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Biomedical subjects

Nikolaus Weiskopf

Publications and source records attributed to Nikolaus Weiskopf.

16 recordsLinked to original sources

Regulation of emotional responses elicited by threat-related stimuli.

The capacity to voluntarily regulate emotions is critical for mental health, especially when coping with aversive events. Several neuroimaging studies of emotion regulation found the amygdala to be a target for downregulation and prefrontal regions to be associated with downregulation. To characterize the role of prefrontal regions in bidirectional emotion regulation and to investigate regulatory influences on amygdala activity and peripheral physiological measures, a functional magnetic resonance imaging (fMRI) study with simultaneous recording of self-report, startle eyeblink, and skin conductance responses was carried out. Subjects viewed threat-related pictures and were asked to up- and downregulate their emotional responses using reappraisal strategies. While startle eyeblink responses (in successful regulators) and skin conductance responses were amplified during upregulation, but showed no consistent effect during downregulation, amygdala activity was increased and decreased according to the regulation instructions. Trial-by-trial ratings of regulation success correlated positively with activity in amygdala during upregulation and orbitofrontal cortex during downregulation. Downregulation was characterized by left-hemispheric activation peaks in anterior cingulate cortex, dorsolateral prefrontal cortex, and orbitofrontal cortex and upregulation was characterized by a pattern of prefrontal activation not restricted to the left hemisphere. Further analyses showed significant overlap of prefrontal activation across both regulation conditions, possibly reflecting cognitive processes underlying both up- and downregulation, but also showed distinct activations in each condition. The present study demonstrates that amygdala responses to threat-related stimuli can be controlled through the use of cognitive strategies depending on recruitment of prefrontal areas, thereby changing the subject's affective state.

Adolescent↗

Dynamic causal modeling: a generative model of slice timing in fMRI.

Dynamic causal modeling (DCM) of functional magnetic resonance imaging (fMRI) data allows one to make inferences about the architecture of distributed networks in the brain, in terms of effective connectivity. fMRI data are usually acquired using echo planar imaging (EPI). EPI sequences typically acquire slices at different times over a few seconds. DCM, in its original inception, was not informed about these slice timings and assumed that all slices were acquired simultaneously. It has been shown that DCM can cope with slice timing differences of up to 1 s. However, many fMRI studies employ a repetition time (TR) of 3 to 5 s, which precludes a straightforward DCM of these data. We show that this limitation can be overcome easily by including slice timing in the DCM. Using synthetic data we show that the extended DCM furnishes veridical posterior means, even if there are large slice-timing differences. Model comparisons show that, in general, the extended DCM out-performs the original model. We contrast the modeling of slice timing, in the context of DCM, with the less effective approach of 'slice-timing correction', prior to modeling. We apply our procedure to real data and show that slice timings are important parameters. We conclude that, generally, one should use DCM with slice timing.

Humans↗

Anterolateral prefrontal cortex mediates the analgesic effect of expected and perceived control over pain.

Perceived control attenuates pain and pain-directed anxiety, possibly because it changes the emotional appraisal of pain. We examined whether brain areas associated with voluntary reappraisal of emotional experiences also mediate the analgesic effect of perceived control over pain. Using functional magnetic resonance imaging, we compared self-controlled noxious stimuli with physically identical stimuli that were externally controlled. Self-controlled stimulation was accompanied by less pain and anxiety and higher activation in dorsal anterior cingulate (dACC), right dorsolateral, and bilateral anterolateral prefrontal (alPFC) cortices. Activation in dACC and right alPFC was negatively correlated with pain intensity ratings. For externally controlled pain, activation in right alPFC was inversely correlated with the participants' general belief to have control over their lives. Our results are consistent with a reappraisal view of control and suggest that the analgesic effect of perceived control relies on activation of right alPFC. Failure to activate right alPFC may explain the maladaptive effects of strong general control beliefs during uncontrollable pain.

Adult↗

Context-dependent human extinction memory is mediated by a ventromedial prefrontal and hippocampal network.

In fear extinction, an animal learns that a conditioned stimulus (CS) no longer predicts a noxious stimulus [unconditioned stimulus (UCS)] to which it had previously been associated, leading to inhibition of the conditioned response (CR). Extinction creates a new CS-noUCS memory trace, competing with the initial fear (CS-UCS) memory. Recall of extinction memory and, hence, CR inhibition at later CS encounters is facilitated by contextual stimuli present during extinction training. In line with theoretical predictions derived from animal studies, we show that, after extinction, a CS-evoked engagement of human ventromedial prefrontal cortex (VMPFC) and hippocampus is context dependent, being expressed in an extinction, but not a conditioning, context. Likewise, a positive correlation between VMPFC and hippocampal activity is extinction context dependent. Thus, a VMPFC-hippocampal network provides for context-dependent recall of human extinction memory, consistent with a view that hippocampus confers context dependence on VMPFC.

Adolescent↗

Optimal EPI parameters for reduction of susceptibility-induced BOLD sensitivity losses: a whole-brain analysis at 3 T and 1.5 T.

Most functional magnetic resonance imaging (fMRI) studies record the blood oxygen level-dependent (BOLD) signal using fast gradient-echo echo-planar imaging (GE EPI). However, GE EPI can suffer from substantial signal dropout caused by inhomogeneities in the static magnetic field. These field inhomogeneities occur near air/tissue interfaces, because they are generated by variations in magnetic susceptibilities. Thus, fMRI studies are often limited by a reduced BOLD sensitivity (BS) in inferior brain regions. Recently, a method has been developed which allows for optimizing the BS in dropout regions by specifically adjusting the slice tilt, the direction of the phase-encoding (PE), and the z-shim moment. However, optimal imaging parameters were only reported for the orbitofrontal cortex (OFC) and inferior temporal lobes. The present study determines the optimal slice tilt, PE direction, and z-shim moment at 3 T and 1.5 T, otherwise using standard fMRI acquisition parameters. Results are reported for all brain regions, yielding a whole-brain atlas of optimal parameters. At both field strengths, optimal parameters increase the BS by more than 60% in many voxels in the OFC and by at least 30% in the other dropout regions. BS gains are shown to be more widespread at 3 T, suggesting an increased benefit from the dropout compensation at higher fields. Even the mean BS of a large brain region, e.g., encompassing the medial OFC, can be increased by more than 15%. The maps of optimal parameters allow for assessing the feasibility and improving fMRI of brain regions affected by susceptibility-induced BS losses.

Adult↗

Self-regulation of local brain activity using real-time functional magnetic resonance imaging (fMRI).

Functional magnetic resonance imaging (fMRI) measures the blood oxygen level-dependent (BOLD) signal related to neuronal activity. So far, this technique has been limited by time-consuming data analysis impeding on-line analysis. In particular, no brain-computer interface (BCI) was available which provided on-line feedback to learn physiological self-regulation of the BOLD signal. Recently, studies have shown that fMRI feedback is feasible and facilitates voluntary control of brain activity. Here we review these studies to make the fMRI feedback methodology accessible to a broader scientific community such as researchers concerned with functional brain imaging and the neurobiology of learning. Methodological and conceptual limitations were substantially reduced by artefact control, sensitivity improvements, real-time algorithms, and adapted experimental designs. Physiological self-regulation of the local BOLD response is a new paradigm for cognitive neuroscience to study brain plasticity and the functional relevance of regulated brain areas by modification of behaviour. Voluntary control of abnormal activity in circumscribed brain areas may even be applied as psychophysiological treatment.

Algorithms↗

Neuronal mechanisms underlying control of a brain-computer interface.

Brain-computer interfaces (BCIs) enable humans or animals to communicate or control external devices without muscle activity using electric brain signals. The BCI used here is based on self-regulation of slow cortical potentials (SCPs), a skill that most people and paralyzed patients can acquire with training periods of several hours up to months. The neurophysiological mechanisms and anatomical sources of SCPs and other event-related brain potentials have been described but the neural mechanisms underlying the self-regulation skill for the use of a BCI are unknown. To uncover the relevant areas of brain activation during regulation of SCPs, the BCI was combined with functional magnetic resonance imaging. The electroencephalogram was recorded inside the magnetic resonance imaging scanner in 12 healthy participants who learned to regulate their SCP with feedback and reinforcement. The results demonstrate activation of specific brain areas during execution of the brain regulation skill allowing a person to activate an external device; a successful positive SCP shift compared with a negative shift was closely related to an increase of the blood oxygen level-dependent response in the basal ganglia. Successful negativity was related to an increased blood oxygen level-dependent response in the thalamus compared with successful positivity. These results may indicate learned regulation of a cortico-striatal-thalamic loop modulating local excitation thresholds of cortical assemblies. The data support the assumption that human subjects learn the regulation of cortical excitation thresholds of large neuronal assemblies as a prerequisite for direct brain communication using an SCP-driven BCI. This skill depends critically on an intact and flexible interaction between the cortico-basal ganglia-thalamic circuits.

Adult↗

Benign partial epilepsy in childhood: selective cognitive deficits are related to the location of focal spikes determined by combined EEG/MEG.

PURPOSE: Benign partial epilepsy (BPE) in childhood is characterized by the occurrence of interictal stereotyped focal spikes with variable localization in the EEG. Children with BPE often exhibit neuropsychological deficits. It is unclear whether a correlation exists between these deficits and the localization of spikes, several EEG studies giving inconsistent results. Magnetoencephalography (MEG) improves the accuracy of spike localization. Therefore by using combined MEG/EEG, we investigated the topographic relation between focal spikes and neuropsychological findings in children with BPE. METHODS: Twenty-seven children diagnosed consecutively with BPE were enrolled in the study. All were examined by combined MEG/EEG and magnetic resonance imaging (MRI). Location of spikes was determined by dipole source estimation. A standardized neuropsychological assessment was conducted, including Kaufman ABC battery, language tests, and motor performance series. All children with sufficient MEG data were included in the correlation analysis (N = 20). RESULTS: Focal spikes were located in the perisylvian region in 13 children, in the occipital region in seven, and in the frontal region in one. Five children had bilateral or multiple foci. Children with left perisylvian spikes did not differ from the others in global IQ, but performed significantly lower in language tests (p = 0.01). Children with occipital spikes performed significantly lower in simultaneous information processing (p = 0.01), especially in visual transformation tasks. CONCLUSIONS: Combined MEG/EEG investigation is a useful tool to examine interictal focal spikes. Our results show a correlation between the location of spikes and selective cognitive deficits in children with BPE. These findings indicate that focal interictal spikes may interfere with complex cognitive functions.

Brain Mapping↗

Single-shot compensation of image distortions and BOLD contrast optimization using multi-echo EPI for real-time fMRI.

Functional magnetic resonance imaging (fMRI) is most commonly based on echo-planar imaging (EPI). With higher field strengths, gradient performance, and computational power, real-time fMRI has become feasible; that is, brain activation can be monitored during the ongoing scan. However, EPI suffers from geometric distortions due to inhomogeneities of the magnetic field, especially close to air-tissue interfaces. Thus, functional activations might be mislocalized and assigned to the wrong anatomical structures. Several techniques have been reported which reduce geometric distortions, for example, mapping of the static magnetic field B(0) or the point spread function for all voxels. Yet these techniques require additional reference scans and in some cases extensive computational time. Moreover, only static field inhomogeneities can be corrected, because the correction is based on a static reference scan. We present an approach which allows for simultaneous acquisition and distortion correction of a functional image without a reference scan. The technique is based on a modified multi-echo EPI data acquisition scheme using a phase-encoding (PE) gradient with alternating polarity. The images exhibit opposite distortions due to the inverted PE gradient. After adjusting the contrast of the images acquired at different echo times, this information is used for the distortion correction. We present the theory, implementation, and applications of this single-shot distortion correction. Significant reduction in geometric distortion is shown both for phantom images and human fMRI data. Moreover, sensitivity to the blood oxygen level-dependent (BOLD) effect is increased by weighted summation of the undistorted images.

Adult↗

Infrared oculography-validation of a new method to monitor startle eyeblink amplitudes during fMRI.

Amplitude modulation of the eyeblink component of the startle response is a commonly used index for the emotional state of an organism. The use of electromyography (EMG) to determine startle eyeblink amplitudes during functional magnetic resonance imaging (fMRI) is limited as interactions between strong switching magnetic fields, radio pulses and electrodes introduce large artefacts in EMG recordings. We demonstrate a robust linear correlation between time courses and amplitudes of startle eyeblinks recorded by EMG and infrared oculography (IOG), an fMRI compatible technique based on infrared light reflection from the subject's eye. Moreover, our data indicate that IOG, like EMG, recordings of startle eyeblink amplitudes are predicted by verbal ratings of the emotional valence of pictorial foreground stimuli. Thus, IOG provides a valid method to record startle eyeblinks and might be used to monitor affective state during fMRI.

Adult↗

Motor affordance and its role for visual working memory: evidence from fMRI studies.

We examined the role of motor affordances of objects for working memory retention processes. Three experiments are reported in which participants passively viewed pictures of real world objects or had to retain the objects in working memory for a comparison with an S2 stimulus. Brain activation was recorded by means of functional magnetic resonance imaging (fMRI). Retaining information about objects for which hand actions could easily be retrieved (manipulable objects) in working memory activated the hand region of the ventral premotor cortex (PMC) contralateral to the dominant hand. Conversely, nonmanipulable objects activated the left inferior frontal gyrus. This suggests that working memory for objects with motor affordance is based on motor programs associated with their use. An additional study revealed that motor program activation can be modulated by task demands: Holding manipulable objects in working memory for an upcoming motor comparison task was associated with left ventral PMC activation. However, retaining the same objects for a subsequent size comparison task led to activation in posterior brain regions. This suggests that the activation of hand motor programs are under top down control. By this they can flexibly be adapted to various task demands. It is argued that hand motor programs may serve a similar working memory function as speech motor programs for verbalizable working memory contents, and that the premotor system mediates the temporal integration of motor representations with other task-relevant representations in support of goal oriented behavior.

Adult↗

Principles of a brain-computer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI).

A brain-computer interface (BCI) based on functional magnetic resonance imaging (fMRI) records noninvasively activity of the entire brain with a high spatial resolution. We present a fMRI-based BCI which performs data processing and feedback of the hemodynamic brain activity within 1.3 s. Using this technique, differential feedback and self-regulation is feasible as exemplified by the supplementary motor area (SMA) and parahippocampal place area (PPA). Technical and experimental aspects are discussed with respect to neurofeedback. The methodology now allows for studying behavioral effects and strategies of local self-regulation in healthy and diseased subjects.

Adult↗

An EEG-driven brain-computer interface combined with functional magnetic resonance imaging (fMRI).

Self-regulation of slow cortical potentials (SCPs) has been successfully used to prevent epileptic seizures as well as to communicate with completely paralyzed patients. The thought translation device (TTD) is a brain-computer interface (BCI) that was developed for training and application of SCP self-regulation. To investigate the neurophysiological mechanisms of SCP regulation the TTD was combined with functional magnetic resonance imaging (fMRI). The technical aspects and pitfalls of combined fMRI data acquisition and EEG neurofeedback are discussed. First data of SCP feedback during fMRI are presented.

Biofeedback, Psychology↗

Mismatch negativity responses in schizophrenia: a combined fMRI and whole-head MEG study.

OBJECTIVE: Mismatch negativity is an event-related brain response sensitive to deviations within a sequence of repetitive auditory stimuli. It is thought to reflect short-term sensory memory and is independent of higher-level cognitive processes. Mismatch negativity response is diminished in patients with schizophrenia. Little is known about the mechanisms of this decreased response, the contribution of the different hemispheres, and its locus of generation. METHOD: Patients with schizophrenia (N=12) and matched comparison subjects (N=12) were studied. A novel design to measure mismatch negativity responses to deviant auditory stimuli was generated by using the switching noises from the functional magnetic resonance imaging (fMRI) scanner, thus avoiding any interfering background sound. Stimuli included deviants of amplitude (9 dB lower) and duration (76 msec shorter) presented in a random sequence. The scanner noise was recorded and applied to the same subjects in a whole-head magnetoencephalography (MEG) device. Neuromagnetic and hemodynamic responses to the identical stimuli were compared between the patients and comparison subjects. RESULTS: As expected, neuromagnetic mismatch fields were smaller in the patient group. More specifically, a lateralization to the right for duration deviance was only found in comparison subjects. For the relative amplitude of the blood-oxygen-level-dependent signal (measured with fMRI), differences emerged in the secondary (planum temporale), but not primary (Heschl's gyrus), auditory cortex. Duration deviants achieved a right hemispheric advantage only in the comparison group. A significantly stronger lateralization to the left was found for the deviant amplitude stimuli in the patients. CONCLUSIONS: The data support the view of altered hemispheric interactions in the formation of the short-term memory traces necessary for the integration of auditory stimuli. This process is predominantly mediated by the planum temporale (secondary auditory cortex). Altered interaction of regions within the superior temporal plane and across hemispheres could be in part responsible for language-mediated cognitive (e.g., verbal memory) and psychopathological (hallucinations, formal thought disorder) symptoms in schizophrenia.

Adult↗

Physiological self-regulation of regional brain activity using real-time functional magnetic resonance imaging (fMRI): methodology and exemplary data.

A brain-computer interface (BCI) based on real-time functional magnetic resonance imaging (fMRI) is presented which allows human subjects to observe and control changes of their own blood oxygen level-dependent (BOLD) response. This BCI performs data preprocessing (including linear trend removal, 3D motion correction) and statistical analysis on-line. Local BOLD signals are continuously fed back to the subject in the magnetic resonance scanner with a delay of less than 2 s from image acquisition. The mean signal of a region of interest is plotted as a time-series superimposed on color-coded stripes which indicate the task, i.e., to increase or decrease the BOLD signal. We exemplify the presented BCI with one volunteer intending to control the signal of the rostral-ventral and dorsal part of the anterior cingulate cortex (ACC). The subject achieved significant changes of local BOLD responses as revealed by region of interest analysis and statistical parametric maps. The percent signal change increased across fMRI-feedback sessions suggesting a learning effect with training. This methodology of fMRI-feedback can assess voluntary control of circumscribed brain areas. As a further extension, behavioral effects of local self-regulation become accessible as a new field of research.

Adult↗

Mismatch responses to randomized gradient switching noise as reflected by fMRI and whole-head magnetoencephalography.

The central auditory system of the human brain uses a variety of mechanisms to analyze auditory scenes, among others, preattentive detection of sudden changes in the sound environment. Electroencephalography (EEG) and magnetoencephalography (MEG) provide a measure to monitor neuronal cortical currents. The mismatch negativity (MMN) or field (MMNm) reflect preattentive activation in response to deviants within a sequence of homogenous auditory stimuli. Functional magnetic resonance imaging (fMRI) allows for a higher spatial resolution as compared to the extracranial electrophysiological techniques. The image encoding gradients of echo planar imaging (EPI) sequences, however, elicit an interfering background noise. To circumvent this shortcoming, the present study applied multi-echo EPI mimicking an auditory oddball design. The gradient trains (SOA = 800 msec, 94.5 dB SPL, stimulus duration = 152 msec) comprised amplitude (-9 dB) and duration (76 msec) deviants in a randomized sequence. Moreover, the scanner noise was recorded and applied in a whole-head MEG device to validate the properties of this specific material. Robust fMRI activation patterns emerged in response to the deviant gradient switching. Changes in amplitude activated the entire auditory cortex, whereas the duration deviants elicited right-lateralized signal increase in secondary areas. The recorded scanner noise evoked reliably right-lateralized mismatch MEG responses. Source localization was in accordance with activation of secondary auditory cortex. The presented paradigm provides a robust and feasible tool to study the functional anatomy of early cognitive auditory processing in clinical populations such as schizophrenia.

Acoustic Stimulation↗