A network analysis of developing brain cultures.

We recorded electrical activity from four developing embryonic brain cultures (4-40 days in vitro) using multielectrode arrays (MEAs) with 60 embedded electrodes. Data were filtered for local field potentials (LFPs) and downsampled to 1 ms to yield a matrix of time series consisting of 60 electrode × 60 000 time samples per electrode per day per MEA. Each electrode time series was rendered stationary and nonautocorrelated by applying an ARIMA (25, 1, 1) model and taking the residuals (i.e. innovations). Two kinds of analyses were then performed. First, a pairwise crosscorrelation (CC) analysis (±25 1 ms lags) revealed systematic changes in CC with lag, day in vitro (DIV), and inter-electrode distance. Specifically, (i) positive CCs were 1.76× more prevalent and 1.44× stronger (absolute value) than negative ones, and (ii) the strength of CC increased with DIV and decreased with lag and inter-electrode distance. Second, a network equilibrium analysis was based on the instantaneous (1 ms resolution) logratio of the number of electrodes that were above or below their mean, called simultaneous departure from equilibrium, SDE. This measure possesses a major computational advantage over the pairwise crosscorrelation approach because it is very simple and fast to calculate, an important factor for the analysis of large networks. The results obtained with SDE covaried highly with CC over DIV, which further validates the usefulness of this measure as a computationally effective tool for large scale network analysis.

True associations between resting fMRI time series based on innovations.

We calculated voxel-by-voxel pairwise crosscorrelations between prewhitened resting-state BOLD fMRI time series recorded from 60 cortical areas (30 per hemisphere) in 18 human subjects (nine women and nine men). Altogether, more than a billion-and-a-quarter pairs of BOLD time series were analyzed. For each pair, a crosscorrelogram was computed by calculating 21 crosscorrelations, namely at zero lag ± 10 lags of 2 s duration each. For each crosscorrelogram, in turn, the crosscorrelation with the highest absolute value was found and its sign, value, and lag were retained for further analysis. In addition, the crosscorrelations at zero lag (irrespective of the location of the peak) were also analyzed as a special case. Based on known varying density of anatomical connectivity, we distinguished four general brain groups for which we derived summary statistics of crosscorrelations between voxels within an area (group I), between voxels of paired homotopic areas across the two hemispheres (group II), between voxels of an area and all other voxels in the same (ipsilateral) hemisphere (group III), and voxels of an area and all voxels in the opposite (contralateral) hemisphere (except those in the homotopic area) (group IV). We found the following. (a) Most of the crosscorrelogram peaks occurred at zero lag, followed by ± 1 lag; (b) over all groups, positive crosscorrelations were much more frequent than negative ones; (c) average crosscorrelation was highest for group I, and decreased progressively for groups II-IV; (d) the ratio of positive over negative crosscorrelations was highest for group I and progressively smaller for groups II-IV; (e) the highest proportion of positive crosscorrelations (with respect to all positive ones) was observed at zero lag; and (f) the highest proportion of negative crosscorrelations (with respect to all negative ones) was observed at lag = 2. These findings reveal a systematic pattern of crosscorrelations with respect to their sign, magnitude, lag and brain group, as defined above. Given that these groups were defined along a qualitative gradient of known overall anatomical connectivity, our results suggest that functional interactions between two voxels may simply reflect the density of such anatomical connectivity between the areas to which the voxels belong.

Post-traumatic stress disorder: a right temporal lobe syndrome?

In a recent paper (Georgopoulos et al 2010 J. Neural Eng. 7 016011) we reported on the power of the magnetoencephalography (MEG)-based synchronous neural interactions (SNI) test to differentiate post-traumatic stress disorder (PTSD) subjects from healthy control subjects and to classify them with a high degree of accuracy. Here we show that the main differences in cortical communication circuitry between these two groups lie in the miscommunication of temporal and parietal and/or parieto-occipital right hemispheric areas with other brain areas. This lateralized temporal-posterior pattern of miscommunication was very similar but was attenuated in patients with PTSD in remission. These findings are consistent with observations (Penfield 1958 Proc. Natl Acad. Sci. USA 44 51-66, Penfield and Perot 1963 Brain 86 595-696, Gloor 1990 Brain 113 1673-94, Banceaud et al 1994 Brain 117 71-90, Fried 1997 J. Neuropsychiatry Clin. Neurosci. 9 420-8) that electrical stimulation of the temporal cortex in awake human subjects, mostly in the right hemisphere, can elicit the re-enactment and re-living of past experiences. Based on these facts, we attribute our findings to the re-experiencing component of PTSD and hypothesize that it reflects an involuntarily persistent activation of interacting neural networks involved in experiential consolidation.

The synchronous neural interactions test as a functional neuromarker for post-traumatic stress disorder (PTSD): a robust classification method based on the bootstrap.

Traumatic experiences can produce post-traumatic stress disorder (PTSD) which is a debilitating condition and for which no biomarker currently exists (Institute of Medicine (US) 2006 Posttraumatic Stress Disorder: Diagnosis and Assessment (Washington, DC: National Academies)). Here we show that the synchronous neural interactions (SNI) test which assesses the functional interactions among neural populations derived from magnetoencephalographic (MEG) recordings (Georgopoulos A P et al 2007 J. Neural Eng. 4 349-55) can successfully differentiate PTSD patients from healthy control subjects. Externally cross-validated, bootstrap-based analyses yielded >90% overall accuracy of classification. In addition, all but one of 18 patients who were not receiving medications for their disease were correctly classified. Altogether, these findings document robust differences in brain function between the PTSD and control groups that can be used for differential diagnosis and which possess the potential for assessing and monitoring disease progression and effects of therapy.

Neurophysiology of the parieto-frontal system during target interception.

We studied the functional properties of neurons of two elements of the parieto-frontal system: area 7a of the PPC and the motor cortex (M1), during an interception task of stimuli moving in real (RM) and apparent motion (AM). The stimulus moved along a circular path with one of 5 speeds, and was intercepted at 6 o'clock by exerting a force pulse on a joystick. A smooth stimulus motion was produced in RM, whereas in AM 5 stimuli were flashed successively at the vertices of a pentagon. The results showed, that a group of neurons in both areas above responded not only during the interception but also during a NOGO task in which the same stimuli were presented in the absence of a motor response. Most of these neurons were tuned to the stimulus angular position. In addition, we found that the time-varying neuronal activity in both areas was related to various aspects of stimulus motion and hand force, with stimulus-related activity prevailing in area 7a and hand-related activity prevailing in M1. Interestingly, the neural activity was selectively associated with the stimulus angle during RM, whereas it was tightly correlated to the time-to-contact during AM. Thus, the results suggest that area 7a was processing high level features of the circularly moving stimuli and was involved in the production of an early command signal for stimulus interception, whereas M1 was still processing some aspect of the visual stimulus that were used to trigger the interception movement using a predictive mechanism.

Impact of path parameters on maze solution time.

In order to compare spatial attention and visual processing capabilities of humans and rhesus macaques, we developed a visual maze task both could perform. Maze stimuli were constructed of orthogonal line segments displayed on a monitor. Each was octagonal in outline and contained a central square (the 'start box'). A single ('main') path, containing a random number of turns, extended outward from the start box, and either reached an exit in the maze's perimeter, or a blind ending within the maze. Subjects maintained ocular fixation within the start box, and indicated their judgment whether the path reached an exit or not by depressing one of two keys (humans) or foot pedals (monkeys). Successful maze solution by human subjects required a minimum viewing time. Replacing the maze with a masking stimulus after a variable interval revealed that the percent correct performance increased systematically with greater viewing time, reaching a plateau of approximately 85% correct if mazes were visible for 500 ms or more. A multiple linear regression analysis determined that the response time of both species depended upon several parameters of the main path, including the number of turns, total length, and exist status. Human and nonhuman primates required comparable time to process each turn in the path, whereas monkeys were faster than humans in processing each unit of path length. The data suggest that a covert analysis of the maze proceeds from the center outward along the main path in the absence of saccadic eye movements, and that both monkeys and humans undertake such an analysis during the solution of visual mazes.

Effects of optic flow in motor cortex and area 7a.

Moving visual stimuli were presented to behaving monkeys who fixated their eyes and did not move their arm. The stimuli consisted of random dots moving coherently in eight different kinds of motion (right, left, up, downward, expansion, contraction, clockwise, and counterclockwise) and were presented in 25 square patches on a liquid crystal display projection screen. Neuronal activity in the arm area of the motor cortex and area 7a was significantly influenced by the visual stimulation, as assessed using an ANOVA. The percentage of cells with a statistically significant effect of visual stimulation was 3 times greater in area 7a (370/587, 63%) than in motor cortex (148/693, 21.4%). With respect to stimulus properties, its location and kind of motion had differential effects on cell activity in the two areas. Specifically, the percentage of cells with a significant stimulus location effect was approximately 2.5 times higher in area 7a (311/370, 84%) than in motor cortex (48/148, 32.4%), whereas the percentage of cells with a significant stimulus motion effect was approximately 2 times higher in the motor cortex (79/148, 53.4%) than in area 7a (102/370, 27.6%). We also assessed the selectivity of responses to particular stimulus motions using a Poisson train analysis and determined the percentage of cells that showed activation in only one stimulus condition. This percentage was 2 times higher in the motor cortex (73.7%) than in area 7a (37.7%). Of all kinds of stimulus motion tested, responses to expanding optic flow were the strongest in both cortical areas. Finally, we compared the activation of motor cortical cells during visual stimulation to that observed during force exertion in a center --> out task. Of 514 cells analyzed for both the motor and visual tasks, 388 (75.5%) showed a significant relation to either or both tasks, as follows: 284/388 (73.2%) cells showed a significant relation only to the motor task, 27/388 (7%) cells showed a significant relation only to the visual task, whereas the remaining 77/388 (19.8%) cells showed significant relations to both tasks. Therefore a total of 361/514 (70.2%) cells were related to the motor task and 104/514 (20.2%) were related to the visual task. Finally, with respect to receptive fields (RFs), there was no clear visual receptive field structure in the motor cortical neuronal responses, in contrast to area 7a where RFs were present and could be modulated by the type of optic flow stimulus.

Guiding contact by coupling the taus of gaps.

Animals control contact with surfaces when locomoting, catching prey, etc. This requires sensorily guiding the rate of closure of gaps between effectors such as the hands, feet or jaws and destinations such as a ball, the ground and a prey. Control is generally rapid, reliable and robust, even with small nervous systems: the sensorimotor processes are therefore probably rather simple. We tested a hypothesis, based on general tau theory, that closing two gaps simultaneously, as required in many actions, might be achieved simply by keeping the taus of the gaps coupled in constant ratio. tau of a changing gap is defined as the time-to-closure of the gap at the current closure-rate. General tau theory shows that tau of a gap could, in principle, be directly sensed without needing to sense either the gap size or its rate of closure. In our experiment, subjects moved an effector (computer cursor) to a destination zone indicated on the computer monitor, to stop in the zone just as a moving target cursor reached it. The results indicated the subjects achieved the task by keeping tau of the gap between effector and target coupled to tau of the gap between the effector and the destination zone. Evidence of tau-coupling has also been found, for example, in bats guiding landing using echolocation. Thus, it appears that a sensorimotor process used by different species for coordinating the closure of two or more gaps between effectors and destinations entails constantly sensing the taus of the gaps and moving so as to keep the taus coupled in constant ratio.

Motor cortical activity during interception of moving targets.

The single-unit activity of 831 cells was recorded in the arm area of the motor cortex of two monkeys while the monkeys intercepted a moving visual stimulus (interception task) or remained immobile during presentation of the same moving stimulus (no-go task). The moving target traveled on an oblique path from either lower corner of a screen toward the vertical meridian, and its movement time (0.5, 1.0, or 1.5 sec) and velocity profile (accelerating, decelerating, or constant velocity) were pseudorandomly varied. The moving target had to be intercepted within 130 msec of target arrival at an interception point. By comparing motor cortical activity at the single-neuron and population levels between the interception and no-go tasks, we tested whether information about parameters of moving target is represented in the primary motor cortex to generate appropriate motor responses. A substantial number of neurons displayed modulation of their activity during the no-go task, and this activity was often affected by the stimulus parameters. These results suggest a role of motor cortex in specifying the timing of movement initiation based on information about target motion. In addition, there was a lack of systematic relation between the onset times of neural activity in the interception and no-go tasks, suggesting that processing of information concerning target motion and generation of hand movement occurs in parallel. Finally, the activity in the most motor cortical neurons was modulated according to an estimate of the time-to-target interception, raising the possibility that time-to-interception may be coded in the motor cortical activity.

Neuronal clusters in the primate motor cortex during interception of moving targets.

Two rhesus monkeys were trained to intercept a moving target at a fixed location with a feedback cursor controlled by a 2-D manipulandum. The direction from which the target appeared, the time from the target onset to its arrival at the interception point, and the target acceleration were randomized for each trial, thus requiring the animal to adjust its movement according to the visual input on a trial-by-trial basis. The two animals adopted different strategies, similar to those identified previously in human subjects. Single-cell activity was recorded from the arm area of the primary motor cortex in these two animals, and the neurons were classified based on the temporal patterns in their activity, using a nonhierarchical cluster analysis. Results of this analysis revealed differences in the complexity and diversity of motor cortical activity between the two animals that paralleled those of behavioral strategies. Most clusters displayed activity closely related to the kinematics of hand movements. In addition, some clusters displayed patterns of activation that conveyed additional information necessary for successful performance of the task, such as the initial target velocity and the interval between successive submovements, suggesting that such information is represented in selective subpopulations of neurons in the primary motor cortex. These results also suggest that conversion of information about target motion into movement-related signals takes place in a broad network of cortical areas including the primary motor cortex.

Functional magnetic resonance imaging of visual object construction and shape discrimination : relations among task, hemispheric lateralization, and gender.

We studied the brain activation patterns in two visual image processing tasks requiring judgements on object construction (FIT task) or object sameness (SAME task). Eight right-handed healthy human subjects (four women and four men) performed the two tasks in a randomized block design while 5-mm, multislice functional images of the whole brain were acquired using a 4-tesla system using blood oxygenation dependent (BOLD) activation. Pairs of objects were picked randomly from a set of 25 oriented fragments of a square and presented to the subjects approximately every 5 sec. In the FIT task, subjects had to indicate, by pushing one of two buttons, whether the two fragments could match to form a perfect square, whereas in the SAME task they had to decide whether they were the same or not. In a control task, preceding and following each of the two tasks above, a single square was presented at the same rate and subjects pushed any of the two keys at random. Functional activation maps were constructed based on a combination of conservative criteria. The areas with activated pixels were identified using Talairach coordinates and anatomical landmarks, and the number of activated pixels was determined for each area. Altogether, 379 pixels were activated. The counts of activated pixels did not differ significantly between the two tasks or between the two genders. However, there were significantly more activated pixels in the left (n = 218) than the right side of the brain (n = 161). Of the 379 activated pixels, 371 were located in the cerebral cortex. The Talairach coordinates of these pixels were analyzed with respect to their overall distribution in the two tasks. These distributions differed significantly between the two tasks. With respect to individual dimensions, the two tasks differed significantly in the anterior--posterior and superior--inferior distributions but not in the left--right (including mediolateral, within the left or right side) distribution. Specifically, the FIT distribution was, overall, more anterior and inferior than that of the SAME task. A detailed analysis of the counts and spatial distributions of activated pixels was carried out for 15 brain areas (all in the cerebral cortex) in which a consistent activation (in > or = 3 subjects) was observed (n = 323 activated pixels). We found the following. Except for the inferior temporal gyrus, which was activated exclusively in the FIT task, all other areas showed activation in both tasks but to different extents. Based on the extent of activation, areas fell within two distinct groups (FIT or SAME) depending on which pixel count (i.e., FIT or SAME) was greater. The FIT group consisted of the following areas, in decreasing FIT/SAME order (brackets indicate ties): GTi, GTs, GC, GFi, GFd, [GTm, GF], GO. The SAME group consisted of the following areas, in decreasing SAME/FIT order : GOi, LPs, Sca, GPrC, GPoC, [GFs, GFm]. These results indicate that there are distributed, graded, and partially overlapping patterns of activation during performance of the two tasks. We attribute these overlapping patterns of activation to the engagement of partially shared processes. Activated pixels clustered to three types of clusters : FIT-only (111 pixels), SAME-only (97 pixels), and FIT + SAME (115 pixels). Pixels contained in FIT-only and SAME-only clusters were distributed approximately equally between the left and right hemispheres, whereas pixels in the SAME + FIT clusters were located mostly in the left hemisphere. With respect to gender, the left-right distribution of activated pixels was very similar in women and men for the SAME-only and FIT + SAME clusters but differed for the FIT-only case in which there was a prominent left side preponderance for women, in contrast to a right side preponderance for men. We conclude that (a) cortical mechanisms common for processing visual object construction and discrimination involve mostly the left hemisphere, (b) cortical mechanisms specific for these tasks engage both hemispheres, and (c) in object construction only, men engage predominantly the right hemisphere whereas women show a left-hemisphere preponderance.

Mental maze solving.

We sought to determine how a visual maze is mentally solved. Human subjects (N = 13) viewed mazes with orthogonal, unbranched paths; each subject solved 200-600 mazes in any specific experiment below. There were four to six openings at the perimeter of the maze, of which four were labeled: one was the entry point and the remainder were potential exits marked by Arabic numerals. Starting at the entry point, in some mazes the path exited, whereas in others it terminated within the maze. Subjects were required to type the number corresponding to the true exit (if the path exited) or type zero (if the path did not exit). In all cases, the only required hand movement was a key press, and thus the hand never physically traveled through the maze. Response times (RT) were recorded and analyzed using a multiple linear regression model. RT increased as a function of key parameters of the maze, namely the length of the main path, the number of turns in the path, the direct distance from entry to termination, and the presence of an exit. The dependence of RT on the number of turns was present even when the path length was fixed in a separate experiment (N = 10 subjects). In a different experiment, subjects solved large and small mazes (N = 3 subjects). The former was the same as the latter but was scaled up by 1.77 times. Thus both kinds of mazes contained the same number of squares but each square subtended 1.77 degrees of visual angle (DVA) in the large maze, as compared to 1 DVA in the small one. We found that the average RT was practically the same in both cases. A multiple regression analysis revealed that the processing coefficients related to maze distance (i.e., path length and direct distance) were reduced by approximately one-half when solving large mazes, as compared to solving small mazes. This means that the efficiency in processing distance-related information almost doubled for scaled-up mazes. In contrast, the processing coefficients for number of turns and exit status were practically the same in the two cases. Finally, the eye movements of three subjects were recorded during maze solution. They consisted of sequences of saccades and fixations. The number of fixations in a trial increased as a linear function of the path length and number of turns. With respect to the fixations themselves, eyes tended to fixate on the main path and to follow it along its course, such that fixations occurring later in time were positioned at progressively longer distances from the entry point. Furthermore, the time the eyes spent at each fixation point increased as a linear function of the length and number of turns in the path segment between the current and the upcoming fixation points. These findings suggest that the maze segment from the current fixation spot to the next is being processed during the fixation time (FT), and that a significant aspect of this processing relates to the length and turns in that segment. We interpreted these relations to mean that the maze was mentally traversed. We then estimated the distance and endpoint of the path mentally traversed within a specific FT; we also hypothesized that the next portion of the main path would be traversed during the ensuing FT, and so on for the whole path. A prediction of this hypothesis is that the upcoming saccade would land the eyes at or near the locus on the path where the mental traversing ended, so that "the eyes would pick up where the mental traversal left off." In this way, a portion of the path would be traversed during a fixation and successive such portions would be strung together closely along the main path to complete the processing of the whole path. We tested this prediction by analyzing the relations between the path distance of mental traverse and the distance along the path between the current and the next fixation spot. (ABSTRACT TRUNCATED)

Motor area activity during mental rotation studied by time-resolved single-trial fMRI.

The functional equivalence of overt movements and dynamic imagery is of fundamental importance in neuroscience. Here, we investigated the participation of the neocortical motor areas in a classic task of dynamic imagery, Shepard and Metzler's mental rotation task, by time-resolved single-trial functional Magnetic Resonance Imaging (fMRI). The subjects performed the mental-rotation task 16 times, each time with different object pairs. Functional images were acquired for each pair separately, and the onset times and widths of the activation peaks in each area of interest were compared to the response times. We found a bilateral involvement of the superior parietal lobule, lateral premotor area, and supplementary motor area in all subjects; we found, furthermore, that those areas likely participate in the very act of mental rotation. We also found an activation in the left primary motor cortex, which seemed to be associated with the right-hand button press at the end of the task period.

Directional tuning profiles of motor cortical cells.

The directional tuning profiles of motor cortical cells are commonly described by a cosine tuning function with three adjustable parameters (Georgopoulos, A.P., Kalaska. J.F., Crutcher, M.D., Caminiti, R., Massey, J.T., 1982. On the relations between the direction of two-dimensional (2D) arm movements and cell discharge in primate motor cortex. J. Neurosci. 2, 1527-1537). In this study the variation in the shape of the directional tuning profiles among a population of cells recorded from the arm area of the motor cortex of monkeys using movements in 20 directions, every 18 degrees, was examined systematically. This allowed the investigation of tuning functions with extra parameters to capture additional features of the tuning curve (i.e. tuning breadth, symmetry, and modality) and determine an 'optimal' tuning function. These functions provided better fit than the standard cosine one. The optimal function for the large majority of tuned cells was unimodal (84%), and only for a few of them (16%) it was bimodal. Of the unimodal cells, 73% exhibited symmetric and 27% asymmetric shape. The half-width, sigma, at the midpoint of optimal tuning curves differed among cells from 30 to 90 degrees, with a median at 56 degrees. This is much narrower than in the standard cosine tuning function with a fixed width of sigma = 90 degrees. It was concluded that motor cortical cells are more sharply tuned than previously thought.

Varied duration of congenital hypothyroidism potentiates perseveration in a response alternation discrimination task.

The behavior of five groups of rats (seven rats per group) made hypothyroid for varying lengths of time and one group of seven normal control rats was assessed under forced alternation fixed-ratio (FR1, FR3, FR5 and FR10), alternating lever cyclic-ratio (ALCR) and progressive-ratio (PR3) schedules of reinforcement. Hypothyroidism was produced by adding methimazole (MMI) to the drinking water of pregnant dams from embryonic day E16 to postnatal day P25. Four groups were given replacement thyroxine (T4) injections beginning at specific time points (P1, P7, P13, and P19). There were no differences in behavioral performance between control and experimental groups under the FR schedule, which indicates that the animals' sensorimotor abilities were intact. Under the forced ALCR schedule, all groups reached criteria similarly. However, under the choice lever ALCR schedule, control animals and those which received T4 replacement from early on (P1, P7, P13 groups) performed well and all had reached criteria by 11 sessions. In contrast, animals which did not receive any T4 replacement or received it late (P19 group) took longer to reach criteria and 5/14 animals had not reached criteria at all by 20 sessions. This deterioration in performance was paralleled by an increase in perseverative behavior as evidenced by an increased frequency of pressing the wrong lever when alternation of lever was required. This suggests that congenital hypothyroidism results in increased perseveration leading to a decrease in learning when a discrimination between correct and incorrect operanda is made available.

Neural aspects of cognitive motor control.

Traditionally, motor and cognitive functions were studied separately; however, the investigation of processes at the interface between cognition and action has become more and more popular recently. Typical research goals include the identification of the processes involved using experimental psychological methods, and understanding the neural mechanisms underlying these processes using neurophysiological and functional neuroimaging methods. Specifically, there has been a special emphasis during the past few years on timing mechanisms, practice effects, and the application of rules in guiding action. New information concerning the neural mechanisms involved is being acquired at a rapid pace, albeit mostly within a descriptive framework. With respect to specific brain areas, a key finding has been the clear involvement of the primary motor cortex in complex tasks engaging diverse motor and cognitive dimensions.

Congenital hypothyroidism impairs response alternation discrimination behavior.

The behavior of six congenitally hypothyroid and six normal control rats was assessed under forced alternation fixed-ratio, alternating lever cyclic-ratio (ALCR) and progressive-ratio schedules of reinforcement. Hypothyroidism was produced by adding methimazole (MMI) to the drinking water of pregnant dams from embryonic day 16 to postnatal day 25. There were no differences in behavioral performance between MMI-treated and control animals under the fixed-ratio and progressive ratio schedules. There were also no differences in circulating triiodothyronine levels between groups at the end of the study. Under the ALCR schedule, when alternation of responding was forced during the first three cycles but both levers (choice) were presented during the last three cycles (correct lever active), the entire control group reached a competency criteria in nine sessions. In contrast, only two MMI-treated animals reached criteria after 17 sessions, and the remaining four MMI-treated animals did not reach criteria by 30 sessions of training. These results suggest that congenital hypothyroidism impairs learning when a discrimination between correct and incorrect operanda is made available.

Cortical populations and behaviour: Hebb's thread.

This paper discusses work on the function of the motor cortex as revealed by single cell recordings in monkeys and artificial neural network modelling. Our key conceptual approach both in behavioural neuroscience and neural network modeling of motor cortical function relies on reconstructing, visualizing, and modelling the activity in neuronal populations, indeed a key concept advanced by Hebb (1949). The behaviour investigated ranges from exertion of isometric force to pointing movements to complex cognitive processing. The functional properties of single cells with respect to the direction of movement in space are described as well as a population code which provides a unique measure for this direction. Finally, the results of modeling studies are discussed in which directional population activity is used as an input to an artificial neural network to drive a simulated arm.