Preparing for a Second Attack: A Lesion Simulation Study on Network Resilience After Stroke.

BACKGROUND: Does the brain become more resilient after a first stroke to reduce the consequences of a new lesion? Although recurrent strokes are a major clinical issue, whether and how the brain prepares for a second attack is unknown. This is due to the difficulties to obtain an appropriate dataset of stroke patients with comparable lesions, imaged at the same interval after onset. Furthermore, timing of the recurrent event remains unpredictable. METHODS: Here, we used a novel clinical lesion simulation approach to test the hypothesis that resilience in brain networks increases during stroke recovery. Sixteen highly selected patients with a lesion restricted to the primary motor cortex were recruited. At 3 time points of the index event (10 days, 3 weeks, 3 months), we mimicked recurrent infarcts by deletion of nodes in brain networks (resting-state functional magnetic resonance imaging). Graph measures were applied to determine resilience (global efficiency after attack) and wiring cost (mean degree) of the network. RESULTS: At 10 days and 3 weeks after stroke, resilience was similar in patients and controls. However, at 3 months, although motor function had fully recovered, resilience to clinically representative simulated lesions was higher compared to controls (cortical lesion P=0.012; subcortical: P=0.009; cortico-subcortical: P=0.009). Similar results were found after random (P=0.012) and targeted (P=0.015) attacks. CONCLUSIONS: Our results suggest that, in this highly selected cohort of patients with lesions restricted to the primary motor cortex, brain networks reconfigure to increase resilience to future insults. Lesion simulation is an innovative approach, which may have major implications for stroke therapy. Individualized neuromodulation strategies could be developed to foster resilient network reconfigurations after a first stroke to limit the consequences of future attacks.

The neural correlates of intermanual transfer.

Intermanual transfer of motor learning is a form of learning generalization that leads to behavioral advantages in various tasks of daily life. It might also be useful for rehabilitation of patients with unilateral motor deficits. Little is known about neural structures and cognitive processes that mediate intermanual transfer. Previous studies have suggested a role for primary motor cortex (M1) and the supplementary motor area (SMA). Here, we investigated the functional neuroanatomy of intermanual transfer with a special emphasis on functional connectivity within the motor network and between motor regions and attentional networks, including the fronto-parietal executive control network and visual attention networks. We designed a finger tapping task, in which young, heathy subjects trained the non-dominant left hand in the MRI scanner. Behaviorally, transfer of sequence learning was observed in most cases, independently of the trained hand's performance. Pre- and post-training functional connectivity patterns of cortical motor seeds were investigated using generalized psychophysiological interaction analyses. Transfer was correlated with the strength of connectivity between the left premotor cortex and structures within the dorsal attention network (superior parietal cortex, left middle temporal gyrus) and executive control network (right prefrontal regions) during pre-training, relative to post-training. Changes in connectivity within the motor network, and more particularly between trained and untrained M1, as well as between the SMA and untrained M1, correlated with transfer after training. Together, these results suggest that the interplay between attentional, executive and motor networks may support processes leading to transfer, whereas, following training, transfer translates into increased connectivity within the motor network.

Classification of postoperative behavior disturbances in preschool children: A qualitative study.

BACKGROUND/AIM: Negative postoperative changes in children are frequent and have been described for decades. However, there is currently no theoretical framework, nor any consensual operational criteria for identifying them. This study aims at characterizing the many dimensions involved in postoperative behavioral disturbances in early childhood, using a qualitative analysis applied for the first time to these symptoms. METHOD: Fifty-seven parents of preschool children (1-5 years old; 38 boys), who underwent general anesthesia, were interviewed 10 days after surgery. Semi-structured interviews investigated behavioral disturbances classically described in preschool children. Qualitative analysis of the transcripts allied both deductive and inductive reasoning, and inductive coding was carried out using constant comparison method with dedicated qualitative software. RESULTS: Parents reported both positive and negative postoperative changes. Negative changes were classified in four main categories: (a) Externalizing and (b) Internalizing problems behaviors, (c) Feeding sleeping disruption and (d) Somatic problems, each comprising different sub-categories. Importantly within these categories, the symptoms distribution changed in 5 years old children, compared to younger children. Finally, our method allowed defining whether these (negative or positive) changes were significant or not, that is, the importance of postoperative behavioral changes. CONCLUSION: The results of this study highlight the heterogeneity of postoperative disturbances in preschool children. These results are of primary importance for the definition and measurement of postoperative behavioral disturbances.

Functional Dissociations Within Posterior Parietal Cortex During Scene Integration and Viewpoint Changes.

The posterior parietal cortex (PPC) is an anatomically heterogeneous brain region implicated in a wide range of cognitive operations, including egocentric spatial processing and both short- and long-term memory. Here, we report functional specificities of cytoarchitectonically defined subregions of PPC during the processing of scenes across changes in viewpoint. Participants (n = 16) saw photographs of familiar and unfamiliar places while undergoing functional magnetic resonance imaging (fMRI). On each trial, 4 viewpoints of the same place were presented, with either a plausible sequence of viewpoints (SEQ) or a scrambled order (SCRA). Distinct response profiles were observed within PPC. Area 7A showed increased activity for SEQ versus SCRA order, regardless of place familiarity, whereas the rostral inferior parietal lobule showed preferential increases for unfamiliar versus familiar places in SEQ series. In contrast, more posterior subregions in both superior and inferior PPC exhibited increases for familiar versus unfamiliar places at the end of the sequence, regardless of order. The data highlight the distinctive contribution of several subregions of PPC during the processing of scenes, with specific cortical areas involved in the progressive integration of spatial information across viewpoint changes, and others involved in the retrieval and maintenance of scene information in memory.

Associative and semantic memory deficits in amnestic mild cognitive impairment as revealed by functional magnetic resonance imaging.

OBJECTIVE: To identify the neural underpinnings of cognitive deficits associated with memory problems in amnestic mild cognitive impairment (aMCI). BACKGROUND: Functional magnetic resonance imaging (fMRI) is increasingly used to assess patients with aMCI and could potentially help predict conversion to Alzheimer disease, but imaging results so far have been inconsistent in identifying brain activation patterns in aMCI. There is an immediate need to identify the neural substrates of different memory components that are affected by aMCI. METHODS: We used fMRI to study 13 patients with aMCI and 15 healthy age-matched controls during an associative memory encoding and recognition task. The picture-pair memory task encompassed different types of recognition trials to investigate recollection versus familiarity, and manipulated the relationship between paired pictures to investigate semantic processing. RESULTS: Brain activation during both encoding and recognition was lower in patients than controls, with greatest implications in the medial temporal lobe during encoding. Patients also had much greater impairment of associative recollection than recognition based on familiarity, along with a failure to recruit regions that normally respond to violations of learned associations. Finally, patients' impaired semantic encoding was reflected by deficient activation of a left frontotemporal network responsible for elaborate semantic processes. CONCLUSIONS: We show that a simple fMRI task may be sensitive to deficits in different memory components in aMCI and could thus prove useful in the development of an fMRI tool to assess and monitor patients.

Does flexibility in perceptual organization compete with automatic grouping?

Segregated objects can be sought simultaneously, i.e., mentally "re-grouped." Although the mechanisms underlying such "re-grouping" clearly differ from automatic grouping, it is unclear whether or not the end products of "re-grouping" and automatic grouping are the same. If they are, they would have similar impact on visual organization but would be in conflict. We compared the consequences of grouping and re-grouping on the performance cost induced by stimuli presented across hemifields. Two identical and contiguous target figures had to be identified within a display of circles and squares alternating around a fixation point. Eye tracking was used to check central fixation. The target pair could be located in the same or separate hemifields. A large cost of presenting targets across hemifields was observed. Grouping by connectedness yielded two types of target pair, connected and unconnected. Subjects prioritized unconnected pairs efficiently when prompted to do so, suggesting "re-grouping." However, unlike automatic grouping, this did not affect the cost of across-hemifield presentation. The suggestion is that re-grouping yields different outputs to automatic grouping, such that a fresh representation resulting from re-grouping complements the one resulting from automatic grouping but does not replace it. This is one step toward understanding how our mental exploration of the world ties in and coexists with ongoing perception.

Periinfarct rewiring supports recovery after primary motor cortex stroke.

After stroke restricted to the primary motor cortex (M1), it is uncertain whether network reorganization associated with recovery involves the periinfarct or more remote regions. We studied 16 patients with focal M1 stroke and hand paresis. Motor function and resting-state MRI functional connectivity (FC) were assessed at three time points: acute (<10 days), early subacute (3 weeks), and late subacute (3 months). FC correlates of recovery were investigated at three spatial scales, (i) ipsilesional non-infarcted M1, (ii) core motor network (M1, premotor cortex (PMC), supplementary motor area (SMA), and primary somatosensory cortex), and (iii) extended motor network including all regions structurally connected to the upper limb representation of M1. Hand dexterity was impaired only in the acute phase (P = 0.036). At a small spatial scale, clinical recovery was more frequently associated with connections involving ipsilesional non-infarcted M1 (Odds Ratio = 6.29; P = 0.036). At a larger scale, recovery correlated with increased FC strength in the core network compared to the extended motor network (rho = 0.71;P = 0.006). These results suggest that FC changes associated with motor improvement involve the perilesional M1 and do not extend beyond the core motor network. Core motor regions, and more specifically ipsilesional non-infarcted M1, could hence become primary targets for restorative therapies.

Hurt but still alive: Residual activity in the parahippocampal cortex conditions the recognition of familiar places in a patient with topographic agnosia.

The parahippocampal cortex (PHC) participates in both perception and memory. However, the way perceptual and memory processes cooperate when we navigate in our everyday life environment remains poorly understood. We studied a stroke patient presenting a brain lesion in the right PHC, which resulted in a mild and quantifiable topographic agnosia, and allowed us to investigate the role of this structure in overt place recognition. Photographs of personally familiar and unfamiliar places were displayed during functional magnetic resonance imaging (fMRI). Familiar places were either recognized or unrecognized by the patient and 6 age- and education-matched controls in a visual post-scan recognition test. In fMRI, recognized places were associated with a network comprising the fusiform gyrus in the intact side, but also the right anterior PHC, which included the lesion site. Moreover, this right PHC showed increased connectivity with the left homologous PHC in the intact hemisphere. By contrasting recognized with unrecognized familiar places, we replicate the finding of the joint involvement of the retrosplenial cortex, occipito-temporal areas, and posterior parietal cortex in place recognition. This study shows that the ability for left and right anterior PHC to communicate despite the neurological damage conditioned place recognition success in this patient. It further highlights a hemispheric asymmetry in this process, by showing the fundamental role of the right PHC in topographic agnosia.

Disruption of information processing in schizophrenia: The time perspective.

We review studies suggesting time disorders on both automatic and subjective levels in patients with schizophrenia. Patients have difficulty explicitly discriminating between simultaneous and asynchronous events, and ordering events in time. We discuss the relationship between these difficulties and impairments on a more elementary level. We showed that for undetectable stimulus onset asynchronies below 20 ms, neither patients nor controls merge events in time, as previously believed. On the contrary, subjects implicitly distinguish between events even when evaluating them to be simultaneous. Furthermore, controls privilege the last stimulus, whereas patients seem to stay stuck on the first stimulus when asynchronies are sub-threshold. Combining previous results shows this to be true for patients even for asynchronies as short as 8 ms. Moreover, this peculiarity predicts difficulties with detecting asynchronies longer than 50 ms, suggesting an impact on the conscious ability to time events. Difficulties on the subjective level are also correlated with clinical disorganization. The results are interpreted within the framework of predictive coding which can account for an implicit ability to update events. These results complement a range of other results, by suggesting a difficulty with binding information in time as well as space, and by showing that information processing lacks continuity and stability in patients. The time perspective may help bridge the gap between cognitive impairments and clinical symptoms, by showing how the innermost structure of thought and experience is disrupted.

On disturbed time continuity in schizophrenia: an elementary impairment in visual perception?

Schizophrenia is associated with a series of visual perception impairments, which might impact on the patients' every day life and be related to clinical symptoms. However, the heterogeneity of the visual disorders make it a challenge to understand both the mechanisms and the consequences of these impairments, i.e., the way patients experience the outer world. Based on earlier psychiatry literature, we argue that issues regarding time might shed a new light on the disorders observed in patients with schizophrenia. We will briefly review the mechanisms involved in the sense of time continuity and clinical evidence that they are impaired in patients with schizophrenia. We will then summarize a recent experimental approach regarding the coding of time-event structure in time, namely the ability to discriminate between simultaneous and asynchronous events. The use of an original method of analysis allowed us to distinguish between explicit and implicit judgments of synchrony. We showed that for SOAs below 20 ms neither patients nor controls fuse events in time. On the contrary subjects distinguish events at an implicit level even when judging them as synchronous. In addition, the implicit responses of patients and controls differ qualitatively. It is as if controls always put more weight on the last occurred event, whereas patients have a difficulty to follow events in time at an implicit level. In patients, there is a clear dissociation between results at short and large asynchronies, that suggest selective mechanisms for the implicit coding of time-event structure. These results might explain the disruption of the sense of time continuity in patients. We argue that this line of research might also help us to better understand the mechanisms of the visual impairments in patients and how they see their environment.

When predictive mechanisms go wrong: disordered visual synchrony thresholds in schizophrenia.

Patients with schizophrenia display an impaired sense of temporal continuity, and we showed that they judge events as being simultaneous even in case of large onset asynchronies. We check here whether this means a fusion of events in time, or on the contrary, a segregation of events and a deficit in coding time-event structure. Subjects decided whether 2 squares were displayed simultaneously or asynchronously on the screen and gave their response by hitting a left or right response key. The implicit processing of asynchrony was explored by means of the Simon effect, which refers to the finding that manual responses are biased to the side of the stimulus. We checked whether responses were biased to the side of the first or second square, when squares were asynchronous and displayed on opposite sides. Results revealed an enlarged time window in patients irrespective of the squares' position (intra- vs interhemispheric presentation). But for asynchronies eliciting "synchronous" judgments, patients' responses were biased to the side of the first square. In contrast, controls were biased in all cases to the side of the second square. The inverse effects observed below thresholds in patients and controls cannot be attributed to a generalized deficit. In controls, elementary predictive mechanisms would allow anticipation of upcoming events, whereas patients appear to process squares as if isolated rather than following each other. Predictive mechanisms would be impaired in patients, who would rather rely on reactive mechanisms in order to perceive asynchrony.

Looking forward: an impaired ability in patients with schizophrenia?

When two visual stimuli occur within 8 to 17 ms of one another, subjects cannot tell they are asynchronous, yet recent results show they are not processed as simultaneous. Two spatially separate squares were presented at an interval ranging from 0 to 92 ms and remained on the screen until subjects responded. Subjects pressed a right or left response key according to the judged simultaneity/asynchrony of the stimuli. We evaluated the Simon effect, i.e., the tendency to press the key on the same side as the stimulus. We found an effect even when the squares were displayed on opposite sides of the screen, with their onsets separated by less than 20 ms. Controls were biased towards the last stimulus, whereas patients with schizophrenia were biased towards the first. We investigate here whether the results are related to spatial or temporal processing. Using the same paradigm, we explored the impact of spatial grouping by comparing connected vs. unconnected stimuli and manipulating the predictability of the second stimulus location. We tested different groups of mildly symptomatic patients and matched controls in two studies. Under 20 ms, when stimuli were connected and the 2nd square location was predictable, patients tended to press the key to the side of the 1st square, whereas controls displayed the opposite tendency. The results suggest that controls put more emphasis on the last occurring event, but not patients with schizophrenia. This impairment is observed when spatial difficulties are removed, suggesting it is related to time rather than space.

Patients with schizophrenia do not preserve automatic grouping when mentally re-grouping figures: shedding light on an ignored difficulty.

Looking at a pair of objects is easy when automatic grouping mechanisms bind these objects together, but visual exploration can also be more flexible. It is possible to mentally "re-group" two objects that are not only separate but belong to different pairs of objects. "Re-grouping" is in conflict with automatic grouping, since it entails a separation of each item from the set it belongs to. This ability appears to be impaired in patients with schizophrenia. Here we check if this impairment is selective, which would suggest a dissociation between grouping and "re-grouping," or if it impacts on usual, automatic grouping, which would call for a better understanding of the interactions between automatic grouping and "re-grouping." Sixteen outpatients with schizophrenia and healthy controls had to identify two identical and contiguous target figures within a display of circles and squares alternating around a fixation point. Eye-tracking was used to check central fixation. The target pair could be located in the same or separate hemifields. Identical figures were grouped by a connector (grouped automatically) or not (to be re-grouped). Attention modulation of automatic grouping was tested by manipulating the proportion of connected and unconnected targets, thus prompting subjects to focalize on either connected or unconnected pairs. Both groups were sensitive to automatic grouping in most conditions, but patients were unusually slowed down for connected targets while focalizing on unconnected pairs. In addition, this unusual effect occurred only when targets were presented within the same hemifield. Patients and controls differed on this asymmetry between within- and across-hemifield presentation, suggesting that patients with schizophrenia do not re-group figures in the same way as controls do. We discuss possible implications on how "re-grouping" ties in with ongoing, automatic perception in healthy volunteers.

Visual organization processes in schizophrenia.

Patients with schizophrenia are known to be impaired at organizing and exploring the visual environment. However, these impairments vary across studies, and the conditions determining whether patients are impaired or not are unclear. We aim to clarify this question by distinguishing different types of visual organization processes. A total of 23 patients and matched controls had to identify 2 identical figures embedded in a global structure made of connectors linking figures by pairs. The 2 targets belonged to either the same perceptual group (linked by a connector) or 2 different pairs (not linked by a connector). In a neutral condition, no connectors were presented. Top-down processes were explored by manipulating the proportion of targets linked or not by a connector in 3 experimental blocks. Patients needed the same processing time as controls to extract targets linked by a connector from the global structure. They could also focus on connectors when incited to do so. Impairments were observed for targets that were part of different pairs. Extracting such targets is effortful and time consuming, and both groups were slower in this condition than in the neutral condition. However, patients were slowed less than controls. This paradoxical improvement illustrates the fact that patients do not structure visual elements that are part of a global structure and not automatically bound together. Our results suggest this is due to impaired top-down processes.

Visuo-perceptual organization and working memory in patients with schizophrenia.

We explore the mechanisms sub-tending the re-organization and memorization of visual information by studying how these mechanisms fail in patients with schizophrenia. Several studies have suggested that patients have difficulties in organizing information in perception and memory. We explore to what extent prompting patients to group items influences memory performance. We distinguish automatic grouping from top-down grouping processes, which are especially involved in re-organizing information. The main task was to memorize pairs of figures. Following manipulation of proximity, pairs of figures were part of the same perceptual group (within-group pair, formed on the basis of automatic grouping) or belonged to different groups (between-group pairs, re-grouped through top-down processes). Prior to the memory task, subjects ran a perception task prompting them to prioritize either within-group or between-group pairs. Unlike patients, controls globally benefited from grouping by proximity in the memory task. In addition, the results showed that prioritizing between-group pairs had a deleterious effect in patients, but with a large decrement in memory performance in the case of within-group rather than between-group figures. This occurred despite preserved focalization on within-group figures, as shown by eye-movement recordings. The suggestion is that when patients are prompted to re-group separate items, they can do so, but the benefit derived from automatic grouping is then not only lost but also reversed. This suggests re-organizing visual information not only involves re-grouping separate items but also integrating these new groups in a unified representation, which is impaired in patients with schizophrenia.