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ABSTRACT: Apolipoprotein E (apoE) is involved in lipid metabolism in the brain, but its effects on brain function are not understood. Three apoE isoforms (E4, E3, and E2) are the result of cysteine-arginine interchanges at two sites: there are zero interchanges in E4, one interchange in E3, and two interchanges in E2. The resulting six apoE genotypes (E4/4, E4/3, E4/2, E3/3, E3/2, E2/2) yield five groups with respect to the number of cysteine residues per mole (CysR/mole), as follows. ApoE4/4 has zero cysteine residues per mole (0-CysR/mole), E4/3 has one (1-CysR/mole), E4/2 and E3/3 each has two (2-CysR/mole), E3/2 has three (3-CysR/mole), and E2/2 has four (4-CysR/mole). The use of the number of CysR/mole to characterize the apoE molecule converts the categorical apoE genotype scale, consisting of 6 distinct genotypes above, to a 5-point continuous scale (0-4 CysR/mole). This allows the use of statistical analyses suitable for continuous variables (e.g. regression) to quantify the relations between various variables and apoE. Using such analyses, here, we show for the first time that apoE affects in a graded and orderly manner neural communication, as assessed by analyzing the relation between the number of CysR/mole and synchronous neural interactions (SNI) measured by magnetoencephalography (MEG) in 130 cognitively healthy women. At the one end of the CysR/mole range, the 4-CysR/mole (E2/2) SNI distribution had the highest mean, lowest variance, lowest range, and lowest coefficient of variation, whereas at the other end, 0-CysR/mole (E4/4) SNI distribution had the lowest mean, highest variance, highest range, and highest coefficient of variation. The special status of the 4-CysR/mole distribution was reinforced by the results of a hierarchical tree analysis where the 4-CysR/mole (E2/2) SNI distribution occupied a separate branch by itself and the remaining CysR/mole SNI distributions were placed at increasing distances from the 4-CysR/mole distribution, according to their number of CysR/mole, with the 0-CysR/mole (E4/4) being farthest away. These findings suggest that the 4-CysR/mole (E2/2) SNI distribution could serve as a reference distribution. When the SNI distributions of individual women were expressed as distances from this reference distribution, there was a substantial overlap among women of various CysR/mole. This refocuses the placement of individual brains along a continuous distance from the 4-CysR/mole SNI distribution, in contrast to the common categorical assignment to a specific apoE genotype. Finally, the orderly variation of SNI with the number of CysR/mole found here is in keeping with recent advances and ideas regarding the molecular mechanisms underlying the differential effects of apoE in the brain which emphasize the healthier stability conferred on the apoE molecule by the increasing number of cysteine-arginine interchanges, with 4-CysR/mole (E2/2) being the best case, as opposed to the instability and increased chance of toxic fragmentation of the apoE molecule with lower number of CysR/mole, with 0-CysR/mole (E4/4) as the worst case (Mahley and Huang in Neuron 76:871-885, 2012a). However, our results also document the appreciable variation of SNI properties within the various CysR/mole groups and individuals which points to the existence and important role of other factors involved in shaping brain function at the network level.
Experimental Brain Research 03/2013; · 2.39 Impact Factor
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ABSTRACT: The exploration of city maps has exploded recently due to the wide availability, increasing use of, and reliance on small positioning and navigational devices for personal use. In this study, subjects explored small, 3-mile diameter circular maps exemplifying five different types of street networks common in the United States, in order to locate a hypothetical city hall. Chosen locations indicated that subjects are able to identify more accessible sites. Monitoring eye position revealed that women explored maps faster, using more widely dispersed but more narrowly focused gaze clusters than men. The type of street network influenced the time spent by the eyes in a locale and differentially affected the size of gaze clusters between women and men, underscoring the complex interactions of gender-specific strategies with street network types.
Experimental Brain Research 09/2012; 223(2):207-17. · 2.39 Impact Factor
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ABSTRACT: Continuous and sequential movements are controlled by widely distributed brain regions. A series of studies have contributed to understanding the functional role of these regions in a variety of visuomotor tasks. However, little is known about the neural interactions underpinning continuous movements. In the current study, we examine the spatiotemporal neural interactions underlying continuous drawing movements and the association of them with behavioral components. We conducted an experiment in which subjects copied a pentagon continuously for ~45 s using an XY joystick, while neuromagnetic fluxes were recorded from their head using a 248-sensor whole-head magnetoencephalography (MEG) device. Each sensor time series was rendered stationary and non-autocorrelated by applying an autoregressive integrated moving average model and taking the residuals. We used the directional variability of the movement as a behavioral measure of the controls generated. The main objective of this study was to assess the relation between neural interactions and the variability of movement direction. That is, we divided the continuous recordings into consecutive periods (i.e., time-bins) of 51 steps duration and computed the pairwise cross-correlations between the prewhitened time series in each time-bin. The circular standard deviation of the movement direction within each time-bin provides an estimate of the directional variability of the 51-ms trajectory segment. We looked at the association between neural interactions and variability of movement direction, separately for each pair of sensors, by running a cross-correlation analysis between the strength of the MEG pairwise cross-correlations and the circular standard deviations. We identified two types of neuronal networks: in one, the neural interactions are correlated with the directional variability of the movement at negative time-lags (feedforward), and in the other, the neural interactions are correlated with the directional variability of the movement at positive time-lags (feedback). Sensors associated mostly with feedforward processes are distributed in the left hemisphere and the right occipital-temporal junction, whereas sensors related to feedback processes are distributed in the right hemisphere and the left cerebellar hemisphere. These results are in line with findings from a series of previous studies showing that specific brain regions are involved in feedforward and feedback control processes to plan, perform, and correct movements. Additionally, we looked at whether changes in movement direction modulate the neural interactions. Interestingly, we found a preponderance of sensors associated with changes in movement direction over the right hemisphere-ipsilateral to the moving hand. These sensors exhibit stronger coupling with the rest of the sensors for trajectory segments with high rather than low directional movement variability. We interpret these results as evidence that ipsilateral cortical regions are recruited for continuous movements when the curvature of the trajectory increases. To the best of our knowledge, this is the first study that shows how neural interactions are associated with a behavioral control parameter in continuous and sequential movements.
Experimental Brain Research 08/2012; 222(1-2):159-71. · 2.39 Impact Factor
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ABSTRACT: In previous work (Georgopoulos et al 2007 J. Neural Eng. 4 349-55) we reported on the use of magnetoencephalographic (MEG) synchronous neural interactions (SNI) as a functional biomarker in Alzheimer's dementia (AD) diagnosis. Here we report on the application of canonical correlation analysis to investigate the relations between SNI and cognitive neuropsychological (NP) domains in AD patients. First, we performed individual correlations between each SNI and each NP, which provided an initial link between SNI and specific cognitive tests. Next, we performed factor analysis on each set, followed by a canonical correlation analysis between the derived SNI and NP factors. This last analysis optimally associated the entire MEG signal with cognitive function. The results revealed that SNI as a whole were mostly associated with memory and language, and, slightly less, executive function, processing speed and visuospatial abilities, thus differentiating functions subserved by the frontoparietal and the temporal cortices. These findings provide a direct interpretation of the information carried by the SNI and set the basis for identifying specific neural disease phenotypes according to cognitive deficits.
Journal of Neural Engineering 08/2012; 9(5):056003. · 3.84 Impact Factor
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ABSTRACT: We used hierarchical tree clustering to derive a functional organizational chart of 52 human cortical areas (26 per hemisphere) from zero-lag correlations calculated between single-voxel, prewhitened, resting-state BOLD fMRI time series in 18 subjects. No special "resting-state networks" were identified. There were four major features in the resulting tree (dendrogram). First, there was a strong clustering of homotopic, left-right hemispheric areas. Second, cortical areas were concatenated in multiple, partially overlapping clusters. Third, the arrangement of the areas revealed a layout that closely resembled the actual layout of the cerebral cortex, namely an orderly progression from anterior to posterior. And fourth, the layout of the cortical areas in the tree conformed to principles of efficient, compact layout of components proposed by Cherniak. Since the tree was derived on the basis of the strength of neural correlations, these results document an orderly relation between functional interactions and layout, i.e., between structure and function.
Frontiers in Neuroanatomy 01/2012; 6:36. · 3.07 Impact Factor
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ABSTRACT: In the present study we characterized the strength and time course of category-selective responses in prefrontal cortex and area 7a of the posterior parietal cortex during a match-to-sample spatial categorization task. A monkey was trained to categorize whether the height of a horizontal sample bar, presented in rectangular frame at one of three vertical locations, was "high" or "low," depending on whether its position was above or below the frame's midline. After the display of this sample bar, and after a delay, choice bars were sequentially flashed in two locations: at the top and at the bottom of the frame ("choice" epoch). If the monkey timed its response to the display of the choice bar that matched the sample bar, he was rewarded. We found that cells in prefrontal cortex discriminated category early after the initial sample bar was shown, and continued to differentiate "up" from "down" trials throughout the delay and choice periods. In contrast, parietal cells did not differentiate category until the choice period. Therefore, our results support the notion of a top-down categorical signal that originates in prefrontal cortex and that is only represented in parietal cortex when it is necessary to express the categorical decision through a movement.
Frontiers in Systems Neuroscience 01/2011; 5:69.
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ABSTRACT: Making an accurate diagnosis of schizophrenia and related psychoses early in the course of the disease is important for initiating treatment and counseling patients and families. In this study, we developed classification models for early disease diagnosis using structural MRI (sMRI) and neuropsychological (NP) testing. We used sMRI measurements and NP test results from 28 patients with recent-onset schizophrenia and 47 healthy subjects, drawn from the larger sample of the Mind Clinical Imaging Consortium. We developed diagnostic models based on Linear Discriminant Analysis (LDA) following two approaches; namely, (a) stepwise (STP) LDA on the original measurements, and (b) LDA on variables created through Principal Component Analysis (PCA) and selected using the Humphrey-Ilgen parallel analysis. Error estimation of the modeling algorithms was evaluated by leave-one-out external cross-validation. These analyses were performed on sMRI and NP variables separately and in combination. The following classification accuracy was obtained for different variables and modeling algorithms. sMRI only: (a) STP-LDA: 64.3% sensitivity and 76.6% specificity, (b) PCA-LDA: 67.9% sensitivity and 72.3% specificity. NP only: (a) STP-LDA: 71.4% sensitivity and 80.9% specificity, (b) PCA-LDA: 78.5% sensitivity and 91.5% specificity. Combined sMRI-NP: (a) STP-LDA: 64.3% sensitivity and 83.0% specificity, (b) PCA-LDA: 89.3% sensitivity and 93.6% specificity. (i) Maximal diagnostic accuracy was achieved by combining sMRI and NP variables. (ii) NP variables were more informative than sMRI, indicating that cognitive deficits can be detected earlier than volumetric structural abnormalities. (iii) PCA-LDA yielded more accurate classification than STP-LDA. As these sMRI and NP tests are widely available, they can increase accuracy of early intervention strategies and possibly be used in evaluating treatment response.
Neuroinformatics 01/2011; 9(4):321-33. · 2.97 Impact Factor
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ABSTRACT: We studied visual perception using an annular random-dot motion stimulus called the racetrack. We recorded neural activity using magnetoencephalography while subjects viewed variants of this stimulus that contained no inherent motion or various degrees of embedded motion. Subjects reported seeing rotary motion during viewing of all stimuli. We found that, in the absence of any motion signals, patterns of brain activity differed between states of motion perception and nonperception. Furthermore, when subjects perceived motion, activity states within the brain did not differ across stimuli of different amounts of embedded motion. In contrast, we found that during periods of nonperception brain-activity states varied with the amount of motion signal embedded in the stimulus. Taken together, these results suggest that during perception the brain may lock into a stable state in which lower-level signals are suppressed.
Proceedings of the National Academy of Sciences 12/2010; 107(52):22677-81. · 9.68 Impact Factor
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ABSTRACT: We used magnetoencephalography (MEG) to investigate the cortical processing of an innocuous facial tactile stimulus in healthy subjects and in a group of subjects suffering from chronic temporomandibular disorder (TMD). Equivalent current dipoles (ECDs) were extracted for a time period of 1 s following stimulus application, and their location, duration and onset time determined. The counts of ECDs extracted did not differ significantly between the two groups. In contrast, we found statistically significant differences in ECD duration and onset time. Specifically, ECD duration was longer in the TMD group in the precentral gyrus, and ECD onset time was earlier in the parietal operculum. In addition, we found differences in the internal organization and clustering of the brain areas involved indicating a less tight association and a less coordinated stimulus information processing in the TMD group. Altogether, these results show that an innocuous facial tactile stimulus is differently processed in the brain of TMD subjects, when compared to controls, reflecting altered brain mechanisms due to chronic pain.
Experimental Brain Research 07/2010; 204(1):33-45. · 2.39 Impact Factor
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ABSTRACT: In human and nonhuman primates parietal cortex is formed by a multiplicity of areas. For those of the superior parietal lobule (SPL) there exists a certain homology between man and macaques. As a consequence, optic ataxia, a disturbed visual control of hand reaching, has similar features in man and monkeys. Establishing such correspondence has proven difficult for the areas of the inferior parietal lobule (IPL). This difficulty depends on many factors. First, no physiological information is available in man on the dynamic properties of cells in the IPL. Second, the number of IPL areas identified in the monkey is paradoxically higher than that so far described in man, although this issue will probably be reconsidered in future years, thanks to comparative imaging studies. Third, the consequences of parietal lesions in monkeys do not always match those observed in humans. This is another paradox if one considers that, in certain cases, the functional properties of neurons in the monkey's IPL would predict the presence of behavioral skills, such as construction capacity, that however do not seem to emerge in the wild. Therefore, constructional apraxia, which is well characterized in man, has never been described in monkeys and apes. Finally, only certain aspects, i.e. hand directional hypokinesia and gaze apraxia (Balint's psychic paralysis of gaze), of the multifaceted syndrome hemispatial neglect have been described in monkeys. These similarities, differences and paradoxes, among many others, make the study of the evolution and function of parietal cortex a challenging case.
European Journal of Neuroscience 06/2010; 31(12):2320-40. · 3.63 Impact Factor
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ABSTRACT: Many factors can influence, or bias, human decision making. A considerable amount of research has investigated the neural correlates of such biases, mostly correlating hemodynamic responses in brain areas with some aspect of the decision. These studies, typically done using functional magnetic resonance imaging or positron emission tomography, have provided useful information about the location of processing in the brain. However, comparatively little research has examined when these processes occur. The present experiment addressed this question by using magnetoencephalography (MEG) to record brain activity while subjects chose preferred options from decision sets. We found that MEG signal deviations for biased decisions occurred as early as 250-750 ms following stimulus onset. Such deviations occurred earliest in sensors over the right anterior cortex. These findings improve our understanding of temporal dynamics of decision biases and suggest ways that existing explanations for this bias could be refined.
Experimental Brain Research 12/2009; 202(1):121-7. · 2.39 Impact Factor
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ABSTRACT: In this study we examined the differential contribution of superior parietal cortex (SPC) and caudal dorsal-lateral prefrontal cortex (dlPFC) to drawing geometrical shapes. Monkeys were trained to draw triangles, squares, trapezoids and inverted triangles while we recorded the activity of small ensembles of neurons in caudal area 46 and areas 5 and 2 of parietal cortex. We analyzed the drawing factors encoded by individual neurons by fitting a step-wise general-linear model using as our dependent variable the firing rate averaged over segments of the produced trajectories. This analysis demonstrated that both cognitive (shape and segment serial position) and motor (maximum speed, position and direction of segment) factors modulated the activity of individual neurons. Furthermore, SPC had an enriched representation of both shape and motor factors, with the motor enrichment being stronger than the shape enrichment. Following this we used the activity in the simultaneously recorded neural ensembles to predict the hand velocity. In these analyses we found that the prediction of the hand velocity was better when we estimated different linear decoding functions for each shape than when we estimated a single function across shapes, although it was a subtle effect. Furthermore, we also found that ensembles of caudal dlPFC neurons carried considerable information about hand velocity, a purely motor factor. However, the SPC ensembles carried more information at the ensemble level as a function of the ensemble size than the caudal dlPFC ensembles, although the differences were not dramatic. Finally, an analysis of the response latencies of individual neurons showed that the caudal dlPFC representation was more sensory than the SPC representation, which was equally sensory and motor. Thus, this neurophysiological evidence suggests that both SPC and caudal dlPFC have a role in drawing, but that SPC plays a larger role in both the cognitive and the motor components.
Cortex 03/2009; 45(3):432-41. · 6.08 Impact Factor
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ABSTRACT: In the present study, we investigated how directional tuning of putative pyramidal cells is sharpened by inhibition from neighboring interneurons. First, different functional and electrophysiological criteria were used to identify putative pyramidal and interneuronal subtypes in a large database of motor cortical cells recorded during performance of the three-dimensional center-out task. Then we analyzed the relationship between the magnitude of inhibition and the tuning width, and a significant decrease of the latter as a function of the former was found in a population of putative pyramidal cells. In fact, the coupling of inhibition with narrow tuning was observed before and during movement execution on a cell-by-cell basis, indicating an important dynamic role of inhibition during movement control. Overall, these results suggest that local inhibition is involved in sculpting the directional specificity of a group of putative pyramidal neurons in the motor cortex.
Journal of Neuroscience 10/2008; 28(37):9164-72. · 7.11 Impact Factor
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ABSTRACT: Differences between men and women in brain size, cognitive performance and lateralization of brain activation have been perennial and controversial issues. Here we show that in a motor mental rotation task where women and men performed equally well, the slope of the functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signal per degree of mental rotation was overall 2.4x higher in men than in women. This was attributed to the much more inefficient engagement (i.e. higher slopes) of the right hemisphere by men (mainly the frontal lobe). These findings indicate that women process information much more efficiently than men, which could offset smaller brain size.
Experimental Brain Research 08/2008; 189(1):79-90. · 2.39 Impact Factor
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Trenton A Jerde,
Scott M Lewis,
Ute Goerke,
Pavlos Gourtzelidis,
Charidimos Tzagarakis,
Joshua Lynch,
Steen Moeller,
Pierre-François Van de Moortele,
Gregor Adriany,
Jeran Trangle,
Kâmil Uğurbil, Apostolos P Georgopoulos
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ABSTRACT: We used ultra-high field (7 T) fMRI and parallel imaging to scan the superior parietal lobule (SPL) of human subjects as they mentally traversed a maze path in one of four directions (up, down, left, right). A counterbalanced design for maze presentation and a quasi-isotropic voxel (1.46 x 1.46 x 2 mm thick) collection were implemented. Fifty-one percent of single voxels in the SPL were tuned to the direction of the maze path. Tuned voxels were distributed throughout the SPL, bilaterally. A nearest neighbor analysis revealed a "honeycomb" arrangement such that voxels tuned to a particular direction tended to occur in clusters. Three-dimensional (3D) directional clusters were identified in SPL as oriented centroids traversing the cortical depth. There were 13 same-direction clusters per hemisphere containing 22 voxels per cluster, on the average; the mean nearest-neighbor, same-direction intercluster distance was 9.4 mm. These results provide a much finer detail of the directional tuning in SPL, as compared to those obtained previously at 4 T (Gourtzelidis et al. Exp Brain Res 165:273-282, 2005). The more accurate estimates of quantitative clustering parameters in 3D brain space in this study were made possible by the higher signal-to-noise and contrast-to-noise ratios afforded by the higher magnetic field of 7 T as well as the quasi-isotropic design of voxel data collection.
Experimental Brain Research 07/2008; 187(4):551-61. · 2.39 Impact Factor
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ABSTRACT: Brain function and its relations to cognition and behavior can be elucidated only by the use of various complementary methods. Over the past 20 years, we have been studying the brain mechanisms underlying spatial processes using different methods, including the recording of single cell activity in behaving monkeys, functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in human subjects, all performing the same tasks. These methods provide partially overlapping perspectives, resulting in a gain in knowledge beyond the province of the individual method. A common aspect in this endeavor is the statistical analysis of the data acquired by different methods, especially regarding the encoding of information in unitary elements (single cell activity in neurophysiology, blood oxygenation level-dependent (BOLD) activation of voxels in fMRI, magnetic field strength in MEG) and the decoding of information from ensembles. In this paper we illustrate the various approaches, their data analysis and possible applications to medicine in the context of operations in space.
Statistics in Medicine 03/2008; 27(3):407-17. · 1.88 Impact Factor
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Apostolos P Georgopoulos,
Elissaios Karageorgiou,
Arthur C Leuthold,
Scott M Lewis,
Joshua K Lynch,
Aurelio A Alonso,
Zaheer Aslam,
Adam F Carpenter,
Angeliki Georgopoulos,
Laura S Hemmy, [......],
Susan E McPherson,
José V Pardo,
Patricia J Pardo,
Gareth J Parry,
Susan J Rottunda,
Barbara M Segal,
Scott R Sponheim,
John J Stanwyck,
Massoud Stephane,
Joseph J Westermeyer
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ABSTRACT: We report on a test to assess the dynamic brain function at high temporal resolution using magnetoencephalography (MEG). The essence of the test is the measurement of the dynamic synchronous neural interactions, an essential aspect of the brain function. MEG signals were recorded from 248 axial gradiometers while 142 human subjects fixated a spot of light for 45-60 s. After fitting an autoregressive integrative moving average (ARIMA) model and taking the stationary residuals, all pairwise, zero-lag, partial cross-correlations (PCC(ij)(0)) and their z-transforms (z(ij)(0)) between i and j sensors were calculated, providing estimates of the strength and sign (positive, negative) of direct synchronous coupling at 1 ms temporal resolution. We found that subsets of z(ij)(0) successfully classified individual subjects to their respective groups (multiple sclerosis, Alzheimer's disease, schizophrenia, Sjögren's syndrome, chronic alcoholism, facial pain, healthy controls) and gave excellent external cross-validation results.
Journal of Neural Engineering 01/2008; 4(4):349-55. · 3.84 Impact Factor
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ABSTRACT: In this review we bring together three different lines of evidence to bear on the issue of local shaping of function in the motor cortex. The first line of evidence comes from the description by Cajal (1904) of the recurrent collaterals of pyramidal cell axons in the precentral gyrus. The second line of evidence comes from the electrophysiological study of the functional effects of these collaterals [Stefanis, C., Jasper, H. 1964a. Intracellular microelectrode studies of antidromic responses in cortical pyramidal tract neurons. J. Neurophysiol. 27, 828-854.; Stefanis, C., Jasper, H. 1964b. Recurrent collateral inhibition in pyramidal tract neurons. J. Neurophysiol. 27, 855-877.] and associated interneurons [Stefanis, C. 1969. Interneuronal mechanisms in the cortex. In: The Interneuron, Brazier, M.A.B. (ed.), Berkeley, CA: University of California Press, pp. 497-526.] using intracellular recordings. And third came the discovery of directional tuning in the motor cortex [Georgopoulos, A.P., Kalaska, J.F., Caminiti, R., Massey, J.T. 1982. On the relations between the direction of two-dimensional arm movements and cell discharge in primate motor cortex. J. Neurosci. 2, 1527-1537.] in the behaving monkey. We hazard the hypothesis that the bell-shaped directional tuning curve is the outcome of orderly, local neuronal interactions in the motor cortex in which the recurrent pyramidal cell collaterals play a crucial role. Specifically, we propose that these collaterals and the intercalated interneurons they impinge upon serve to spatially sharpen the motor cortical activation to a locus corresponding to the direction of the intended movement. Thus, the originally proposed role of the pyramidal cell collaterals in enhancing "motor contrast" [Stefanis, C. 1969. Interneuronal mechanisms in the cortex. In: The Interneuron, Brazier, M.A.B. (ed.), Berkeley, CA: University of California Press, pp. 497-526.] would translate to creating a "directional tuning field" on the motor cortical surface, where the enhanced motor contrast would correspond to high activity at the center of directional field, and the suppression of the fringe would correspond to lower activity at the periphery of the field, resulting, together in spatial tuning.
Brain Research Reviews 11/2007; 55(2):383-9. · 10.34 Impact Factor
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ABSTRACT: Directional tuning is a basic functional property of cell activity in the motor cortex. Previous work has indicated that cells with similar preferred directions are organized in columns perpendicular to the cortical surface. Here we show that these columns are organized in an orderly fashion in the tangential dimension on the cortical surface. Based on a large number of microelectrode penetrations and systematic exploration of the proximal arm area of the motor cortex while monkeys made free reaching 3D movements, it was estimated that (i) directional minicolumns are approximately 30 mum in width, (ii) minicolumns with similar preferred directions tend to occur in doublets or triplets, and (iii) such minicolumns tend to repeat every approximately 240 mum (estimated width of a column), with intermediate preferred directions represented in a gradient. These findings provide evidence for an orderly mapping of the preferred direction in the motor cortex.
Proceedings of the National Academy of Sciences 07/2007; 104(26):11068-72. · 9.68 Impact Factor
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ABSTRACT: Despite substantial efforts to connect cognitive-linguistic models with appropriate anatomical correlates, the question of which cognitive model best accounts for the neuropsychological and functional neuroimaging evidence remains open. The two most popular models are grounded in conceptually different bases and thus make quasi-distinct predictions in regard to the patterns of activation that should be observed in imaging investigations of linguistic processing. Dual-mechanism models propose that high-frequency regular and irregular words are processed through a lexicon-based word code, which facilitates their processing and pronunciation latencies relative to pseudowords. In contrast, single-mechanism models suggest the same behavioral effects can be explained through semantic mediation without the existence of a lexicon. In most previous studies, words and pronounceable pseudowords were presented in lexical-decision or word reading paradigms, and hemodynamic techniques were utilized to distinguish involved anatomical areas. The results typically indicated that both word classes activated largely congruent tissues, with a magnitude advantage for pseudowords in most or all activated regions. However, since the dual-mechanism model predicts both word types utilize the entire linguistic network, but that certain operations are merely obligatorily involved, these results do not sharply refute nor clearly support the model's main tenets. In the current study, we approach the dual- versus single-mechanism question differently by focusing on the temporal dynamics of MEG imaged neuronal activity, during performance of an oddball version of continuous lexical-decision, to determine whether the onset latency of any cortical language region shows effects of word class that are indicative of preferential versus obligatory processing pathways. The most remarkable aspect of our results indicated that both words and pseudowords initially activate the left posterior fusiform region, but that the spatiotemporal dynamics clearly distinguish the two word classes thereafter. For words, this left fusiform activation was followed by engagement of the left posterior inferior temporal, and subsequently activation reached the left posterior superior temporal region. For pseudowords, this sequential order of left temporal area activations was reversed, as activity proceeded from the left fusiform to the left superior temporal and then the left inferior temporal region. For both classes, this dynamic sequential spread manifested within the first 300 ms of stimulus processing. We contend these results provide strong support for the existence of dual-mechanisms underlying reading in a deep orthographic language (i.e., English).
Experimental Brain Research 07/2007; 180(2):247-62. · 2.39 Impact Factor
