Association of individual resting state EEG alpha frequency and cerebral blood flow

Cognitive task performance differs considerably between individuals. Besides cognitive capacities, attention might be a source of such differences. The individual's EEG alpha frequency (IAF) is a putative marker of the subject's state of arousal and attention, and was found to be associated with task performance and cognitive capacities. However, little is known about the metabolic substrate (i.e. the network) underlying IAF. Here we aimed to identify this network. Correlation of IAF with regional Cerebral Blood Flow (rCBF) in fifteen young healthy subjects revealed a network of brain areas that are associated with the modulation of attention and preparedness for external input, which are relevant for task execution. We hypothesize that subjects with higher IAF have pre-activated task-relevant networks and thus are both more efficient in the task-execution, and show a reduced fMRI-BOLD response to the stimulus, not because the absolute amount of activation is smaller, but because the additional activation by processing of external input is limited due to the higher baseline.

Semantic memory involvement in the default mode network: a functional neuroimaging study using independent component analysis

The Default Mode Network (DMN) is a higher order functional neural network that displays activation during passive rest and deactivation during many types of cognitive tasks. Accordingly, the DMN is viewed to represent the neural correlate of internally-generated self-referential cognition. This hypothesis implies that the DMN requires the involvement of cognitive processes, like declarative memory. The present study thus examines the spatial and functional convergence of the DMN and the semantic memory system. Using an active block-design functional Magnetic Resonance Imaging (fMRI) paradigm and Independent Component Analysis (ICA), we trace the DMN and fMRI signal changes evoked by semantic, phonological and perceptual decision tasks upon visually-presented words. Our findings show less deactivation during semantic compared to the two non-semantic tasks for the entire DMN unit and within left-hemispheric DMN regions, i.e., the dorsal medial prefrontal cortex, the anterior cingulate cortex, the retrosplenial cortex, the angular gyrus, the middle temporal gyrus and the anterior temporal region, as well as the right cerebellum. These results demonstrate that well-known semantic regions are spatially and functionally involved in the DMN. The present study further supports the hypothesis of the DMN as an internal mentation system that involves declarative memory functions.

Core networks for visual-concrete and abstract thought content: a brain electric microstate analysis

Commonality of activation of spontaneously forming and stimulus-induced mental representations is an often made but rarely tested assumption in neuroscience. In a conjunction analysis of two earlier studies, brain electric activity during visual-concrete and abstract thoughts was studied. The conditions were: in study 1, spontaneous stimulus-independent thinking (post-hoc, visual imagery or abstract thought were identified); in study 2, reading of single nouns ranking high or low on a visual imagery scale. In both studies, subjects' tasks were similar: when prompted, they had to recall the last thought (study 1) or the last word (study 2). In both studies, subjects had no instruction to classify or to visually imagine their thoughts, and accordingly were not aware of the studies' aim. Brain electric data were analyzed into functional topographic brain images (using LORETA) of the last microstate before the prompt (study 1) and of the word-type discriminating event-related microstate after word onset (study 2). Conjunction analysis across the two studies yielded commonality of activation of core networks for abstract thought content in left anterior superior regions, and for visual-concrete thought content in right temporal-posterior inferior regions. The results suggest that two different core networks are automatedly activated when abstract or visual-concrete information, respectively, enters working memory, without a subject task or instruction about the two classes of information, and regardless of internal or external origin, and of input modality. These core machineries of working memory thus are invariant to source or modality of input when treating the two types of information.

Imagery of a moving object: the role of occipital cortex and human MT/V5+

Visual imagery – similar to visual perception – activates feature-specific and category-specific visual areas. This is frequently observed in experiments where the instruction is to imagine stimuli that have been shown immediately before the imagery task. Hence, feature-specific activation could be related to the short-term memory retrieval of previously presented sensory information. Here, we investigated mental imagery of stimuli that subjects had not seen before, eliminating the effects of short-term memory. We recorded brain activation using fMRI while subjects performed a behaviourally controlled guided imagery task in predefined retinotopic coordinates to optimize sensitivity in early visual areas. Whole brain analyses revealed activation in a parieto-frontal network and lateral–occipital cortex. Region of interest (ROI) based analyses showed activation in left hMT/V5+. Granger causality mapping taking left hMT/V5+ as source revealed an imagery-specific directed influence from the left inferior parietal lobule (IPL). Interestingly, we observed a negative BOLD response in V1–3 during imagery, modulated by the retinotopic location of the imagined motion trace. Our results indicate that rule-based motion imagery can activate higher-order visual areas involved in motion perception, with a role for top-down directed influences originating in IPL. Lower-order visual areas (V1, V2 and V3) were down-regulated during this type of imagery, possibly reflecting inhibition to avoid visual input from interfering with the imagery construction. This suggests that the activation in early visual areas observed in previous studies might be related to short- or long-term memory retrieval of specific sensory experiences.

Because someone has recommended it - Patients’ reasons for choosing acupuncture or qigong

Question: Recent research has indicated a considerable contribution of placebo effects to the outcome of acupuncture treatments: especially patients’ expectations seem to have an influence [1] and [2]. In this context it is important to better understand the patient–practitioner relationship. The aim of this study was to investigate why patients in Switzerland choose acupuncture or qigong, and what they expect from the treatment and the practitioners [3]. Methods: A qualitative survey with open questions was performed among 38 patients newly enrolled for treatment in 7 different practices for Traditional Chinese Medicine ((TCM); 6 practices for acupuncture, 1 for qigong). Questions aimed to identify reasons for choosing TCM, knowledge about its range of indications, and patients’ expectations towards method and therapist. Answers were categorised and analysed by frequency. Results: The most common reasons for choosing TCM were recommendation by acquaintances, the idea of trying a new treatment and the perception of TCM as being a gentle method. The majority of respondents had poor knowledge about the range of conditions to be treated with TCM: pain of the musculoskeletal system, headaches and chronic problems were considered as main indications. Surprisingly, gynaecological or gastro-intestinal diseases were not mentioned by the respondents. Practitioners were expected to have professional competence, provide information, empathy and understanding. Conclusions: The most striking result of this survey was the fact that patients knew very little about TCM and its indications. Thus, more precise information about TCM and other complementary methods should be offered to the general public, which would help patients to decide whether to consider TCM for the treatment of their disease. And, on the other hand, for the therapists it is important to better understand and respond to patients’ expectations in order to achieve better treatment results. The results of this qualitative survey were briefly discussed with the participating practitioners, who found them remarkable and support further quantitative studies. We plan to further investigate this topic. References 1. J. Pariente, P. White, R.S.J. Frackowiak, G. Lewith. Neuroimage, 25 (2005), pp. 1161–1167 2. M. Karst, D. Schneidewind, D. Scheinichen. Forsch Komplementmed, 17 (2010), pp. 21–27 3. S.D. Klein. Dt Ztschr f Akup, 52 (2009), pp. 18–23

Intermittent spike-wave dynamics in a heterogeneous, spatially extended neural mass model

Generalised epileptic seizures are frequently accompanied by sudden, reversible transitions from low amplitude, irregular background activity to high amplitude, regular spike-wave discharges (SWD) in the EEG. The underlying mechanisms responsible for SWD generation and for the apparently spontaneous transitions to SWD and back again are still not fully understood. Specifically, the role of spatial cortico-cortical interactions in ictogenesis is not well studied. We present a macroscopic, neural mass model of a cortical column which includes two distinct time scales of inhibition. This model can produce both an oscillatory background and a pathological SWD rhythm. We demonstrate that coupling two of these cortical columns can lead to a bistability between out-of-phase, low amplitude background dynamics and in-phase, high amplitude SWD activity. Stimuli can cause state-dependent transitions from background into SWD. In an extended local area of cortex, spatial heterogeneities in a model parameter can lead to spontaneous reversible transitions from a desynchronised background to synchronous SWD due to intermittency. The deterministic model is therefore capable of producing absence seizure-like events without any time dependent adjustment of model parameters. The emergence of such mechanisms due to spatial coupling demonstrates the importance of spatial interactions in modelling ictal dynamics, and in the study of ictogenesis.

The link between visual exploration and neuronal activity: A multi-modal study combining eye tracking, functional magnetic resonance imaging and transcranial magnetic stimulation

In the present multi-modal study we aimed to investigate the role of visual exploration in relation to the neuronal activity and performance during visuospatial processing. To this end, event related functional magnetic resonance imaging er-fMRI was combined with simultaneous eye tracking recording and transcranial magnetic stimulation (TMS). Two groups of twenty healthy subjects each performed an angle discrimination task with different levels of difficulty during er-fMRI. The number of fixations as a measure of visual exploration effort was chosen to predict blood oxygen level-dependent (BOLD) signal changes using the general linear model (GLM). Without TMS, a positive linear relationship between the visual exploration effort and the BOLD signal was found in a bilateral fronto-parietal cortical network, indicating that these regions reflect the increased number of fixations and the higher brain activity due to higher task demands. Furthermore, the relationship found between the number of fixations and the performance demonstrates the relevance of visual exploration for visuospatial task solving. In the TMS group, offline theta bursts TMS (TBS) was applied over the right posterior parietal cortex (PPC) before the fMRI experiment started. Compared to controls, TBS led to a reduced correlation between visual exploration and BOLD signal change in regions of the fronto-parietal network of the right hemisphere, indicating a disruption of the network. In contrast, an increased correlation was found in regions of the left hemisphere, suggesting an intent to compensate functionality of the disturbed areas. TBS led to fewer fixations and faster response time while keeping accuracy at the same level, indicating that subjects explored more than actually needed.

A multi-center study: Intra-scan and inter-scan variability of diffusion spectrum imaging

The objective of this study was to investigate whether it is possible to pool together diffusion spectrum imaging data from four different scanners, located at three different sites. Two of the scanners had identical configuration whereas two did not. To measure the variability, we extracted three scalar maps (ADC, FA and GFA) from the DSI and utilized a region and a tract-based analysis. Additionally, a phantom study was performed to rule out some potential factors arising from the scanner performance in case some systematic bias occurred in the subject study. This work was split into three experiments: intra-scanner reproducibility, reproducibility with twin-scanner settings and reproducibility with other configurations. Overall for the intra-scanner and twin-scanner experiments, the region-based analysis coefficient of variation (CV) was in a range of 1%-4.2% and below 3% for almost every bundle for the tract-based analysis. The uncinate fasciculus showed the worst reproducibility, especially for FA and GFA values (CV 3.7-6%). For the GFA and FA maps, an ICC value of 0.7 and above is observed in almost all the regions/tracts. Looking at the last experiment, it was found that there is a very high similarity of the outcomes from the two scanners with identical setting. However, this was not the case for the two other imagers. Given the fact that the overall variation in our study is low for the imagers with identical settings, our findings support the feasibility of cross-site pooling of DSI data from identical scanners.

Theta burst TMS increases cerebral blood flow in the primary motor cortex during motor performance as assessed by arterial spin labeling (ASL)

Theta burst stimulation (TBS) is a novel variant of repetitive transcranial magnetic stimulation (rTMS), which induces changes in neuronal excitability persisting up to 1h. When elicited in the primary motor cortex, such physiological modulations might also have an impact on motor behavior. In the present study, we applied TBS in combination with pseudo continuous arterial spin labeling (pCASL) in order to address the question of whether TBS effects are measurable by means of changes in physiological parameters such as cerebral blood flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right-handed healthy subjects were stimulated using an inhibitory TBS protocol at subthreshold stimulation intensity targeted over the right motor cortex. The control condition consisted of within-subject Sham treatment in a crossover design. PCASL was performed before (pre TBS/pre Sham) and immediately after treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a sequential fingertapping task with the left hand at individual maximum speed. There was a significant increase of CBF in the primary motor cortex after TBS, but not after Sham. It is assumed that inhibitory TBS induced a "local virtual lesion" which leads to the mobilization of more neuronal resources. There was no TBS-specific modulation in motor behavior, which might indicate that acute changes in brain plasticity caused by TBS are immediately compensated. This compensatory reaction seems to be observable at the metabolic, but not at the behavioral level.

Self-organised transients in a neural mass model of epileptogenic tissue dynamics

Stimulation of human epileptic tissue can induce rhythmic, self-terminating responses on the EEG or ECoG. These responses play a potentially important role in localising tissue involved in the generation of seizure activity, yet the underlying mechanisms are unknown. However, in vitro evidence suggests that self-terminating oscillations in nervous tissue are underpinned by non-trivial spatio-temporal dynamics in an excitable medium. In this study, we investigate this hypothesis in spatial extensions to a neural mass model for epileptiform dynamics. We demonstrate that spatial extensions to this model in one and two dimensions display propagating travelling waves but also more complex transient dynamics in response to local perturbations. The neural mass formulation with local excitatory and inhibitory circuits, allows the direct incorporation of spatially distributed, functional heterogeneities into the model. We show that such heterogeneities can lead to prolonged reverberating responses to a single pulse perturbation, depending upon the location at which the stimulus is delivered. This leads to the hypothesis that prolonged rhythmic responses to local stimulation in epileptogenic tissue result from repeated self-excitation of regions of tissue with diminished inhibitory capabilities. Combined with previous models of the dynamics of focal seizures this macroscopic framework is a first step towards an explicit spatial formulation of the concept of the epileptogenic zone. Ultimately, an improved understanding of the pathophysiologic mechanisms of the epileptogenic zone will help to improve diagnostic and therapeutic measures for treating epilepsy.

End-tidal CO(2). An important parameter for a correct interpretation in functional brain studies using speech tasks

The aim was to investigate the effect of different speech tasks, i.e. recitation of prose (PR), alliteration (AR) and hexameter (HR) verses and a control task (mental arithmetic (MA) with voicing of the result on end-tidal CO2 (PETCO2), cerebral hemodynamics and oxygenation. CO2 levels in the blood are known to strongly affect cerebral blood flow. Speech changes breathing pattern and may affect CO2 levels. Measurements were performed on 24 healthy adult volunteers during the performance of the 4 tasks. Tissue oxygen saturation (StO2) and absolute concentrations of oxyhemoglobin ([O2Hb]), deoxyhemoglobin ([HHb]) and total hemoglobin ([tHb]) were measured by functional near-infrared spectroscopy (fNIRS) and PETCO2 by a gas analyzer. Statistical analysis was applied to the difference between baseline before the task, 2 recitation and 5 baseline periods after the task. The 2 brain hemispheres and 4 tasks were tested separately. A significant decrease in PETCO2 was found during all 4 tasks with the smallest decrease during the MA task. During the recitation tasks (PR, AR and HR) a statistically significant (p < 0.05) decrease occurred for StO2 during PR and AR in the right prefrontal cortex (PFC) and during AR and HR in the left PFC. [O2Hb] decreased significantly during PR, AR and HR in both hemispheres. [HHb] increased significantly during the AR task in the right PFC. [tHb] decreased significantly during HR in the right PFC and during PR, AR and HR in the left PFC. During the MA task, StO2 increased and [HHb] decreased significantly during the MA task. We conclude that changes in breathing (hyperventilation) during the tasks led to lower CO2 pressure in the blood (hypocapnia), predominantly responsible for the measured changes in cerebral hemodynamics and oxygenation. In conclusion, our findings demonstrate that PETCO2 should be monitored during functional brain studies investigating speech using neuroimaging modalities, such as fNIRS, fMRI to ensure a correct interpretation of changes in hemodynamics and oxygenation.

Examining the gateway to the limbic system with diffusion tensor imaging: the perforant pathway in dementia

Current treatments for Alzheimer's disease (AD) are only able to slow the progression of mental deterioration, making early and reliable diagnosis an essential part of any promising therapeutic strategy. In the initial stages of AD, the first neuropathological alterations occur in the perforant pathway (PP), a large neuronal fiber tract located at the entrance to the limbic system. However, to date, there is no sensitive diagnostic tool for performing in vivo assessments of this structure. In the present bimodal magnetic resonance imaging (MRI) study, we examined 10 elderly controls, 10 subjects suffering from mild cognitive impairment (MCI), and 10 AD patients in order to evaluate the sensitivity of diffusion tensor imaging (DTI), a new MRI technique, for detecting changes in the PP. Furthermore, the diagnostic explanatory power of DTI data of the PP should be compared to high-resolution MRI volumetry and intervoxel coherences (COH) of the hippocampus and the entorhinal cortex, two limbic regions also involved in the pathophysiology of early AD. DTI revealed a marked decrease in COH values in the PP region of MCI (right side: 26%, left side: 29%, as compared to controls) and AD patients (right side: 37%, left side: 43%, as compared to controls). Reductions in COH values of the PP region were significantly correlated with cognitive impairment. DTI data of the PP zone were the only parameter differing significantly between control subjects and MCI patients, while the volumetric measures and the COH values of the hippocampus and the entorhinal cortex did not. DTI of medial temporal brain regions is a promising non-invasive tool for the in vivo diagnosis of the early/preclinical stages of AD.

Lateralized and frequency-dependent effects of prefrontal rTMS on regional cerebral blood flow

Repetitive transcranial magnetic stimulation (rTMS) is a means to study the function and connectivity of brain areas. The present study addressed the question of hemispheric asymmetry of frontal regions and aimed to further understand the acute effects of high- and low-frequency rTMS on regional cerebral blood flow (rCBF). Sixteen healthy right-handed men were imaged using H(2)(15)O positron emission tomography (PET) immediately after stimulation. High (10 Hz)- and low (1 Hz)-frequency suprathreshold short-duration rTMS was applied over either the left or right dorsolateral prefrontal cortex (DLPFC). Slow and fast rTMS applied over the left DLPFC significantly increased CBF in the stimulated area. Compared to baseline, slow rTMS induced a significant increase in CBF contralateral to the stimulation site, in the right caudate body and in the anterior cingulum. Furthermore, slow rTMS decreased CBF in the orbitofrontal cortex (OFC, ipsilateral to stimulation side). Fast rTMS applied over the right DLPFC was associated with increased activity at the stimulation site, in the bilateral orbitofrontal cortex and in the left medial thalamus compared to 1-Hz rTMS. These results show that rCBF changes induced by prefrontal rTMS differ upon hemisphere stimulated and vary with stimulation frequency. These differential neurophysiological effects of short-train rTMS with respect to side and frequency suggest hemisphere-dependent functional circuits of frontal cortico-subcortical areas.

Dissociated lateralization of transient and sustained blood oxygen level-dependent signal components in human primary auditory cortex

Among other auditory operations, the analysis of different sound levels received at both ears is fundamental for the localization of a sound source. These so-called interaural level differences, in animals, are coded by excitatory-inhibitory neurons yielding asymmetric hemispheric activity patterns with acoustic stimuli having maximal interaural level differences. In human auditory cortex, the temporal blood oxygen level-dependent (BOLD) response to auditory inputs, as measured by functional magnetic resonance imaging (fMRI), consists of at least two independent components: an initial transient and a subsequent sustained signal, which, on a different time scale, are consistent with electrophysiological human and animal response patterns. However, their specific functional role remains unclear. Animal studies suggest these temporal components being based on different neural networks and having specific roles in representing the external acoustic environment. Here we hypothesized that the transient and sustained response constituents are differentially involved in coding interaural level differences and therefore play different roles in spatial information processing. Healthy subjects underwent monaural and binaural acoustic stimulation and BOLD responses were measured using high signal-to-noise-ratio fMRI. In the anatomically segmented Heschl's gyrus the transient response was bilaterally balanced, independent of the side of stimulation, while in opposite the sustained response was contralateralized. This dissociation suggests a differential role at these two independent temporal response components, with an initial bilateral transient signal subserving rapid sound detection and a subsequent lateralized sustained signal subserving detailed sound characterization.