Structural hallmarks of amyotrophic lateral sclerosis progression revealed by probabilistic fiber tractography.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive limb and/or bulbar muscular weakness and atrophy. Although ALS-related alterations of motor and extra-motor neuronal networks have repeatedly been reported, their temporal dynamics during disease progression are not well understood. Recently, we reported a decline of motor system activity and a concurrent increase of hippocampal novelty-evoked modulations across 3 months of ALS progression. To address whether these functional changes are associated with structural ones, the current study employed probabilistic fiber tractography on diffusion tensor imaging (DTI) data using a longitudinal design. Therein, motor network integrity was assessed by DTI-based tracking of the intracranial corticospinal tract, while connectivity estimates of occipito-temporal tracts (between visual and entorhinal, perirhinal or parahippocampal cortices) served to assess structural changes that could be related to the increased novelty-evoked hippocampal activity across time described previously. Complementing these previous functional observations, the current data revealed an ALS-related decrease in corticospinal tract structural connectivity compared to controls, while in contrast, visuo-perirhinal connectivity was relatively increased in the patient group. Importantly, beyond these between-group differences, a rise in the patients' occipito-temporal tract strengths occurred across a 3-month interval, while at the same time no changes in corticospinal tract connectivity were observed. In line with previously identified functional alterations, the dynamics of these structural changes suggest that the affection of motor- and memory-related networks in ALS emerges at distinct disease stages: while motor network degeneration starts primarily during early (supposedly pre-symptomatic) phases, the hippocampal/medial temporal lobe dysfunctions arise at later stages of the disease.

Structural and functional hallmarks of amyotrophic lateral sclerosis progression in motor- and memory-related brain regions.

Previous studies have shown that in amyotrophic lateral sclerosis (ALS) multiple motor and extra-motor regions display structural and functional alterations. However, their temporal dynamics during disease-progression are unknown. To address this question we employed a longitudinal design assessing motor- and novelty-related brain activity in two fMRI sessions separated by a 3-month interval. In each session, patients and controls executed a Go/NoGo-task, in which additional presentation of novel stimuli served to elicit hippocampal activity. We observed a decline in the patients' movement-related activity during the 3-month interval. Importantly, in comparison to controls, the patients' motor activations were higher during the initial measurement. Thus, the relative decrease seems to reflect a breakdown of compensatory mechanisms due to progressive neural loss within the motor-system. In contrast, the patients' novelty-evoked hippocampal activity increased across 3 months, most likely reflecting the build-up of compensatory processes typically observed at the beginning of lesions. Consistent with a stage-dependent emergence of hippocampal and motor-system lesions, we observed a positive correlation between the ALSFRS-R or MRC-Megascores and the decline in motor activity, but a negative one with the hippocampal activation-increase. Finally, to determine whether the observed functional changes co-occur with structural alterations, we performed voxel-based volumetric analyses on magnetization transfer images in a separate patient cohort studied cross-sectionally at another scanning site. Therein, we observed a close overlap between the structural changes in this cohort, and the functional alterations in the other. Thus, our results provide important insights into the temporal dynamics of functional alterations during disease-progression, and provide support for an anatomical relationship between functional and structural cerebral changes in ALS.

Distinct representations of attentional control during voluntary and stimulus-driven shifts across objects and locations.

Efficient interaction with the sensory environment requires the rapid reallocation of attentional resources between spatial locations, perceptual features, and objects. It is still a matter of debate whether one single domain-general network or multiple independent domain-specific networks mediate control during shifts of attention across features, locations, and objects. Here, we employed functional magnetic resonance imaging to directly compare the neural mechanisms controlling attention during voluntary and stimulus-driven shifts across objects and locations. Subjects either maintained or switched voluntarily and involuntarily their attention to objects located at the same or at a different visual location. Our data demonstrate shift-related activity in multiple frontoparietal, extrastriate visual, and default-mode network regions, several of which were commonly recruited by voluntary and stimulus-driven shifts between objects and locations. However, our results also revealed object- and location-selective activations, which, moreover, differed substantially between voluntary and stimulus-driven attention. These results suggest that voluntary and stimulus-driven shifts between objects and locations recruit partially overlapping, but also separable, cortical regions, implicating the parallel existence of domain-independent and domain-specific reconfiguration signals that initiate attention shifts in dependence of particular demands.

Spatiotemporal dynamics of feature-based attention spread: evidence from combined electroencephalographic and magnetoencephalographic recordings.

Attentional selection on the basis of nonspatial stimulus features induces a sensory gain enhancement by increasing the firing-rate of individual neurons tuned to the attended feature, while responses of neurons tuned to opposite feature-values are suppressed. Here we recorded event-related potentials (ERPs) and magnetic fields (ERMFs) in human observers to investigate the underlying neural correlates of feature-based attention at the population level. During the task subjects attended to a moving transparent surface presented in the left visual field, while task-irrelevant probe stimuli executing brief movements into varying directions were presented in the opposite visual field. ERP and ERMF amplitudes elicited by the unattended task-irrelevant probes were modulated as a function of the similarity between their movement direction and the task-relevant movement direction in the attended visual field. These activity modulations reflecting globally enhanced processing of the attended feature were observed to start not before 200 ms poststimulus and were localized to the motion-sensitive area hMT. The current results indicate that feature-based attention operates in a global manner but needs time to spread and provide strong support for the feature-similarity gain model.

Neural correlates of somatosensory processing in patients with neglect.

PURPOSE: Recent evidence from neuroimaging studies using visual tasks suggests that the right superior parietal cortex plays a pivotal role for the recovery of neglect. Importantly, neglect-related deficits are not limited to the visual system and have a rather multimodal nature. We employed somatosensory stimulation in patients with neglect in order to analyze activity changes in networks that are presumably associated with this condition. METHODS: Eleven chronic neglect patients with right hemispherical stroke were investigated with a fMRI paradigm in which the affected and unaffected hand were passively moved. RESULTS: Brain activation was correlated with the performance in clinical neglect tests. Significant positive correlations with brain activation were found for the lesion duration, the performance in bells and letter cancellation tests and the line bisection test. These activated areas formed a distributed pattern in the right superior parietal cortex. CONCLUSIONS: The results suggest a shared representation of visual and somatosensory networks in the right superior parietal cortex in patients with right hemispherical strokes and neglect. The spatial pattern of activity in the superior parietal cortex points out to a different representation of changes related to lesion duration and neglect.

Feature-based attention modulates direction-selective hemodynamic activity within human MT.

Attending to the spatial location or to nonspatial features of a stimulus modulates neural activity in cortical areas that process its perceptual attributes. The feature-based attentional selection of the direction of a moving stimulus is associated with increased firing of individual neurons tuned to the direction of the movement in area V5/MT, while responses of neurons tuned to opposite directions are suppressed. However, it is not known how these multiplicatively scaled responses of individual neurons tuned to different motion-directions are integrated at the population level, in order to facilitate the processing of stimuli that match the perceptual goals. Using functional magnetic resonance imaging (fMRI) the present study revealed that attending to the movement direction of a dot field enhances the response in a number of areas including the human MT region (hMT) as a function of the coherence of the stimulus. Attending the opposite direction, however, lead to a suppressed response in hMT that was inversely correlated with stimulus-coherence. These findings demonstrate that the multiplicative scaling of single-neuron responses by feature-based attention results in an enhanced direction-selective population response within those cortical modules that processes the physical attributes of the attended stimuli. Our results provide strong support for the validity of the "feature similarity gain model" on the integrated population response as quantified by parametric fMRI in humans.

Neural processing of reward magnitude under varying attentional demands.

Central to the organization of behavior is the ability to represent the magnitude of a prospective reward and the costs related to obtaining it. Therein, reward-related neural activations are discounted in dependence of the effort required to resolve a given task. Varying attentional demands of the task might however affect reward-related neural activations. Here we employed fMRI to investigate the neural representation of expected values during a monetary incentive delay task with varying attentional demands. Following a cue, indicating at the same time the difficulty (hard/easy) and the reward magnitude (high/low) of the upcoming trial, subjects performed an attention task and subsequently received feedback about their monetary reward. Consistent with previous results, activity in anterior-cingulate, insular/orbitofrontal and mesolimbic regions co-varied with the anticipated reward-magnitude, but also with the attentional requirements of the task. These activations occurred contingent on action-execution and resembled the response time pattern of the subjects. In contrast, cue-related activations, signaling the forthcoming task-requirements, were only observed within attentional control structures. These results suggest that anticipated reward-magnitude and task-related attentional demands are concurrently processed in partially overlapping neural networks of anterior-cingulate, insular/orbitofrontal, and mesolimbic regions.

Neural correlates of exemplar novelty processing under different spatial attention conditions.

The detection of novel events and their identification is a basic prerequisite in a rapidly changing environment. Recently, the processing of novelty has been shown to rely on the hippocampus and to be associated with activity in reward-related areas. The present study investigated the influence of spatial attention on neural processing of novel relative to frequently presented standard and target stimuli. Never-before-seen Mandelbrot-fractals absent of semantic content were employed as stimulus material. Consistent with current theories, novelty activated a widespread network of brain areas including the hippocampus. No activity, however, could be observed in reward-related areas with the novel stimuli absent of a semantic meaning employed here. In the perceptual part of the novelty-processing network a region in the lingual gyrus was found to specifically process novel events when they occurred outside the focus of spatial attention. These findings indicate that the initial detection of unexpected novel events generally occurs in specialized perceptual areas within the ventral visual stream, whereas activation of reward-related areas appears to be restricted to events that do possess a semantic content indicative of the biological relevance of the stimulus.

Neural mechanisms of spatial- and feature-based attention: a quantitative analysis.

Attentional selection can be based on spatial locations, non-spatial stimulus features, or entire objects as integrated feature ensembles. Several studies reported attentional modulations in those regions that process the constituent features of the presented stimuli. Here we employed functional magnetic resonance imaging (fMRI) to directly compare the magnitude of space- and/or feature-based attentional modulations while subjects directed their attention to a particular color (red or green) of a transparent surface and at the same time to a spatial location (left or right visual field). The experimental design made it possible to disentangle and quantify the hemodynamic activity elicited by identical physical stimuli when attention was directed to spatial locations and/or stimulus features. The highest modulations were observed when the attentional selection was based on spatial location. Attended features also elicited a response increase relative to unattended features when their spatial location was attended. Importantly, at unattended locations, a response increase upon feature-based selection was observed in motion-sensitive but not in color-related areas. This suggests that compared to color, motion stimuli are more effective in capturing attention at unattended locations leading to a competitive advantage. These results support the idea of a high biological relevance of the feature motion in the visual world.