Unseen food images capture the attention of hungry viewers: Evidence from event-related potentials.

Motivationally relevant visual targets appear to capture visuospatial attention. This capture is evident behaviorally as faster and more accurate responses, and neurally as an enhanced-amplitude of the N2pc - an index of spatial attention allocation, which is observed even when observers are unaware of the target. In the case of reinforcers such as food or substances of dependence, it is likely that the motivational state of craving accompanying deprivation potentiates this capture. The automaticity of such attentional capture by reward-associated stimuli, as well as its possible interaction with craving, is as yet not completely understood, though it is likely a major explanatory factor in motivated behaviors. For the present experiment, participants completed two EEG recording sessions: one just after eating lunch (sated/non-craving), and the other following a minimum 12-h period of fasting (hungry/craving). For both sessions, participants identified food- and clothing-related targets embedded in an object-substitution masking paradigm, which yielded trials of full target visibility, as well as trials for which targets were present but undetected. Although masking equally disrupted visual awareness of both classes of targets as measured behaviorally, a three-way hunger by visibility by target interaction was observed in the neural data, with unseen food targets eliciting an enhanced N2pc. Interestingly, this subliminal attentional capture by food-related items was observed only during the "hungry" session. No such capture was evident under conditions of full visibility. These findings indicate that attentional capture by food-related images, and reflected in enhancements of the N2pc, is spurred by hunger, and that this effect can be viewed as automatic, or independent of explicit awareness of food-relevant target content.

Vascular hippocampal plasticity after aerobic exercise in older adults.

Aerobic exercise in young adults can induce vascular plasticity in the hippocampus, a critical region for recall and recognition memory. In a mechanistic proof-of-concept intervention over 3 months, we investigated whether healthy older adults (60-77 years) also show such plasticity. Regional cerebral blood flow (rCBF) and volume (rCBV) were measured with gadolinium-based perfusion imaging (3 Tesla magnetic resonance image (MRI)). Hippocampal volumes were assessed by high-resolution 7 Tesla MRI. Fitness improvement correlated with changes in hippocampal perfusion and hippocampal head volume. Perfusion tended to increase in younger, but to decrease in older individuals. The changes in fitness, hippocampal perfusion and volume were positively related to changes in recognition memory and early recall for complex spatial objects. Path analyses indicated that fitness-related changes in complex object recognition were modulated by hippocampal perfusion. These findings indicate a preserved capacity of the aging human hippocampus for functionally relevant vascular plasticity, which decreases with progressing age.

Nucleus Accumbens Deep Brain Stimulation for Alcohol Addiction - Safety and Clinical Long-term Results of a Pilot Trial.

We report on the long-term clinical outcome (up to 8 years) of 5 patients who received deep brain stimulation (DBS) of the nucleus accumbens to treat their long-lasting and treatment-resistant alcohol addiction. All patients reported a complete absence of craving for alcohol; 2 patients remained abstinent for many years and 3 patients showed a marked reduction of alcohol consumption. No severe or long-standing side effects occurred. Therefore, DBS could be a promising, novel treatment option for severe alcohol addiction, but larger clinical trials are needed to further investigate the efficacy of DBS in addiction.

Neural correlates of multiple object tracking strategies.

Amazingly, human observers can track four independently moving targets. The present study investigated the neural correlates of multiple-object tracking (MOT). Based on previous work we used a modified MOT-task to which subjects exhibited different behaviors. One half of the subjects showed slower RTs and higher error rates with increasing correspondence between tracked items and a probe consisting of 4 highlighted items presented after the tracking. The other half of the subjects had better performance when the probe fully matched the tracked items. Here we sought to investigate the neural representation of the two divergent behavior types. Using multivariate pattern analysis we observed two partly overlapping functional networks associated with the different behaviors. Subjects that responded fast and accurate to full-congruity trials predominantly showed a functional pattern for the full-congruity condition that was very different from patterns associated with any of the partly congruent conditions. This "deviant" pattern was observed in frontal, parietal and extrastriate visual brain areas. In the group of subjects with decreasing performance for increasing target-probe congruity these same regions exhibited a very different functional relationship, in which increasing congruities were associated with linearly changing neural activity patterns. Early low-tier visual areas exclusively exhibited the linear classification pattern while area LO and the primary motor cortex exclusively showed the deviant pattern across all subjects. The coexistence of both networks in groups with different behaviors provides the neural basis for a flexible behavior that can be flexibly adjusted as a function of the strategy employed in the task.

Progranulin levels in status epilepticus as a marker of neuronal recovery and neuroprotection.

INTRODUCTION: Recently, a mouse model showed that progranulin, a mediator in neuroinflammation and a neuronal growth factor, was elevated in the hippocampus after status epilepticus (SE). This elevated level might mirror compensating neuronal mechanisms after SE. Studies concerning neuronal recovery and neuroprotective mechanisms after SE in humans are scarce, so we tested for progranulinin the cerebrospinal fluid (CSF) after various types of SE. METHOD: We performed a retrospective analysis of progranulin levels in CSF in patients (n = 24) who underwent lumbar puncture as part of diagnostic workup after having SE and in patients after having one single tonic-clonic seizure who comprised the control group (n = 8). RESULTS: In our group with SE, progranulin levels in CSF were not significantly elevated compared to our control group. Furthermore, there was no correlation between progranulin levels and the time interval between lumbar puncture and SE. Additionally, in cases of higher CSF progranulin levels, we found no impact on the clinical outcome after SE. CONCLUSION: Although our cohort is heterogeneous and not fully sufficient, we conclude that progranulin in CSF is not elevated after SE in our cohort. Therefore, our results do not suggest a change in cerebral progranulin metabolism as a possible neuroregenerative or neuroprotective mechanism in humans after SE in acute and subacute phases. A larger cohort study is needed to further strengthen this result. This article is part of a Special Issue entitled "Status Epilepticus".

Local cortical thinning links to resting-state disconnectivity in major depressive disorder.

BACKGROUND: Local structural and metabolic as well as inter-regional connectivity abnormalities have been implicated in the neuropathology of major depressive disorder (MDD). How local tissue properties affect intrinsic functional connectivity is, however, unclear. Using a cross-sectional, multi-modal imaging approach, we investigated the relationship between local cortical tissue abnormalities and intrinsic resting-state functional connectivity (RSFC) in MDD. METHOD: A total of 20 MDD in-patients and 20 healthy controls underwent magnetic resonance imaging at 3 T for structural and functional imaging. Whole-brain cortical thickness was calculated and compared between groups. Regions with reduced cortical thickness defined seeds for subsequent whole-brain RSFC analyses. Contributions of structural tissue abnormalities on inter-regional RSFC were explicitly investigated. RESULTS: Lower cortical thickness was observed in MDD in the right dorsomedial prefrontal cortex (PFC), superior temporal gyrus/temporal pole, middle-posterior cingulate cortex, and dorsolateral PFC. No differences in local fractional amplitude of low-frequency fluctuations were observed. Lower thickness in patients' dorsomedial PFC further directly and selectively affected its RSFC with the precuneus, which was unaffected by symptom severity. No effects of cortical thickness in other regions showing abnormal thickness were observed to influence functional connectivity. CONCLUSIONS: Abnormal cortical thickness in the dorsomedial PFC in MDD patients was observed to selectively and directly affect its intrinsic connectivity with the precuneus in MDD patients independent of depression severity, thereby marking a potential vulnerability for maladaptive mood regulation. Future studies should include an unmedicated sample and replicate findings using independent component analysis to test for morphometric effects on network integrity.

Tactile stimulation and hemispheric asymmetries modulate auditory perception and neural responses in primary auditory cortex.

Although multisensory integration has been an important area of recent research, most studies focused on audiovisual integration. Importantly, however, the combination of audition and touch can guide our behavior as effectively which we studied here using psychophysics and functional magnetic resonance imaging (fMRI). We tested whether task-irrelevant tactile stimuli would enhance auditory detection, and whether hemispheric asymmetries would modulate these audiotactile benefits using lateralized sounds. Spatially aligned task-irrelevant tactile stimuli could occur either synchronously or asynchronously with the sounds. Auditory detection was enhanced by non-informative synchronous and asynchronous tactile stimuli, if presented on the left side. Elevated fMRI-signals to left-sided synchronous bimodal stimulation were found in primary auditory cortex (A1). Adjacent regions (planum temporale, PT) expressed enhanced BOLD-responses for synchronous and asynchronous left-sided bimodal conditions. Additional connectivity analyses seeded in right-hemispheric A1 and PT for both bimodal conditions showed enhanced connectivity with right-hemispheric thalamic, somatosensory and multisensory areas that scaled with subjects' performance. Our results indicate that functional asymmetries interact with audiotactile interplay which can be observed for left-lateralized stimulation in the right hemisphere. There, audiotactile interplay recruits a functional network of unisensory cortices, and the strength of these functional network connections is directly related to subjects' perceptual sensitivity.

Distinct neural correlates of attending speed vs. coherence of motion.

Attention to specific features of moving visual stimuli modulates the activity in human cortical motion sensitive areas. In this study we employed combined event-related electrophysiological, magnetencephalographic (EEG, MEG) and hemodynamic functional magnetic resonance imaging (fMRI) measures of brain activity to investigate the precise time course and the neural correlates of feature-based attention to speed and coherence. Subjects were presented with an aperture of dots randomly moving either slow or fast, at the same time displaying a high or low level of coherence. The task was to attend either the speed or the coherence and press a button upon the high speed or high coherence stimulus respectively. When attention was directed to the speed of motion enhanced neural activity was found in the dorsal visual area V3a and in the IPL, areas previously shown to be specialized for motion processing. In contrast, when attention was directed to the coherence of motion significant hemodynamic activity was observed in the parietal areas fIPS and SPL that are specialized for the processing of complex motion patterns. Concurrent recordings of the event-related electro- and magnetencephalographic responses revealed that the speed-related attentional modulations of activity occurred at an earlier time range (around 240-290 ms), while the coherence-related ones occurred later (around 320-370 ms) post-stimulus. The current results suggest that the attentional selection of motion features modulates neural processing in the lowest-tier regions required to perform the task-critical discrimination.

Single trial discrimination of individual finger movements on one hand: a combined MEG and EEG study.

It is crucial to understand what brain signals can be decoded from single trials with different recording techniques for the development of Brain-Machine Interfaces. A specific challenge for non-invasive recording methods are activations confined to small spatial areas on the cortex such as the finger representation of one hand. Here we study the information content of single trial brain activity in non-invasive MEG and EEG recordings elicited by finger movements of one hand. We investigate the feasibility of decoding which of four fingers of one hand performed a slight button press. With MEG we demonstrate reliable discrimination of single button presses performed with the thumb, the index, the middle or the little finger (average over all subjects and fingers 57%, best subject 70%, empirical guessing level: 25.1%). EEG decoding performance was less robust (average over all subjects and fingers 43%, best subject 54%, empirical guessing level 25.1%). Spatiotemporal patterns of amplitude variations in the time series provided best information for discriminating finger movements. Non-phase-locked changes of mu and beta oscillations were less predictive. Movement related high gamma oscillations were observed in average induced oscillation amplitudes in the MEG but did not provide sufficient information about the finger's identity in single trials. Importantly, pre-movement neuronal activity provided information about the preparation of the movement of a specific finger. Our study demonstrates the potential of non-invasive MEG to provide informative features for individual finger control in a Brain-Machine Interface neuroprosthesis.

Pulsatility Index in the Basal Ganglia Arteries Increases with Age in Elderly with and without Cerebral Small Vessel Disease.

BACKGROUND AND PURPOSE: Cerebral small vessel disease contributes to stroke and cognitive impairment and interacts with Alzheimer disease pathology. Because of the small dimensions of the affected vessels, in vivo characterization of blood flow properties is challenging but important to unravel the underlying mechanisms of the disease. MATERIALS AND METHODS: A 2D phase-contrast sequence at 7T MR imaging was used to assess blood flow velocity and the pulsatility index of the perforating basal ganglia arteries. We included patients with cerebral amyloid angiopathy (n = 8; identified through the modified Boston criteria), hypertensive arteriopathy (n = 12; identified through the presence of strictly deep or mixed cerebral microbleeds), and age- and sex-matched controls (n = 28; no cerebral microbleeds). RESULTS: Older age was related to a greater pulsatility index, irrespective of cerebral small vessel disease. In hypertensive arteriopathy, there was an association between lower blood flow velocity of the basal ganglia and the presence of peri-basal ganglia WM hyperintensities. CONCLUSIONS: Our results suggest that age might be the driving factor for altered cerebral small vessel hemodynamics. Furthermore, this study puts cerebral small vessel disease downstream pathologies in the basal ganglia region in relation to blood flow characteristics of the basal ganglia microvasculature.

Rapid recurrent processing gates awareness in primary visual cortex.

Visual awareness has been proposed to depend on recurrent processing in early visual cortex areas including the primary visual cortex (V1). Here, we address this hypothesis with high spatiotemporal resolution magnetoencephalographic recordings in subjects performing a substitution masking paradigm. Neural activity reflecting awareness is assessed by directly comparing the neuromagnetic response elicited by effectively and ineffectively masked targets after the proportion of trials leading to masking was individually adjusted to match the proportion of trials without masking. This revealed a modulation of recurrent activity in the primary visual cortex rapidly after the onset of the feedforward sweep of processing in striate and extrastriate areas but significantly before the onset of attention-dependent recurrent modulations in V1. Our data provide direct support for the notion that (i) recurrent processing in V1 correlates with visual awareness and (ii) that attention and awareness involve distinct recurrent processing operations.

Detecting artery occlusion and critical flow diminution in the case of an acute ischemic stroke--methodological pitfalls of common vascular diagnostic methods.

PURPOSE: None of the vascular emergency diagnostic methods commonly used in the case of acute ischemic stroke, i. e. CTA, color-coded duplex sonography (CCDS), MRA, and DSA, is free of restrictions due to physical and physiological characteristics. As a result, misleading results initiating an inappropriate acute therapeutic intervention or hampering a promising one cannot be excluded. We aimed to assess the type and frequency of methodological pitfalls occurring in this situation. MATERIALS AND METHODS: We retrospectively analyzed data of 269 consecutive patients admitted to our stroke unit with a clinical syndrome of an acute stroke. All patients underwent one or more vascular emergency diagnostic methods on a routine basis. RESULTS: 37 patients were excluded because of a final diagnosis other than ischemic stroke. 76 of 232 ischemic stroke patients underwent emergency diagnostic methods with two or more vascular examination techniques. Controversial results occurred in 20 patients and related to the detection and localization of large artery occlusion and its differentiation from a low/slow flow situation and the identification of critical cerebral flow diminution distal to large artery occlusion/severe stenosis. Methodological pitfalls were able to be most reliably resolved by CCDS. Within the whole cohort of ischemic stroke patients, vascular constellations susceptible to misinterpretation were diagnosed in 40 (17.2 %) patients. CONCLUSION: We recommend providing several techniques including CCDS in an emergency stroke setting and applying techniques with respect to diagnostic findings.

Sensory MEG responses predict successful and failed inhibition in a stop-signal task.

In the present study magnetoencephalographic recordings were performed to investigate the neural mechanisms underlying the stopping of manual responses. Subjects performed in a Stop-signal task in which Go-stimuli (S1), requiring a rapid motor response, were sometimes rapidly followed by a Stop-stimulus (S2) indicating to withhold the already initiated response to S1. Success of stopping strongly depended on the early perceptual processing of S1 and S2 reflected by the magnetic N1 component. Enhanced processing of S1 facilitated the execution of the movement, whereas enhanced processing of S2 favored its inhibition. This suggests that the processing resources for the subsequent stimuli are limited and need to be shared. This sharing of resources appeared to arise from adjustments made on a trial-by-trial basis, in that systematic reaction time prolongations on Go-trials following Stop-trials versus following Go-trials were accompanied by attenuated sensory processing to the Go-stimulus similar to that seen in successful versus unsuccessful stopping in Stop-trials.

The center-surround profile of the focus of attention arises from recurrent processing in visual cortex.

We recently demonstrated with magnetoencephalographic recordings in human observers that the focus of attention in visual search has a spatial profile consisting of a center enhancement surrounded by a narrow zone of sensory attenuation. Here, we report new data from 2 experiments providing insights into the cortical processes that cause the surround attenuation. We show that surround suppression appears in search tasks that require spatial scrutiny, that is the precise binding of search-relevant features at the target's location but not in tasks that permit target discrimination without precise localization. Furthermore, we demonstrate that surround attenuation is linked with a stronger recurrent activity modulation in early visual cortex. Finally, we show that surround suppression appears with a delay (more than 175 ms) that is beyond the time course of the initial feedforward sweep of processing in the visual system. These observations together indicate that the suppressive surround is associated with recurrent processing and binding in the visual cortex.

Dyspnea in amyotrophic lateral sclerosis: The Dyspnea-ALS-Scale (DALS-15) essentially contributes to the diagnosis of respiratory impairment.

BACKGROUND: Dyspnea is a cardinal but often underestimated symptom in amyotrophic lateral sclerosis (ALS). The newly developed Dyspnea-ALS-Scale (DALS-15) is highly relevant for therapeutic decisions because dyspnea is a separate criterion to consider noninvasive ventilation (NIV) in ALS. In comparison to the limited effects of neuroprotective compounds, NIV has the greatest impact on survival and improves quality of life. OBJECTIVE: To investigate whether dyspnea corresponds to parameters of respiratory status mainly used in clinical neurological practice. We also investigated if the DALS-15 could help identify patients for consideration of NIV in whom neither spirometry nor blood gas parameters indicate the need for NIV (forced vital capacity (FVC) < 50% or probable <75%, pCO2 ≥45  mmHg). METHODS: Seventy ALS patients with dyspnea according to the DALS-15 obtained blood gas analysis and spirometry (FVC in sitting and supine positions). The supine decline in FVC was calculated. RESULTS: There was no linear relationship between dyspnea and spirometry as well as blood gases. 83% of our patients had an upright FVC still greater than 50% and no daytime hypercapnia. CONCLUSIONS: Our study clearly shows that dyspnea can occur independently of objective indicators of respiratory impairment like spirometry or blood gases. Hence, the DALS-15 covers another aspect of respiratory impairment than these tests and refers to the subjective component of respiratory impairment. It detects dyspnea in a considerable proportion of patients in whom NIV should thus be considered although their spirometric and blood gas results do not point towards NIV. The DALS-15 therefore may help to improve the stratification of patients with respiratory impairment for more efficient symptom management and timely coordination of care.

Neuronal spiking in the pedunculopontine nucleus in progressive supranuclear palsy and in idiopathic Parkinson's disease.

The pedunculopontine nucleus (PPN) is engaged in posture and gait control, and neuronal degeneration in the PPN has been associated with Parkinsonian disorders. Clinical outcomes of deep brain stimulation of the PPN in idiopathic Parkinson's disease (IPD) and progressive supranuclear palsy (PSP) differ, and we investigated whether the PPN is differentially affected in these conditions. We had the rare opportunity to record continuous electrophysiological data intraoperatively in 30 s blocks from single microelectrode contacts implanted in the PPN in six PSP patients and three IPD patients during rest, passive movement, and active movement. Neuronal spikes were sorted according to shape using a wavelet-based clustering approach to enable comparisons between individual neuronal firing rates in the two disease states. The action potential widths showed a bimodal distribution consistent with previous findings, suggesting spikes from noncholinergic (likely glutamatergic) and cholinergic neurons. A higher PPN spiking rate of narrow action potentials was observed in the PSP than in the IPD patients when pooled across all three conditions (Wilcoxon rank sum test: p = 0.0141). No correlation was found between firing rate and disease severity or duration. The firing rates were higher during passive movement than rest and active movement in both groups, but the differences between conditions were not significant. PSP and IPD are believed to represent distinct disease processes, and our findings that the neuronal firing rates differ according to disease state support the proposal that pathological processes directly involving the PPN may be more pronounced in PSP than IPD.

The resting brain and our self: self-relatedness modulates resting state neural activity in cortical midline structures.

The resting brain shows high neural activity in various regions, the default-mode network, chief among them the cortical midline structures (CMS). The psychological correlate of high resting state neural activity in CMS remains however unclear though speculatively it has been associated with processing of internally-oriented self-relatedness. We used functional MRI to examine internally-oriented self-relatedness during the resting state period. This was indirectly done by letting subjects perceive emotional pictures followed by a fixation cross; the very same pictures were then rated subjectively according to their degree of self-relatedness in a postscanning session. This allowed us to correlate the picture ratings of self-relatedness with signal changes in the subsequent resting state period, i.e. fixation period. The emotional pictures' degree of self-relatedness parametrically modulated subsequent resting state signal changes in various CMS, including ventro- and dorsomedial prefrontal cortex and posterior cingulate cortex. This modulation could be distinguished from effects of emotion dimensions (e.g. valence, intensity) and evoked effects of self-relatedness during the stimulus period itself the latter being observed rather in subcortical regions, e.g. amygdala, ventral striatum, and tectum. In sum, our findings suggest that resting state neural activity in CMS is parametrically and specifically modulated by the preceding stimulus's degree of self-relatedness. This lends further support to the presumed involvement of these regions in processing internally-oriented self-relatedness as distinguished from externally-oriented self-relatedness.

Involvement of striate and extrastriate visual cortical areas in spatial attention.

We investigated the cortical mechanisms of visual-spatial attention while subjects discriminated patterned targets within distractor arrays. Functional magnetic resonance imaging (fMRI) was used to map the boundaries of retinotopic visual areas and to localize attention-related changes in neural activity within several of those areas, including primary visual (striate) cortex. Event-related potentials (ERPs) and modeling of their neural sources, however, indicated that the initial sensory input to striate cortex at 50-55 milliseconds after the stimulus was not modulated by attention. The earliest facilitation of attended signals was observed in extrastriate visual areas, at 70-75 milliseconds. We hypothesize that the striate cortex modulation found with fMRI may represent a delayed, re-entrant feedback from higher visual areas or a sustained biasing of striate cortical neurons during attention. ERP recordings provide critical temporal information for analyzing the functional neuroanatomy of visual attention.

Increased pre-SMA activation in early PD patients during simple self-initiated hand movements.

The slowness of movement, termed bradykinesia, is one of the main symptoms of Parkinson's disease (PD). This symptom may be due to the inability of PD patients to maximise the speed of internally driven movements. The mesial premotor areas and in particular the pre-supplementary motor area (pre-SMA) seem to play a crucial role in the temporal initiation of movements in humans and animals. However, this activation seems to be debatable in imaging studies of PD patients. We performed a motor paradigm with temporally self-initiated movements in nine de novo PD patients before and after initiation of dopaminergic medication. The main finding was an increased activation of the pre-SMA in de novo PD patients compared with healthy age-matched control subjects. This result indicates the contribution of the pre-SMA in the temporal initiation of self-generated movements and in the disease pathology of PD. Increased bilateral activation of the superior cerebellum, mainly on the ipsilateral side, and a decreased activation of the ipsilateral inferior cerebellum in PD patients were also present. These findings provide new insights into the activation pattern of the cerebellum in PD patients.

Cardiac involvement in limb-girdle muscular dystrophy 2I : conventional cardiac diagnostic and cardiovascular magnetic resonance.

BACKGROUND: The C826A mutation in the fukutin-related protein (FKRP) gene is typically associated with autosomal recessive limb-girdle muscular dystrophy 2I (LGMD2I) but oligosymptomatic phenotypes and patients with predominant cardiac involvement are also described. OBJECTIVE: To assess cardiac involvement in patients with LGMD2I. PATIENTS: Nine patients from 5 families (2 female, 7 male) homozygous for the 826C > A FKRP mutation were included. METHODS: Additional to conventional cardiac investigations (electrocardiography and echocardiography) the patients underwent cardiovascular magnetic resonance imaging (CMR). RESULTS/CONCLUSION: Cardiac involvement was detected by CMR in eight of nine patients (reduced left ventricular ejection fraction in 6, enlargement of left ventricular end-diastolic volume in 2 and left ventricular mass in 2) and in four patients by conventional cardiac diagnostic investigations. Two of the nine patients showed no muscle weakness or atrophy but suffered myalgias; both had cardiac manifestation of the disease. CMR is a sensitive method for detecting cardiac abnormalities in patients with LGMD2I and can be used for early detection of mild or subclinical cardiac involvement.