Contraversive Movements Research Articles

Inter- and Intrahemispheric Sources of Vestibular Signals to V1.

Head movements are sensed by the vestibular organs. Unlike classical senses, signals from vestibular organs are not conveyed to a dedicated cortical area but are broadcast throughout the cortex. Surprisingly, the routes taken by vestibular signals to reach the cortex are still largely uncharted. Here we show that the primary visual cortex (V1) receives real-time head movement signals - direction, velocity, and acceleration - from the ipsilateral pulvinar and contralateral visual cortex. The ipsilateral pulvinar provides the main head movement signal, with a bias toward contraversive movements (e.g. clockwise movements in left V1). Conversely, the contralateral visual cortex provides head movement signals during ipsiversive movements. Crucially, head movement variables encoded in V1 are already encoded in the pulvinar, suggesting that those variables are computed subcortically. Thus, the convergence of inter- and intrahemispheric signals endows V1 with a rich representation of the animal's head movements.

Interhemispherically dynamic representation of an eye movement-related activity in mouse frontal cortex.

Cortical plasticity is fundamental to motor recovery following cortical perturbation. However, it is still unclear how this plasticity is induced at a functional circuit level. Here, we investigated motor recovery and underlying neural plasticity upon optogenetic suppression of a cortical area for eye movement. Using a visually-guided eye movement task in mice, we suppressed a portion of the secondary motor cortex (MOs) that encodes contraversive eye movement. Optogenetic unilateral suppression severely impaired contraversive movement on the first day. However, on subsequent days the suppression became inefficient and capability for the movement was restored. Longitudinal two-photon calcium imaging revealed that the regained capability was accompanied by an increased number of neurons encoding for ipsiversive movement in the unsuppressed contralateral MOs. Additional suppression of the contralateral MOs impaired the recovered movement again, indicating a compensatory mechanism. Our findings demonstrate that repeated optogenetic suppression leads to functional recovery mediated by the contralateral hemisphere.

Chemogenetic Targeting of Dorsomedial Direct-pathway Striatal Projection Neurons Selectively Elicits Rotational Behavior in Mice

The striatum of the basal ganglia is pivotal for voluntary movements and is implicated in debilitating movement disorders such as Parkinsonism and dystonia. Striatum projects to downstream nuclei through direct (dSPN) and indirect (iSPN) pathway projection neurons thought to exert opposite effects on movement. In rodent models of striatal function, unilateral dopamine deprivation induces ipsiversive rotational behavior. The dSPNs of the dorsal striatum are believed to engage distinct motor programs but underlying mechanisms remain unclear. Here, we show by employing chemogenetics [Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)] that unilateral inhibition of dorsomedial dSPNs is sufficient to selectively impair contraversive movement and elicit ipsiversive rotational behavior in mice. Adeno-associated virus (AAV) encoding Cre-dependent Gi-coupled DREADD was injected unilaterally into the dorsomedial striatum of Drd1-Cre mice, resulting in expression of the modified human M4 muscarinic receptor (hM4Di) in ∼20% of dorsostriatal dSPNs. Upon hM4Di activation, a striking positive linear correlation was found between turn ratio and viral expression, which corroborates a relationship between unilateral inhibition of dorsomedial dSPNs and rotational behavior. Bursts of ipsiversive rotations were interspersed with normal ambulation. However, partial unilateral inhibition of ∼20% of dorsostriatal dSPNs did not affect horizontal and vertical locomotion or forelimb use preference. Overall, our results substantiate a unique role of dSPNs in promoting response bias in rotational behavior and show this to be a highly sensitive measure of dSPN performance.

Response Properties of Motor Equivalence Neurons of the Primate Premotor Cortex.

To study the response properties of cells that could participate in eye-hand coordination we trained two macaque monkeys to perform center-out saccades and pointing movements with their right or left forelimb toward visual targets presented on a video display. We analyzed the phasic movement related discharges of neurons of the periarcuate cortex that fire before and during saccades and movements of the hand whether accompanied by movements of the other effector or not. Because such cells could encode an abstract form of the desired displacement vector without regard to the effector that would execute the movement we refer to such cells as motor equivalence neurons (Meq). Most of them (75%) were found in or near the smooth pursuit region and the grasp related region in the caudal bank of the arcuate sulcus. The onset of their phasic discharges preceded saccades by about 70 ms and hand movements by about 150 ms and was often correlated to both the onset of saccades and the onset of hand movements. The on-direction of Meq cells was uniformly distributed without preference for ipsiversive or contraversive movements. In about half of the Meq cells the preferred direction for saccades was the preferred direction for hand movements as well. In the remaining cells the difference was considerable (>90 deg), and the on-direction for eye-hand movements resembled that for isolated saccades in some cells and for isolated hand movements in others. A three layer neural network model that used Meq cells as its input layer showed that the combination of effector invariant discharges with non-invariant discharges could help reduce the number of decoding errors when the network attempts to compute the correct movement metrics of the right effector.

Balanced activity in basal ganglia projection pathways is critical for contraversive movements.

The basal ganglia, and the striatum in particular, have been implicated in the generation of contraversive movements. The striatum projects to downstream basal ganglia nuclei through two main circuits, originating in striatonigral and striatopallidal neurons, and different models postulate that the two pathways can work in opposition or synergistically. Here we show striatonigral and striatopallidal neurons are concurrently active during spontaneous contraversive movements. Furthermore, we show that unilateral optogenetic inhibition of either or both projection pathways disrupts contraversive movements. Consistently, simultaneous activation of both neuron types produces contraversive movements. Still, we also show that imbalanced activity between the pathways can result in opposing movements being driven by each projection pathway. These data show that balanced activity in both striatal projection pathways is critical for the generation of contraversive movements and highlights that imbalanced activity between the two projection pathways can result in opposing motor output.

Concurrent activation of striatal direct and indirect pathways during action initiation

SummaryThe basal ganglia are subcortical nuclei that control voluntary actions, and are affected by a number of debilitating neurological disorders1–4. The prevailing model of basal ganglia function proposes that two orthogonal projection circuits originating from distinct populations of spiny projection neurons (SPNs) in the striatum5,6 - the so-called direct and indirect pathways - have opposing effects on movement: while activity of direct-pathway SPNs purportedly facilitates movement, activity of indirect-pathway SPNs inhibits movement1,2. This model has been difficult to test due to the lack of methods to selectively measure the activity of direct- and indirect-pathway SPNs in freely moving animals. We developed a novel in-vivo method that allowed us to specifically measure direct- and indirect-pathway SPN activity using Cre-dependent viral expression of the genetically encoded calcium indicator (GECI) GCAMP3 in the dorsal striatum of D1-Cre (direct-pathway specific6,7) and A2A-Cre (indirect-pathway specific8,9) mice10. Using fiber optics and time-correlated single photon counting (TCSPC) in mice performing an operant task, we observed transient increases in neural activity in both direct- and indirect-pathway SPNs when animals initiated actions, but not when they were inactive. Concurrent activation of SPNs from both pathways in one hemisphere preceded the initiation of contraversive movements, and predicted the occurrence of specific movements within 500 ms. These observations challenge the classical view of basal ganglia function, and may have implications for understanding the origin of motor symptoms in basal ganglia disorders.

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats.

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses.

Contribution of the rostral fastigial nucleus to the control of orienting gaze shifts in the head-unrestrained cat.

The implication of the caudal part of the fastigial nucleus (cFN) in the control of saccadic shifts of the visual axis is now well established. In contrast a possible involvement of the rostral part of the fastigial nuceus (rFN) remains unknown. In the current study we investigated in the head-unrestrained cat the contribution of the rFN to the control of visually triggered saccadic gaze shifts by measuring the deficits after unilateral muscimol injection in the rFN. A typical gaze dysmetria was observed: gaze saccades directed toward the inactivated side were hypermetric, whereas those with an opposite direction were hypometric. For both movement directions, gaze dysmetria was proportional to target retinal eccentricity and could be described as a modified gain in the translation of visual signals into eye and head motor commands. Correction saccades were triggered when the target remained visible and reduced the gaze fixation error to 2.7 +/- 1.3 degrees (mean +/- SD) on average. The hypermetria of ipsiversive gaze shifts resulted predominantly from a hypermetric response of the eyes, whereas the hypometria of contraversive gaze shifts resulted from hypometric responses of both eye and head. However, even in this latter case, the eye saccade was more affected than the motion of the head. As a consequence, for both directions of gaze shift the relative contributions of the eye and head to the overall gaze displacement were altered by muscimol injection. This was revealed by a decreased contribution of the head for ipsiversive gaze shifts and an increased head contribution for contraversive movements. These modifications were associated with slight changes in the delay between eye and head movement onsets. Inactivation of the rFN also affected the initiation of eye and head movements. Indeed, the latency of ipsiversive gaze and head movements decreased to 88 and 92% of normal, respectively, whereas the latency of contraversive ones increased to 149 and 145%. The deficits induced by rFN inactivation were then compared with those obtained after muscimol injection in the cFN of the same animals. Several deficits differed according to the site of injection within the fastigial nucleus (tonic orbital eye rotation, hypermetria of ipsiversive gaze shifts and fixation offset, relationship between dysmetria and latency of contraversive gaze shifts, postural deficit). In conclusion, the present study demonstrates that the rFN is involved in the initiation and the control of combined eye-head gaze shifts. In addition our findings support a functional distinction between the rFN and cFN for the control of orienting gaze shifts. This distinction is discussed with respect to the segregated fastigiofugal projections arising from the rFN and cFN.

Tectal codification of eye movements in goldfish studied by electrical microstimulation

This work compares the tectal codification of eye movements in goldfish with those reported for other vertebrate groups. Focal electrical stimulation was applied in various tectal zones and the characteristics of evoked eye movements were examined as a function of (i) the position of the stimulation over the tectal surface, (ii) the initial position of the eyes and (iii) the parameters (pulse rate, current strength, duration) of the stimulus. In a large medial zone, stimulation within the intermediate and deep layers of the tectum evoked contraversive saccades of both eyes, whose direction and amplitude were roughly congruent with the retinotopic representation of the visual world within overlying layers. These saccades were minimally influenced by the initial position of the eye in the orbit. The topographical arrangement of evoked saccades and body movements suggests that this tectal zone triggers orienting responses in a similar way to those described in other vertebrates. Stimulations applied within the caudal tectum also evoked contraversive saccades, but—in disagreement with the overlying retinotopic map—the vertical component was absent. Taken together with electrically evoked body movements reported in free-swimming fish, these saccades could reveal that this zone is involved in escape responses. When stimulations were applied within the anteromedial zone of the tectum, contraversive movements of both eyes appeared much more dependent on initial eye position. Saccades elicited from this area displayed characteristics of “goal-directed saccades” which were similar to those described in the cat. The generation of goal-directed movements from the anteromedial zone suggests that this portion of the goldfish optic tectum has a different intrinsic organization or is connected with the brainstem saccade generator in a different fashion than the medial zone. Finally, stimulation of the extreme anteromedial zone evoked convergent eye movements. These movements and those reported in free-swimming fish following electrical stimulation of this tectal area suggest that this zone could be involved in feeding responses. The relationships between the parameters of electrical stimulation and the characteristics of elicited saccades suggest that the stimulated location within the tectum determines a constant direction in the evoked saccade, whereas the amount and duration of tectal activity, as mimicked by changes in stimulus parameters, together with the tectal locus, determine the velocity and amplitude of the evoked saccade.

Central mesencephalic reticular formation (cMRF) neurons discharging before and during eye movements

1. One hundred twenty neurons were recorded in the central mesencephalic reticular formation (cMRF) of four rhesus monkeys, trained to make visually guided and targeted saccadic eye movements. Eye movements were recorded with the head fixed, using electrooculography (EOG) or subconjunctival scleral search coils. Seventy-six percent (92/120) of cells discharged before and during contraversive visually guided or targeted rapid eye movements, and 76% of these (70/92) responded during contraversive spontaneous saccades in the dark. cMRF neurons had large contraversive movement fields and either a high (> 10 spikes/s) or low background level of spontaneous activity in the dark. The optimal movement vectors (i.e., saccades with greatest response) were predominantly horizontal, although many had a vertical component. Cells with optimal movement vectors within +/- 25 degrees of pure vertical were more rostral in the MRF and were excluded from the analysis. 2. A subgroup of cMRF neurons (31 of 92) that discharged before and during visually guided saccades were examined for visual sensitivity. Slightly less than one-half of these cells (42%, 13/31) were visuomotor units, i.e., they responded to visual targets in the absence of eye movement. The other 58% (n = 18) did not discharge during the visual probe trial; they were movement-related cells. 3. Microstimulation (threshold 40-60 microA at 333 Hz) at the sites of many of these cMRF neurons produced contraversive saccadic eye movements at short latency (< 40 ms). The amplitude and direction of the elicited saccades were similar to the optimal movement vector determined from single-unit recording. This suggested that cMRF cells recorded at the same locus of electrical microstimulation participated in the network responsible for the production and control of rapid eye movements. 4. The 92 saccade-related neurons were divided into two groups on the basis of their background discharge rate. Firing rates for both low background (28%, n = 26) and high background (72%, n = 66) cells increased approximately 30 ms before contraversive saccades and reached a peak discharge just before saccade onset. The low background neurons had either no activity or generated a few spikes just before the end of ipsiversive saccades. The steady rate of discharge (> 10 spikes/s) of high background neurons was inhibited from approximately 20 ms before ipsiversive saccades until just before saccade end. 5. Cells were also subdivided on the basis of how their discharge rates fell at the end of saccades. Clipped cells (38%, n = 35) had activity that fell sharply with saccade offset. Partially clipped cells (62%, n = 57) had persistent firing in the 100 ms following the saccade that was > 20% higher than the firing during the 100 ms before the saccade. 6. Latencies between the 90% point on the rising edge of the peak discharge and the start of the saccade were < or = 5.3 ms for eye movement-related cells in two monkeys. Longer latencies (11-19 ms) were found when measured between the 10% point on the rising edge of the peak discharge and saccade onset. These latencies were equal to or shorter than those obtained for eye movement-related burst neurons in the intermediate and deep layers of the superior colliculus analyzed similarly. Delays between the peak discharge and peak eye velocity were 13.6-15.1 ms for the same group of cMRF eye movement-related cells. These were significantly shorter than the delays measured for eye movement neurons in the superior colliculus (SC) of one of the monkeys. These findings suggest that the buildup discharge of cMRF neurons occurs early enough before saccades to contribute to saccade triggering. The peak discharge, however, occurs with or after the burst in the SC, suggesting that this portion of the discharge serves a function other than saccade triggering. 7. The number of spikes in bursts associated with eye movement was correlated with saccade parameters.

Epileptogenic spikes and seizures but not high voltage spindles are induced by local frontal cortical application of γ-hydroxybutyrate

Combining the methods of microdialysis and EEG recording, we have examined the effect of unilaterally, intracortically applied y-hydroxybutyrate (GHB) on frontal cortical EEG activity in freely moving rats. GHB, a natural endogenous GABA metabolite, is known to induce rhythmic spike and wave activity, resembling generalized petit mal epilepsy. Without GHB, spontaneous high voltage spindles (HVS, 6–9 Hz) were observed during awake and immobile behavior in most of the animals (HVS rats), while others never had any HVS. In those both groups of animals intracortical application of GHB induced epileptogenic spikes (<0.5 Hz) behaviorally accompanied by occasional myoclonic jerks and epileptic discharges (<2 Hz) with behavioral convulsions and contraversive movements towards the left hindlimb (seizures) but did not induce HVS or spike and waves, as reported after systemic application. In the group of rats with spontaneous occurring HVS the amplitude of the HVS on the side of the microdialysis probe was suppressed by GHB and GHB-induced spikes invading the contralateral cortex frequently triggered and terminated local HVS. The results point to different neural mechanisms for the generation of HVS and spikes and epileptic discharges (seizures) induced after local intracortical application of GHB.

Quantitative analysis of visual receptive fields of neurons in nucleus of the optic tract and dorsal terminal nucleus of the accessory optic tract in macaque monkey.

1. The visual receptive field properties of neurons in the nucleus of the optic tract (NOT) in the pretectum and the dorsal terminal nucleus (DTN) of the accessory optic tract were analyzed quantitatively in anesthetized, paralyzed macaque monkeys. 2. Visual latencies to reversals in direction of stimulus movement ranged from 40 to 80 ms [61 +/- 13.5 (SD) ms]. 3. All neurons increased their discharge rate during ipsiversive movement and decreased their ongoing activity during contraversive movement of single stimuli or whole-field random dot patterns. The population of neurons in the left NOT-DTN was excited most strongly by leftward movement pointing 4 degrees down; neurons in the right NOT-DTN were excited most strongly by rightward movement pointing 6 degrees down. The mean angle between the directions yielding the highest and the lowest discharge rate in the two populations of NOT-DTN neurons was 177 degrees. 4. The deviation of the preferred excitatory directions from the horizon in individual neurons varied with recording depth. Within the first 500 microns below the midbrain surface, neurons preferred near-horizontal directions, whereas neurons recorded more deeply preferred more oblique directions of stimulus movement. 5. The tuning widths of NOT-DTN neurons in the preferred excitatory direction were very broad. The mean halfwidth defined as the range of directions eliciting responses greater than 50% of the maximum was 127 +/- 25 degrees. 6. Moving a random dot pattern and a single bar of light simultaneously but in opposite directions caused NOT-DTN neurons to increase their discharge rate as soon as one of the two stimuli moved in the ipsiversive direction. The reduction in overall discharge rates when two stimuli moved in opposite directions indicates mainly inhibitory interactions. 7. All NOT-DTN neurons could be activated from both eyes. Interactions between the two eyes were modest and unspecific. Misalignment of the visual axes of the two eyes had no influence on response strength. 8. Optimal speeds of stimulus movement varied widely for different NOT-DTN neurons. The effective range of speeds to elicit direction-selective responses in the total population was very broad (0.1400 degrees/s. With oscillating horizontal stimulation, NOT-DTN neurons followed repetition rates up to 4 Hz at excursions of 40 degrees. Speeds greater than 500 degrees/s were either not effective or resulted in a suppression of ongoing activity in all directions of movement.(ABSTRACT TRUNCATED AT 400 WORDS)

Epileptiform EEG Activities of the Centromedian Thalamic Nuclei in Patients with Intractable Partial Motor, Complex Partial, and Generalized Seizures

Centromedian thalamic nuclei (CM) epileptiform EEG activities were recorded in patients with intractable partial motor, complex partial, and generalized seizures through implanted recording-stimulating electrodes, used for seizure control. CM epileptiform activities showed either little or no correlation to focal surface cortical and amygdaloid activities in patients with partial motor and complex partial seizures: CM paroxysmal discharges were correlated to focal epileptiform ictal activities only during the contraversive movements of partial motor and complex partial seizures. In contrast, CM epileptiform activities were consistently correlated to widespread surface cortical activities and clinical symptoms of fully developed nonconvulsive and convulsive tonic-clonic generalized seizures; i.e., unilateral CM double spike-wave complex discharges significantly preceded (p less than 0.001) the contralateral CM and bilateral surface cortical discharges and symptoms of nonconvulsive generalized seizures. Unilateral CM fast-slow-fast paroxysmal discharges significantly preceded (p less than 0.005) those of the contralateral CM and bilateral surface cortical regions and symptoms of the convulsive tonic-clonic generalized seizures. Individual spike-wave complexes from the frontal region preceded (p less than 0.001 and p less than 0.005) those at CM and other cortical regions during the nonconvulsive and clonic generalized attacks. No correlations between CM and cortical epileptiform activities were found, however, in the case of abortive, subclinical thalamocortical EEG discharges.

Correlation between pulvinar-lateralis posterior complex unit activity and eye movements in the cat

In 15 encéphale isolé cats, 130 units were recorded in the pulvinar-lateralis posterior complex (P-LP); 19 units responded in relation to horizontal eye movements (15%), 9 of which discharged when ipsiversive movements were recorded and the remaining 10 to contraversive movements. Three units discharged during spontaneous nystagnoid eye movement. All units always responded after initiation of the eye movement, with a latency range between 50 and 250 ms. The eye movement-related units were preferentially located (80%) in the border between the pulvinar and the lateralis posterior complex. Our results show the presence of eye movement-related units in the cat's P-LP, and their probable participation in ocular motility.

The fronto-striatal arrest response in man

The “arrest response” produced by stimulation in the posterior frontal region and adjacent striatum has been studied in 30 patients. In essence it consists in the arrest of voluntary movement and may show additional features such as post-stimulation confusion, inappropriate or garbled speech, overt mood changes, contraversive movement of head and eyes, and occasionally somatic sensation. In two cases the response was produced from both hemispheres in the same individual. There was no evidence of a relationship between the lateralization of effective stimuli and handedness. In addition to interruption of speech, simple repetitive movements of the hand were usually inhibited and a formal continuous performance test (pressing a key to specific visual stimuli) showed marked impairment during stimulation. EEG monitoring failed to show post-stimulation epileptiform activation in 285 stimuli in thirteen patients at currents sufficient to produce arrest. In one case with prolonged post-stimulation confusion, slow wave activity was recorded from the stimulation site and recovery from this coincided with return of the patient's responses to normal. Autonomic responses, predominantly arrest of respiration, were recorded from areas overlapping those of the arrest response. Ancillary evidence was reviewed supporting the role of the striatum as a modulator of sensory-motor activity and in this way being an essential mechanism in the anatomical representation of consciousness.