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.

[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.

Dynamics of parietofrontal networks underlying visuospatial short-term memory encoding.

Brain imaging studies in TEP, functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) have shown that visuospatial short-term memory tasks depend on dorsal parietofrontal networks. Knowing the spatiotemporal dynamics of this network would provide further understanding of the neural bases of the encoding process. We combined magnetoencephalography (MEG) with EEG and fMRI techniques to study this network in a task, in which participants had to judge the symmetry in position of two dots, presented either simultaneously ("immediate comparison") or successively ("memorization" of a first dot and "delayed comparison", after 3 s, with a second dot). With EEG, larger amplitude was observed in the parietocentral P3b component (350-500 ms) in the immediate and "delayed comparisons" than in "memorization" condition, where topography at this time was more anterior and right lateralized. MEG provided a more accurate localization and temporal variations of sources, revealing a strong M4 component at 450 ms in the "memorization" condition, with two sources localized in parietal and right premotor regions. These localizations are consistent with both fMRI foci and EEG cortical current source densities (CSD), but only MEG revealed the strong increase in premotor region at 450 ms related to "memorization". These combined results suggest that EEG P3B and MEG M4 components reflect two different dynamics in parietofrontal networks: the parietocentral P3b indexes a decision mechanism during the immediate and "delayed comparisons", whereas the MEG M4 component, with a larger right premotor source, reflects the encoding process in visuospatial short-term memory.

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.

Development of a global motor rating scale for young children (0-4 years) including eye-hand grip coordination.

A comparative study of the eight motor rating scales available in Western countries demonstrated methodological differences in the choice of items and standardization. We have developed a global motor rating scale that includes items which measure postural-motor, locomotor (PML) and eye-hand grip coordination (EHGC), and which allows the assessment of an average of motor function level (MFL), PML and EHGC development. Scores obtained were used to define the acquisition of motor age based on the skills completed. The items were selected on the basis of the average age at which the function developed in two populations of healthy full-term French infants, followed from birth to 4 months (n = 60) and from 4 months to 4 years (n = 63). Recent French developmental standards (mean age and standard deviation) of acquisition allow the identification of neuro-psychomotor deviations from normal motor behaviour. This includes both static and dynamic motor coordination sequences. Inter-examiner correlations (n = 3) for 15 randomly selected children indicated a coefficient of 0.90. The scale revealed a sequence in the organization of learned postural-motor, locomotor and eye-hand gripping skills which can contribute to the understanding of brain areas implicated in this maturation process.

Recoding arm position to learn visuomotor transformations.

There is strong experimental evidence that guiding the arm toward a visual target involves an initial vectorial transformation from direction in visual space to direction in motor space. Constraints on this transformation are imposed (i) by the neural codes for incoming information: the desired movement direction is thought to be signalled by populations of broadly tuned neurons and arm position by populations of monotonically tuned neurons; and (ii) by the properties of outgoing information: the actual movement direction results from the collective action of broadly tuned neurons whose preferred directions rotate with the position of the arm. A neural network model is presented that computes the visuomotor mapping, given these constraints. Appropriate operations are learned by the network in an unsupervised fashion through repeated action- perception cycles by recoding the arm-related proprioceptive information. The resulting solution has two interesting properties: (i) the required transformation is executed accurately over a large part of the reaching space, although few positions are actually learned; and (ii) properties of single neurons and populations in the network closely resemble those of neurons and populations in parietal and motor cortical regions. This model thus suggests a realistic scenario for the calculation of coordinate transformations and initial motor command for arm reaching movements.

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.

Script knowledge after severe traumatic brain injury.

Severe diffuse traumatic brain injury (TBI) may impair the performance of daily-life complex activities. The aim of the present study was to assess whether these difficulties are related to a representational impairment of action knowledge. Two tasks requiring the manipulation of scripts were used. The first (script reconstitution) required subjects to sort cards describing actions belonging to 4 different scripts, presented in a random order. The second (script generation) required subjects to generate actions belonging to a given script. The results showed that TBI patients had preserved access to goal representation and action knowledge. However, they demonstrated (1) significant impairments when they had to deal with simultaneous competing sources of information and (2) a lack of inhibitory control on routine overlearned skills. Patients' performance was significantly correlated with behavioral modifications in everyday life. These data suggest that action impairment in severe TBI patients cannot be attributed to an impairment of action knowledge per se. As previously suggested by Schwartz et al., a restriction of limited-capacity processing resources may account for the observed deficits.

A model study of cellular short-term memory produced by slowly inactivating potassium conductances.

We analyzed the cellular short-term memory effects induced by a slowly inactivating potassium (Ks) conductance using a biophysical model of a neuron. We first described latency-to-first-spike and temporal changes in firing frequency as a function of parameters of the model, injected current and prior history of the neuron (deinactivation level) under current clamp. This provided a complete set of properties describing the Ks conductance in a neuron. We then showed that the action of the Ks conductance is not generally appropriate for controlling latency-to-first-spike under random synaptic stimulation. However, reliable latencies were found when neuronal population computation was used. Ks inactivation was found to control the rate of convergence to steady-state discharge behavior and to allow frequency to increase at variable rates in sets of synaptically connected neurons. These results suggest that inactivation of the Ks conductance can have a reliable influence on the behavior of neuronal populations under real physiological conditions.

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.

Parieto-frontal coding of reaching: an integrated framework.

In the last few years, anatomical and physiological studies have provided new insights into the organization of the parieto-frontal network underlying visually guided arm-reaching movements in at least three domains. (1) Network architecture. It has been shown that the different classes of neurons encoding information relevant to reaching are not confined within individual cortical areas, but are common to different areas, which are generally linked by reciprocal association connections. (2) Representation of information. There is evidence suggesting that reach-related populations of neurons do not encode relevant parameters within pure sensory or motor "reference frames", but rather combine them within hybrid dimensions. (3) Visuomotor transformation. It has been proposed that the computation of motor commands for reaching occurs as a simultaneous recruitment of discrete populations of neurons sharing similar properties in different cortical areas, rather than as a serial process from vision to movement, engaging different areas at different times. The goal of this paper was to link experimental (neurophysiological and neuroanatomical) and computational aspects within an integrated framework to illustrate how different neuronal populations in the parieto-frontal network operate a collective and distributed computation for reaching. In this framework, all dynamic (tuning, combinatorial, computational) properties of units are determined by their location relative to three main functional axes of the network, the visual-to-somatic, position-direction, and sensory-motor axis. The visual-to-somatic axis is defined by gradients of activity symmetrical to the central sulcus and distributed over both frontal and parietal cortices. At least four sets of reach-related signals (retinal, gaze, arm position/movement direction, muscle output) are represented along this axis. This architecture defines informational domains where neurons combine different inputs. The position-direction axis is identified by the regular distribution of information over large populations of neurons processing both positional and directional signals (concerning the arm, gaze, visual stimuli, etc.) Therefore, the activity of gaze- and arm-related neurons can represent virtual three-dimensional (3D) pathways for gaze shifts or hand movement. Virtual 3D pathways are thus defined by a combination of directional and positional information. The sensory-motor axis is defined by neurons displaying different temporal relationships with the different reach-related signals, such as target presentation, preparation for intended arm movement, onset of movements, etc. These properties reflect the computation performed by local networks, which are formed by two types of processing units: matching and condition units. Matching units relate different neural representations of virtual 3D pathways for gaze or hand, and can predict motor commands and their sensory consequences. Depending on the units involved, different matching operations can be learned in the network, resulting in the acquisition of different visuo-motor transformations, such as those underlying reaching to foveated targets, reaching to extrafoveal targets, and visual tracking of hand movement trajectory. Condition units link these matching operations to reinforcement contingencies and therefore can shape the collective neural recruitment along the three axes of the network. This will result in a progressive match of retinal, gaze, arm, and muscle signals suitable for moving the hand toward the target.

Bayesian inference in populations of cortical neurons: a model of motion integration and segmentation in area MT.

A major issue in cortical physiology and computational neuroscience is understanding the interaction between extrinsic signals from feedforward connections and intracortical signals from lateral connections. We propose here a computational model for motion perception based on the assumption that the local cortical circuits in the medio-temporal area (area MT) implement a Bayesian inference principle. This approach establishes a functional balance between feedforward and lateral, excitatory and inhibitory, inputs. The model reproduces most of the known properties of the neurons in area MT in response to moving stimuli. It accounts for important motion perception phenomena including motion transparency, spatial and temporal integration/segmentation. While integrating several properties of previously proposed models, it makes specific testable predictions concerning, in particular, temporal properties of neurons and the architecture of lateral connections in area MT. In addition, the proposed mechanism is consistent with the known properties of local cortical circuits in area V1. This suggests that Bayesian inference may be a general feature of information processing in cortical neuron populations.

Planning dysfunction in schizophrenia: impairment of potentials preceding fixed/free and single/sequence of self-initiated finger movements.

To test the hypothesis of a planning dysfunction in schizophrenia using a precise temporal definition, the readiness potential (RP), a negative cortical wave preceding self-initiated movements and reflecting motor preparation processes, was studied in patients under stable medication and in controls. The supplementary motor area (SMA), known to be involved in the generation of the RP, has also been implicated in movement selection (fixed versus free) and complexity (single versus sequence). This is the first study using RP for the assessment of the influence of these factors on motor preparation in schizophrenics. Our results show that schizophrenics' RP amplitude is significantly lower than in controls at central and contralateral electrodes. However, RP amplitude increases with task difficulty in both groups, offering important new insight into classical SMA hypoactivation in schizophrenics performing motor tasks. Topographic analysis shows that RP amplitude is, for both groups, significantly higher in sequence than in single movements at fronto-central sites and higher for free than for fixed movements at centro-parietal sites. Finally, RP onset occurs significantly later in schizophrenics than in controls. These results support the view of a motor-preparation and decision-making dysfunction in schizophrenia. They are interpreted within the framework of a fronto-striatal disorder in this disease.

Brain activation in response to a tactile stimulation: functional magnetic resonance imaging (FMRI) versus cognitive analysis.

Objective. The aim of this study was to compare fMRI analysis of somatosensory areas activated by passive touch, to cognitive analysis of the psychological profile of human subjects. Methods. The study was carried out on 21 females, after informed consent. Two artificial textures (smooth and rough), and two natural textures (the skin of an operator modified or not by a cosmetic product), were applied on the fingers of the subjects. A period of imagination to be touched was also included in the study. MR images of the somatosensory cortex were acquired on a 1.5T MRI system during the different behavioral conditions. Series of images were first processed to compensate for the inter-frame motions and then activation was assessed with a statistical method based on conditional analysis. After the MRI protocol, each subject was interviewed following a questionnaire from which psychological descriptors were extracted. Results. 1) Activations were quite similar for all textures in the contralateral sensory areas 2) In the ipsilateral sensory areas, activations were more important in response to a stimulation with the skin of an operator than with artificial textures. The activation was even more important after application of a cosmetic product on the skin. 3) Imagination of the tactile stimulation resulted in an activation mostly localized in the ipsilateral cortex. 4) A PLS analysis assessed that 2 psychological descriptors, rationality and sensorial reactivity, were related to an activation in the contralateral cortex, while 2 others, imagination and sensitivity, were related to ipsilateral areas activation. Conclusion. fMRI and cognitive analysis allowed us to map the physical component of the tactile perception in the contralateral cortex. This study also gave rise to a better understanding of the activation in ipsilateral areas, which was found to be mainly related to the subjective component of the stimulation.

Early motor influences on visuomotor transformations for reaching: a positive image of optic ataxia.

Coding of reaching in the cerebral cortex is based on the operation of distributed populations of parietal and frontal neurons, whose main functional characteristics reside in their combinatorial power, i.e., in the capacity for combining different information related to the spatial aspects of reaching. The tangential distribution of reach-related neurons endowed with different functional properties changes gradually in the cortex and defines, in the parieto-frontal network, trends of functional properties. These visual-to-somatic gradients imply the existence of cortical regions of functional overlaps, i.e., of combinatorial domains, where the integration of different reach-related signals occurs. Studies of early coding of reaching in the mesial parietal areas show how somatomotor information, such as that related to arm posture and movement, influences neuronal activity in the very early stages of the visuomotor transformation underlying the composition of the motor command and is not added "downstream" in the frontal cortex. This influence is probably due to re-entrant signals traveling through fronto-parietal-association connections. Together with the gradient architecture of the network and the reciprocity of cortico-cortical connections, this implies that coding of reaching cannot be regarded as a top-down, serial sequence of coordinate transformation, each performed by a given cortical area, but as a recursive process, where different signals are progressively matched and further elaborated locally, due to intrinsic cortical connections. This model of reaching is also supported by psychophysical studies stressing the parallel processing of the different relevant parameters and the "hybrid" nature of the reference frame where they are combined. The theoretical frame presented here can also offer a background for a new interpretation of a well-known visuomotor disorder, due to superior parietal lesions, i.e., optic ataxia. More than a disconnection syndrome, this can now be interpreted as the consequence of the breakdown of the operations occurring in the combinatorial domains of the superior parietal segment of the parieto-frontal network.

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.

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.