Longitudinal study of motor recovery after stroke: recruitment and focusing of brain activation.

BACKGROUND AND PURPOSE: The goal of this study was to characterize cortical reorganization after stroke and its relation with the site of the stroke-induced lesion and degree of motor recovery using functional MRI (fMRI). METHODS: Fourteen stroke patients with an affected upper limb were studied longitudinally. Three fMRI sessions were performed over a period of 1 to 6 months after stroke. Upper limb recovery, Wallerian degeneration of the pyramidal tract, and responses to transcranial magnetic stimulation were assessed. RESULTS: Two main patterns of cortical reorganization were found. Pattern 1 was focusing, in which, after initial recruitment of additional ipsilateral and contralateral areas, activation gradually developed toward a pattern of activation restricted to the contralateral sensorimotor cortex in 9 patients. Five patients were found to have pattern 2, persistent recruitment, in which there was an initial and sustained recruitment of ipsilateral activity. Occurrence of recruitment or focusing seemed to depend mainly on whether the primary motor cortex (M1) was lesioned; persistent recruitment was observed in 3 of 4 patients with M1 injury, and focusing was seen in 8 of 10 patients with spared M1. These patterns had no relation to the degree of recovery; in particular, focusing did not imply recovery. However, there was a clear relation between the degree of recovery and the degree of Wallerian degeneration. CONCLUSIONS: These results suggest that ipsilateral recruitment after stroke corresponds to a compensatory corticocortical process related to the lesion of the contralateral M1 and that the process of compensatory recruitment will persist if M1 is lesioned; otherwise, it will be transient.

Functional MRI in double cortex: functionality of heterotopia.

A 12-year-old boy with epilepsy and subcortical laminar heterotopia (band heterotopia) underwent a functional MRI protocol to study voluntary motor activity in the hand. Finger tapping produced an activation of a contralateral limited and focused frontal cortical area both in the subcortical band heterotopia and the overlying cortex. Despite its epileptogenic activity, subcortical laminar heterotopia seems to be responsible for part of the functional activity of the brain. This has to be pointed out for epilepsy surgery resecting cortical dysplasia.

A synaptically evoked late hyperpolarization in the rat dorsolateral geniculate neurons in vitro.

Intracellular potentials were recorded from presumed relay neurons in the rat dorsolateral geniculate nucleus maintained in vitro preparations. In this material, the neuronal circuit includes the excitatory optic tract which innervates monosynaptically both relay and intrinsic neurons, the latter providing a feed-forward GABAergic inhibition on the former. Electrical stimulation of the optic tract evokes in the dorsolateral geniculate neurons an early excitatory postsynaptic potential followed by an inhibitory postsynaptic potential which precedes a so far unreported long-lasting late hyperpolarization. The properties of the inhibitory postsynaptic potential are consistent with the notion that they are of disynaptic (feed-forward) origin and that they are the consequence of GABAA receptor activation. In contrast, the late hyperpolarization, which was found in almost every neuron, was enhanced by GABAA blockers, without accompanying changes in the resting membrane potential or the input resistance of the recorded cells. The late hyperpolarization had a lower threshold than the excitatory postsynaptic potential, a long latency (m = 38 +/- 4 ms, n = 10) and was of long duration (m = 308 +/- 57 ms, n = 10). The occurrence and threshold for producing these two potentials were uncorrelated, and paired stimulations of the optic tract showed a marked difference of their recovery time-courses. The late hyperpolarization could be elicited only by afferent stimulations; it never followed intracellularly induced depolarizations and/or anodal break calcium spikes. It was associated with a small conductance increase, sufficient, however, to inhibit high-frequency discharges induced by intracellular injection of depolarizing currents. The late hyperpolarization decreased in amplitude with membrane hyperpolarization and ultimately reversed polarity. The apparent reversal potential followed shifts in extracellular potassium concentration in an almost Nernstian relation (47 mV for a tenfold increase in [K]0). Involvement of GABAB receptors in the generation of this potential may be postulated since baclofen readily hyperpolarized the neurons and decreased their input resistance in the presence of GABAA blockers. We conclude that the late hyperpolarization is a postsynaptic potential mediated by an increased conductance to K ions. Our results further suggest that a minimal disynaptic feed-forward circuit impinging on the relay neurons of the dorsolateral geniculate nucleus is sufficient to subserve this late hyperpolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Temporal order and spatial memory in schizophrenia: a parametric study.

Spatial working memory has been shown to be impaired in schizophrenia. In contrast, memory for temporal order has been poorly studied in patients with schizophrenia. The aim of this study was to compare and to further characterize spatial working memory and sequence reproduction deficits in patients with schizophrenia under stable medication by manipulating cues (pattern versus sequence), delay, set-size and response type in various recall and recognition tasks. This allowed us to dissociate processes as encoding, retention and retrieval and to compare the performance of patients with schizophrenia to the performance of patients with prefrontal lesions, who have been previously tested in the same tasks. Our results show that increase of the set-size and of the delay decreased performance of both groups, and that these factors had larger detrimental effects in patients with schizophrenia than in controls. Furthermore, comparison between tasks revealed retention and retrieval deficits in schizophrenia. Finally, patients with schizophrenia showed impairments not only in recall but also in sequence recognition tasks with delay. This is in contrast to patients with prefrontal lesions, who have previously been shown to have intact recognition of sequences after a delay. These results suggest that the working memory deficit in schizophrenia cannot be restricted to a prefrontal dysfunction.

Learning a new visuomotor transformation: error correction and generalization.

The use of an aiming tool requires learning a new transformation between visual and proprioceptive information and motor command. We have examined this question by quantifying the kinematics of the movement during the transitory phase of adaptation to a rotational bias (60 degrees counterclockwise, then clockwise) added to a standard mouse-cursor device in the plane of the screen. Control-aiming movements were almost linear with a bell-shaped velocity profile. The bias induced an equivalent initial directional error which was usually corrected within 20 trials. The learning trajectories were combinations of spirals and fast or slow straight movements. The posture of the hand was slightly (less than 10 degrees) modified by the bias. These features suggest three corrective processes: on-line continuous correction based on evaluation of the relative cursor-to-target position, discrete correction based on assessment of the discrepancy angle between the cursor-to-target direction and the effective cursor direction, and memorization of trial-to-trial correction. These results are interpreted in the light of neurophysiological data and neural net modeling, which suggest that the visuomotor transformation performed by cortical areas for reaching is effected by projecting the visual information on a reference frame that rotates with the arm. The initial directional error reappeared when the direction of the target was changed and increased with degree of change. The limited generalization suggests that bias correction is stored in relation to the coding of the target direction and that movement towards a new direction is computed as a projection of the previously learned bias on the new visual direction.

Bistable behaviour in a neocortical neurone model.

Intracellular recordings have shown that neocortical pyramidal neurones have an intrinsic capacity for regenerative firing. The cellular mechanism of this firing was investigated by computer simulations of a model neurone endowed with standard action potential and persistent sodium (gNaP) conductances. The firing mode of the neurone was determined as a function of leakage and NaP maximal conductances (gl and gNaP). The neurone had two stable states of activity (bistable) over wide range of gl and gNaP, one at the resting potential and the other in a regenerative firing mode, that could be triggered by a transient input. This model points to a cellular mechanism that may contribute to the generation and maintenance of long-lasting sustained neuronal discharges in the cerebral cortex.

Functional MR imaging of the human sensorimotor cortex during haptic discrimination.

This study attempted to determine whether haptic discriminations of shape (haptic task) activate the same tissue in the central cortical region of normal human subjects as do finger movements (opposition task). Opposition and haptic tasks both activated the central sulcus, as expected from previous imaging studies. The haptic task activated about 50% of the cortical territory activated by the opposition task. The results suggest that exploratory digital movements performed to collect precise somatosensory information and automatic movements performed during finger positioning activate partially overlapping parts of the sensorimotor cortex.

Dynamical computational properties of local cortical networks for visual and motor processing: a bayesian framework.

A major unsolved question concerns the interaction between the coding of information in the cortex and the collective neural operations (such as perceptual grouping, mental rotation) that can be performed on this information. A key property of the local networks in the cerebral cortex is to combine thalamocortical or feedforward information with horizontal cortico-cortical connections. Among different types of neural networks compatible with the known functional and architectural properties of the cortex, we show that there exist interesting bayesian solutions resulting in an optimal collective decision made by the neuronal population. We suggest that thalamo-cortical and cortico-cortical synaptic plasticity can be differentially modulated to optimize this collective bayesian decision process. We take two examples of cortical dynamics, one for perceptual grouping in MT, and the other one for mental rotation in M1. We show that a neural implementation of the bayesian principle is both computationally efficient to perform these tasks and consistent with the experimental data on the related neuronal activities. A major implication is that a similar collective decision mechanism should exist in different cortical regions due to the similarity of the cortical functional architecture.

Neural network models of cortical functions based on the computational properties of the cerebral cortex.

We describe a biologically plausible modelling framework based on the architectural and processing characteristics of the cerebral cortex. Its key feature is a multicellular processing unit (cortical column) reflecting the modular nature of cortical organization and function. In this framework, we describe a neural network model organization and function. In this framework, we describe a neural network model of the neuronal circuits of the cerebral cortex that learn different functions associated with different parts of the cortex: 1) visual integration for invariant pattern recognition, performed by a cooperation between temporal and parietal areas; 2) visual-to-motor transformation for 3D arm reaching movements, performed by parietal and motor areas; and 3) temporal integration and storage of sensorimotor programs, performed by networks linking the prefrontal cortex to associative sensory and motor areas. The architecture of the network is inspired from the features of the architecture of cortical pathways involved in these functions. We propose two rules which describe neural processing and plasticity in the network. The first rule (adaptive tuning if gating) is an analog of operant conditioning and permits to learn to anticipate an action. The second rule (adaptive timing) is based on a bistable state of activity and permits to learn temporally separate events forming a behavioral sequence.

Principal component analysis: a suitable method for the 3-dimensional study of the shape, dimensions and orientation of dendritic arborizations.

Our study proposes an objective method of describing 3-dimensional dendritic arborizations of neurons in the best possible conditions. The method is based upon a particular exploitation of statistical "principal component analysis". For each arborization, 3 principal axes are calculated which are its axes of inertia. The first two axes define the "principal plane" of the arborization. The shape of the arborization is determined from the statistical distribution of its dendritic points along each of these axes. Shapes are quantified by using an "index of axialization" (a) and an "index of flatness" (p) both of which may vary from zero to 1. The dimensions of the arborization, "length" (1), "width" (w) and "thickness" (t) are also measured along the principal axes. Orientation of arborizations is quantified by considering the orientation of the first principal axis for axialized arborization (a close to 1) and/or the orientation of the principal plane for flattened arborizations (p close to 1). In both cases 2 angles (azimuth and polar angle) are calculated. For spherical arborizations (a and p close to 1), no orientation is significant. The significance level of the defined orientations is evaluated from the values of the shape indices. Several examples are illustrated and other existing methods are discussed.

Evolution of myoelectrical and precentral cell activities during learning of a new amplitude of movement.

The object of these experiments was to determine if changes in precentral neuron activity may be related to learning of a new amplitude of movement. Data were obtained from two monkeys trained to stop, in a given position, an elbow flexion movement in order to get a reward. A screen prevented the animal from seeing its forearm. The terminal position was not indicated by a cue, and movements were self-initiated. Motor performance and cell activity were analyzed during the period of learning of a new amplitude of movement. The cells studied presented the reciprocal patterns of activity: they were active flexion but discharged during passive extension. Results clearly indicated that: (1) amplitude was the actual parameter which was learned; (2) the peak frequency of discharge of motor cortex neurons increased during learning, as did the frequency of reward; and (3) the peak frequency of discharge related to passive movements was not changed by conditioning. The results support the hypothesis that the increase of the activity tied to active movements which is observed during conditioning may not be related to an increase of peripheral feedback but expresses a greater 'corticalization' of the movement.

Dorsolateral geniculate neurons in vitro: reduced postsynaptic excitability following repetitive activation of the optic tract.

Monosynaptic activation of dorsolateral geniculate neurons of the rat was studied in the in vitro slice preparation. (1) As previously described by others, monosynaptic excitatory postsynaptic potentials (EPSPs) trigger at membrane potential negative to -60 mV a low threshold spike (Lts). In addition, we report that the Lts amplitude is linked to that of its underlying EPSP. (2) EPSPs, EPSP-Lts sequences and nonsynaptic Lts are followed by a long period of refractoriness during which a test response is decreased in amplitude and the Lts component is cut off. These results are discussed in relation to the generation of spontaneous bursting activity of thalamic neurons during natural sleep, which could be accounted for by the properties of the Lts alone.

Modelling the acquisition of goal-directed behaviors by populations of neurons.

Recent neurophysiological studies have revealed the patterns of neuronal activity during the acquisition of goal-directed behaviors, both in single cells, and in large populations of neurons. We propose a model which helps three sets of experimental results in the monkey to be understood: (1) activity of single cells vary greatly and only population activities are causally related to behavior. The model shows how a population of stochastic neurons, whose behaviors vary widely, can learn a skilled conditioned movement with only local activity-dependent synaptic changes. (2) typical changes in neuronal activity occur when the rules governing the behavior are changed, i.e. when the relationship between cues and actions to reach a goal changes over time. There are two types of neuronal patterns during changes in reward contingency: a monotonic increasing pattern and a non-monotonic pattern which follows the change in the way the reward is obtained. Units in the model display these two types of change, which correspond to synaptic modifications related to the encoding of the behavioral significance of sensory and motor events. (3) These two patterns of neuronal activity define two populations whose anatomical distributions in the frontal lobe overlap with a gradient organized in the rostro-caudal direction. The model consists of two artificial neural networks, defined by the same set of equations, but which differ in the values of two parameters (P and Q). P defines the adaptive properties of processing units and Q describes the coding of information. The model suggests that a balance in the relative strengths of these parameters distributed along a rostro-caudal gradient can explain the distribution of neuronal types in the frontal lobe of the monkey.

[Cortical response in age-related macular degeneration (part I). Methodology and subject specificities]. / Réponse corticale dans la DMLA (Première partie). Méthodologie et spécificités des sujets.

PURPOSE: To evaluate the cortical response to visual stimulation in patients with age-related macular degeneration (ARMD). MATERIAL AND METHODS: We conducted a prospective functional MRI study at 1.5 Testa in ten patients presenting with unilateral or bilateral ARMD and five age-matched controls. The visual stimulus was a sequence of resting phase (presentation of a fixation point on a black background) followed by an activation phase (flashes at 2 Hz). Functional data were recorded with anatomy; significant hemodynamic response secondary to neuronal activation was statistically determined using the SPM 99 software. RESULTS: The first objective was to estimate the feasibility of a functional study in the elderly. Controls and patients complained about the duration of the examination, although each of the two active functional sessions lasted only 4.5 min. The central point fixation was impaired for the patients; some deviated their gaze to center the fixation point on a perimacular retinal area. Because of substantial movement during MRI acquisitions, the data from two patients and one control were withdrawn from statistic processing. DISCUSSION AND CONCLUSION: This study is one of the few evaluations reported on functional MRI in the elderly, because of technical constraints, patient fragility and their ophthalmologic pathology. Optimizing the visual stimulus and the paradigm of stimulation, repeating patient information and support have helped demonstrate significant cortical hemodynamic response in most subjects, even in the most affected patients. Evaluation of the visual cortex by functional MRI appears feasible in the ophthalmologic pathology of the elderly, providing an adapted management of the subject's conditions.

[Cortical response to age-related macular degeneration (Part II). Functional MRI study]. / Réponse corticale dans la DMLA (Deuxième partie). Etude en IRM fonctionnelle.

UNLABELLED: PURPOSE AND MATERIALS: To evaluate the cortical response to visual stimulation in patients with age-related macular degeneration (ARMD), we conducted a functional MRI study in ten patients presenting unilateral or bilateral ARMD and five age-matched controls, using white flashes during activation phases (see Part I). RESULTS: After anatomical conformation, eight patients and four controls showed significant cortical hemodynamic response to monocular stimulations. Individual analysis was preferred to group evaluation, because of the differences in visual loss in a small number of patients. In controls, we observed cortical response in the primary visual cortex, especially at occipital poles corresponding to the macula. Patients showed a qualitative and quantitative restriction in cortical response and exclusion of occipital poles after stimulation of the affected eye, whereas activation was found in the peripheral striate and peristriate cortex. Cortical response showed hemispheric asymmetry in some patients. DISCUSSION: Our study demonstrated an activation defect in the macular projected striate cortex, corresponding to visual impairment in ARMD patients. Nevertheless, at a given visual acuity, cortical response may vary among subjects. Patients' subjective apprehension may account for such variations, as well as objective visual capacity stemming from residual functional retinal areas within the affected macula. The hemispheric asymmetry in cortical activation may result from gaze deviation onto the new fixation area in the perimacular retina, thus altering the global visual field. Enhancement in the peripheral striate and peristriate areas suggests changes in cortical interactions, possibly by a lowering of the feedback from macular projected V1. Finally, cortical evaluations must take into account degenerative phenomena delaying the hemodynamic response in the elderly. CONCLUSION: Aiming at a specific population of weakened patients with a serious visual impairment, we obtained significant results concerning cortical plasticity for visual perception in central vision deletion. Our preliminary findings must be confirmed in a larger population and correlated with other techniques exploring vision, in particular with multifocal electroretinography for retinal evaluation.

A hierarchy of associations in hippocampo-cortical systems: cognitive maps and navigation strategies.

In this letter we describe a hippocampo-cortical model of spatial processing and navigation based on a cascade of increasingly complex associative processes that are also relevant for other hippocampal functions such as episodic memory. Associative learning of different types and the related pattern encoding-recognition take place at three successive levels: (1) an object location level, which computes the landmarks from merged multimodal sensory inputs in the parahippocampal cortices; (2) a subject location level, which computes place fields by combination of local views and movement-related information in the entorhinal cortex; and (3) a spatiotemporal level, which computes place transitions from contiguous place fields in the CA3-CA1 region, which form building blocks for learning temporospatial sequences. At the cell population level, superficial entorhinal place cells encode spatial, context-independent maps as landscapes of activity; populations of transition cells in the CA3-CA1 region encode context-dependent maps as sequences of transitions, which form graphs in prefrontal-parietal cortices. The model was tested on a robot moving in a real environment; these tests produced results that could help to interpret biological data. Two different goal-oriented navigation strategies were displayed depending on the type of map used by the system. Thanks to its multilevel, multimodal integration and behavioral implementation, the model suggests functional interpretations for largely unaccounted structural differences between hippocampo-cortical systems. Further, spatiotemporal information, a common denominator shared by several brain structures, could serve as a cognitive processing frame and a functional link, for example, during spatial navigation and episodic memory, as suggested by the applications of the model to other domains, temporal sequence learning and imitation in particular.

Organizational levels of the cerebral cortex: an integrated model.

We propose a theoretical model of the cerebral cortex which is based on its cellular components and integrates its different levels of organization: (1) cells have general adaptive and memorization properties; (2) cortical columns are repetitive interneuronal circuits which determine an adaptive processing specific to the cerebral cortex; (3) cortical maps effect selective combinations which are very efficient to learn basic behavioural adaptations such as invariant recognition of forms, visually-guided hand movements, or execution of structured motor programs; (4) the network between cortical areas has a global architecture which integrates successive learning experiences into coherent functions such as the human language.

Dual Population Coding in the Neocortex: A Model of Interaction between Representation and Attention in the Visual Cortex.

The text describes a model that extends the population coding principles to any multidimensional attribute. The model distinguishes between the distribution of cell activity and the overall activity of a population. The distribution of cell activity is assumed to encode attribute information, while overall activity is assumed to reflect the significance or pertinence of the encoded attribute in the cerebral cortex, according to the dual coding principle. Three basic mechanisms of interaction between the representation of attribute and pertinence are defined and are applied to the motion (MT-MST) cortical pathway in the visual cortex. This framework determines three sources of pertinence that model cognitive processing, including preattentive processing, spatial-selective attention, and object-selective attention. The model accommodates most of the published psychophysical, neurophysiological, and neuroanatomical data and makes several testable predictions about the representations of attribute and enhanced effects in these areas.

Consequences of stochastic release of neurotransmitters for network computation in the central nervous system.

Neuronal membrane potentials vary continuously due largely to background synaptic noise produced by ongoing discharges in their presynaptic afferents and shaped by probabilistic factors of transmitter release. We investigated how the random activity of an identified population of interneurons with known release properties influences the performance of central cells. In stochastic models such as thermodynamic ones, the probabilistic input-output function of a formal neuron is sigmoid, having its maximal slope inversely related to a variable called "temperature." Our results indicate that, for a biological neuron, the probability that given excitatory input signals reach threshold is also sigmoid, allowing definition of a temperature that is proportional to the mean number of quanta comprising noise and can be modified by activity in the presynaptic network, a notion which could be included in neural models. By introducing uncertainty to the input-output relation of central neurons, synaptic noise could be a critical determinant of neuronal computational systems, allowing assemblies of cells to undergo continuous transitions between states.