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Journal of Clinical EEG & Neuroscience, July, 2009
Symposia
Abstracts of presentations at the 5th Annual Joint Meeting of the EEG and Clinical Neuroscience Society (ECNS) and the International Society for NeuroImaging in Psychiatry (ISNIP), in Frankfurt, Germany, September 10-13, 2008.
Abstracts continued from Vol.40, No.1
Neural Correlates of Memory Function in Mild Cognitive Impairment and Mild Alzheimer’s Disease: A BrainPerfusion 123I-IMP SPECT Study with Statistical Parametric Mapping
Ansar AB, Hiroaki K, Naohiko O, Yasuyuki K, Nobuyo K, Begum NN, Hiromasa T,
Tetsuhiko Y, Yoshihiko K, Jun H, Masatoshi T, Osaka University Graduate School of Medicine, Osaka, Japan
Amnesia is the hallmark clinical feature of Alzheimer’s disease (AD) and the cardinal feature of amnestic mild cognitive impairment (aMCI). It was reported that aMCI patients converted to AD within 2-4 years from the baseline diagnosis at a rate approximately 3.1 times higher than in subjects without cognitive impairment. In various disciplines of neuroscience research aMCI has been paid attention as the group that includes very early stage of AD more than normally aged subjects. To date, neural basis of amnesia in aMCI and mild AD is not well documented. A number of studies carried behavioral experiments as a primary concern with little focus on the specific brain regions involved. Functional imaging studies paid attention to detect regional cerebral involvement, neuroimaging and neuropsychological assessments have always been addressed separately. We examined rCBF distribution and its relation with recent memory function in aMCI and mild AD patients. 12 aMCI (Petersen’s criteria), 11 mild AD (NINCDS-ADRDA for probable AD) patients and 15 normal subjects comparable for age, sex and years of education were recruited. Memory functions were evaluated by Wechsler Memory Scale-Revised (WMS-R) scores. Brain perfusion SPECT 123I-IMP was assessed for each subject. We examined the pattern of hypoperfusion and the correlation between WMS-R General Memory and resting rCBF by SPM99 in aMCI and AD patients. SPM revealed a similar pattern of hypoperfusion observed in the left hippocampus, bilateral cingulate, precuneus, parietal and frontal cortices in aMCI and AD. The extent of hypoperfusion was greater in the AD group. WMS-R general memory scores correlated significantly to rCBF in the bilateral hippocampus, left superior parietal and right lingual gyrus in aMCI patients (P<0.01). In mild AD, SPM showed significant correlations in the bilateral posterior cingulate, precuneus, and superior parietal and inferior parietal lobules (P<0.01). These results suggest that medial temporal cortices play a central role solving the recent memory tasks in aMCI patients whereas a greater neural network involving the association cortices come into play an important role for the same task given to mild AD patients.
Recording of Electrically Evoked Auditory Brainstem Responses (E-ABR) With an Integrated Stimulus Generator in Matlab
Bahmer A, Baumann U, University of Frankfurt, Germany
Peter O, University of Innsbruck, Austria
Electrical auditory brainstem responses (E-ABRs) of subjects with cochlear implants are used for monitoring the physiologic responses of early signal processing of the auditory system. Additionally, E-ABR measurements allow the diagnosis of retro-cochlear diseases. Therefore, E-ABR should be available in every cochlear implant center as a diagnostic tool. A low-cost setup was designed to perform an E- as well as a conventional ABR for research purposes. The distributable form was developed with Matlab and the Matlab Compiler (The Mathworks Inc.). For the ABR, only a PC with a soundcard, conventional system headphones, and an EEG pre-amplifier are necessary; for E-ABR, in addition, an interface to the cochlea implant are required. For our purposes, we implemented an interface for the Combi 40+/Pulsar implant (MED-EL, Innsbruck).
Relationship Between Interictal Spiking, Behavior, and Environment in a Rat Model
Barkmeier D, Mears R, Loeb JA, Boutros N, Wayne State University, Detroit, Michigan, USA
The effect of electrical discharges occurring between seizures on behavior is poorly understood, yet they are frequently observed in neuropsychiatric conditions. Equally unknown are the effects of environment on interictal spiking. To better understand the relationship between behavior, interictal spiking and environment, we developed a focal rat model of progressive neocortical interictal spiking.
Interictal spiking was induced by injecting tetanus toxin into the left somatosensory cortex of rats, and discharges were monitored using six epidural electrodes. EEG was recorded daily in a behavioral chamber, and the effects of auditory stimuli on interictal spiking were measured.
Once significant spontaneous interictal spiking developed, the spiking animals rotated clockwise significantly more than control animals. During this time, a startling sound produced an interictal spike in a spontaneously spiking animal identical to its normal spike field, but nothing in control animals.
Here we provide the first observations of a clear effect of interictal spiking on behavior. The findings of auditory-induced spiking only in animals with pre-existing spiking suggests that the environment can have profound effects on interictal spiking which in turn influences behavior. These results have important clinical implications on how interictal spiking and environment interact in human neuropsychiatric disorders.
Neural Correlates of Working Memory in Cannabis Users
Becker B, Daumann J, University Hospital Cologne, Germany
Cannabis is the most commonly used illicit drug in western industrial countries with particularly high prevalence rates among adolescents and young adults. Several neuropsychological studies have identified cannabis-associated short-term memory deficits. More recently these deficits were associated to specific parameters of cannabis use, such as the age of onset and the frequency of use. In neuroimaging studies cannabis users usually displayed altered brain activity, despite normal task performance. However it remains unclear, whether specific parameters of cannabis use might account for a varying degree of altered cortical activation patterns. Functional magnetic resonance imaging at 1.5 T was used to examine cortical activation patterns in cannabis users (n = 42) during a verbal working memory task with increasing memory load.
In a simple regression only the age of onset of cannabis-use showed a significant relation to cortical activation in the working memory network. An earlier start of use was associated with greater cortical activation in frontal and parietal regions. Additionally, in a group comparison between early and late onset users (<>16) early-onset users displayed more pronounced and more widespread cortical activation, particularly in the left superior parietal lobule (SPL; x, y, z=-22, -57, 54; BA 7; z = 4.38). In contrast, cognitive performance did not differ significantly.
These results suggest that among all cannabis use parameters the age of onset of use might have a particular critical impact on cognitive processing. Increased activation of the SPL might reflect a compensatory neuropsychological mechanism in order to perform within the normal range.
A Method for Automatic Alpha Peak Characterization
Chiang A, Rennie C, Robinson P, University of Sydney, New South Wales 2006, Australia
Chiang A, Rennie C, Robinson P, Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales Australia
The quantification of alpha rhythm in the human electroencephalogram (EEG) is generally a laborious task involving visual inspection of the spectrum. Moreover the occurrence of multiple alpha rhythms is often overlooked. This paper seeks to automate the process of identifying alpha peaks and their frequencies, amplitudes and widths as functions of position on the scalp. The algorithm comprises two stages: in the first stage experimental EEGs at each electrode site are numerically fitted with parameterized spectra spanning the alpha range, the second stage integrates these fits across sites to rule out noise to seek out robust alpha peaks. The results are categorized into three classes: no distinguishable alpha peak, a single robust alpha peak, and two robust alpha peaks. The technique avoids visual bias, integrates spatial information, and is automated. We show that multiple alpha peaks are a common feature of many spectra, with over 40% of the subjects exhibiting two alpha peaks. Double alpha peaks do not only occur in the obvious case where there exist two independent robust peaks at each site, but also when there is only one robust peak per site for all sites but different frequencies at different locations. Distribution of the alpha peak characteristics (amplitudes, frequencies, and widths) are obtained for each electrode site and their spatial morphologies are explored.
Brain Serotonin Transporter Binding in Euthymic State of Patients With Bipolar Disorder: a SPECT Study
Chou Y-H, Wang S-J, Yang B-H, Taipei Veterans General Hospital & National Yang Ming University, Taipei, Taiwan
Lin C-L, Taoyuan Armed Forces General Hospital & National Defense Medical Center, Taoyuan, Taiwan
Mao W-C,Tri-Service General Hospital & National Defense Medical Center, Taipei, Taiwan
Lee S-M, Yu-Li Hospital, Executive Yuan, Taiwan
The aim of this study was to assess serotonin transporter (SERT) binding in the midbrain in euthymic state of patients with bipolar disorder. Twenty-eight healthy controls and 24 euthymic state of medicated patients with bipolar disorder (included 10 for type I bipolar disorder (BD I) and 14 for type II bipolar disorder (BD II)) were recruited. Single photon emission computed tomography with radiotracer 123I-ADAM was used to measure brain SERT binding. Specific uptake ratio (SUR) that represents the availability of brain SERT was the primary measurement outcome. The averaged SURs were not different between controls and euthymic state of medicated patients with bipolar disorder (BD) (1.10±0.27 v.s. 1.01±0.32, p=0.27). One-way ANOVA (F=3.637, p=0.034) with Bonferroni post hoc test demonstrated SURs was significantly lower in patients with BD I than BD II (p=0.048) and normal controls (p=0.05). The decreased SURs in patients with BD I were well correlated with illness duration (-0.742, p=0.014). SURS in BD II were not correlated with these clinical factors. Our findings provide the biological evidence and demonstrate the different biological regulations of BD I and II after pharmacological treatment. This result may support the idea of dichotomy in BD.
MAOA Genotype: Impact on Cortico-Limbic Functional Connectivity in Major Depression
Dannlowski U, Ohrmann P, Konrad C, Domschke K, Bauer J, Kugel H, Hohoff C, Schöning S,
Kersting A, Arolt V, Zwitserlood P, Deckert J, Heindel W, Suslow T, University of Münster, Germany
Baune B, James Cook University, Townsville, Australia
Deckert J, University of Würzburg, Germany
The amygdala plays a pivotal role in a cortico-limbic circuitry implicated in emotion processing and regulation. In the present study, functional connectivity of the amygdala with prefrontal areas involved in emotion regulation was investigated during a facial expression processing task in a sample of 34 depressed inpatients and 31 healthy controls. All patients were genotyped for a common functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the monoamine oxidase A gene (MAOA u-VNTR) which has been previously associated with major depression as well as reduced cortico-limbic connectivity in healthy subjects. In our control group, we observed tight coupling of the amygdala and dorsal prefrontal areas comprising the dorsolateral prefrontal cortex (DLPFC), dorsal parts of the anterior cingulate cortex (dACC), and lateral orbitofrontal cortex. Amygdala-prefrontal connectivity was significantly reduced in depressed patients and carriers of the higher active MAOA risk alleles (MAOA-H). Hence, depressed MAOA-H carriers showed the weakest amygdala-prefrontal coupling of the investigated subgroups. Furthermore, reduced coupling of this circuitry predicted more than 40% variance of clinical variables characterizing a longer and severer course of disease. We conclude that genetic variation in the MAOA gene may affect the course of major depression by disrupting cortico-limbic connectivity.
Source Localization (sLORETA) of Mismatch Negativity Generators in Response to Across-Phoneme Deviants
Fisher D, Knott V, Carleton University, Ottawa, ON, Canada
Knott V, University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada
Fisher D, Knott V, Royal Ottawa Mental Health Centre, Ottawa, ON, Canada
The preconscious auditory change detector mismatch negativity (MMN) is a well established event-related potential (ERP) index of pre-attentive auditory cortex function. Despite years of research examining the MMN, the cortical locations of its generators are still not well understood. Previous efforts to localize MMN generators have been focused on temporal generators, with minimal success identifying frontal generators. MMNs, derived from across phoneme deviants (standard: /a/, deviant: /o/) within a 2-stimulus auditory oddball paradigm, were assessed in 12 healthy controls and then mapped onto the cortex using standardized Low Resolution Electromagnetic Brain Tomography (sLORETA), providing a report of MMN source generators.Current source density analysis at the time of peak MMN amplitude shows bilateral activation of the temporal and parietal lobes, particularly around the left auditory cortex (BA 22, BA 41, BA 42) and some activation at the precentral gyrus (BA 6, BA 44) and inferior frontal gyrus (BA 47) of the frontal lobe. However as time progresses, there is progressive anterior shift of activation towards the inferior and middle frontal gyri of the frontal lobe and insula (BA 13). Staggered analysis with sLORETA at multiple time points allows for mapping of early temporal-parietal dominant and later frontal dominant MMN cortical generators with a high degree of temporal resolution, albeit relatively low (~5mm) spatial resolution.
Interactions Between Selective Attention and Encoding into Spatial Working Memory: Evidence From fMRI
Fusser F, Rahm B, Maurer K, Haenschel C, Mayer JS, Goethe-University, Frankfurt, Germany
Linden DEJ, University of Wales, Bangor, United Kingdom
Haenschel C, Max-Planck Institute for Brain Research, Frankfurt, Germany
Models of working memory (WM) implicate restricted attentional resources as a limiting factor for the storage capacity of visual WM. We used fMRI to test the hypothesis that this limitation is due to common neural resources shared by visual WM and attention. Participants were presented with a search array and performed easy or difficult visual search in order to encode one, three, or five positions of target items into WM. Overlapping activation for attention-demanding visual search and WM encoding was observed in distributed posterior and frontal regions. Within this set of regions there was a segregation between prefrontal regions where neural activation additively increased under conditions of joint demand on both processes and more posterior regions (visual, parietal and premotor cortex) where the WM load-related activation increases were severely reduced in the condition with high attentional demand. Activity related to the performance of eye movements recorded during fMRI did not account for the task effects. We propose that the limited capacity of spatial WM stems from the competition for resources shared by spatial attention and spatial WM encoding in distributed posterior and premotor, but not prefrontal, brain regions. Our results provide neurophysiological evidence for attention-based models of visual WM.
Visual and Auditory EEG Biofeedback in Anxious Patients Compared With Healthy Controls
Gregory C, Derrick M, Rainey L, Holt J, Wallace S, Wilson T, Miller B, Miller M, Moore NC, Quillen College of Medicine,
East Tennessee State University, Johnson City, Tennessee, USA
Most therapists use eyes-closed auditory EEG biofeedback (neurotherapy; NT) for Generalized Anxiety Disorder (GAD). Anxiety is mostly experienced with eyes open, so it is important to know whether eyes-open feedback is effective in the NT of GAD. Visual was compared with auditory alpha-enhancement NT in 8 GAD and 10 controls (5 one-hour sessions eyes-open visual; 5 eyes-closed auditory NT; 5 eyes-open auditory + visual). Leikert and Hamilton Anxiety Scales were administered at baseline and at end of each treatment.Controls showed significantly increased alpha of 6.2 + 2.2 mV (p=0.01 one-tail; 0.02 two-tail) with eyes-closed auditory, accompanied by significantly decreased anxiety (p= 0.01 one-tail; 0.02 two-tail). In GAD patients neither visual nor auditory NT increased alpha or decreased anxiety. Eyes-open increased anxiety significantly in patients (p= 0.02 one tail; 0.05 two-tail). Five sessions of auditory NT were shown to significantly increase alpha and decrease anxiety in healthy subjects only, supporting the hypothesis that an increase in alpha is necessary for a decrease in anxiety. More than 5 sessions are necessary for anxious patients to show significant improvement, in accordance with previously reported data stating that 30 sessions are necessary.
A Semantic Priming Paradigm That Allows Disentangling Abstract and Concrete Word Processing With Neurophysiological Methods
Grieder M, Kneubühler B, Wirth M, Horn H, Strik W, Dierks T, University Hospital of Psychiatry, University of Bern, Switzerland
Subgroups of patients with dementia or schizophrenia show distinct deficits in semantic memory for concrete words. However, little is known about semantic impairments for abstract words. Accordingly, we aimed to establish a paradigm that is useful to investigate concrete and abstract semantic memory. It was tested in healthy subjects. The participants performed a lexical decision task implemented in a semantic priming paradigm. The paradigm consisted of abstract and concrete noun-noun word pairs, either semantically related or non-related and pronounceable non-words. Subjects were asked to press a choice of two buttons as an indication for whether the second word was a word or non-word. All subjects revealed significant priming effects (reaction time decrease in related compared to non-related words), both for the abstract and the concrete condition. This implies that our semantic priming paradigm is suitable to investigate processes in the abstract and concrete semantic system. Thus, this paradigm can be combined with neurophysiological methods and applied to patients in a next step.
Vigilance Regulation in Psychiatric Disorders
Hegerl U, Sander C, Olbrich S, Trenner M, Schönknecht P, Universitätsklinikum Leipzig AöR, Germany
During quiet wakefulness, the temporo-spatial pattern of EEG activity allows to separate different states of global brain function (vigilance stages A1-A3, B1-B3). The regulation of EEG-vigilance is a state-modulated trait. There are two types of non-physiologic vigilance regulation: Hyperstable vigilance regulation (no decline in vigilance stages under resting conditions over a period of several minutes) and unstable vigilance regulation (rapid declines to lower vigilance stages during the first seconds of EEG-recordings). Empirical evidence will be provided for a pathogenetic role of vigilance regulation in affective disorders linking hyperstable vigilance regulation to depression and unstable vigilance regulation to mania.
A Review of Evoked Potential Findings in PTSD
Javenbakht A, Boutros NN, Amirsadri A, Wayne State University School of Medicine, Detroit, Michigan, USA
While psychotic processes are not uncommon in PTSD patients, evoked potential (EP) studies probing information processing have been sparse. In order to assess currently available knowledge regarding EP studies in PTSD and their implications for the nature of information processing abberations in this disorder, we performed an exhaustive Medline review of EP studies in PTSD. The keywords included PTSD, post traumatic stress disorder, EEG, electrophysiology, ERP, evoked potential and sensory gating. After filtering out the irrelevant search results, we had 27 papers in English and one in French which was omitted due to unavailability of an abstract. P50, pre-pulse inhibition (PPI), contingent negative variation (CNV), N100, P200 and P300 in both visual and auditory modalities were studied. Stimuli used were either simple sounds or a comparison of responses to trauma-related and unrelated stimuli. PTSD patients were compared to non-PTSD traumatized and healthy subjects. Most of the studies had evaluated more than one component. Overall, four measured P50 gating, two PPI, four CNV, five N100, eight P200 and seventeen P300. We comment on the two largest data sets (i.e, P200 and P300). P200 amplitudes were smaller to non-trauma-related and larger to trauma-related stimuli. P300 amplitudes were smaller with longer latencies in response to neutral stimuli and bigger and earlier to trauma-specific stimuli.
The above review highlights the need for further electrophysiological studies of PTSD patients and strongly suggests that EP studies are a good probe for information processing aberrations in this patient population.
Theory of Mind (TOM) in a Sample of Japanese Schizophrenia Patients: A Combined Diffusion-Tensor (DTI) and Functional Magnetic Resonance Imaging (fMRI) Study
Koelkebeck K, Ohrmann P, Bauer J, Pedersen A, Arolt V, University of Muenster, Muenster, Germany
Hirao K, Saze T, Miyata J, Kawada R, Murai T, Graduate School of Medicine, Kyoto University, Kyoto, Japan
FMRI-studies have shown reduced activation in certain brain areas during performance of ToM-tasks in schizophrenia patients. Moreover, structural deficits have been found by DTI showing a reduction of white fibers. In our study we combine a ToM-paradigm used by Abell et al. (2000) with fMRI and DTI in a sample of schizophrenia patients. Reduced activation patterns during ToM-task performance might be related to a reduction of white matter integrity of ToM-relevant brain areas. Eleven schizophrenia patients and 12 healthy controls participated in the study and were assessed with an fMRI-paradigm comprising short videos of geometrical shapes acting in social patterns. Furthermore, DTI has been applied. Results indicate differential activation patterns in patients in areas related to the ToM neuronal network, the ACC and the temporal lobes were, e.g., more extensively activated. Analyses of white matter tracts revealed lower FA-values in the left arcuate fasciculus and right deep white matter of the temporal lobe in patients. Functional imaging findings hint on a compensatory activation of ToM-related areas in patients and analyses of white matter tracts show lower FA-values in these areas. Our study reveals functional and structural abnormalities in schizophrenia patients and might elucidate the neurobiological basis of social cognition deficits.
Working Memory in Remitted Major Depression Assessed by 3T fMRI
Konrad C, Schöning S, Kugel H, Engelien A, Behnken A, Pyka M,
Zwitserlood P, Kersting A, Zwanzger P, Arolt V, University of Münster, Germany
Reker T, LWL Clinic Münster, Germany
While impairments of cognitive functions have frequently been reported in patients with major depression, the extent of working memory involvement remains unclear. We investigated if these functional abnormalities persist after remission of mood symptoms. Twenty-eight patients with major depression and 28 age- and sex-matched healthy controls were examined with functional MRI at 3 T. Subjects performed a verbal n-back paradigm with letters. Subjects had to decide whether a letter was or was not presented in earlier presentations by pressing a button. Both groups activated a network of prefrontal and parietal areas. The activations of this prefrontal-parietal network increased with increasing working memory load. In the absence of behavioural differences, remitted patients showed significantly higher activation of the anterior cingulate cortex than healthy volunteers. In line with previous studies, verbal working memory is represented in a fronto-parietal network. Increased anterior cingulate activation has previously only been reported in patients in the acute depressive episode. For the first time we show that this pattern persists in patients just recovered from a depressive episode. Increased recruitment of the underlying neuronal network or increased cognitive effort might be necessary to maintain working memory function in patients with major depression.
Neuronal Correlates of Emotionally Biased Face Recognition
Liu D, Li Y, Shanghai University, Shanghai, China
Li Y, Kohler A, Singer W, Max Planck Institute for Brain Research, Frankfurt am Main, Germany
Tang Y, Shanghai Jiao Tong University, Shanghai, China
It is well known that a recognition bias can be observed when subjects are asked to recognize the faces from their own race and other races, which was a kind of “own-race bias”. Recently, this bias in relation to emotion cognition arose wide interests. However, underlying mechanisms of the bias in emotion cognition remain unclear.
In this research, we chose 24 Chinese volunteers (12 male, 12 female), showing them Chinese and western emotional faces (positive vs. negative). They were asked to perform a study-recognition task, judging whether the second face was the same as the first one. The faces from two races were presented block by block. At the same time, event-related potentials (ERPs) were recorded. We calculated the global power of data between 500-600ms. Interesting differences were found in central and parietal sites (at C3, C4, Cz, Cp5, Cp6, Cpz, P3, P4, Pz, P7 and P8). When subjects recognized their own-race faces, the power of a late ERP component evoked by the negative stimuli was significantly larger than that evoked by the positive stimuli. However, when the western faces were recognized, no significant difference between different emotional faces could be found. This result indicates that there is a significant correlation between emotion cognition and race.
First Measurements of Multi-Feature MMN Profiles in the Clinical Application With Schizophrenic Patients Using EEG and MEG
Norra CH, Thönnessen H, Zvyagintsev M, Harke KC, Mathiak K, RWTH Aachen University, Germany
Norra CH, LWL-University Hospital, Ruhr University Bochum, Germany
Boers F, Dammers J, Institute of Medicine, Research Center Juelich, Juelich, Germany
Mismatch negativity (MMN) has consistently detected neural pre-attentive information processing deficits in schizophrenia using different methods (electroencephalography, EEG; magnetoencephalography, MEG) and different paradigms using the “traditional” oddball (20% rare deviants) or “optimized” multi-feature designs (50% rare deviants varying in one of five parameters each); but the latter has only been applied to non-clinical issues.
Both designs were compared in 12 patients with schizophrenia and 12 healthy controls using MEG and EEG. Automated, observer-independent data analysis rendered the procedures suitable for clinical applications. The optimized design was fastest to detect MMN changes. MMN was mostly reduced in schizophrenia if measured with MEG in the optimized paradigm reaching mean effect sizes of 0.85 (max. 1.5) as opposed to 0.65 in the traditional MMN profile recorded with EEG. Interestingly, the amplitude of MMNm of the left auditory cortex correlated significantly with positive symptoms for schizophrenia in both paradigms.
Optimized MMN paradigms, especially MMNm, revealed improved sensitivity and speed for the detection of schizophrenia endophenotypes. Especially the relationship of MMN deficits to psychopathometry will have to be further clarified. Of note, the different MMN optimized profiles may not reflect one unitary mechanism that is equally affected in schizophrenia.
EEG-Vigilance and fMRI Resting State Networks
Olbrich S, Trenner M, Schönknecht P, Hegerl U, Universitätsklinikum Leipzig AöR, Germany
Mulert C, Ludwig-Maximilian-Universität, München, Deutschland
Recently fMRI research has revealed that several cortical areas show coherent BOLD signal fluctuations during rest. These neuronal networks have been called “resting state networks” (RSNs). The functional meaning of these networks remains unclear. Parallel EEG recordings allow to separate distinct functional brain states which represent different organisational levels of brain activity. We hypothesize that resting state networks are related to different vigilance stages.
We investigated 12 healthy subjects with simultaneous EEG/fMRI. EEG-vigilance stages were used as regressors for the analysis of the fMRI data. Further RSNs were identified using independent component analysis (ICA) of the fMRI-data. Brain areas with a significant correlation between BOLD signal and EEG-vigilance stages were compared with the RSNs using region-level conjunction analysis.There was a strong comparability between the identified RSNs and the brain regions which showed a significant correlation between EEG-vigilance stages and BOLD signals. These networks comprised the anterior cingulate cortex, the occipital cortex, parietal and temporal cortices and thalamic areas.
Our results suggest that activity within the RSNs might reflect different functional brain states during rest.
Attention Effects on Auditory Sensory Gating in Scalp and Intracranial Recordings
Rosburg T, Trautner P, Elger CE, Kurthen M, University of Bonn, Bonn, Germany
Kurthen M, Swiss Epilepsy Center, Zurich, Switzerland
Auditory sensory gating has been studied intensively in schizophrenia research. The impact of attention on this function has not been fully resolved in previous studies though attention effects on auditory evoked potentials (AEPs) have been described already three decades ago (Hillyard et al., 1973). In the current study, we investigated the impact of attention on sensory gating by scalp and intracranial recordings in a sample of epilepsy and tumor patients, undergoing presurgical evaluation by means of implanted electrodes. In the baseline condition, patients had no task but watching a silent movie. In the attention condition, patients had to count the presented double clicks and in addition interspersed single clicks. The AEPs in the active condition were characterized by an additional underlying negativity both for scalp and neocortical recordings, reaching its maximum at the N100 latency of the 2nd stimulus. A time-frequency analysis revealed that this attention effect comprised only low frequency signals (< 3 Hz). In line with that, P50 amplitude and P50 gating were unaffected by attention when data were filtered from 10 to 50 Hz. In addition, attention effects were revealed for intrahippocampal event-related potential components and for induced high-frequency neocortical gamma band activity. Findings indicate that N100 and P200 gating measures can potentially be affected by attention and have to be interpreted carefully when studying clinical populations.
Sensation Seeking and Aversive Stimulation – A 3 T fMRI Study
Sehlmeyer C, Kugel H, Schöning S, Kleemeyer M, Herper K, Rauch A, Schiffbauer H,
Pfleiderer B, Arolt V, Zwitserlood P, Konrad C, University of Münster, Germany
Sensation Seeking (SENS) is a dimension of human personality characterized by the need for “varied, novel, and complex sensations and experience and the willingness to take physical and social risks for the sake of such experience” (Zuckerman, 1979). People with high and low SENS scores differ in their tendency to avoid or seek threatening stimuli or situations as well as in their anxiety reactivity (Lissek & Powers 2003; De Pascalis et al. 2007). Subjects who score high on SENS experience a positive reward and “approach“ behavioural tendencies in response to intense, aversive stimuli, whereas low sensation seekers avoid intense and dangerous sensory stimulations. In the present study, we examine the association between Sensation Seeking and the neurobiological mechanisms involved in fear processing in functional magnetic resonance imaging (fMRI). It was supposed that the personality trait SENS correlates significantly with neuronal responses to fear-stimuli.
In this ongoing study, the German Version of the Sensation-Seeking Scale (SSS-V; Beauducel 2003) was used to asses each participant’s level of SENS. Thirty healthy controls were examined with functional MRI at 3 T (Gyroscan Intera 3.0 T, Philips, Best, NL). They were presented with acoustic startle stimuli (95dB) in an event-related design. Skin conductance responses (SCR) were sampled simultaneously with MR scans. Statistical analysis of fMRI-data was performed using SPM5. A linear regression analysis was calculated to determine if neuronal activation of “fear circuits” was associated with magnitude of SENS-scores.
Analysis of pilot fMRI-data demonstrated enhanced activation in fear-related areas like amygdala, insula and anterior cingulated cortex. Significant correlations emerged between Sensation Seeking and BOLD-signals in some of these areas, mainly in the anterior cingulate cortex. These results provide support for the association between SENS and fear-circuitry reactivity. A greater expressiveness of SENS influences the processing of threatening stimuli and neurobiological reactions to fear.
Pre- and Post-QEEG and Neuropsychological Effects of Left Frontal Magnetic Stimulation (rTMS) in Depression
Spronk D, Arns M, Brainclinics Diagnostics B.V., Nijmegen, The Netherlands
Arns M, Bootsma A, Ruth R van, Brainclinics Treatment B.V., Nijmegen, The Netherlands
Fitzgerald PB, The Alfred and Monash University School of Psychology, Psychiatry and Psychological Medicine, Melbourne, Australia
rTMS treatment for Depression has been under investigation in many controlled studies over the last 20 years. Most studies used a single stimulation protocol to treat all patients in the same way. Little is known about inter-individual differences, contraindications for treatment as well as the neurobiological action of rTMS in patients. We therefore developed a personalized stimulation protocol based on the QEEG and neuropsychological data and also investigated pre- and post treatment effects on QEEG and neuropsychology. rTMS treatment was applied in 8 subjects for a maximum of 20 sessions to the Left Dorsolateral Prefrontal Cortex. Prior to treatment clients were assessed on a full QEEG and neuropsychological evaluation. Clients were stimulated over the left DLPFC with 10 Hz rTMS.
All subjects showed full remission within 20 sessions and there was a 65% reduction in Depressive symptomatology (BDI score) in 15 sessions. There was also a clear decrease in the Neuroticism scale of the NEO-FFI personality questionnaire. Pre- and post-QEEG measurements did not reveal treatment specific effects, but only an indirect right frontal increase in delta power. On the other hand, ERP measures did reveal treatment specific effects by showing an increased positivity in the post-treatment ERP’s specifically left frontal. The P2 amplitude demonstrated a significant left frontal increase in amplitude, whereas for the negative N1 and N2 a significant decrease in amplitude was observed.
The results of this pilot study demonstrate that rTMS can be a safe and efficacious treatment modality for depression. Furthermore, a specific left frontal increase in positivity for the ERP’s were found (increase P2 and decreased N1 and N2 components) most likely related to the rTMS over the left DLPFC. Furthermore, there was no change in the alpha asymmetry lending support to the fact that frontal alpha asymmetry can be considered a trait marker for depression. The findings from this pilot study require future replication with larger sample sizes. The updated BDI results from the entire patient population to date will be presented as well.
QEEG- Neurometric Analysis Guided Neurofeedback Treatment in Schizophrenia
Case study: 52 Patients
How Neurometric Analysis is Important at the Treatment of Schizophrenia as Well as Diagnosis?
Sürmeli T, LHC for Research and Education, Istanbul, Turkey
EEG studies of schizophrenic patients indicate a higher number of patients with abnormal records decreased in alpha activity, increased delta and theta activity and possibly more left sided abnormalities, and some coherence abnormalities. The clinical Antipsychotic Trials for Interventions Effectiveness raise important questions about relapse treatment resistance, minimizing adverse effects and improving treatment adherence in schizophrenia. We thought neurofeedback treatment may address those problems.
Most of the patients were diagnosed with chronic schizophrenia before coming to our center and did not improve in their symptoms with antipsychotic medications. Neurometric analysis of the QEEG of the patients suggested chronic schizophrenia consistant with the clinical judgement of the author. All 52 patients recieved QEEG analysis with the Nxlink data bank, PANSS and 31 out of 52 patients also recieved T.O.V.A. and MMPI at baseline and at the end of the treatment. Responses to PANSS were analyzed to evaluate the effectiveness of neurofeedback between 40-120 training sessions. Forty-three patients improved after neurofeedback treatment. 7 dropped the treatment and 2 did not respond. The patients who showed coherence abnormalities in the QEEG responded better and quicker to treatment. Antipsychotic medications may increase coherence abnormalities in the brain but coherence abnormalities can be diminished with neurofeedback treatment to get a better outcome. NF treatment may increase adherence to treatment and reduce possible side effects of antipsychotics in schizophrenia. Further study with controls is warranted.
Different Time Course of Event-Related Potentials in Spatial Search for Emotionally Loaded Faces
Tang Y, Zhu Y, Shanghai Jiao Tong University, Shanghai, China
Li Y, Liu D, School of Communication and Information Engineering, Shanghai University, Shanghai, China
Li Y, Kohler A, Singer W, Max Planck Institute for Brain Research, Frankfurt am Main, Germany
Recognition of facial expressions, contributing to the social interpersonal behavior, has been investigated extensively over the last decade. However, it remains unclear which stages of face processing were affected by facial expressions. In our study, a face-in-the-crowd task with crowds of neutral and emotionally biased faces was performed in 18 normal subjects. Event-related potentials were recorded and analyzed in response to (a) different facial expressions (neutral/positive/negative) (b) different detection difficulties induced by varying the number of faces. Results show that: (1)When responding to negative faces a late component (500-800 ms post-stimulus) that was negative for positive/neutral faces showed a positive shift; (2) A unique negative component for negative faces was observed at ~400ms at fronto-central regions. In addition, the N2 amplitude decreased with increasing detection difficulty. Our results suggest that the time course of ERPs to negative and positive/neutral faces differs, which might be due to different search strategies for negative and positive/neutral faces. This warrants further investigation of contextual influences on emotion processing.
Behavioral and Neurochemical Effects of Brain Stimulation in an Animal Model for Depressive Behavior
Toth E, Gersner R, Zangen A, Weizmann Institute of Sciences, Rehovot, Israel
ECT is the most effective antidepressant treatment to date, but incorporates drawbacks, the need for general anesthesia, and an accompanied generalized seizure, resulting in cognitive side-effects. We tested whether sub-convulsive electrical stimulation (SCES) of specific reward-related brain regions such as prelimbic cortex (PLC) or nucleus accumbens (NAC) can induce an antidepressant effect and alter brain-derived neurotrophic factor (BDNF) levels in reward-related brain regions. The CMS model in rats was followed by repeated application of either ECT or SCES delivered to specific brain sites by left-side electrode implantation. Anhedonia (sucrose preference), exploration, home-cage locomotion, learning and short-term memory were measured after treatment completion. Rats were sacrificed and punches of brain regions were taken for BDNF evaluation by ELISA. We tested whether SCES of the NAC can increase sexual drive and sexual partner preference.
Sucrose preference significantly decreased in CMS animals relative to controls. ECT and SCES of the ventral PLC and NAC, but not dorsal PLC, significantly increased sucrose preference in CMS animals. In sexual behavior test the number of mounts in CMS sham animals was significantly lower than control sham animals. SCES treatment of NAC increased sexual drive. Control animals preferred to mount more often the new stimulus female compared to previous partners while CMS sham and SCES treated animals showed no preference. In the exploration test upon CMS, area center visits decreased, but ECT can normalize this. ECT (but not SCES) induced impairment in the learning curve and in memory probe test. ECT increased BDNF level in dorsal hippocampus and striatum but decreased in nucleus accumbens. SCES increased BDNF level in dorsal hippocampus and striatum.
Changes in Cortical Thickness Specific to Auditory Verbal Hallucination in Hallucinating Schizophrenic Patients
van Swam C, Federspiel A, Hubl D, Kreis R, Vermathen P, Boesch C, Strik W, Dierks T, University of Bern, Switzerland
Functional and structural studies have substantially increased our knowledge regarding the neurobiological mechanisms of auditory verbal hallucinations (AVH). In this context functional and structural alterations in areas important for language-production and perception including the primary auditory cortex repeatedly have been discussed. However, especially investigations of gray matter in the context of AVH have reported conflicting results. Cortical thickness analysis is a method to investigate subtle structural changes in brain gray matter.
Using cortical thickness analysis the present study aimed to investigate changes in cortical thickness specific to AVH in schizophrenic patients. Anatomical data from 10 patients with chronic schizophrenia suffering from persistent AVH and 10 patients with chronic schizophrenia who never have experienced AVH were acquired. Based on comparison of the cortical thickness of the left hemisphere (speech dominant) between the two patients groups, brain regions with changes being specific for the patients of the hallucinating group were identified.
AH patients demonstrated cortical thinning in regions responsible for sensory processing (parietal operculum, Herschl’s gyrus and postcentral gyrus) than areas related to motor and speech production (premotor cortex and dorsolateral inferior frontal gyrus) in the speech dominant hemisphere.
The results suggest that AVH arise by a complex interplay of slow changing rather enduring structural changes in white and gray matter and faster dynamic functional conditions.
Perturbations in Positive Middle Latency Auditory Evoked Potential: Relationship with Hallucinatory Behavior in Schizophrenia
Vedeniapin A, Penn State University, Hershey, Pennsylvania, USA
Boutros NN, Elfakhani M, Burroughs S, Fuerst D, Wayne State University, Detroit, Michigan, USA
Earlier findings suggested auditory evoked potentials as diagnostic measure in schizophrenia. However, the relationship between different components of middle latency auditory evoked responses (MLAER) and clinical symptoms of schizophrenia is unclear. In this study we explored the relationship between the amplitude of positive MLAER and hallucinatory behavior in medicated schizophrenic patients. MLAER were measured from 37 outpatient, schizophrenic patients (26 males, mean age 43.5 years, SD = 11.7), stable on atypical antipsychotic medications. The evoked potentials were elicited in a paired click paradigm. The first positive component of the MLAER (averaged peak latency 50 ms.), measured from pre-stimulus baseline, was studied. The bandpass filter was 1-50 Hz. Sensory gating was calculated by the stimulus2/stimulus1 response ratio. All the patients were administered Positive and Negative Symptoms Scale (PANSS). Twenty seven (20 males) patients experienced hallucinatory behavior. Schizophrenic patients with hallucinatory behavior had significantly (p<0.05) smaller amplitude of the first positive component of the MLAER, elicited by both first and second clicks in the pair. The difference between groups of patients with and without hallucinations was stronger (p=0.008) for the sensory gating parameter.
Preliminary analysis suggests that the amplitude of the first positive MLAER component, measured from the pre-stimulus baseline, and sensory gating of such response in a paired click paradigm is related to hallucinatory behavior in schizophrenic patients.
Are Some Panic Attacks Really Temporal Lobe Seizures?
Vyas U, Moore NC, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA
Boutros NN, Wayne State University, Detroit, Michigan, USA
Anxiety Disorders are the most prevalent psychiatric disorders, Panic Disorder (PD) is characterized by recurrent unexpected Panic Attacks, about which there is persistent concern. Life time prevalence of PD is 1.5 to 3.5%. Panic Attacks often have the same clinical signs as Temporal Lobe Seizures (TLE) with psychic content. Reports of concomitant PD and epilepsy are highly suggestive of an intimate relationship between them. SSRI is currently first-line treatment for all Anxiety Disorders. However, they are ineffective in approximately 40 to 50% of patients, and cause unacceptable side effects. Benzodiazepines are both anxiolytic and anticonvulsants. However, long-term use can cause tolerance, dependence and withdrawal. Levetiracetam (Anti-Epileptic Drug, AED) is effective in PD. EEG abnormalities have been reported in patients with PD, although controlled studies are lacking. 20 to 40% of clinically proven Complex Partial Seizure patients have normal routine clinical EEG. At least 30% of routine EEG of PD patients is abnormal. Many reported normal in routine EEGs show abnormalities in long term EEGs including sleep. No studies were found which address the circumstances in which AEDs should be used in treatment of PD. Further investigation is warranted to determine the association between PD and TLE, and choice of treatment.
Neural Correlates of Visual and Auditory Alerting in the Human 5HT2A Agonist and NMDA Antagonist Model of Psychosis
Wagner D, Gouzoulis-Mayfrank E, Heekeren K, Daumann J, University of Cologne, Germany
Thiel CM, Institute of Medicine, Research Centre Jülich, Germany
Deficits in attentional functions are counted among the core cognitive symptoms in schizophrenic patients. Alertness is a nonselective attention component that refers to a state of general readiness that improves stimulus processing and response initiation. The main goal of the present study was to investigate cerebral correlates of alertness in the human 5HT2A agonist and NMDA antagonist model of psychosis. Fourteen healthy volunteers participated in a randomized double-blind, cross-over event-related functional magnetic resonance imaging (fMRI) study with dimethyltryptamine (DMT) and S-ketamine. A target detection task with cued and uncued trials in both the visual and the auditory modality was used. Administration of DMT led to decreased blood oxygenation level-dependent response during performance of an alertness task, particularly in extrastriate regions during visual alerting and in temporal regions during auditory alerting. In general, the effects for the visual modality were more pronounced. In contrast, administration of S-ketamine led to increased cortical activation in the left insula and precentral gyrus in the auditory modality. The results of the present study might deliver more insight into potential differences and overlapping pathomechanisms in schizophrenia. These conclusions must remain preliminary and should be explored by further fMRI studies with schizophrenic patients performing modality-specific alertness tasks.
Does “Food” Have Influence on Word Memory in Patients With Anorexia Nervosa as Reflected by an Event-Related Potential Study?
Zhang Y, Hauser U, Schmid-Ott G, Chen J, Hanschmidt A, Wilhelm A, Emrich HM, Dietrich DE, Hanover Medical School, Germany
Diverse cognitive disturbances were found in anorexia nervosa. However, it is still unknown how food-related words influence on memory processing in these patients. To explore this question, ERPs were recorded in a continuous word recognition paradigm in anorexia female patients (n = 16) and in matched healthy controls (n = 16). Half of words were included with food contents and another half were without food contents. Parts of food- and non-food words were repeatedly presented. Typically ERPs to repeated items are characterized by more positive waveforms beginning approximately 250 ms post-stimulus. This “old/new effect” has been shown to be relevant for memory processing.
The patient group showed a normal early old/new effect and a reduced late old/new effect compared to the control group. The food/non-food effect significantly differed in the patient group from in the healthy controls in the late time window (450 - 650 ms). Source analyses for the food items showed statistically reduced cerebral activations in the limbic lobe (BA20) for the anorexia group in contrast to for the control group. The patients with anorexia nervosa showed an impaired conscious recollection of the word memory, which suggested an impairment of working memory capacity in these patients.
Posters
Cognitive and Clinical Profile of 20 Patients With Large Proportion of White Matter Lesions
Alves GS, Alves CE, Sudo F, Lanna ME, Valente LE, Mukamal R, Moreira D, Laks J, Engelhardt E,
Federal University of Rio de Janeiro, Brazil
White-matter vascular lesions (WML) are a common finding in individuals older than 65 and can be associated to executive control and behaviour impairments. We conducted an MRI (n=68), with severity of WML rated by the Fazekas neuroimaging scale. Those presenting the highest score (value=6) in Fazekas were selected and had clinical and functional characteristics reported. Twenty individuals were selected, age range 60-86 years (75,35 ±7,31), schooling 7,4±4,84, Hachinski score 8,45±3,86, Cornell scale 7,95±5,85, CAMCOG 63,40±19,47, NPI 19,95±15,20, MMSE 21±5,70, Pfeffer questionnaire 11,40±10,14. The majority of individuals (85%, n=17) showed executive dysfunction (trail B/A proportion>3, verbal fluency below scores for age and schooling). Apathy (5,9±4,65) and depression (3,05±3,67) were the most frequent behaviour disturbances and showed strong correlation with functional impairment (p<0,001). Patients with WML presented a typical pattern of subcortical ischaemic vascular disease. The co-existence of WML, executive dysfunction, apathy and depression underlines frontal lobe syndrome as the major characteristic of this disorder.
Effect of a Subanesthetic Dose of Ketamine on Cortical Activity in the Model of Schizophrenia: a sLORETA and 3-T Proton MRS Study
Brunovsky M, Horacek J, Tislerova B, Sos P, Novak T, Spaniel F, Krajca V, Tintera J, Dezortova M
Faculty Hospital Bulovka, ZRIR, Institute for Clinical and Experimental Medicine, Czech Republic
The aim of our study was to detect the changes in brain electric activity and glutamate/GABA level following ketamine administration to healthy volunteers by means of sLORETA and proton magnetic resonance spectroscopy. EEG data were obtained from 20 subjects in the placebo/ketamine randomized design. Ketamine (0.27mg/kg) was applied within first 10min followed by a maintenance infusion (0.27mg/kg/h) for 20min. The localization of the current density differences was computed by voxel-by-voxel paired t-tests of sLORETA images. 3T 1H-MRS was used to detect the changes of glutamate and GABA level in anterior cingulate and right superior temporal gyrus in 9 subjects.
Compared to placebo we found significant decrease of alpha sources over posterior cortical regions and a decrease of magnitude of beta-1 and beta-2 sources in the posterior cingulate and precuneus. Cortical beta-3 and gamma sources significantly increased in the cingulated, parahippocampal structures and over the right frontotemporal cortex. 1H-MRS revealed a significant increase of glutamate in anterior cingulate following ketamine administration. We observed the involvement of heteromodal association cortex and limbic structures in the neurophysiological effects elicited by ketamine accompanied with the increase of glutamate release in the anterior cingulate cortex.
Evidence for Sensory Gating in the Visual Modality From Visually Evoked Potentials: Preliminary Results
Gjini K, Sundaresan K, Boutros NN, Wayne State University, Detroit, Michigan, USA
Sensory gating refers to the suppression of the neuronal response to a repeating stimulus. One previous study showed no significant change in the amplitude of P100 visual evoked potential (VEP) to two consecutive flash stimuli, in both healthy and schizophrenic participants (Adler et al., 1985). In this study we assessed VEPs (N75, P100, N150) in nine healthy individuals. The visual stimulus (two identical stimuli) consisted of large white circles flashed centrally on a black background on a computer monitor. The participants were instructed to fixate a central cross on the same monitor where the stimuli were displayed. Recordings were made from O1 and O2 referenced to linked ears. The amplitudes and latencies of VEPs were measured and compared. Paired samples t-tests were used to assess statistical significance of the results.
Results of this study showed a significant decrease of the P100 amplitude at O2, and N150 amplitude at both occipital sites; furthermore a significant increase in the latency for N75 and P100 for the second stimulus of the pair compared to the first one. These results may indicate a gating effect in the visual modality which should be explored further in healthy and patient populations.
Neurological Soft Signs in First Episode Psychosis – an Optimized Voxel Based Morphometry Analysis
Heuser M, Thomann P, Santos VD, Schröder J, University of Heidelberg, Germany
Essig M, German Cancer Research Center, Heidelberg, Germany
Bachmann S, University of Halle-Wittenberg, Halle, Germany
Neurological soft signs (NSS) are common among patients with first episode of schizophrenia. However the morphological cerebral correlates of NSS are only partly understood. Included were 103 patients with a first episode of psychosis. NSS were assessed after remission of the acute symptoms and before discharge using the Heidelberg scale. They were correlated to density values by using optimized voxel-based morphometry (VBM).
The NSS-Total-Score was significantly associated with reduced gray matter densities in the pre- and postcentral gyrus, middle and inferior frontal gyrus, lingual gyrus, caudate nucleus, thalamus and cerebellum. Similar results were found for the subscales “motor coordination” and “complex movements”. Our study confirms the association between NSS and morphological changes in the motor and sensory areas. The variety of cerebral sites corresponds to the heterogeneity of NSS which comprise both, motor and sensory dysfunction. These results provide further support for the model of “cognitive dysmetria”.
New Research of Sleep in Schizophrenia
Ilankovic N, Ilankovic A, Lakovic T, Ilankovic V, Ilankovic LM, Pasterova 2, Belgrade, Yugoslavia
Emil Kraepelin introduced a disorder called “paranoid depression,” but “paranoid” became linked to schizophrenia, not to mood disorders. We made Polysomnographic (PSG) measurement of sleep by schizophrenic patients (acute, paranoid and chronic) to investigate models of sleep disturbances in different types of schizophrenia.
Neurophysiologic measurement of sleep using electroencephalography, electrooculography and electromyography was carried out in 30 patients with an acute schizophrenic state (F23.1 & F 23.2 in ICD-10) and in 30 patients with a chronic/residual schizophrenic state (F 20.5 in ICD-10). Recording of sleep patterns, statistical analysis and estimation of the discriminative models of sleep was made in these two groups of psychotic patients. The Electrophysiological Profile of Sleep (EPS) was derived from these measures and contained 130 variables of nocturnal sleep. Statistical analysis was by step-wise discriminative function analysis. The most discriminative variable in this battery was the Index of Endogenous Periodicity/Perturbation (IEP-P1, N. Ilankovic, 1983): IEP-P1=REM-1/NREM-1, where REM-1 and NREM-1 are the first periods of REM and NREM sleep, respectively. Two patterns were seen: (1) The Index of Endogenous Perturbation (IEP-P1) was LOW in the first group which we call the “REM DEFICIT” type of sleep disturbance (with reduction of “REM-1 phase”) in acute schizophrenic states; IEP-P1 < 0.3. (2) The IEP-P1 index was HIGH in the second group which we call the “DELTA DEFICIT” type of disturbed sleep (with reduction of “delta-sleep”) in paranoid and chronic (residual) schizophrenia states; IEP-P1 > 2.40, very similar to sleep disturbances by affective (psychotic mood) disorders.
The results of our investigations demonstrate that the Index of endogenous sleep perturbation (IEP-P1) is a highly reliable indicator of sleep disturbance in acute, chronic paranoid schizophrenia; the IEP-P1 could be very useful in differential diagnosis of clinical subtype of schizophrenia; the IEP-P1 is a possible neurophysiologic state marker by psychotic disorders.
The Moderating Effects of Nicotine on EEG Activity and Mood in Adolescent Major Depressive Disorder: A Pilot Study
Jaworska N, McIntosh J, Villeneuve C, Thompson A, Fisher D, Milin R, Knott V,
University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada
Villeneuve C, Fisher D, Knott V, Carleton University, Ottawa, ON, Canada
Electroencephalographic (EEG) work has documented abnormal patterns of cortical activation, indexed by increased alpha in left anterior and right parietal regions, in individuals with major depressive disorder (MDD). Smoking, which is highly co-morbid with MDD, modulates alpha-indexed hemispheric asymmetry in adult smokers. Consequently, we investigated if acute nicotine administration in depressed adolescent smokers would alter resting EEG and affect. Given that adolescence is a period in brain development uniquely sensitive to nicotine, depressed adolescents may be most susceptible to its neuromodulatory activity. This study was conducted in eight depressed adolescent female smokers, abstaining over-night from tobacco. Using a within-subject, randomized and double-blind design, subjective mood ratings and EEG recordings were acquired before and two hours after transdermal placebo or nicotine (21 mg) patch administration. Acute nicotine treatment attenuated hemispheric asymmetry in beta2, alpha1 and alpha2. Additionally, decreased theta was observed in the right parietal region, consistent with nicotine’s arousal effects. No nicotine-induced mood alterations were evident, although a trend for reduced negative affect existed. A significant reduction in smoking withdrawal/craving ratings after nicotine was also found. This pilot study is among the first to extend research on nicotine’s effect on mood and brain activity to an adolescent psychiatric population.
Role of Hippocampal Integrity in the Development and Maintenance of Posttraumatic Stress Disorder-Like Symptoms in Mice
Kaltwasser SF, Golub Y, Mauch CP, Holsboer F, Czisch M, Wotjak CT, Max Planck Institute of Psychiatry, Munich, Germany,
Siegmund A, Charité- Universitätsmedizin Berlin, Campus Charité Mitte, Berlin, Germany
In our mouse model of Post Traumatic Stress Disorder (PTSD) we studied the role of hippocampal integrity in the susceptibility, manifestation and prevention of PTSD-like symptoms with different nuclear magnetic resonance (NMR) tools .With Magnetic Resonance Spectroscopy (MRS) we studied the NAA level, as a marker of neural integrity, in the hippocampus of C57BL/6N mice before trauma and determined if it serves as a susceptibility marker for the subsequent development of PTSD-like symptoms. A coherence of low NAA levels in the left dorsal hippocampus before trauma and vulnerability to the development and maintenance PTSD-like symptoms could be shown for the first time. Using Manganese Enhanced Magnetic Resonance Imaging (MEMRI) we studied the alteration of hippocampal volume in response to environmental enrichment before and/or after shock exposure and the influence on PTSD-like symptoms. We observed that environmental enrichment leads to an increase of hippocampal volume and to an amelioration of PTSD-like symptoms.
These results are in line with several magnetic resonance imaging (MRI) and MRS studies that report smaller hippocampal volume and NAA-levels in PTSD patients. They also indicate that reduced hippocampal integrity is a vulnerability factor rather than the consequence of PTSD. Overall these results point out a crucial role of hippocampal integrity in the susceptibility, manifestation and prevention of PTSD-like symptoms.
Emotional Influences on Executive Attentional Control in Subclinical Anxiety and Depression
Kanske P, Kotz SA, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
Humans make coherent goal-directed decisions even in the presence of conflicting stimuli. This faculty has been investigated with Stroop, Simon, or flanker tasks and is referred to as executive control of attention. It has been suggested that negative emotional stimuli trigger attentional control. We tested this possibility with variants of the flanker and Simon tasks and found reduced behavioral conflict in emotional stimuli. This enhanced attentional control was also found in a modulation of the N200 EEG response, and in fMRI activation of the ventral anterior cingulate cortex (ACC) for conflict processing in emotional stimuli. The dorsal ACC was activated for conflict independent of emotion. Activity in the amygdala was present for emotional stimuli independent of conflict. Anxiety and depression are generally associated with deficient processing of emotional stimuli. It may therefore be, that participants high in depression and anxiety do not show the beneficial effect of emotional stimuli on attentional control. This is exactly what we found when assessing subclinical anxiety and depression scores in the participants. Not only was the RT effect reduced, there was also less increase in the N200 amplitude and ventral ACC activation in negative emotional trials in high anxiety and depression participants.
Anatomical Abnormalities of Heschl Gyrus in Schizophrenia Patients and Unaffected Relatives
Knöchel C, Oertel V, Schönmeyer R, Lindner M, Haenschel C, Maurer K, Goethe Univ., Frankfurt/Main, Germany
Rotarska-Jagiela A, University of Cologne, Germany
van de Ven V, University of Maastricht, Maastricht, The Netherlands
Haenschel C, Max-Planck-Institute for Brain Research, Frankfurt/Main, Germany
Linden DEJ, University of Wales, Bangor, United Kingdom
In this study, we did a gray matter volume analysis of the Heschl gyrus, and compared it to the psychopathological symptoms. We enlarged the results of several studies in examining not only 15 SZ patients and 15 healthy controls, but also 15 first-degree relatives. The gray matter volume of Heschl gyrus and the normal hemispheric asymmetry was lower for patients than controls and intermediate for relatives. The gray matter volume loss correlated with the severity of symptoms, measured with the PANSS (Kay et al., 1987) and the Revised Hallucination Scale (RHS; Morrison et al., 2002). The results show that the volume loss and the loss of normal hemispheric asymmetry may be a biological marker of schizophrenia.
Investigation of the Functional Relevance of Left and Right Inferior Frontal Gyrus for Pitch Processing and Imagination – a Combined fMRI and TMS Study
Lindner M, Unger H, Prvulovic D, Konrad M, Fabian F, University Clinic of Frankfurt, Germany
In this functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) study, we investigated the differential roles of the opercular parts of the right and left inferior frontal gyri (IFG) for processing and imagery of speech and pitch. While speech is normally lateralized to the left hemisphere, music perception and production is assumed to be located in the right hemisphere. The right superior temporal gyrus is known to be critically involved in processing and imagination of pitches and pitch differences. However, the role of IFG for pitch processing has not been evaluated so far.
An event-related design was employed in which subjects had to either passively listen to tones and spoken letters or to actively imagine them. In experimental conditions four tones/letters were presented acoustically. After a delay of eight seconds subjects had to perform a comparison task on two of these stimuli. This task required active imagery and manipulation of the previously presented stimuli. To avoid ongoing imaginations between experimental trials, a simple visual reaction task was presented during inter-trial-intervals. Three control conditions for auditory (letters and tones) and visual (flickering checkerboard) perception were presented as well. In a subsequent experiment, performance in the same speech and pitch processing tasks were tested before and after a session of slow (1 Hz) repetitive TMS over left or right IFG. We hypothesize that inhibition of right IFG would selectively impair performance during pitch processing while inhibition of left IFG would decrease performance in the speech task even if the fMRI exam would not be sensitive enough to reveal significant activation lateralisation.
Neuroradiological Pecularities of Neuropsychiatric Complications After Stroke
Lobjanidze N, Janelidze M, Shakarishvili R, Beridze M, Kvirkvelia N, State Medical University Clinic, Tbilisi, Georgia
Neuropsychiatric comlication may have a negative effect on the recovery and life quality of stroke survivors. Establishing neuropsychiatric symptoms after stroke might be helpfull to prevent it in early stages of disease. For assessment of prevalence, clinical and MRI correlates of poststroke neupsychiatric complication, type, side and site of 168 stroke patients was evaluated by conventional MRI and assessed by NHISS. In acute stage and 3 months later neuropsychiatric symptoms were evaluated with Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Catastrophic Reaction Scale, Pathological Crying and Laughing Scale. Statistical data were calculated by SPSS.
Depression and anxiety disorder (34.5% and 20.8%) are two of the most common poststroke neuropsychiatric disorders and they did not differ significantly between stroke side, type, size and location, but comorbidity of the depression/anxiety (10.7%) in acute stage and 3 month later correlated with anterior fronto-temporal and basal ganglia stroke in the right hemishere. Catastrophic reactions, pathological affect (7.14%) correlated with subcortical and basal ganglia-ponto-medullary area circuit lesion. Psychosis (1.19%) is a rare and transient complication and has been related with right frontal lobe and ventricular hemorrhage. The study revealed a significant share of hypertension in the development of depression and anxiety.
Neuronal Correlates of Autobiographical Memory in aMCI Patients: Findings From fMRI and Voxel Based Morphometry
Matura S, Muth K, Prvulovic D, Maurer K, Pilatus U, Magerkurth J, Haenschel C, Pantel J, University Clinic Frankfurt am Main, Germany
Haenschel C, Max Planck Institute for Brain Research, Frankfurt am Main, Germany
Walter H, University Clinic Bonn, Germany
Amnestic mild cognitive impairment (aMCI) is characterized by slight cognitive deficits especially regarding memory in the context of otherwise normal daily functioning. Deficits are particularly pronounced in episodic memory. Amnestic MCI patients show deficits both in encoding and recalling personal experiences. The aim of our study was to uncover aMCI specific changes in autobiographical memory in the behavioral domain as well as in the underlying neuronal structures and in neuronal activation patterns.
Thirteen aMCI patients and 13 matched controls between the age of 59 and 77 years were administered an autobiographical memory task (BAGI). Using fMRI we investigated differences between aMCI patients and healthy controls regarding the neuronal activation pattern during autobiographical memory retrieval. Brain atrophy in the patient group was investigated using voxel-based morphometry.
Performance in the autobiographical memory task did not differ significantly between aMCI patients and healthy controls. Also, the neuronal activation pattern during autobiographical memory retrieval was very similar for both groups. Voxel-based morphometry revealed grey matter atrophy in the patient group. In conclusion our data suggest that the neuronal network supporting autobiographical memories is still functioning in aMCI patients despite neurodegenerative processes in memory related brain structures
Interactions Between Visual Attention and Encoding into Spatial Working Memory in Schizophrenia: an fMRI Study
Mayer JS, Fusser F, Maurer K, Haenschel C, Johann Wolfgang Goethe-University, Frankfurt, Germany
Haenschel C, Max Planck Institute for Brain Research, Frankfurt, Germany
Impairments in working memory (WM) are regarded as a core cognitive deficit in schizophrenia. Behavioral findings suggest that reduced WM performance is caused by deficits of both encoding and maintenance processes. In healthy subjects we have previously demonstrated common processing limitations for visual WM encoding and attention in distributed visual, parietal, and premotor regions. In the present study we used functional magnetic resonance imaging to test the hypothesis that visual WM deficits in schizophrenic patients are due to impaired processing capabilities shared by visual WM and attention in these posterior regions. We combined visual search and delayed discrimination of spatial locations and independently modulated the demands on selective attention and WM encoding. Attention was manipulated by the difficulty of the search (difficult vs. easy search), and WM load was varied parametrically (1 or 3 locations). Patients performed worse than healthy controls in all conditions. They showed an increase in reaction time and a decrease in accuracy from WM load 1 to WM load 3 under easy and difficult search. The fMRI analysis focussed on the encoding phase. For patients, preliminary results revealed regions in the posterior parietal cortex (intraparietal sulcus, precuneus) that were reduced in their memory load response (WM load 3 vs. 1) under the condition with high vs. low attentional demand. Thus, deficits in visual WM encoding in schizophrenic patients appear to be a consequence of increased competition for resources shared by visual WM and attention in the posterior parietal cortex.
Temporal Lobe Abnormalities and Reduced Hemispheric Lateralization in Schizophrenia Patients and Unaffected Relatives
Oertel V, Knöchel C, Schönmeyer R, Lindner M, Haenschel C, Uhlhaas P, Maurer K, Goethe Univ., Frankfurt/Main, Germany
Rotarska-Jagiela A, University of Cologne, Germany
Haenschel C, Uhlhaas P, Max-Planck-Institute for Brain Research, Frankfurt, Germany
Linden DEJ, University of Wales, Bangor, United Kingdom
van de Ven V, University of Maastricht, Netherlands
In this study, we examined the activation pattern during the presentation of auditory stimuli and a structural analysis of auditory areas of 11 first-degree relatives, 15 schizophrenia patients and 15 control subjects. High-resolution 3D-anatomical 3T-MRI and functional MRI with auditory stimulation were performed. Cortical activation to auditory stimuli and the lateralization of language areas towards the left hemisphere of auditory areas was lower for patients than controls and intermediate for relatives compared to the control group. This decrease of lateralisation correlated with the severity of symptoms (measured with the PANSS; Kay et al., 1987). The gray matter volume analysis mirrored the results from functional imaging, with a pronounced loss of temporal lobe volume in patients, and less severe reductions in relatives.
High- and Low-Frequency Oscillations During Visuo-Spatial Working Memory in MEG-Data
Roux F, Wibral M, Sireteanu R, Singer W, Uhlhaas P, Max Planck Institute for Brain Research, Frankfurt, Germany
Roux F, MEG Center, Brain Imaging Center Frankfurt am Main, Germany
Roux F, Mohr H, Poznanski K, Triezmiel J, Sireteanu R, Uhlhaas P, Johann Wolfgang Goethe Universität, Frankfurt am Main, Germany
Empirical and theoretical evidence suggests that synchronous, oscillatory neural activity is involved in the neural dynamics required for working memory (WM). During encoding of information, a dynamic neural mechanism is required to bind stimulus features into coherent representations. A further role of neural synchrony is the manipulation and maintenance of WM items when information is no longer available in the environment.
While a wealth of evidence implicated oscillations to each of these processes, it is unclear how memory load and task difficulty affect the strength of high-frequency oscillations. We investigated oscillatory activity in theta, alpha, beta, and gamma- (30-130 Hz) bands during encoding, delay and retrieval phase of a delayed sample to match task in 13 healthy participants using MEG-signals. These were analyzed in the time and frequency domain by a multitaper time frequency decomposition for frequencies above 40 Hz and morlet wavelets for frequencies below 40 Hz. The task consisted of spatially distributed patterns of colored dots simultaneously presented in a 4x4 grid. Task difficulty was manipulated by varying the number of targets that had to be encoded (3 or 6 Items) and the presence of distractors during the encoding phase. After a brief delay, participants were shown a test stimulus at a single position and asked to report whether location of the probe matched one of the positions in the initial pattern. Results showed a clear task-related increase of spectral power in the gamma band during encoding, delay and retrieval phase. Topographical analyses revealed a load dependent increase of gamma power over occipitoparietal areas, while during maintenance gamma power increased over central and frontal areas. The strongest increase in gamma-power was found for the distractor condition. We observed modulation of theta- and alpha-band activity during the delay phase over frontal and central areas.
Application of Hierarchical Artificial Neural Networks for Detection of Depressive Patterns in Neuropsychological Performance
Weber B, Gapp V, Menzer A, Weber G, Helbing N, Maurer K, Goethe University Frankfurt / Main, Germany
Wiebel B, Evangelisches Krankenhaus Luetgendortmund, Dortmund, Germany
Neuropsychological impairment in depression is varying between patients and over time in the natural course of illness. Furthermore it depends on various co-variables. These characteristics make the detection of depressive patterns in neuropsychological performance very difficult for conventional statistics. Artificial neural networks are used for pattern recognition, classification and regression tasks in different fields and might be superior to conventional linear statistics in the analysis of complex data.
Neuropsychological test results (NEUROBAT) of 1100 psychiatric patients with varying diagnoses and healthy controls were used to train different types of artificial neural networks: multilayer perceptrons, radial basis function networks, probabilistic neural networks and linear networks. Trained multilayer perceptrons and radial basis function networks allowed a significant recognition of depressive neuropsychological patterns. Patients were classified correctly in up to 71% of cases, whereas up to 64% of depressive disorders were recognized correctly by linear artificial neural networks.
Recognition of depressive neuropsychological patterns by nonlinear artificial neural networks seems to be possible. Superiority to linear classification models could not be shown clearly. In a current complementary evaluation more complex hierarchical neural networks are trained with the same data in order to improve classification results.
Using Transfer Entropy to Unveil Effective Connectivity for MEG Measurements: an Application to a Simon Task
Wibral M, MEG Unit, Brain Imaging Center, Goethe University, Frankfurt, Germany
Pipa G, Triesch J, Vicente R, Frankfurt Institute for Advanced Studies, JW Goethe University, Frankfurt, Germany
Pipa G, Vicente R, Max Planck Institute for Brain Research, Frankfurt, Germany
Functional connectivity describes the correlated activities of different brain areas. However, correlation does not imply causality and synchronization measures do not distinguish causal/non-causal interactions. Identification of causal interactions is fundamental to understanding the information processing. Detecting causal interactions in non-invasive Magnetoencephalographic (MEG) recordings is hampered by volume conduction. Here, we use transfer entropy (TE) to establish causal interactions. TE is a quantification of the information flow among interacting systems. In contrast to Granger causality, TE is a non-linear measure not influenced by volume conduction. We evaluate TE on MEG data recorded during a Simon task. Subjects were presented with a ”L” or ”R” letter in either the left or the right hemifield and had to press a left-side (right -side) key in response to the ”L” (“R”) letter. The sequential organization of this task allows to infer effective connectivity: Visual input has to be processed and the letter recognised before motor action can be planned. Hence, effective connectivity from visual to frontal and motor areas was expected. We expected changing connectivity patterns depending on task. TE revealed that different neuronal circuits were recruited for the four different experimental conditions, in accordance to the physiological expectation.
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