that only immature vasopressin neurons survived grafting under the condition employed. Magnocellular neurons had a limited fiber outgrowth into the host brain and median eminence. Most large neurons only stained with non-specific neurophysin antiserum, not with specific vasopressin-associated neurophysin antiserum. Thin fibers of the parvocellular vasopressin neurons provided only occasional and sparse innervation of the host median eminence and lateral septum (one case), but several examples of massive fiber bundles running dorsally from graft into host brain were observed. These fibers terminated in the thalamic periventricular area, a nucleus that is normally innervated by the vasopressin neurons of the suprachiasmatic nucleus. The failure of the grafts to provide adequate vasopressinergic innervation of the host median eminence probably explains why none of the nearly 200 Brattleboro neonates operated upon showed any sign of relief of their diabetes insipidus. It suggests, however, that the present procedures might be useful in restoring central vasopressinergic functions in the developing Brattleboro rat.

A procedure for small-volume brain grafting; vasopressin cells in neonatal and adult Brattleboro rats.

A simple and reliable technique is described for the transplantation of fetal vasopressin (VP) neurons in the third ventricle of the brain of homozygous Brattleboro neonates. Small-volume grafting is introduced by microdissection of paraventricular and supraoptic areas and by pelleting the minced tissue for insertion into the transplantation cannula. Morphological and immunocytochemical evaluation yielded results in both neonatal and adult host brain that were similar to those described for anterior hypothalamic grafts in adult Brattleboro brain. The present protocol circumvents some of the general problems encountered when the use of small grafts is imperative, and is also applicable to the implantation of pelleted cell suspensions.