Alcohol dependence decreases functional activation of the caudate nucleus during model-based decision processes.

BACKGROUND: Impaired decision making, a key characteristic of alcohol dependence (AD), manifests in continuous alcohol consumption despite severe negative consequences. The neural basis of this impairment in individuals with AD and differences with known neural decision mechanisms among healthy subjects are not fully understood. In particular, it is unclear whether the choice behavior among individuals with AD is based on a general impairment of decision mechanisms or is mainly explained by altered value attribution, with an overly high subjective value attributed to alcohol-related stimuli. METHODS: Here, we use a functional magnetic resonance imaging (fMRI) monetary reward task to compare the neural processes of model-based decision making and value computation between AD individuals (n = 32) and healthy controls (n = 32). During fMRI, participants evaluated monetary offers with respect to dynamically changing constraints and different levels of uncertainty. RESULTS: Individuals with AD showed lower activation associated with model-based decision processes in the caudate nucleus than controls, but there were no group differences in value-related neural activity or task performance. CONCLUSIONS: Our findings highlight the role of the caudate nucleus in impaired model-based decisions of alcohol-dependent individuals.

Dynamic computation of value signals via a common neural network in multi-attribute decision-making.

Studies in decision neuroscience have identified robust neural representations for the value of choice options. However, overall values often depend on multiple attributes, and it is not well understood how the brain evaluates different attributes and integrates them to combined values. In particular, it is not clear whether attribute values are computed in distinct attribute-specific regions or within the general valuation network known to process overall values. Here, we used a functional magnetic resonance imaging choice task in which abstract stimuli had to be evaluated based on variations of the attributes color and motion. The behavioral data showed that participants responded faster when overall values were high and attribute value differences were low. On the neural level, we did not find that attribute values were systematically represented in areas V4 and V5, even though these regions are associated with attribute-specific processing of color and motion, respectively. Instead, attribute values were associated with activity in the posterior cingulate cortex, ventral striatum and posterior inferior temporal gyrus. Furthermore, overall values were represented in dorsolateral and ventromedial prefrontal cortex, and attribute value differences in dorsomedial prefrontal cortex, which suggests that these regions play a key role for the neural integration of attribute values.

Faster speed of onset of the depressive episode is associated with lower cytokine serum levels (IL-2, -4, -6, -10, TNF-α and IFN-γ) in patients with major depression.

INTRODUCTION: Cytokines might play a key role in the pathophysiology of major depressive disorder (MDD). The speed of onset of depressive episodes has been discussed as an important clinical parameter in MDD. The aim of this study was to investigate a potential influence of the speed of onset of the depressive episode on cytokine serum levels. METHOD: Serum level of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) granulocyte and monocyte colony stimulating factor (GM-CSF) were measured in a total of 92 patients with MDD that did not respond to at least one previous antidepressant treatment. Patients were retrospectively divided in two groups: Faster (≤4 weeks) and slower (>4 weeks) onset of the depressive episode defined as the time passing from the first depressive symptoms to a full-blown depressive episode by using information from a clinical interview. RESULTS: We found significantly lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with a faster onset compared to patients with a slower onset of the depressive episodes. Furthermore, lower cytokine serum levels of IL-2, IL-8, IL-10 and IFN-γ were found in patients with a shorter duration (less than 6 months) compared to a longer duration (6-24 months) of the current depressive episode. This effect on cytokines was independent from the effect of the speed of onset of the depressive episode. CONCLUSIONS: Patients with faster onset of the depressive episode might represent a biological subtype of MDD with lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ.

German Translation and Validation of the Cognitive Style Questionnaire Short Form (CSQ-SF-D).

BACKGROUND: The Cognitive Style Questionnaire is a valuable tool for the assessment of hopeless cognitive styles in depression research, with predictive power in longitudinal studies. However, it is very burdensome to administer. Even the short form is still long, and neither this nor the original version exist in validated German translations. METHODS: The questionnaire was translated from English to German, back-translated and commented on by clinicians. The reliability, factor structure and external validity of an online form of the questionnaire were examined on 214 participants. External validity was measured on a subset of 90 subjects. RESULTS: The resulting CSQ-SF-D had good to excellent reliability, both across items and subscales, and similar external validity to the original English version. The internality subscale appeared less robust than other subscales. A detailed analysis of individual item performance suggests that stable results could be achieved with a very short form (CSQ-VSF-D) including only 27 of the 72 items. CONCLUSIONS: The CSQ-SF-D is a validated and freely distributed translation of the CSQ-SF into German. This should make efficient assessment of cognitive style in German samples more accessible to researchers.

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.

Neural correlates of visual motion processing without awareness in patients with striate cortex and pulvinar lesions.

Patients with striate cortex lesions experience visual perception loss in the contralateral visual field. In few patients, however, stimuli within the blind field can lead to unconscious (blindsight) or even conscious perception when the stimuli are moving (Riddoch syndrome). Using functional magnetic resonance imaging (fMRI), we investigated the neural responses elicited by motion stimulation in the sighted and blind visual fields of eight patients with lesions of the striate cortex. Importantly, repeated testing ensured that none of the patients exhibited blindsight or a Riddoch syndrome. Three patients had additional lesions in the ipsilesional pulvinar. For blind visual field stimulation, great care was given that the moving stimulus was precisely presented within the borders of the scotoma. In six of eight patients, the stimulation within the scotoma elicited hemodynamic activity in area human middle temporal (hMT) while no activity was observed within the ipsilateral lesioned area of the striate cortex. One of the two patients in whom no ipsilesional activity was observed had an extensive lesion including massive subcortical damage. The other patient had an additional focal lesion within the lateral inferior pulvinar. Fiber-tracking based on anatomical and functional markers (hMT and Pulvinar) on individual diffusion tensor imaging (DTI) data from each patient revealed the structural integrity of subcortical pathways in all but the patient with the extensive subcortical lesion. These results provide clear evidence for the robustness of direct subcortical pathways from the pulvinar to area hMT in patients with striate cortex lesions and demonstrate that ipsilesional activity in area hMT is completely independent of conscious perception.

Determinants of Global Color-Based Selection in Human Visual Cortex.

Feature attention operates in a spatially global way, with attended feature values being prioritized for selection outside the focus of attention. Accounts of global feature attention have emphasized feature competition as a determining factor. Here, we use magnetoencephalographic recordings in humans to test whether competition is critical for global feature selection to arise. Subjects performed a color/shape discrimination task in one visual field (VF), while irrelevant color probes were presented in the other unattended VF. Global effects of color attention were assessed by analyzing the response to the probe as a function of whether or not the probe's color was a target-defining color. We find that global color selection involves a sequence of modulations in extrastriate cortex, with an initial phase in higher tier areas (lateral occipital complex) followed by a later phase in lower tier retinotopic areas (V3/V4). Importantly, these modulations appeared with and without color competition in the focus of attention. Moreover, early parts of the modulation emerged for a task-relevant color not even present in the focus of attention. All modulations, however, were eliminated during simple onset-detection of the colored target. These results indicate that global color-based attention depends on target discrimination independent of feature competition in the focus of attention.

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.

Fast construction of voxel-level functional connectivity graphs.

BACKGROUND: Graph-based analysis of fMRI data has recently emerged as a promising approach to study brain networks. Based on the assessment of synchronous fMRI activity at separate brain sites, functional connectivity graphs are constructed and analyzed using graph-theoretical concepts. Most previous studies investigated region-level graphs, which are computationally inexpensive, but bring along the problem of choosing sensible regions and involve blurring of more detailed information. In contrast, voxel-level graphs provide the finest granularity attainable from the data, enabling analyses at superior spatial resolution. They are, however, associated with considerable computational demands, which can render high-resolution analyses infeasible. In response, many existing studies investigating functional connectivity at the voxel-level reduced the computational burden by sacrificing spatial resolution. METHODS: Here, a novel, time-efficient method for graph construction is presented that retains the original spatial resolution. Performance gains are instead achieved through data reduction in the temporal domain based on dichotomization of voxel time series combined with tetrachoric correlation estimation and efficient implementation. RESULTS: By comparison with graph construction based on Pearson's r, the technique used by the majority of previous studies, we find that the novel approach produces highly similar results an order of magnitude faster. CONCLUSIONS: Its demonstrated performance makes the proposed approach a sensible and efficient alternative to customary practice. An open source software package containing the created programs is freely available for download.

Reward prospect rapidly speeds up response inhibition via reactive control.

Response inhibition is an important cognitive-control function that allows for already-initiated or habitual behavioral responses to be promptly withheld when needed. A typical paradigm to study this function is the stop-signal task. From this task, the stop-signal response time (SSRT) can be derived, which indexes how rapidly an already-initiated response can be canceled. Typically, SSRTs range around 200 ms, identifying response inhibition as a particularly rapid cognitive-control process. Even so, it has recently been shown that SSRTs can be further accelerated if successful response inhibition is rewarded. Since this earlier study effectively ruled out differential preparatory (proactive) control adjustments, the reward benefits likely relied on boosted reactive control. Yet, given how rapidly such control processes would need to be enhanced, alternative explanations circumventing reactive control are important to consider. We addressed this question with an fMRI study by gauging the overlap of the brain networks associated with reward-related and response-inhibition-related processes in a reward-modulated stop-signal task. In line with the view that reactive control can indeed be boosted swiftly by reward availability, we found that the activity in key brain areas related to response inhibition was enhanced for reward-related stop trials. Furthermore, we observed that this beneficial reward effect was triggered by enhanced connectivity between task-unspecific (reward-related) and task-specific (inhibition-related) areas in the medial prefrontal cortex (mPFC). The present data hence suggest that reward information can be translated very rapidly into behavioral benefits (here, within ~200 ms) through enhanced reactive control, underscoring the immediate responsiveness of such control processes to reward availability in general.

Spatio-temporal patterns of brain activity distinguish strategies of multiple-object tracking.

Human observers can readily track up to four independently moving items simultaneously, even in the presence of moving distractors. Here we combined EEG and magnetoencephalography recordings to investigate the neural processes underlying this remarkable capability. Participants were instructed to track four of eight independently moving items for 3 sec. When the movement ceased a probe stimulus consisting of four items with a higher luminance was presented. The location of the probe items could correspond fully, partly, or not at all with the tracked items. Participants reported whether the probe items fully matched the tracked items or not. About half of the participants showed slower RTs and higher error rates with increasing correspondence between tracked items and the probe. The other half, however, showed faster RTs and lower error rates when the probe fully matched the tracked items. This latter behavioral pattern was associated with enhanced probe-evoked neural activity that was localized to the lateral occipital cortex in the time range 170-210 msec. This enhanced response in the object-selective lateral occipital cortex suggested that these participants performed the tracking task by visualizing the overall shape configuration defined by the vertices of the tracked items, thereby producing a behavioral advantage on full-match trials. In a later time range (270-310 msec) probe-evoked neural activity increased monotonically as a function of decreasing target-probe correspondence in all participants. This later modulation, localized to superior parietal cortex, was proposed to reflect the degree of mismatch between the probe and the automatically formed visual STM representation of the tracked items.

Reward- and attention-related biasing of sensory selection in visual cortex.

Attention to task-relevant features leads to a biasing of sensory selection in extrastriate cortex. Features signaling reward seem to produce a similar bias, but how modulatory effects due to reward and attention relate to each other is largely unexplored. To address this issue, it is critical to separate top-down settings defining reward relevance from those defining attention. To this end, we used a visual search paradigm in which the target's definition (attention to color) was dissociated from reward relevance by delivering monetary reward on search frames where a certain task-irrelevant color was combined with the target-defining color to form the target object. We assessed the state of neural biasing for the attended and reward-relevant color by analyzing the neuromagnetic brain response to asynchronously presented irrelevant distractor probes drawn in the target-defining color, the reward-relevant color, and a completely irrelevant color as a reference. We observed that for the prospect of moderate rewards, the target-defining color but not the reward-relevant color produced a selective enhancement of the neuromagnetic response between 180 and 280 msec in ventral extrastriate visual cortex. Increasing reward prospect caused a delayed attenuation (220-250 msec) of the response to reward probes, which followed a prior (160-180 msec) response enhancement in dorsal ACC. Notably, shorter latency responses in dorsal ACC were associated with stronger attenuation in extrastriate visual cortex. Finally, an analysis of the brain response to the search frames revealed that the presence of the reward-relevant color in search distractors elicited an enhanced response that was abolished after increasing reward size. The present data together indicate that when top-down definitions of reward relevance and attention are separated, the behavioral significance of reward-associated features is still rapidly coded in higher-level cortex areas, thereby commanding effective top-down inhibitory control to counter a selection bias for those features in extrastriate visual cortex.

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.

The role of the pulvinar in distractor processing and visual search.

The pulvinar nuclei of the thalamus are hypothesized to coordinate attentional selection in the visual cortex. Different models have, however, been proposed for the precise role of the pulvinar in attention. One proposal is that the pulvinar mediates shifts of spatial attention; a different proposal is that it serves the filtering of distractor information. At present, the relation between these possible operations and their relative importance in the pulvinar remains unresolved. We address this issue by contrasting these proposals in two fMRI experiments. We used a visual search paradigm that permitted us to dissociate neural activity reflecting shifts of attention from activity underlying distractor filtering. We find that distractor filtering, but not the operation of shifting attention, is associated with strong activity enhancements in dorsal and ventral regions of the pulvinar as well as in early visual cortex areas including the primary visual cortex. Our observations indicate that distractor filtering is the preponderant attentional operation subserved by the pulvinar, presumably mediated by a modulation of processing in visual areas where spatial resolution is sufficiently high to separate target from distractor input.

Separable mechanisms underlying global feature-based attention.

Feature-based attention is known to operate in a spatially global manner, in that the selection of attended features is not bound to the spatial focus of attention. Here we used electromagnetic recordings in human observers to characterize the spatiotemporal signature of such global selection of an orientation feature. Observers performed a simple orientation-discrimination task while ignoring task-irrelevant orientation probes outside the focus of attention. We observed that global feature-based selection, indexed by the brain response to unattended orientation probes, is composed of separable functional components. One such component reflects global selection based on the similarity of the probe with task-relevant orientation values ("template matching"), which is followed by a component reflecting selection based on the similarity of the probe with the orientation value under discrimination in the focus of attention ("discrimination matching"). Importantly, template matching occurs at ∼150 ms after stimulus onset, ∼80 ms before the onset of discrimination matching. Moreover, source activity underlying template matching and discrimination matching was found to originate from ventral extrastriate cortex, with the former being generated in more anterolateral and the latter in more posteromedial parts, suggesting template matching to occur in visual cortex higher up in the visual processing hierarchy than discrimination matching. We take these observations to indicate that the population-level signature of global feature-based selection reflects a sequence of hierarchically ordered operations in extrastriate visual cortex, in which the selection based on task relevance has temporal priority over the selection based on the sensory similarity between input representations.

Assessment of cortical hemodynamics by multichannel near-infrared spectroscopy in steno-occlusive disease of the middle cerebral artery.

BACKGROUND AND PURPOSE: In a pilot study we evaluated near-infrared spectroscopy as to its potential benefit in monitoring patients with steno-occlusive disease of a major cerebral artery for alterations in cortical hemodynamics. METHODS: Cortical maps of time-to-peak (TTP) in 10 patients unilaterally affected by severe stenosis or occlusion of the middle cerebral artery were acquired by multichannel near-infrared spectroscopy after bolus application of indocyanine green. Hemodynamic manifestations were assessed by comparison between affected and unaffected hemisphere and evaluated for common constituents by principal component analysis. In one patient, TTP values were compared with those obtained by dynamic susceptibility contrast imaging. RESULTS: TTP was increased on the affected hemisphere in 9 patients. Mean difference in TTP between hemispheres was 0.44 second (P<0.05) as compared with a mean lateral difference of 0.12 second found in a control group of 10 individuals. In group analysis a significant rise in TTP was found in the distribution of the affected middle cerebral artery, whereas principal component analysis suggests augmentation of hemodynamic effects toward the border zones as a dominant pattern. A linear correlation of 0.61 between TTP values determined by dynamic susceptibility contrast MRI and near-infrared spectroscopy was found to be statistically significant (P<0.001). CONCLUSIONS: Multichannel near-infrared spectroscopy might facilitate detection of disease-related hemodynamic changes as yet only accessible by tomographic imaging modalities. Being indicative for hypoperfusion and collateral flow increased values of TTP, as found to a varying extent in the present patient group, might be of clinical relevance.

Motivating inhibition - reward prospect speeds up response cancellation.

Reward prospect has been demonstrated to facilitate various cognitive and behavioral operations, particularly by enhancing the speed and vigor of processes linked to approaching reward. Studies in this domain typically employed task regimes in which participants' overt responses are facilitated by prospective rewards. In contrast, we demonstrate here that even the cancellation of a motor response can be accelerated by reward prospect, thus signifying reward-related benefits on restraint rather than approach behavior. Importantly, this facilitation occurred independent of strategy-related adjustments of response speed, which are known to systematically distort the estimation of response-cancellation speed. The fact that motivational factors can indeed facilitate response inhibition is not only relevant for understanding how motivation and response inhibition interact in healthy participants but also for work on various patient groups that display response-inhibition deficits, suggesting that core differences in the ability to inhibit motor responses have to be differentiated from motivational factors.

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.