Variations in clustering of multielectrode local field potentials in the motor cortex of macaque monkeys during a reach-and-grasp task.

There is experimental evidence of varying correlation among the elements of the neuromuscular system over the course of the reach-and-grasp task. Several neuromuscular disorders are accompanied by anomalies in muscular coupling during the task. The aim of this study was to investigate if modifications in correlations and clustering can be detected in the Local Field Potential (LFP) recordings of the motor cortex during the task. To this end, we analyzed the LFP recordings from a previously published study on monkeys which performed a reach-and-grasp task for targets with a vertical or horizontal orientation. LFP signals were recorded from the motor and premotor cortex of macaque monkeys as they performed the task. We found very robust changes in the correlations of the multielectrode LFP recordings which corresponded to task epochs. Mean LFP correlation increased significantly during reaching and then decreased during grasp. This pattern was very robust for both left and right arm reaches irrespective of target orientation. A hierarchical cluster analysis supported the same conclusion - a decreased number of clusters during reach followed by an increase for grasp. As most previous LFP studies have focused on the question of LFP amplitude, our study has contributed to the understanding of this signal and its relationship to movement by focusing on correlations. A sliding window computation of the number of clusters was performed to probe the capacities of these LFP clusters for detecting upcoming task events. For a very high percentage of trials (97.89%), there was a downturn in cluster number following the Pellet Drop (GO signal) which reached a minimum preceding the Start of grasp, hence indicating that cluster analyses of LFP signals could add to signaling the increased probability of the Start of grasp.Significance Statement The creation of muscular groups also called synergies for accomplishing an action is a well known feature of motor control. Since the motor cortex plays an important role in creating motor commands, it is only to be expected that such features might also be seen in this brain area. This study is among the first to show that alterations in local field potential (LFP) correlations as a function of task phase can be observed during the reach-and-grasp task by macaque monkeys. The LFPs recorded using multielectrode arrays in the motor cortex, showed increased correlations during reach, followed by decreased correlations at the start of grasp. This pattern was robust and held irrespective of which arm was employed or hand orientation.

Differential Modulation of Local Field Potentials in the Primary and Premotor Cortices during Ipsilateral and Contralateral Reach to Grasp in Macaque Monkeys.

Hand movements are associated with modulations of neuronal activity across several interconnected cortical areas, including the primary motor cortex (M1) and the dorsal and ventral premotor cortices (PMd and PMv). Local field potentials (LFPs) provide a link between neuronal discharges and synaptic inputs. Our current understanding of how LFPs vary in M1, PMd, and PMv during contralateral and ipsilateral movements is incomplete. To help reveal unique features in the pattern of modulations, we simultaneously recorded LFPs in these areas in two macaque monkeys performing reach and grasp movements with either the right or left hand. The greatest effector-dependent differences were seen in M1, at low (≤13 Hz) and γ frequencies. In premotor areas, differences related to hand use were only present in low frequencies. PMv exhibited the greatest increase in low frequencies during instruction cues and the smallest effector-dependent modulation during movement execution. In PMd, δ oscillations were greater during contralateral reach and grasp, and ß activity increased during contralateral grasp. In contrast, ß oscillations decreased in M1 and PMv. These results suggest that while M1 primarily exhibits effector-specific LFP activity, premotor areas compute more effector-independent aspects of the task requirements, particularly during movement preparation for PMv and production for PMd. The generation of precise hand movements likely relies on the combination of complementary information contained in the unique pattern of neural modulations contained in each cortical area. Accordingly, integrating LFPs from premotor areas and M1 could enhance the performance and robustness of brain-machine interfaces.

Autonomous optimization of neuroprosthetic stimulation parameters that drive the motor cortex and spinal cord outputs in rats and monkeys.

Neural stimulation can alleviate paralysis and sensory deficits. Novel high-density neural interfaces can enable refined and multipronged neurostimulation interventions. To achieve this, it is essential to develop algorithmic frameworks capable of handling optimization in large parameter spaces. Here, we leveraged an algorithmic class, Gaussian-process (GP)-based Bayesian optimization (BO), to solve this problem. We show that GP-BO efficiently explores the neurostimulation space, outperforming other search strategies after testing only a fraction of the possible combinations. Through a series of real-time multi-dimensional neurostimulation experiments, we demonstrate optimization across diverse biological targets (brain, spinal cord), animal models (rats, non-human primates), in healthy subjects, and in neuroprosthetic intervention after injury, for both immediate and continual learning over multiple sessions. GP-BO can embed and improve "prior" expert/clinical knowledge to dramatically enhance its performance. These results advocate for broader establishment of learning agents as structural elements of neuroprosthetic design, enabling personalization and maximization of therapeutic effectiveness.

A machine learning approach to characterize sequential movement-related states in premotor and motor cortices.

Nonhuman primate (NHP) movement kinematics have been decoded from spikes and local field potentials (LFPs) recorded during motor tasks. However, the potential of LFPs to provide network-like characterizations of neural dynamics during planning and execution of sequential movements requires further exploration. Is the aggregate nature of LFPs suitable to construct informative brain state descriptors of movement preparation and execution? To investigate this, we developed a framework to process LFPs based on machine-learning classifiers and analyzed LFP from a primate, implanted with several microelectrode arrays covering the premotor cortex in both hemispheres and the primary motor cortex on one side. The monkey performed a reach-to-grasp task, consisting of five consecutive states, starting from rest until a rewarding target (food) was attained. We use this five-state task to characterize neural activity within eight frequency bands, using spectral amplitude and pairwise correlations across electrodes as features. Our results show that we could best distinguish all five movement-related states using the highest frequency band (200-500 Hz), yielding an 87% accuracy with spectral amplitude, and 60% with pairwise electrode correlation. Further analyses characterized each movement-related state, showing differential neuronal population activity at above-γ frequencies during the various stages of movement. Furthermore, the topological distribution for the high-frequency LFPs allowed for a highly significant set of pairwise correlations, strongly suggesting a concerted distribution of movement planning and execution function is distributed across premotor and primary motor cortices in a specific fashion, and is most significant in the low ripple (100-150 Hz), high ripple (150-200 Hz), and multiunit frequency bands. In summary, our results show that the concerted use of novel machine-learning techniques with coarse grained queue broad signals such as LFPs may be successfully used to track and decode fine movement aspects involving preparation, reach, grasp, and reward retrieval across several brain regions.NEW & NOTEWORTHY Local field potentials (LFPs), despite lower spatial resolution compared to single-neuron recordings, can be used with machine learning classifiers to decode sequential movements involving motor preparation, execution, and reward retrieval. Our results revealed heterogeneity of neural activity on small spatial scales, further evidencing the utility of micro-electrode array recordings for complex movement decoding. With further advancement, high-dimensional LFPs may become the gold standard for brain-computer interfaces such as neural prostheses in the near future.

Rapid and Bihemispheric Reorganization of Neuronal Activity in Premotor Cortex after Brain Injury.

Brain injuries cause hemodynamic changes in several distant, spared areas from the lesion. Our objective was to better understand the neuronal correlates of this reorganization in awake, behaving female monkeys. We used reversible inactivation techniques to "injure" the primary motor cortex, while continuously recording neuronal activity of the ventral premotor cortex in the two hemispheres, before and after the onset of behavioral impairments. Inactivation rapidly induced profound alterations of neuronal discharges that were heterogeneous within each and across the two hemispheres, occurred during movements of either the affected or nonaffected arm, and varied during different phases of grasping. Our results support that extensive, and much more complex than expected, neuronal reorganization takes place in spared areas of the bihemispheric cortical network involved in the control of hand movements. This broad pattern of reorganization offers potential targets that should be considered for the development of neuromodulation protocols applied early after brain injury.SIGNIFICANCE STATEMENT It is well known that brain injuries cause changes in several distant, spared areas of the network, often in the premotor cortex. This reorganization is greater early after the injury and the magnitude of early changes correlates with impairments. However, studies to date have used noninvasive brain imaging approaches or have been conducted in sedated animals. Therefore, we do not know how brain injuries specifically affect the activity of neurons during the generation of movements. Our study clearly shows how a lesion rapidly impacts neurons in the premotor cortex of both hemispheres. A better understanding of these complex changes can help formulate hypotheses for the development of new treatments that specifically target neuronal reorganization induced by lesions in the brain.

Interhemispheric modulations of motor outputs by the rostral and caudal forelimb areas in rats.

In rats, forelimb movements are evoked from two cortical regions, the caudal and rostral forelimb areas (CFA and RFA, respectively). These areas are densely interconnected and RFA induces complex and powerful modulations of CFA outputs. CFA and RFA also have interhemispheric connections, and these areas from both hemispheres send projections to common targets along the motor axis, providing multiple potential sites of interactions for movement production. Our objective was to characterize how CFA and RFA in one hemisphere can modulate motor outputs of the opposite hemisphere. To do so, we used paired-pulse protocols with intracortical microstimulation techniques (ICMS), while recording electromyographic (EMG) activity of forelimb muscles in sedated rats. A subthreshold conditioning stimulation was applied in either CFA or RFA in one hemisphere simultaneously or before a suprathreshold test stimulation in either CFA or RFA in the opposite hemisphere. Both CFA and RFA tended to facilitate motor outputs with short (0-2.5 ms) or long (20-35 ms) delays between the conditioning and test stimuli. In contrast, they tended to inhibit motor outputs with intermediate delays, in particular 10 ms. When comparing the two areas, we found that facilitatory effects from RFA were more frequent and powerful than the ones from CFA. In contrast, inhibitory effects from CFA on its homolog were more frequent and powerful than the ones from RFA. Our results demonstrate that interhemispheric modulations from CFA and RFA share some similarities but also have clear differences that could sustain specific functions these cortical areas carry for the generation of forelimb movements.NEW & NOTEWORTHY We show that caudal and rostral forelimb areas (CFA and RFA) have distinct effects on motor outputs from the opposite hemisphere, supporting that they are distinct nodes in the motor network of rats. However, the pattern of interhemispheric modulations from RFA has no clear equivalent among premotor areas in nonhuman primates, suggesting they contribute differently to the generation of ipsilateral hand movements. Understanding these interspecies differences is important given the common use of rodent models in motor control and recovery studies.

Modulatory effects of the supplementary motor area on primary motor cortex outputs.

Premotor areas of primates are specialized cortical regions that can contribute to hand movements by modulating the outputs of the primary motor cortex (M1). The goal of the present work was to study how the supplementary motor area (SMA) located within the same hemisphere [i.e., ipsilateral SMA (iSMA)] or the opposite hemisphere [i.e., contralateral (cSMA)] modulate the outputs of M1. We used paired-pulse protocols with intracortical stimulations in sedated capuchin monkeys. A conditioning stimulus in iSMA or cSMA was delivered simultaneously or before a test stimulus in M1 with different interstimulus intervals (ISIs) while electromyographic activity was recorded in hand and forearm muscles. The pattern of modulation from iSMA and cSMA shared some clear similarities. In particular, both areas predominantly induced facilitatory effects on M1 outputs with shorter ISIs and inhibitory effects with longer ISIs. However, the incidence and strength of facilitatory effects were greater for iSMA than cSMA. We then compared the pattern of modulatory effects from SMA to the ones from the dorsal and ventral premotor cortexes (PMd and PMv) collected in the same series of experiments. Among premotor areas, the impact of SMA on M1 outputs was always weaker than the one of either PMd or PMv, and this was regardless of the hemisphere, or the ISI, tested. These results show that SMA exerts a unique set of modulations on M1 outputs, which could support its specific function for the production of hand movements.NEW & NOTEWORTHY We unequivocally isolated stimulation to either the ipsilateral or contralateral supplementary motor area (SMA) using invasive techniques and compared their modulatory effects on the outputs of primary motor cortex (M1). Modulations from both SMAs shared many similarities. However, facilitatory effects evoked from ipsilateral SMA were more common and more powerful. This pattern differs from the ones of other premotor areas, which suggests that each premotor area makes unique contributions to the production of motor outputs.

Contrasting Modulatory Effects from the Dorsal and Ventral Premotor Cortex on Primary Motor Cortex Outputs.

The dorsal and ventral premotor cortices (PMd and PMv, respectively) each take part in unique aspects for the planning and execution of hand movements. These premotor areas are components of complex anatomical networks that include the primary motor cortex (M1) of both hemispheres. One way that PMd and PMv could play distinct roles in hand movements is by modulating the outputs of M1 differently. However, patterns of effects from PMd and PMv on the outputs of M1 have not been compared systematically. Our goals were to study how PMd within the same (i.e., ipsilateral or iPMd) and in the opposite hemisphere (i.e., contralateral or cPMd) can shape M1 outputs and then compare these effects with those induced by PMv. We used paired-pulse protocols with intracortical microstimulation techniques in sedated female cebus monkeys while recording EMG signals from intrinsic hand and forearm muscles. A conditioning stimulus was delivered in iPMd or cPMd concurrently or before a test stimulus in M1. The patterns of modulatory effects from PMd were compared with those from PMv collected in the same animals. Striking differences were revealed. Conditioning stimulation in iPMd induced more frequent and powerful inhibitory effects on M1 outputs compared with iPMv. In the opposite hemisphere, cPMd conditioning induced more frequent and powerful facilitatory effects than cPMv. These contrasting patterns of modulatory effects could allow PMd and PMv to play distinct functions for the control of hand movements and predispose them to undertake different, perhaps somewhat opposite, roles in motor recovery after brain injury.SIGNIFICANCE STATEMENT The dorsal and ventral premotor cortices (PMd and PMv, respectively) are two specialized areas involved in the control of hand movements in primates. One way that PMd and PMv could participate in hand movements is by modulating or shaping the primary motor cortex (M1) outputs to hand muscles. Here, we studied the patterns of modulation from PMd within the same and in the opposite hemisphere on the outputs of M1 and compared them with those from PMv. We found that PMd and PMv have strikingly different effects on M1 outputs. These contrasting patterns of modulation provide a substrate that may allow PMd and PMv to carry distinct functions for the preparation and execution of hand movements and for recovery after brain injury.

Modulatory Effects of the Ipsi and Contralateral Ventral Premotor Cortex (PMv) on the Primary Motor Cortex (M1) Outputs to Intrinsic Hand and Forearm Muscles in Cebus apella.

The ventral premotor cortex (PMv) is a key node in the neural network involved in grasping. One way PMv can carry out this function is by modulating the outputs of the primary motor cortex (M1) to intrinsic hand and forearm muscles. As many PMv neurons discharge when grasping with either arm, both PMv within the same hemisphere (ipsilateral; iPMv) and in the opposite hemisphere (contralateral; cPMv) could modulate M1 outputs. Our objective was to compare modulatory effects of iPMv and cPMv on M1 outputs to intrinsic hand and forearm muscles. We used paired-pulse protocols with intracortical microstimulations in capuchin monkeys. A conditioning stimulus was applied in either iPMv or cPMv simultaneously or prior to a test stimulus in M1 and the effects quantified in electromyographic signals. Modulatory effects from iPMv were predominantly facilitatory, and facilitation was much more common and powerful on intrinsic hand than forearm muscles. In contrast, while the conditioning of cPMv could elicit facilitatory effects, in particular to intrinsic hand muscles, it was much more likely to inhibit M1 outputs. These data show that iPMv and cPMv have very different modulatory effects on the outputs of M1 to intrinsic hand and forearm muscles.

Parallel Cortical Networks Formed by Modular Organization of Primary Motor Cortex Outputs.

In primates, the refinement of motor behaviors, in particular hand use, is associated with the establishment of more direct projections from primary motor cortex (M1) onto cervical motoneurons [1, 2] and the appearance of additional premotor and sensory cortical areas [3]. All of these areas have reciprocal connections with M1 [4-7]. Thus, during the evolution of the sensorimotor network, the number of interlocutors with which M1 interacts has tremendously increased. It is not clear how these additional interconnections are organized in relation to one another within the hand representation of M1. This is important because the organization of connections between M1 and phylogenetically newer and specialized cortical areas is likely to be key to the increased repertoire of hand movements in primates. In cebus monkeys, we used injections of retrograde tracers into the hand representation of different cortical areas of the sensorimotor network (ventral and dorsal premotor areas [PMv and PMd], supplementary motor area [SMA], and posterior parietal cortex [area 5]), and we analyzed the pattern of labeled neurons within the hand representation of M1. Instead of being uniformly dispersed across M1, neurons sending projections to each distant cortical area were largely segregated in different subregions of M1. These data support the view that primates split the cortical real estate of M1 into modules, each preferentially interconnected with a particular cortical area within the sensorimotor network. This modular organization could sustain parallel processing of interactions with multiple specialized cortical areas to increase the behavioral repertoire of the hand.

Different Patterns of Cortical Inputs to Subregions of the Primary Motor Cortex Hand Representation in Cebus apella.

The primary motor cortex (M1) plays an essential role in the control of hand movements in primates and is part of a complex cortical sensorimotor network involving multiple premotor and parietal areas. In a previous study in squirrel monkeys, we found that the ventral premotor cortex (PMv) projected mainly to 3 regions within the M1 forearm representation [rostro-medial (RM), rostro-lateral (RL), and caudo-lateral (CL)] with very few caudo-medial (CM) projections. These results suggest that projections from premotor areas to M1 are not uniform, but rather segregated into subregions. The goal of the present work was to study how inputs from diverse areas of the ipsilateral cortical network are organized within the M1 hand representation. In Cebus apella, different retrograde neuroanatomical tracers were injected in 4 subregions of the hand area of M1 (RM, RL, CM, and CL). We found a different pattern of input to each subregion of M1. RM receives inputs predominantly from dorsal premotor cortex, RL from PMv, CM from area 5, and CL from area 2. These results support that the M1 hand representation is composed of several subregions, each part of a unique cortical network.

Which Aspects of Stroke Do Animal Models Capture? A Multitracer Micro-PET Study of Focal Ischemia with Endothelin-1.

BACKGROUND: Cortical injections of the vasoconstrictor endothelin-1 (ET1) have widely been used to induce focal circumscribed ischemic lesions in the motor cortex of rodents in the context of stroke recovery studies. In order to apply this model correctly, it is essential to understand the time course of regional flow changes and of the development of penumbra and infarction. METHODS: Multitracer micro-PET of ET1 focal ischemia in rats was performed using [11C]-flumazenil ([11C]FMZ) as a flow- and viability tracer and [18F]-fluoromisonidazole ([18F]FMISO) as hypoxia marker in order to characterize the physiological time-course of this model. Nine adult Sprague-Dawley rats received stereotaxic injections of ET1 into the right primary motor cortex, 3 served as controls. PET imaging was started 2, 3 and 20 h after the last ET1 injection. Histology was obtained at the end of the scans. Standardized uptake value ratios reflecting cerebral blood flow (CBF), [11C]FMZ-binding and [18F]FMISO-retention were calculated for the region of hypoperfusion and the normoperfused cortex. RESULTS: CBF in the hypoperfused cortex was significantly reduced (p < 0.01) at 5 h (0.58 ± 0.025), 6 h (0.54 ± 0.043) and 23 h (0.66 ± 0.024) compared to controls (1.00 ± 0.011) and moderately reduced (p < 0.05) in the remainder of the affected hemisphere at 5 h (0.93 ± 0.036). [11C]FMZ-binding was within the control range at all time points. Significant [18F]FMISO-retention (1.16 ± 0.091, p < 0.05) was observed only after 6 h in the ischemic core that later turned into infarct. CONCLUSION: ET1 injections yield reproducible, slowly developing ischemic lesions with constant levels of hypoperfusion. This multitracer micro-PET study suggests that the ET1 model is appropriate for inducing chronic circumscribed ischemic lesions but seems to be less suited for studying acute stroke pathophysiology.

The Effect of Lesion Size on the Organization of the Ipsilesional and Contralesional Motor Cortex.

Recovery of hand function following lesions in the primary motor cortex (M1) is associated with a reorganization of premotor areas in the ipsilesional hemisphere, and this reorganization depends on the size of the lesion. It is not clear how lesion size affects motor representations in the contralesional hemisphere and how the effects in the 2 hemispheres compare. Our goal was to study how lesion size affects motor representations in the ipsilesional and contralesional hemispheres. In rats, we induced lesions of different sizes in the caudal forelimb area (CFA), the equivalent of M1. The effective lesion volume in each animal was quantified histologically. Behavioral recovery was evaluated with the Montoya Staircase task for 28 days after the lesion. Then, the organization of the CFA and the rostral forelimb area (RFA)--the putative premotor area in rats--in the 2 cerebral hemispheres was studied with intracortical microstimulation mapping techniques. The distal forelimb representation in the RFA of both the ipsilesional and contralesional hemispheres was positively correlated with the size of the lesion. In contrast, lesion size had no effect on the contralesional CFA, and there was no relationship between movement representations in the 2 hemispheres. Finally, only the contralesional RFA was negatively correlated with chronic motor deficits of the paretic forelimb. Our data show that lesion size has comparable effects on motor representations in premotor areas of both hemispheres and suggest that the contralesional premotor cortex may play a greater role in the recovery of the paretic forelimb following large lesions.

Acute inactivation of the contralesional hemisphere for longer durations improves recovery after cortical injury.

A rapidly growing number of studies using inhibition of the contralesional hemisphere after stroke are reporting improvement in motor performance of the paretic hand. These studies have used different treatment onset time, duration and non-invasive methods of inhibition. Whereas these results are encouraging, several questions regarding the mechanisms of inhibition and the most effective treatment parameters are currently unanswered. In the present study, we used a rat model of cortical lesion to study the effects of GABA-mediated inactivation on motor recovery. In particular, we were interested in understanding better the effect of inactivation duration when it is initiated within hours following a cortical lesion. Cortical lesions were induced with endothelin-1 microinjections. The contralesional hemisphere was inactivated with continuous infusion of the GABA-A agonist Muscimol for 3, 7 or 14days in three different groups of animals. In a fourth group, Muscimol was infused at slower rate for 14days to provide additional insights on the relation between the effects of inactivation on the non-paretic forelimb behavior and the recovery of the paretic forelimb. In spontaneously recovered animals, the lesion caused a sustained bias to use the non-paretic forelimb and long-lasting grasping deficits with the paretic forelimb. Contralesional inactivation produced a general decrease of behavioral activity, affected the spontaneous use of the forelimbs and caused a specific reduction of the non-paretic forelimb function. The intensity and the duration of these behavioral effects varied in the different experimental groups. For the paretic forelimb, increasing inactivation duration accelerated the recovery of grasping function. Both groups with 14days of inactivation had similar recovery profiles and performed better than animals that spontaneously recovered. Whereas the plateau performance of the paretic forelimb correlated with the duration of contralesional inactivation, it was not correlated with the spontaneous use of the forelimbs or with grasping performance of the non-paretic hand. Our results support that contralesional inactivation initiated within hours after a cortical lesion can improve recovery of the paretic forelimb. In our model, increasing the duration of the inactivation improved motor outcomes but the spontaneous use and motor performance of the non-paretic forelimb had no impact on recovery of the paretic forelimb.

The locus of motor activity in the superior colliculus of the rhesus monkey is unaltered during saccadic adaptation.

The location of motor-related activity in the deeper layers of the superior colliculus (SC) is thought to generate a desired displacement command specifying the amplitude and direction of saccadic eye movements. However, the amplitude of saccadic eye movements made to visual targets can be systematically altered by surreptitiously moving the target location after the saccade has been initiated. Depending on whether the target is moved closer to or further from the fixation location, adaptation of saccade amplitude results in movements that are either smaller or larger than control movements. It remains an open question whether the SC specifies the desired movement to the original target location or whether SC activity specifies the vector of the amplitude-altered movement that is observed as adaptation progresses. We investigated this question by recording the activity of saccade-related burst neurons in the SC of head-restrained rhesus monkeys during both backward and forward saccadic adaptation. During adaptation in each direction, we find no evidence that is consistent with a change in the locus of SC activity despite changes in saccade amplitude; the location of SC motor-related activity does not appear to be remapped during either forward or backward saccadic adaptation. These data are inconsistent with hypotheses that propose a key role for the SC in mediating the changes in saccade amplitude observed during adaptation.

Multisensory integration shortens physiological response latencies.

Individual superior colliculus (SC) neurons integrate information from multiple sensory sources to enhance their physiological response. The response of an SC neuron to a cross-modal stimulus combination can not only exceed the best component unisensory response but can also exceed their arithmetic sum (i.e., superadditivity). The present experiments were designed to investigate the temporal profile of multisensory integration in this model system. We found that cross-modal stimuli frequently shortened physiological response latencies (mean shift, 6.2 ms) and that response enhancement was greatest in the initial phase of the response (the phenomenon of initial response enhancement). The vast majority of the responses studied evidenced superadditive computations, most often at the beginning of the multisensory response.

Evaluating the operations underlying multisensory integration in the cat superior colliculus.

It is well established that superior colliculus (SC) multisensory neurons integrate cues from different senses; however, the mechanisms responsible for producing multisensory responses are poorly understood. Previous studies have shown that spatially congruent cues from different modalities (e.g., auditory and visual) yield enhanced responses and that the greatest relative enhancements occur for combinations of the least effective modality-specific stimuli. Although these phenomena are well documented, little is known about the mechanisms that underlie them, because no study has systematically examined the operation that multisensory neurons perform on their modality-specific inputs. The goal of this study was to evaluate the computations that multisensory neurons perform in combining the influences of stimuli from two modalities. The extracellular activities of single neurons in the SC of the cat were recorded in response to visual, auditory, and bimodal visual-auditory stimulation. Each neuron was tested across a range of stimulus intensities and multisensory responses evaluated against the null hypothesis of simple summation of unisensory influences. We found that the multisensory response could be superadditive, additive, or subadditive but that the computation was strongly dictated by the efficacies of the modality-specific stimulus components. Superadditivity was most common within a restricted range of near-threshold stimulus efficacies, whereas for the majority of stimuli, response magnitudes were consistent with the linear summation of modality-specific influences. In addition to providing a constraint for developing models of multisensory integration, the relationship between response mode and stimulus efficacy emphasizes the importance of considering stimulus parameters when inducing or interpreting multisensory phenomena.

Electrical stimulation of rhesus monkey nucleus reticularis gigantocellularis. I. Characteristics of evoked head movements.

The nucleus reticularis gigantocellularis (NRG) receives monosynaptic input from the superior colliculus (SC) and projects directly to neck motor neuron pools. Neurons in NRG are well situated to play a critical role in transforming SC signals into head movement commands. A previous study of movements evoked by NRG stimulation in the primate reported a variety of ipsilateral and contralateral head movements with horizontal, vertical and torsional components. In addition to head movements, it was reported that NRG stimulation could evoke movements of the pinnae, face, upper torso, and co-contraction of neck muscles. In this report, the role of the rhesus monkey NRG in head movement control was investigated using electrical stimulation of the rostral portion of the NRG. The goal was to characterize head movements evoked by NRG stimulation, describe the effects of altering stimulation parameters, and assess the relative movements of the eyes and head. Results indicate that electrical stimulation in the rostral portion of the NRG of the primate can consistently evoke ipsilateral head rotations in the horizontal plane. Head movement amplitude and peak velocity depend upon stimulation parameters (primarily frequency and duration of stimulation trains). During stimulation-induced head movements the eyes counter-rotate (presumably a result of the vestibulo-ocular reflex: VOR). At 46 stimulation sites from two subjects the average gain of this counter-rotation was -0.38 (+/-0.18). After the end of the stimulation train the head generally continued to move. During this epoch, after electrical stimulation ceased, VOR gain remained at this reduced level. In addition, VOR gain was similarly low when electrical stimulation was carried out during active fixation of a visual target. These data extend existing descriptions of head movements evoked by electrical stimulation of the NRG, and add to the understanding of the role of this structure in producing head movements.

Electrical stimulation of rhesus monkey nucleus reticularis gigantocellularis. II. Effects on metrics and kinematics of ongoing gaze shifts to visual targets.

Saccade kinematics are altered by ongoing head movements. The hypothesis that a head movement command signal, proportional to head velocity, transiently reduces the gain of the saccadic burst generator (Freedman 2001, Biol Cybern 84:453-462) can account for this observation. Using electrical stimulation of the rhesus monkey nucleus reticularis gigantocellularis (NRG) to alter the head contribution to ongoing gaze shifts, two critical predictions of this gaze control hypothesis were tested. First, this hypothesis predicts that activation of the head command pathway will cause a transient reduction in the gain of the saccadic burst generator. This should alter saccade kinematics by initially reducing velocity without altering saccade amplitude. Second, because this hypothesis does not assume that gaze amplitude is controlled via feedback, the added head contribution (produced by NRG stimulation on the side ipsilateral to the direction of an ongoing gaze shift) should lead to hypermetric gaze shifts. At every stimulation site tested, saccade kinematics were systematically altered in a way that was consistent with transient reduction of the gain of the saccadic burst generator. In addition, gaze shifts produced during NRG stimulation were hypermetric compared with control movements. For example, when targets were briefly flashed 30 degrees from an initial fixation location, gaze shifts during NRG stimulation were on average 140% larger than control movements. These data are consistent with the predictions of the tested hypothesis, and may be problematic for gaze control models that rely on feedback control of gaze amplitude, as well as for models that do not posit an interaction between head commands and the saccade burst generator.

Visual search is facilitated by scene and sequence familiarity in rhesus monkeys.

Whether searching for targets in a familiar scene leads to improved performance was tested in monkeys. We found that search performance improved for a familiar scene when target locations were always randomized. However, when target locations repeatedly followed a predictable sequence, performance improvement for a familiar scene was manifested only for targets presented in a familiar sequence, suggesting that scene memory might be masked by the learning of target sequences. These results suggest that information about a visual scene can facilitate the performance of visual search, and that this memory is coupled to the learned sequence of target locations.