Biomedical subjects

Apostolos P Georgopoulos

Publications and source records attributed to Apostolos P Georgopoulos.

At least 19 recordsLinked to original sources

PubMed2006

Large-scale organization of preferred directions in the motor cortex. I. Motor cortical hyperacuity for forward reaching.

We used statistical methods for spherical density estimation to evaluate the distribution of preferred directions of motor cortical cells recorded from monkeys making reaching movements in 3D space. We found that this distribution, although broad enough to represent the entire 3D continuum of reaching directions, exhibited an enrichment for reaching forward from the body and, to a lesser degree, for reaching backward toward the body. The distribution of preferred directions of cells in the motor cortex may have important implications for motor cortical function and for the decoding of arm trajectories from population activity.

Algorithms↗

PubMed2006

Large-scale organization of preferred directions in the motor cortex. II. Analysis of local distributions.

The spatial arrangement of preferred directions (PDs) in the primary motor cortex has revealed evidence for columnar organization and short-range order. We investigated the large-scale properties of this arrangement. We recorded neural activity at sites on a grid covering a large region of the arm area of the motor cortex while monkeys performed a 3D reaching task. Sites were projected to the cortical surface along anatomically defined cortical columns and a PD was extracted from each site with directionally tuned activity. We analyzed the resulting 2D surface map of PDs. Consistent with previous studies, we found that any particular reaching direction was re-represented at many points across the recorded area. In particular, we determined that the median radius of a cortical region required to represent the full complement of reaching directions is at most 1 mm. We also found that for the majority of regions of this size, the distribution of PDs within them exhibits an enrichment for the representation of forward and backward reaching directions (see companion paper). Finally, we found that the error of a population vector estimate of reaching direction constructed from neural activity within these regions is small on average, but varies significantly across different sections of the motor cortex, with the highest levels of error sustained near the fundus of the central sulcus and lowest levels achieved near the crown. We interpret these findings in the context of two well-known features of motor cortex, that is, its highly distributed anatomical organization and its behaviorally dependent plasticity.

Algorithms↗

PubMed2006

Classification of adolescent psychotic disorders using linear discriminant analysis.

BACKGROUND: The differential diagnosis between schizophrenia and bipolar disorder during adolescence presents a major clinical problem. Can these two diagnoses be differentiated objectively early in the courses of illness? METHODS: We used linear discrimination analysis (LDA) to classify 28 adolescent subjects into one of three diagnostic categories (healthy, N=8; schizophrenia, N=10; bipolar, N=10) using subsets from a pool of 45 variables as potential predictors (22 neuropsychological test scores and 23 quantitative structural brain measurements). The predictor variables were adjusted for age, gender, race, and psychotropic medication. All possible subsets composed of k=2-12 variables, from the set of 45 variables available, were evaluated using the robust leaving-one-subject-out method. RESULTS: The highest correct classification (96%) of the 3 diagnostic categories was yielded by 9 sets of k=12 predictors, comprising both neuropsychological and brain structural measures. Although each one of these sets misclassified one case, each set correctly classified (100%) at least one group, such that a fully correct diagnosis could be reached by a tree-type decision procedure. CONCLUSIONS: We conclude that LDA with 12 predictor variables can provide correct and robust classification of subjects into the three diagnostic categories above. This robust classification relies upon both neuropsychological and brain structural information. Our results demonstrate that, despite overlapping clinical symptoms, schizophrenia and bipolar disorder can be differentiated early in the course of disease. This finding has two important implications. Firstly, schizophrenia and bipolar disorder are different illnesses. If schizophrenia and bipolar are dissimilar clinical manifestations of the same disease, we would not be able to use non-clinical information to classify ('diagnose') schizophrenia and bipolar disorder. Secondly, if this study's findings are replicated, brain structure (MRI) and brain function (neuropsychological) used together may be useful in the diagnosis of new patients.

Adolescent↗

PubMed2006

Neurophysiology of perceptual and motor aspects of interception.

The interception of moving targets is a complex activity that involves a dynamic interplay of several perceptual and motor processes and therefore involves a rich interaction among several brain areas. Although the behavioral aspects of interception have been studied for the past three decades, it is only during the past decade that neural studies have been focused on this problem. In addition to the interception itself, several neural studies have explored, within that context, the underlying mechanisms concerning perceptual aspects of moving stimuli, such as optic flow and apparent motion. In this review, we discuss the wealth of knowledge that has accumulated on this topic with an emphasis on the results of neural studies in behaving monkeys.

Animals↗

PubMed2005

Synchronous dynamic brain networks revealed by magnetoencephalography.

We visualized synchronous dynamic brain networks by using prewhitened (stationary) magnetoencephalography signals. Data were acquired from 248 axial gradiometers while 10 subjects fixated on a spot of light for 45 s. After fitting an autoregressive integrative moving average model and taking the residuals, all pairwise, zero-lag, partial cross-correlations (PCC(ij)(0)) between the i and j sensors were calculated, providing estimates of the strength and sign (positive and negative) of direct synchronous coupling between neuronal populations at a 1-ms temporal resolution. Overall, 51.4% of PCC(ij)(0) were positive, and 48.6% were negative. Positive PCC(ij)(0) occurred more frequently at shorter intersensor distances and were 72% stronger than negative ones, on the average. On the basis of the estimated PCC(ij)(0), dynamic neural networks were constructed (one per subject) that showed distinct features, including several local interactions. These features were robust across subjects and could serve as a blueprint for evaluating dynamic brain function.

Adult↗

PubMed2005

Dipole analysis of magnetoencephalographic data during continuous shape copying.

High density, whole head magnetoencephalography (MEG) was used to study ten healthy human subjects (five females and five males) participating in a continuous shape-copying task. The task was performed with eyes open and fixated. The three-part task began with 45 s of fixation on a blue dot, after which the dot turned red, and a pentagon was presented around it. Subjects continued to fixate on the red dot for 45 s, after which it turned green. The green dot instructed subjects to begin copying the shape continuously for 45 s, without visual feedback, using a joystick mounted at arm's length. Data were collected at 1,017.25 Hz with a 248 sensor axial-gradiometer system. After cardiac artifact subtraction (Leuthold 2003), each corner was identified, and 1 s epochs (centered on each corner) were averaged and filtered from 1 to 44 Hz. Grand average flux maps demonstrated dipolar distributions identifying the most relevant sensors. With these sensors, which were located over flux extrema (Valaki et al. 2004), dipole models were used for source localization within subjects. Consistent dipole locations included the left motor cortex, bilateral parietal, frontal and temporal regions, and the occipital cortex. These results indicate that MEG source-localization may be derived from a limited number of trials of continuous data, and that visual cortex activity may be consistently present during continuous motor activity despite the absence of novel visual stimulation and eye-movements.

Adult↗

PubMed2005

Cognitive dimensions of orthographic stimuli affect occipitotemporal dynamics.

Previous research documented letter-string specific cortices in the ventral visual stream near the left occipitotemporal junction (i.e., anterior fusiform gyrus). These neural areas potentially code the perceptual elements comprising orthographic stimuli, and thus function as feature detectors in high-level vision. While abundant evidence supports this region's role in detecting isomorphic perceptual features, any influence cognitive dimensions (e.g., the lexicality of letter-strings) may play in modulating this area's processing remains an open question. To investigate this, we examined the spatiotemporal dynamics of high-density magnetoencephalographic signals, recorded as subjects completed a rhyme-judgment task on stimuli varying in the cognitive property of lexicality. Our data demonstrate that the time course of occipitotemporal cortices discriminates cognitive attributes of orthographic stimuli. The dynamics in this brain region may indicate interactive processes unfolding later in the time course, when more anterior fronto-temporal circuits are activated by semantic correlates of real words.

Adolescent↗

PubMed2005

Magnetoencephalographic signals predict movement trajectory in space.

Brain-machine interface (BMI) efforts have been focused on using either invasive implanted electrodes or training-extensive conscious manipulation of brain rhythms to control prosthetic devices. Here we demonstrate an excellent prediction of movement trajectory by real-time magnetoencephalography (MEG). Ten human subjects copied a pentagon for 45 s using an X-Y joystick while MEG signals were being recorded from 248 sensors. A linear summation of weighted contributions of the MEG signals yielded a predicted movement trajectory of high congruence to the actual trajectory (median correlation coefficient: r=0.91 and 0.97 for unsmoothed and smoothed predictions, respectively). This congruence was robust since it remained high in cross-validation analyses (based on the first half of data to predict the second half; median correlation coefficient: r=0.76 and 0.85 for unsmoothed and smoothed predictions, respectively).

Brain↗

PubMed2005

Dynamics of parietal neural activity during spatial cognitive processing.

Dynamic neural processing unrelated to changes in sensory input or motor output is likely to be a hallmark of cognitive operations. Here we show that neural representations of space in parietal cortex are dynamic while monkeys perform a spatial cognitive operation on a static visual stimulus. We recorded neural activity in area 7a during a visual maze task in which monkeys mentally followed a path without moving their eyes. We found that the direction of the followed path could be recovered from neuronal population activity. When the monkeys covertly processed a path that turned, the population representation of path direction shifted in the direction of the turn. This neural population dynamic took place during a period of unchanging visual input and showed characteristics of both serial and parallel processing. The data suggest that the dynamic evolution of parietal neuronal activity is associated with the progression of spatial cognitive operations.

Action Potentials↗

PubMed2005

Logarithmic transformation for high-field BOLD fMRI data.

Parametric statistical analyses of BOLD fMRI data often assume that the data are normally distributed, the variance is independent of the mean, and the effects are additive. We evaluated the fulfilment of these conditions on BOLD fMRI data acquired at 4 T from the whole brain while 15 subjects fixated a spot, looked at a geometrical shape, and copied it using a joystick. We performed a detailed analysis of the data to assess (a) their frequency distribution (i.e. how close it was to a normal distribution), (b) the dependence of the standard deviation (SD) on the mean, and (c) the dependence of the response on the preceding baseline. The data showed a strong departure from normality (being skewed to the right and hyperkurtotic), a strong linear dependence of the SD on the mean, and a proportional response over the baseline. These results suggest the need for a logarithmic transformation. Indeed, the log transformation reduced the skewness and kurtosis of the distribution, stabilized the variance, and made the effect additive, i.e. independent of the baseline. We conclude that high-field BOLD fMRI data need to be log-transformed before parametric statistical analyses are applied.

Adult↗

PubMed2005

Mental maze solving: directional fMRI tuning and population coding in the superior parietal lobule.

The superior parietal lobule (SPL) of six human subjects was imaged at 4 T during mental traversing of a directed maze path. Here we demonstrate the orderly involvement of the SPL in this function, as follows. Forty-two percent of the voxels were tuned with respect to the direction of the maze path. This suggests a coherent tuning of local neuronal populations contributing to the change of the single-voxel BOLD signal. Preferred directions ranged throughout the directional continuum of 360 degrees. Voxels with similar preferred directions tended to cluster together: on average there were seven same-direction clusters per slice, with an average cluster membership of five voxels/cluster and an average nearest-neighbor same-direction intercluster distance of 13.1 mm. On the other hand, the average nearest-neighbor intercluster distance between a given direction and all other directions was 3.1 mm. This suggests a patchy arrangement such that patches of directionally tuned voxels, containing voxels with different preferred directions, alternate with patches of non-tuned voxels. Finally, the population vector predicted accurately the direction of the maze path (with an error of 12.7 degrees), and provided good estimates (with an error of 29 degrees) when calculated within parts of the SPL. Altogether, these findings document a new, orderly functional organization of the SPL with respect to mental tracing.

Adult↗

PubMed2005

Time series analysis of magnetoencephalographic data during copying.

We used standard time series modeling to analyze magnetoencephalographic (MEG) data acquired during three tasks. Each task lasted 45 s, for a total data acquisition period of 135 s. Ten healthy human subjects fixated their eyes on a central blue point for 45 s (fixation only, "F" task). Then a pentagon (visual template) appeared surrounding the fixation point which simultaneously became red (fixation + template, "FT" task). After 45 s, the fixation point changed to green, which was the "go" signal for the subjects to begin continuously copying the pentagon for 45 s using a joystick and without visual feedback of their movement trajectory (fixation + template + copying, "FTC" task). MEG data were acquired continuously from 248 axial gradiometers at a sampling rate of 1017.25 Hz. After removal of cardiac artifacts and rejection of records with eyeblink artifacts, a Box-Jenkins autoregressive integrative moving average (ARIMA) analysis was applied to the unsmoothed, unaveraged MEG time series for model identification and estimation within 25 time lags (approximately 25 ms). We found that an ARIMA model of 25th order autoregressive, first order differencing, and first order moving average (p=25, d=1, q=1) adequately modeled the series and yielded residuals practically stationary with respect to their mean, variance, and autocorrelation structure. These "prewhitened" residuals were then used for assessing pairwise associations between series using crosscorrelation analysis with +/-25 time lags (approximately +/-25 ms). The cross-correlograms thus obtained revealed rich and consistent patterns of interactions between series with respect to positive and/or negative correlations. The overall prevalence of these patterns was very similar in the three tasks used, and, for particular sensor pairs, they tended to be preserved across tasks.

Adult↗

PubMed2005

Neural correlates of spatial judgement during object construction in parietal cortex.

We recorded the activity of parietal area 7a neurons in monkeys performing an object construction task. In each trial, a model object consisting of a variable arrangement of squares was presented, followed after a delay by a copy of the model object that was missing a single square. Monkeys replaced the missing square to reconstruct the model configuration. Activity of many 7a neurons varied systematically with the position of the missing square and predicted where monkeys were going to add parts to the object they were building. The location of the missing square was a computed spatial datum important to object construction which did not correlate with the retinal location of a visual stimulus or the direction of the required motor response. The population of cells coding this coordinate was generally inactive when the same spatial locations were made relevant by visual targets to which monkeys either planned saccades or directed attention in other behavioral contexts. The data suggest that some parietal neurons participate in neural representations of space that reflect spatial cognitive as opposed to sensorimotor processing, coding the results of spatial computations performed on visual stimuli to meet cognitive objectives.

Animals↗

PubMed2004

Decoding of path-guided apparent motion from neural ensembles in posterior parietal cortex.

We compared quantitatively the psychometric capacity of human subjects to detect path-guided apparent motion (PAM) and the accuracy of cell ensembles in area 7a to code the same type of stimuli. Nine human subjects performed a detection task of PAM. They were instructed to indicate with a key-press whether they perceived a circularly moving object when five stimuli were flashed successively at the vertices of a regular pentagon. The stimuli were presented along a low contrast circular path with one of 33 speeds (150-600 degrees /s). The average psychometric curve revealed that the threshold for PAM detection was 314 degrees /s. The minimum and maximum thresholds for individual subjects were 277 degrees and 378 degrees /s, respectively. In addition, the activity of cells in area 7a that were modulated by the stimulus position in real or apparent motion was used in a multivariate linear regression analysis to recover the stimulus position over time. Real stimulus motion was decoded successfully from neural ensemble activity at all speeds. In contrast, the decoding of PAM was poor at low stimulus speeds but improved markedly above 300 degrees /s: in fact, this was very close to the threshold above for human subjects to perceive continuous stimulus motion in this condition. These results suggest that the posterior parietal cortex is part of a high-level system that is directly involved in the dynamic representation of complex motion.

Adult↗

PubMed2004

Spatial reconstruction of trajectories of an array of recording microelectrodes.

We present a method for estimating the locations of sites visited by an array of microelectrodes. The method relies on visualization of tracks made by electrodes coated in a fluorescent dye. These tracks are used to estimate the parameters of a simple geometrical model that generates coordinates for each recording site. We describe several ways to measure the error of this procedure and present experimental results from recordings in the motor cortex of macaque monkeys that suggest that errors are of the order of 230 microm. We also introduce a coordinate transformation that takes into account the convoluted structure of the cortex near sulci to conveniently visualize recording site locations in a rectilinear representation. This method greatly extends the capabilities of microelectrodes for studying the three-dimensional structure of topographic maps in the cortex.

Animals↗

PubMed2004

The time and space of lexicality: a neuromagnetic view.

Illuminating the neural mechanisms subserving lexico-semantic processing is requisite to further understanding the neurophysiological basis of the dyslexias. Yet, despite numerous functional neuroimaging experiments, the location and temporal behavior of brain regions mediating word-level language processing remain an area of debate. Such investigations typically utilize the word/pseudoword contrast within hemodynamic measurements, and report several left hemisphere regions that respond more strongly to pseudowords but fail to replicate neural areas unique to real word processing. The present experiment addressed this problem from a different perspective. Mainly, we hypothesized that the time course, but not the neuroanatomy, would show within-subject across-condition disparities. For that purpose, we applied dipole-modeling techniques to high-density magnetoencephalographic recordings of healthy subjects, and utilized excellent spatiotemporal accuracy to demonstrate significant across-condition differences in the time domain, along with indistinguishable neural correlates within-subject. In all participants, both words and pseudowords elicited activity in left perisylvian language areas, with words consistently activating these regions approximately 100 ms earlier than pseudowords. Considerable functional heterogeneity was also observed, and this might underlie the inconsistencies among previous studies. We conclude that the neural distinction in word/pseudoword processing is not in spatial localization, but is better conceptualized as a dynamic difference in processing time.

Adolescent↗

PubMed2004

Parietal representation of hand velocity in a copy task.

We recorded neural activity from ensembles of neurons in areas 5 and 2 of parietal cortex, while two monkeys copied triangles, squares, trapezoids, and inverted triangles and used both linear and nonlinear models to predict the hand velocity from the neural activity of the ensembles. The linear model generally outperformed the nonlinear model, suggesting a reasonably linear relation between the neural activity and the hand velocity. We also found that the average transfer function of the linear model fit to individual cells was a low-pass filter because the neural response had considerable high-frequency power, whereas the hand velocity only had power at frequencies below approximately 5 Hz. Increasing the width of the transfer function, up to a width of 700-800 ms, improved the fit of the model. Furthermore, the Rsqr of the linear model improved monotonically with the number of cells in the ensemble, saturating at 60-80% for a filter width of 700 ms. Finally, it was found that including an interaction term, which allowed the transfer function to shift with the eye position, did not improve the fit of the model. Thus ensemble neural responses in superior parietal cortex provide a high-fidelity, linear representation of hand kinematics within our task.

Action Potentials↗

PubMed2004

Participation of primary motor cortical neurons in a distributed network during maze solution: representation of spatial parameters and time-course comparison with parietal area 7a.

Traditionally, primary motor cortex (M1) has been thought to be involved solely in planning and generating movements. Recent evidence suggests that the arm area of M1 plays a role in other functions, such as the representation of serial order (Pellizzer et al. 1995, Science 269:702-705; Carpenter et al. 1999, Science 283:1752-1757) and spatial processing (Georgopoulos et al. 1989, Science 243:234-236). Previous studies of such cognitive processes have used tasks in which a directed arm movement was required, raising a question as to whether this brain area is involved in cognitive processing per se, or whether such cognitive signals may be gated into the arm area of M1 only when arm movements are required. To study this question, we developed a task that required a spatial analysis of a complex visual stimulus, but required no arm movement as a response. In this task, monkeys were shown an octagonal maze. After an imposed delay of 2 to 2.5 s, they indicated whether a path that emanated from the center of the maze exited at the perimeter (exit maze) or terminated within the maze (no-exit maze) by pressing a pedal with their left or right foot, respectively. We recorded from 785 cells from the arm area of M1 from two monkeys during the delay period of the maze task. We found that cell activity was influenced by both the exit status and the direction of the path, beginning soon after the maze was displayed. This activity was not related to the activation of arm muscles, suggesting that the directional signals observed represented abstract spatial aspects of maze processing. Finally, we compared maze-related activity of M1 neurons with those recorded from posterior parietal area 7a, reported previously (Crowe et al. 2004). Interestingly, cells from each area exhibited similar properties. Both the exit status and path direction were encoded by cells in M1 and 7a, although to different extents. An analysis of the time-course of the neural representation of these factors revealed that area 7a and M1 begin to encode these factors at the same time, suggesting these brain areas are part of a distributed system performing the spatial computations involved in maze solution.

Action Potentials↗