Topographic time-frequency decomposition of the EEG

Frequency-transformed EEG resting data has been widely used to describe normal and abnormal brain functional states as function of the spectral power in different frequency bands. This has yielded a series of clinically relevant findings. However, by transforming the EEG into the frequency domain, the initially excellent time resolution of time-domain EEG is lost. The topographic time-frequency decomposition is a novel computerized EEG analysis method that combines previously available techniques from time-domain spatial EEG analysis and time-frequency decomposition of single-channel time series. It yields a new, physiologically and statistically plausible topographic time-frequency representation of human multichannel EEG. The original EEG is accounted by the coefficients of a large set of user defined EEG like time-series, which are optimized for maximal spatial smoothness and minimal norm. These coefficients are then reduced to a small number of model scalp field configurations, which vary in intensity as a function of time and frequency. The result is thus a small number of EEG field configurations, each with a corresponding time-frequency (Wigner) plot. The method has several advantages: It does not assume that the data is composed of orthogonal elements, it does not assume stationarity, it produces topographical maps and it allows to include user-defined, specific EEG elements, such as spike and wave patterns. After a formal introduction of the method, several examples are given, which include artificial data and multichannel EEG during different physiological and pathological conditions.

Ventral striatum gray matter density reduction in patients with schizophrenia and psychotic emotional dysregulation

INTRODUCTION: Substantial heterogeneity remains across studies investigating changes in gray matter in schizophrenia. Differences in methodology, heterogeneous symptom patterns and symptom trajectories may contribute to inconsistent findings. To address this problem, we recently proposed to group patients by symptom dimensions, which map on the language, the limbic and the motor systems. The aim of the present study was to investigate whether patients with prevalent symptoms of emotional dysregulation would show structural neuronal abnormalities in the limbic system. METHOD: 43 right-handed medicated patients with schizophrenia were assessed with the Bern Psychopathology Scale (BPS). The patients and a control group of 34 healthy individuals underwent structural imaging at a 3T MRI scanner. Whole brain voxel-based morphometry (VBM) was compared between patient subgroups with different severity of emotional dysregulation. Group comparisons (comparison between patients with severe emotional dysregulation, patients with mild emotional dysregulation, patients with no emotional dysregulation and healthy controls) were performed using a one way ANOVA and ANCOVA respectively. RESULTS: Patients with severe emotional dysregulation had significantly decreased gray matter density in a large cluster including the right ventral striatum and the head of the caudate compared to patients without emotional dysregulation. Comparing patients with severe emotional dysregulation and healthy controls, several clusters of significant decreased GM density were detected in patients, including the right ventral striatum, head of the caudate, left hippocampus, bilateral thalamus, dorsolateral prefrontal and orbitofrontal cortex. The significant effect in the ventral striatum was lost when patients with and without emotional dysregulation were pooled and compared with controls. DISCUSSION: Decreased gray matter density in a large cluster including the right ventral striatum was associated with severe symptoms of emotional dysregulation in patients with schizophrenia. The ventral striatum is an important part of the limbic system, and was indicated to be involved in the generation of incentive salience and psychotic symptoms. Only patients with severe emotional dysregulation had decreased gray matter in several brain structures associated with emotion and reward processing compared to healthy controls. The results support the hypothesis that grouping patients according to specific clinical symptoms matched to the limbic system allows identifying patient subgroups with structural abnormalities in the limbic network.

On the use of Cramér-Rao minimum variance bounds for the design of magnetic resonance spectroscopy experiments

Localized Magnetic Resonance Spectroscopy (MRS) is in widespread use for clinical brain research. Standard acquisition sequences to obtain one-dimensional spectra suffer from substantial overlap of spectral contributions from many metabolites. Therefore, specially tuned editing sequences or two-dimensional acquisition schemes are applied to extend the information content. Tuning specific acquisition parameters allows to make the sequences more efficient or more specific for certain target metabolites. Cramér-Rao bounds have been used in other fields for optimization of experiments and are now shown to be very useful as design criteria for localized MRS sequence optimization. The principle is illustrated for one- and two-dimensional MRS, in particular the 2D separation experiment, where the usual restriction to equidistant echo time spacings and equal acquisition times per echo time can be abolished. Particular emphasis is placed on optimizing experiments for quantification of GABA and glutamate. The basic principles are verified by Monte Carlo simulations and in vivo for repeated acquisitions of generalized two-dimensional separation brain spectra obtained from healthy subjects and expanded by bootstrapping for better definition of the quantification uncertainties.

Atypical visual processing in posttraumatic stress disorder

BACKGROUND: Many patients with Posttraumatic Stress Disorder (PTSD) feel overwhelmed in situations with high levels of sensory input, as in crowded situations with complex sensory characteristics. These difficulties might be related to subtle sensory processing deficits similar to those that have been found for sounds in electrophysiological studies. METHOD: Visual processing was investigated with functional magnetic resonance imaging in trauma-exposed participants with (N = 18) and without PTSD (N = 21) employing a picture-viewing task. RESULTS: Activity observed in response to visual scenes was lower in PTSD participants 1) in the ventral stream of the visual system, including striate and extrastriate, inferior temporal, and entorhinal cortices, and 2) in dorsal and ventral attention systems (P < 0.05, FWE-corrected). These effects could not be explained by the emotional salience of the pictures. CONCLUSIONS: Visual processing was substantially altered in PTSD in the ventral visual stream, a component of the visual system thought to be responsible for object property processing. Together with previous reports of subtle auditory deficits in PTSD, these findings provide strong support for potentially important sensory processing deficits, whose origins may be related to dysfunctional attention processes.

Magnetic resonance spectroscopy investigations of functionally defined language areas in schizophrenia patients with and without auditory hallucinations

Background: Cerebral dysfunction occurring in mental disorders can show metabolic disturbances which are limited to circumscribed brain areas. Auditory hallucinations have been shown to be related to defined cortical areas linked to specific language functions. Here, we investigated if the study of metabolic changes in auditory hallucinations requires a functional rather than an anatomical definition of their location and size to allow a reliable investigation by magnetic resonance spectroscopy (MRS). Methods: Schizophrenia patients with (AH; n = 12) and without hallucinations (NH; n = 8) and healthy controls (HC; n = 11) underwent a verbal fluency task in functional MRI (fMRI) to functionally define Broca's and Wernicke's areas. Left and right Heschl's gyri were defined anatomically. Results: The mean distances in native space between the fMRI-defined regions and a corresponding anatomically defined area were 12.4 ± 6.1 mm (range: 2.7–36.1 mm) for Broca's area and 16.8 ± 6.2 mm (range: 4.5–26.4 mm) for Wernicke's area, respectively. Hence, the spatial variance was of similar extent as the size of the investigated regions. Splitting the investigations into a single voxel examination in the frontal brain and a spectroscopic imaging part for the more homogeneous field areas led to good spectral quality for almost all spectra. In Broca's area, there was a significant group effect (p = 0.03) with lower levels of N-acetyl-aspartate (NAA) in NH compared to HC (p = 0.02). There were positive associations of NAA levels in the left Heschl's gyrus with total (p = 0.03) and negative (p = 0.006) PANSS scores. In Broca's area, there was a negative association of myo-inositol levels with total PANSS scores (p = 0.008). Conclusion: This study supports the neurodegenerative hypothesis of schizophrenia only in a frontal region whereas the results obtained from temporal regions are in contrast to the majority of previous studies. Future research should test the hypothesis raised by this study that a functional definition of language regions is needed if neurochemical imbalances are expected to be restricted to functional foci.

A review on continuous wave functional near-infrared spectroscopy and imaging instrumentation and methodology

This year marks the 20th anniversary of functional near-infrared spectroscopy and imaging (fNIRS/fNIRI). As the vast majority of commercial instruments developed until now are based on continuous wave technology, the aim of this publication is to review the current state of instrumentation and methodology of continuous wave fNIRI. For this purpose we provide an overview of the commercially available instruments and address instrumental aspects such as light sources, detectors and sensor arrangements. Methodological aspects, algorithms to calculate the concentrations of oxy- and deoxyhemoglobin and approaches for data analysis are also reviewed. From the single-location measurements of the early years, instrumentation has progressed to imaging initially in two dimensions (topography) and then three (tomography). The methods of analysis have also changed tremendously, from the simple modified Beer-Lambert law to sophisticated image reconstruction and data analysis methods used today. Due to these advances, fNIRI has become a modality that is widely used in neuroscience research and several manufacturers provide commercial instrumentation. It seems likely that fNIRI will become a clinical tool in the foreseeable future, which will enable diagnosis in single subjects.

Changes in cerebral hemodynamics and oxygenation induced by different speech tasks – an assessment by combining functional near‐infrared spectroscopy and capnography

Introduction In several studies, we found that during guided rhythmic speech exercises, a decrease in cerebral hemodynamics and oxygenation occurred as the result of a decrease in the partial pressure of carbon dioxide in the arterial blood (PaCO2) during speaking. To further explore the effect of PaCO2 variations on cerebral hemodynamics and oxygenation, the aim of the present study was to investigate the impact of spoken, inner and heard speech tasks on these parameters. Material and Methods Speech tasks included recitation or inner recitation or listening to hexameter, alliteration, prose, or performing mental arithmetic. The following physiological parameters were measured: tissue oxygen saturation (StO2) and absolute concentrations of oxyhemoglobin, deoxyhemoglobin, total hemoglobin (over the left and right anterior prefrontal cortex, using an ISS OxiplexTS frequency domain near-infrared spectrometer) and end-tidal CO2 (PETCO2; using Nellcor N1000 and Datex NORMOCAP capnographs). Statistical analysis was applied to the differences between baseline, 2 tasks, and 3 post-baseline periods. Data of 3 studies with 24, 7 and 29 healthy subjects, respectively, were combined, and linear regression analyses were calculated. Results Linear regression analyses revealed significant relations between changes in oxyhemoglobin, deoxyhemoglobin, total hemoglobin or StO2 and the participants’ age, the baseline PETCO2 or certain speech tasks. While hexameter verses affected changes during the tasks, alliteration verses only affected changes during the recovery phase. Discussion and Conclusion The observed effects in hemodynamics and oxygenation indicate a combination of neurovascular coupling (increased neuronal activity leading to an increase in the cerebral metabolic rate of oxygen resulting in an increase in cerebral flood flow/volume) and CO2 reactivity (increased breathing during speech tasks causing a decrease in PaCO2 leading to vasoconstriction and decrease in cerebral blood flow). The neurovascular coupling characteristics are task-dependent. References Scholkmann F, Gerber U, Wolf M, Wolf U. End-tidal CO2: An important parameter for a correct interpretation in functional brain studies using speech tasks. Neuroimage 2013;66:71-79. Scholkmann F, Wolf M, Wolf U. The effect of inner speech on arterial CO2, cerebral hemodynamics and oxygenation – A functional NIRS study. Adv Exp Med Biol 2013;789:81-87.

"Because someone has recommended it" - patients' reasons for choosing acupuncture or qigong

Background 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, 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]. Method 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. Discussion 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. Literature 1 Pariente J et al., Neuroimage 2005;25:1161-67 2 Karst M et al., Forsch Komplementmed 2010;17:21-7 3 Klein SD., Dt Ztschr f Akup. 2009;52:18-23

Impartiality in humans is predicted by brain structure of dorsomedial prefrontal cortex.

The moral force of impartiality (i.e. the equal treatment of all human beings) is imperative for providing justice and fairness. Yet, in reality many people become partial during intergroup interactions; they demonstrate a preferential treatment of ingroup members and a discriminatory treatment of outgroup members. Some people, however, do not show this intergroup bias. The underlying sources of these inter-individual differences are poorly understood. Here we demonstrate that the larger the gray matter volume and thickness of the dorsomedial prefrontal cortex (DMPFC), the more individuals in the role of an uninvolved third-party impartially punish outgroup and ingroup perpetrators. Moreover, we show evidence for a possible mechanism that explains the impact of DMPFC's gray matter volume on impartiality, namely perspective-taking. Large gray matter volume of DMPFC seems to facilitate equal perspective-taking of all sides, which in turn leads to impartial behavior. This is the first evidence demonstrating that brain structure of the DMPFC constitutes an important source underlying an individual's propensity for impartiality.

Modulation of anticipatory emotion and perception processing by cognitive control.

Strategies of cognitive control are helpful in reducing anxiety experienced during anticipation of unpleasant or potentially unpleasant events. We investigated the associated cerebral information processing underlying the use of a specific cognitive control strategy during the anticipation of affect-laden events. Using functional magnetic resonance imaging, we examined differential brain activity during anticipation of events of unknown and negative emotional valence in a group of eighteen healthy subjects that used a cognitive control strategy, similar to "reality checking" as used in psychotherapy, compared with a group of sixteen subjects that did not exert cognitive control. While expecting unpleasant stimuli, the "cognitive control" group showed higher activity in left medial and dorsolateral prefrontal cortex areas but reduced activity in the left extended amygdala, pulvinar/lateral geniculate nucleus and fusiform gyrus. Cognitive control during the "unknown" expectation was associated with reduced amygdalar activity as well and further with reduced insular and thalamic activity. The amygdala activations associated with cognitive control correlated negatively with the reappraisal scores of an emotion regulation questionnaire. The results indicate that cognitive control of particularly unpleasant emotions is associated with elevated prefrontal cortex activity that may serve to attenuate emotion processing in for instance amygdala, and, notably, in perception related brain areas.

Neural correlates of a 'pessimistic' attitude when anticipating events of unknown emotional valence

Since we do not know what future holds for us, we prepare for expected emotional events in order to deal with a pleasant or threatening environment. From an evolutionary perspective, it makes sense to be particularly prepared for the worst-case scenario. We were interested to evaluate whether this assumption is reflected in the central nervous information processing associated with expecting visual stimuli of unknown emotional valence. While being scanned with functional magnetic resonance imaging, healthy subjects were cued to expect and then perceive visual stimuli with a known emotional valence as pleasant, unpleasant, and neutral, as well as stimuli of unknown valence that could have been either pleasant or unpleasant. While anticipating pictures of unknown valence, the activity of emotion processing brain areas was similar to activity associated with expecting unpleasant pictures, but there were no areas in which the activity was similar to the activity when expecting pleasant pictures. The activity of the revealed regions, including bilateral insula, right inferior frontal gyrus, medial thalamus, and red nucleus, further correlated with the individual ratings of mood: the worse the mood, the higher the activity. These areas are supposedly involved in a network for internal adaptation and preparation processes in order to act according to potential or certain unpleasant events. Their activity appears to reflect a 'pessimistic' bias by anticipating the events of unknown valence to be unpleasant.

Classes of multichannel EEG microstates in light and deep hypnotic conditions

The study assessed the brain electric mechanisms of light and deep hypnotic conditions in the framework of EEG temporal microstates. Multichannel EEG of healthy volunteers during initial resting, light hypnosis, deep hypnosis, and eventual recovery was analyzed into temporal EEG microstates of four classes. Microstates are defined by the spatial configuration of their potential distribution maps ([Symbol: see text]potential landscapes') on the head surface. Because different potential landscapes must have been generated by different active neural assemblies, it is reasonable to assume that they also incorporate different brain functions. The observed four microstate classes were very similar to the four standard microstate classes A, B, C, D [Koenig, T. et al. Neuroimage, 2002;16: 41-8] and were labeled correspondingly. We expected a progression of microstate characteristics from initial resting to light to deep hypnosis. But, all three microstate parameters (duration, occurrence/second and %time coverage) yielded values for initial resting and final recovery that were between those of the two hypnotic conditions of light and deep hypnosis. Microstates of the classes B and D showed decreased duration, occurrence/second and %time coverage in deep hypnosis compared to light hypnosis; this was contrary to microstates of classes A and C which showed increased values of all three parameters. Reviewing the available information about microstates in other conditions, the changes from resting to light hypnosis in certain respects are reminiscent of changes to meditation states, and changes to deep hypnosis of those in schizophrenic states.

Time-course of "off-line" prefrontal rTMS effects--a PET study.

Low-frequency "off-line" repetitive transcranial magnetic stimulation (rTMS) over the course of several minutes has attained considerable attention as a research tool in cognitive neuroscience due to its ability to induce functional disruptions of brain areas. This disruptive rTMS effect is highly valuable for revealing a causal relationship between brain and behavior. However, its influence on remote interconnected areas and, more importantly, the duration of the induced neurophysiological effects, remain unknown. These aspects are critical for a study design in the context of cognitive neuroscience. In order to investigate these issues, 12 healthy male subjects underwent 8 H(2)(15)O positron emission tomography (PET) scans after application of long-train low-frequency rTMS to the right dorsolateral prefrontal cortex (DLPFC). Immediately after the stimulation train, regional cerebral blood flow (rCBF) increases were present under the stimulation site as well as in other prefrontal cortical areas, including the ventrolateral prefrontal cortex (VLPFC) ipsilateral to the stimulation site. The mean increases in rCBF returned to baseline within 9 min. The duration of this unilateral prefrontal rTMS effect on rCBF is of particular interest to those who aim to influence behavior in cognitive paradigms that use an "off-line" approach.

Functional connectivity in BOLD and CBF data: similarity and reliability of resting brain networks

Resting-state functional connectivity (FC) fMRI (rs-fcMRI) offers an appealing approach to mapping the brain's intrinsic functional organization. Blood oxygen level dependent (BOLD) and arterial spin labeling (ASL) are the two main rs-fcMRI approaches to assess alterations in brain networks associated with individual differences, behavior and psychopathology. While the BOLD signal is stronger with a higher temporal resolution, ASL provides quantitative, direct measures of the physiology and metabolism of specific networks. This study systematically investigated the similarity and reliability of resting brain networks (RBNs) in BOLD and ASL. A 2×2×2 factorial design was employed where each subject underwent repeated BOLD and ASL rs-fcMRI scans on two occasions on two MRI scanners respectively. Both independent and joint FC analyses revealed common RBNs in ASL and BOLD rs-fcMRI with a moderate to high level of spatial overlap, verified by Dice Similarity Coefficients. Test-retest analyses indicated more reliable spatial network patterns in BOLD (average modal Intraclass Correlation Coefficients: 0.905±0.033 between-sessions; 0.885±0.052 between-scanners) than ASL (0.545±0.048; 0.575±0.059). Nevertheless, ASL provided highly reproducible (0.955±0.021; 0.970±0.011) network-specific CBF measurements. Moreover, we observed positive correlations between regional CBF and FC in core areas of all RBNs indicating a relationship between network connectivity and its baseline metabolism. Taken together, the combination of ASL and BOLD rs-fcMRI provides a powerful tool for characterizing the spatiotemporal and quantitative properties of RBNs. These findings pave the way for future BOLD and ASL rs-fcMRI studies in clinical populations that are carried out across time and scanners.