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ABSTRACT: The default-mode network (DMN) of the human brain has become a central topic of cognitive neuroscience research. Although alterations in its resting state activity and in its recruitment during tasks have been reported for several mental and neurodegenerative disorders, its role in emotion processing has received relatively little attention. We investigated brain responses to different categories of emotional faces with functional magnetic resonance imaging (fMRI) and found deactivation in ventromedial prefrontal cortex (VMPFC), posterior cingulate gyrus (PC) and cuneus. This deactivation was modulated by emotional category and was less prominent for happy than for sad faces. These deactivated areas along the midline conformed to areas of the DMN. We also observed emotion-dependent deactivation of the left middle frontal gyrus, which is not a classical component of the DMN. Conversely, several areas in a fronto-parietal network commonly linked with attention were differentially activated by emotion categories. Functional connectivity patterns, as obtained by correlation of activation levels, also varied between emotions. VMPFC, PC or cuneus served as hubs between the DMN-type areas and the fronto-parietal network. These data support recent suggestions that the DMN is not a unitary system but differentiates according to task and even type of stimulus. The emotion-specific differential pattern of DMN deactivation may be explored further in patients with mood disorder, where the quest for biological markers of emotional biases is still ongoing.
Neuroscience Letters 11/2011; 506(2):229-34. · 2.11 Impact Factor
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ABSTRACT: Real-time functional magnetic resonance imaging can be used to feed back signal changes from the brain to participants such that they can train to modulate activation levels in specific brain areas. Here we present the first study combining up-regulation of brain areas for positive emotions with psychometric measures to assess the effect of successful self-regulation on subsequent mood. We localized brain areas associated with positive emotions through presentation of standardized pictures with positive valence. Participants up-regulated activation levels in their target area during specific periods, alternating with rest. Participants attained reliable self-control of the target area by the last of three seven-minute runs. This training effect was supported by an extensive network outside the targeted brain region, including higher sensory areas, paralimbic and orbitofrontal cortex. Self-control of emotion areas was not accompanied by clear changes in self-reported emotions; trend-level improvements on depression scores were counteracted by increases on measures of fatigue, resulting in no overall mood improvement. It is possible that benefits of self-control of emotion networks may only appear in people who display abnormal emotional homeostasis. The use of only a single, short, training session, overlap between positive and negative emotion networks and aversive reactions to the scanning environment may have prevented the detection of subtle changes in mood.
Cognitive Affective & Behavioral Neuroscience 11/2010; 11(1):44-51. · 3.57 Impact Factor
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ABSTRACT: Classification of brain images obtained through functional magnetic resonance imaging (fMRI) poses a serious challenge to pattern recognition and machine learning due to the extremely large feature-to-instance ratio. This calls for revision and adaptation of the current state-of-the-art classification methods. We investigate the suitability of the random subspace (RS) ensemble method for fMRI classification. RS samples from the original feature set and builds one (base) classifier on each subset. The ensemble assigns a class label by either majority voting or averaging of output probabilities. Looking for guidelines for setting the two parameters of the method-ensemble size and feature sample size-we introduce three criteria calculated through these parameters: usability of the selected feature sets, coverage of the set of ¿important¿ features, and feature set diversity. Optimized together, these criteria work toward producing accurate and diverse individual classifiers. RS was tested on three fMRI datasets from single-subject experiments: the Haxby data (Haxby, 2001.) and two datasets collected in-house. We found that RS with support vector machines (SVM) as the base classifier outperformed single classifiers as well as some of the most widely used classifier ensembles such as bagging, AdaBoost, random forest, and rotation forest. The closest rivals were the single SVM and bagging of SVM classifiers. We use kappa-error diagrams to understand the success of RS.
IEEE Transactions on Medical Imaging 03/2010; · 3.64 Impact Factor
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ABSTRACT: We combined functional imaging and genetics to investigate the behavioral and neural effects of a dysbindin-1 (DTNBP1) genotype associated with the expression level of this important synaptic protein, which has been implicated in schizophrenia. On a working memory (WM) task for emotional faces, participants with the genotype related to increased expression showed higher WM capacity for happy faces compared with the genotype related to lower expression. Activity in several task-related brain areas with known DTNBP1 expression was increased, including hippocampal, temporal and frontal cortex. Although these increases occurred across emotions, they were mostly observed in areas whose activity correlated with performance for happy faces. This suggests effects of variability in DTNBP1 on emotion-specific WM capacity and region-specific task-related brain activation in humans. Synaptic effects of DTNBP1 implicate that altered dopaminergic and/or glutamatergic neurotransmission may be related to the increased WM capacity. The combination of imaging and genetics thus allows us to bridge the gap between the cellular/molecular and systems/behavioral level and extend the cognitive neuroscience approach to a comprehensive biology of cognition.
Molecular psychiatry 12/2009; 16(2):145-55. · 15.05 Impact Factor
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ABSTRACT: Real-time functional magnetic resonance imaging (fMRI) affords the opportunity to explore the feasibility of self-regulation of functional brain networks through neurofeedback. We localised emotion networks individually in thirteen participants using fMRI and trained them to upregulate target areas, including the insula and amygdala. Participants achieved a high degree of control of these networks after a brief training period. We observed activation increases during periods of upregulation of emotion networks in the precuneus and medial prefrontal cortex and, with increasing training success, in the ventral striatum. These findings demonstrate the feasibility of fMRI-based neurofeedback of emotion networks and suggest a possible development into a therapeutic tool.
NeuroImage 08/2009; 49(1):1066-72. · 5.89 Impact Factor
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D E J Linden
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ABSTRACT: Auditory verbal hallucinations are a common symptom of schizophrenia. In general, hallucinations can affect all sensory modalities and occur in many neuropsychiatric disorders. They also serve the psychology of perception as the classic example of sensory experience in the absence of adequate external stimuli. Functional imaging studies showed the auditory cortex, the limbic system and language areas, both motor and sensory, to be active during auditory hallucinations. The psychological and neurophysiological models of hallucination can be integrated if we consider that patients with schizophrenia might ascribe internal monologues or dialogues to external sources. The activity of language areas during hallucinations would conform to such a model while the activity in auditory cortex might explain why auditory hallucinations are often so vivid and real for the patients suffering from them. Moreover, the activation of the limbic system might correspond to the emotional aspects of the content of the voices and the accompanying arousal. While the neurophysiological models of hallucination are thus already rather refined, the attempt at suppressing auditory cortex activity with repetitive transcranial magnetic stimulation in order to alleviate treatment-resistant acoustic hallucinations, which is based on the functional imaging findings, still needs further study. Treatment schemes that are based on the psychological theories are more varied and have shown more consistent and long lasting effects but also suffer from the difficulty in measuring hallucinations quantitatively. Future research with functional and structural imaging should go beyond correlating brain activity and symptoms and also address the functional and structural connectivity patterns in the brain that enable hallucinations.
Fortschritte der Neurologie · Psychiatrie 06/2008; 76 Suppl 1:S33-9. · 0.74 Impact Factor
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D E J Linden
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ABSTRACT: A thorough investigation of the neural effects of psychotherapy is needed in order to provide a neurobiological foundation for widely used treatment protocols. This paper reviews functional neuroimaging studies on psychotherapy effects and their methodological background, including the development of symptom provocation techniques. Studies of cognitive behavioural therapy (CBT) effects in obsessive-compulsive disorder (OCD) were consistent in showing decreased metabolism in the right caudate nucleus. Cognitive behavioural therapy in phobia resulted in decreased activity in limbic and paralimbic areas. Interestingly, similar effects were observed after successful intervention with selective serotonin reuptake inhibitors (SSRI) in both diseases, indicating commonalities in the biological mechanisms of psycho- and pharmacotherapy. These findings are discussed in the context of current neurobiological models of anxiety disorders. Findings in depression, where both decreases and increases in prefrontal metabolism after treatment and considerable differences between pharmacological and psychological interventions were reported, seem still too heterogeneous to allow for an integrative account, but point to important differences between the mechanisms through which these interventions attain their clinical effects. Further studies with larger patient numbers, use of standardised imaging protocols across studies, and ideally integration with molecular imaging are needed to clarify the remaining contradictions. This effort is worthwhile because functional imaging can then be potentially used to monitor treatment effects and aid in the choice of the optimal therapy. Finally, recent advances in the functional imaging of hypnosis and the application of neurofeedback are evaluated for their potential use in the development of psychotherapy protocols that use the direct modulation of brain activity as a way of improving symptoms.
Molecular Psychiatry 07/2006; 11(6):528-38. · 13.67 Impact Factor
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D Prvulovic,
D Hubl,
A T Sack,
L Melillo,
K Maurer,
L Frölich,
H Lanfermann,
F E Zanella,
R Goebel, D E J Linden,
T Dierks
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ABSTRACT: Alzheimer's disease (AD) is known to cause a variety of disturbances of higher visual functions that are closely related to the neuropathological changes. Visual association areas are more affected than primary visual cortex. Additionally, there is evidence from neuropsychological and imaging studies during rest or passive visual stimulation that the occipitotemporal pathway is less affected than the parietal pathway. Our goal was to investigate functional activation patterns during active visuospatial processing in AD patients and the impact of local cerebral atrophy on the strength of functional activation. Fourteen AD patients and fourteen age-matched controls were measured with functional magnetic resonance imaging (fMRI) while they performed an angle discrimination task. Both groups revealed overlapping networks engaged in angle discrimination including the superior parietal lobule (SPL), frontal and occipitotemporal (OTC) cortical regions, primary visual cortex, basal ganglia, and thalamus. The most pronounced differences between the two groups were found in the SPL (more activity in controls) and OTC (more activity in patients). The differences in functional activation between the AD patients and controls were partly explained by the differences in individual SPL atrophy. These results indicate that parietal dysfunction in mild to moderate AD is compensated by recruitment of the ventral visual pathway. We furthermore suggest that local cerebral atrophy should be considered as a covariate in functional imaging studies of neurodegenerative disorders.
NeuroImage 12/2002; 17(3):1403-14. · 5.89 Impact Factor
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ABSTRACT: We combined repetitive transcranial magnetic stimulation (rTMS) and functional magnetic resonance imaging (fMRI) to investigate the functional relevance of parietal cortex activation during the performance of visuospatial tasks. fMRI provides information about local transient changes in neuronal activation during behavioural or cognitive tasks. Information on the functional relevance of this activation was obtained by using rTMS to induce temporary regional deactivations. We thereby turned the physiological parameter of brain activity into an independent variable controlled and manipulated by the experimenter and investigated its effect on the performance of the cognitive tasks within a controlled experimental design. We investigated cognitive tasks that were performed on the same visual material but differed in the demand on visuospatial functions. For the visuospatial tasks we found a selective enhancement of fMRI signal in the superior parietal lobule (SPL) and a selective impairment of performance after rTMS to this region in comparison to a control group. We could thus show that the parietal cortex is functionally important for the execution of spatial judgements on visually presented material and that TMS as an experimental tool has the potential to interfere with higher cognitive functions such as visuospatial information processing.
Cognitive Brain Research 03/2002; 13(1):85-93. · 3.77 Impact Factor
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Methods and Findings in Experimental and Clinical Pharmacology 02/2002; 24 Suppl D:23. · 0.93 Impact Factor
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European Journal of Neuroscience 12/2001; 12(9):3452 - 3452. · 3.63 Impact Factor
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D. Prvulovic,
D. Hubl,
A.T. Sack,
L. Melillo,
K. Maurer,
L. Frölich,
H. Lanfermann,
F.E. Zanella,
R. Goebel, D.E.J. Linden,
T. Dierks
[show abstract]
[hide abstract]
ABSTRACT: Alzheimer's disease (AD) is known to cause a variety of disturbances of higher visual functions that are closely related to the neuropathological changes. Visual association areas are more affected than primary visual cortex. Additionally, there is evidence from neuropsychological and imaging studies during rest or passive visual stimulation that the occipitotemporal pathway is less affected than the parietal pathway. Our goal was to investigate functional activation patterns during active visuospatial processing in AD patients and the impact of local cerebral atrophy on the strength of functional activation. Fourteen AD patients and fourteen age-matched controls were measured with functional magnetic resonance imaging (fMRI) while they performed an angle discrimination task. Both groups revealed overlapping networks engaged in angle discrimination including the superior parietal lobule (SPL), frontal and occipitotemporal (OTC) cortical regions, primary visual cortex, basal ganglia, and thalamus. The most pronounced differences between the two groups were found in the SPL (more activity in controls) and OTC (more activity in patients). The differences in functional activation between the AD patients and controls were partly explained by the differences in individual SPL atrophy. These results indicate that parietal dysfunction in mild to moderate AD is compensated by recruitment of the ventral visual pathway. We furthermore suggest that local cerebral atrophy should be considered as a covariate in functional imaging studies of neurodegenerative disorders.
NeuroImage.
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ABSTRACT: The functional relevance of brain activity during visuospatial tasks was investigated by combining functional magnetic resonance imaging with unilateral repetitive transcranial magnetic stimulation (rTMS). The cognitive tasks involved visuospatial operations on visually presented and mentally imagined material ("mental clock task"). While visuospatial operations were associated with activation of the intraparietal sulcus region bilaterally, only the group which received rTMS to the right parietal lobe showed an impairment of performance during and immediately after rTMS. This functional parietal asymmetry might indicate a capacity of the right parietal lobe to compensate for a temporary suppression of the left. This is compatible with current theories of spatial hemineglect and constitutes a constraint for models of distributed information processing in the parietal lobes.
Neuron, v.35, 195-204 (2002).
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ABSTRACT: Hallucinations are sensory experiences in the absence of external stimulation. They are a hallmark of various psychiatric and neurological diseases but also occur as a response to reduction of peripheral sensory input. The nature and content of hallucinations is often heavily influenced by the patients' post experiences. Hallucinations can reach a high degree of complexity and have an enormous impact on patients' lives. The study of the underlying cortical mechanisms is thus a promising tool for the investigation of the neuronal substrate of complex mental phenomena. We report a functional magnetic resonance study of auditory verbal hallucinations in patients with chronic schizophrenia. The discovery of primary auditory cortex activation during auditory hallucinations confirmed the theory that hallucinations in a particular modality are subserved by a cortical system that recruits at least central parts of the network involved in normal sensory processing in that modality.
Nervenheilkunde, v.21, 331-335 (2002).
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ABSTRACT: Transcranial magnetic stimulation (TMS) is a widely used tool for the non-invasive study of basic neurophysiological processes and the relationship between brain and behavior. We review the physical and physiological background of TMS and discuss the large body of perceptual and cognitive studies, mainly in the visual domain, that have been performed with TMS in the past 15 years. We compare TMS with other neurophysiological and neuropsychological research tools and propose that TMS, compared with the classical neuropsychological lesion studies, can make its own unique contribution. As the main focus of this review, we describe the different approaches of combining TMS with functional neuroimaging techniques. We also discuss important shortcomings of TMS, especially the limited knowledge concerning its physiological effects, which often make the interpretation of TMS results ambiguous. We conclude with a critical analysis of the resulting conceptual and methodological limitations that the investigation of functional brain-behavior relationships still has to face. We argue that while some of the methodological limitations of TMS applied alone can be overcome by combination with functional neuroimaging, others will persist until its physical and physiological effects can be controlled. (C) 2003 Elsevier B.V. All rights reserved.
Brain Research Reviews, v.43, 41-56 (2003).
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ABSTRACT: Working memory (WM) capacity limitations and their neurophysiological correlates are of special relevance for the understanding of higher cognitive functions. Evidence from behavioral studies suggests that restricted attentional resources contribute to these capacity limitations. In an event-related functional magnetic resonance imaging (fMRI) study, we probed the capacity of the human visual WM system for up to four complex nonnatural objects using a delayed discrimination task. A number of prefrontal and parietal areas bilaterally showed increased blood oxygen level-dependent activity, relative to baseline, throughout the task when more than one object had to be held in memory. Monotonic increases in response to memory load were observed bilaterally in the dorsolateral prefrontal cortex (DLPFC) and the presupplementary motor area (pre-SMA). Conversely, activity in the frontal eye fields (FEFs) and in areas along the intraparietal sulcus (IPS) peaked when subjects had to maintain only two or three objects and decreased in the highest load condition. This dissociation of memory load effects on cortical activity suggests that the cognitive operations subserved by the IPS and FEF, which are most likely related to attention, fail to support visual WM when the capacity limit is approached. The correlation of brain activity with performance implies that only the operations performed by the DLPFC and pre-SMA, which support an integrated representation of visual information, helped subjects to maintain a reasonable level of performance in the highest load condition. These results indicate that at least two distinct cortical subsystems are recruited for visual WM, and that their interplay changes when the capacity limit is reached.
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ABSTRACT: Real-time functional magnetic resonance imaging (fMRI) affords the opportunity to explore the feasibility of self-regulation of functional brain networks through neurofeedback. We localised emotion networks individually in thirteen participants using fMRI and trained them to upregulate target areas, including the insula and amygdala. Participants achieved a high degree of control of these networks after a brief training period. We observed activation increases during periods of upregulation of emotion networks in the precuneus and medial prefrontal cortex and, with increasing training success, in the ventral striatum. These findings demonstrate the feasibility of fMRI-based neurofeedback of emotion networks and suggest a possible development into a therapeutic tool.
NeuroImage.
