Werner Strik

Three-dimensional tomography of event-related potentials during response inhibition: evidence for phasic frontal lobe activation

OBJECTIVES Spatial analysis of the evoked brain electrical fields during a cued continuous performance test (CPT) revealed an extremely robust anteriorization of the positivity of a P300 microstate in the NoGo compared to the Go condition (NoGo-anteriorization in a previous study). To allow a neuroanatomical interpretation the NoGo-anteriorization was investigated with a new three-dimensional source tomography method (LORETA) was applied. METHODS The CPT contains subsets of stimuli requiring the execution (Go) or the inhibition (NoGo) of a cued motor response which can be considered as mutual control conditions for the event-related potential (ERP) study of inhibitory brain functions 21-channel ERPs were obtained from 10 healthy subjects during a cued CPT, and analyzed with LORETA. RESULTS Topographic analyses revealed significantly different scalp distributions between the Go and the NoGo conditions in both P100 and P300 microstates, indicating that already at an early stage different neural assemblies are activated. LORETA disclosed a significant hyperactivity located in the right frontal lobe during the NoGo condition in the P300 microstate. CONCLUSIONS The results indicate that right frontal sources are responsible for the NoGo-anteriorization of the scalp P300 which is consistent with animal and human lesion studies of inhibitory brain functions. Furthermore, it demonstrates that frontal activation is confined to a brief microstate and time-locked to phasic inhibitory motor control. This adds important functional and chronometric specificity to findings of frontal activation obtained with PET and Near-Infrared-Spectroscopy studies during the cued CPT, and suggests that these metabolic results are not due to general task demands.

Functional imbalance of visual pathways indicates alternative face processing strategies in autism

Objective: To investigate whether autistic subjects show a different pattern of neural activity than healthy individuals during processing of faces and complex patterns. Methods: Blood oxygen level–dependent (BOLD) signal changes accompanying visual processing of faces and complex patterns were analyzed in an autistic group (n = 7; 25.3 [6.9] years) and a control group (n = 7; 27.7 [7.8] years). Results: Compared with unaffected subjects, autistic subjects demonstrated lower BOLD signals in the fusiform gyrus, most prominently during face processing, and higher signals in the more object-related medial occipital gyrus. Further signal increases in autistic subjects vs controls were found in regions highly important for visual search: the superior parietal lobule and the medial frontal gyrus, where the frontal eye fields are located. Conclusions: The cortical activation pattern during face processing indicates deficits in the face-specific regions, with higher activations in regions involved in visual search. These findings reflect different strategies for visual processing, supporting models that propose a predisposition to local rather than global modes of information processing in autism.

The NoGo-anteriorization as a neurophysiological standard-index for cognitive response control.

Event related potentials (ERPs) during the Go- and the NoGo-condition of the Continuous Performance Test (CPT) were applied to investigate the neurophysiological basis of cognitive response control. These conditions of the test represent the execution and the inhibition of an anticipated motor response. In a previous study, the comprehensive spatial analysis of the ERPs allowed to define a parameter which robustly reflected the anteriorization of the positive P300 field area during the NoGo- compared to the Go-condition (NoGo-anteriorisation, NGA). The result was found consistently in all investigated subjects. The present study replicated the finding in 27 healthy subjects without any exception. Moreover, the latencies were longer and the amplitudes showed a trend to be higher in the NoGo- compared to the Go-ERP. This is interpreted as a sign of higher processing demands in the NoGo-condition. In conclusion, the ability of the NGA to express reliably the differences of brain activity leading to execution or suppression of a prepared motor response qualifies this parameter as a topographical standard-index for cognitive response control.

Altered response control and anterior cingulate function in attention-deficit/hyperactivity disorder boys

OBJECTIVE To investigate mechanisms and structures underlying prefrontal response control and inhibition in boys suffering from attention-deficit/hyperactivity disorder (ADHD). METHOD Sixteen boys with ADHD and 19 healthy controls were investigated electrophysiologically during performance of a visual Go-Nogo task (Continuous Performance Test, CPT). An electrophysiological source localization method was employed to further analyze the data. RESULTS The ADHD boys showed a significantly diminished central Nogo-P3, due to a lack of Nogo-related frontalization of the positive brain electrical field in this group. This two-dimensional effect was associated with a significantly reduced activation of the anterior cingulate cortex (ACC) in the ADHD boys in the Nogo condition of the CPT. Both groups did not significantly differ regarding the amplitude of the Nogo-N2. CONCLUSIONS The results indicate deficits in prefrontal response control in unmedicated ADHD boys that do not seem to be specifically inhibitory in nature. A supposed dysfunction of the ACC in ADHD was confirmed.

Adaptive segmentation of spontaneous EEG map series into spatially defined microstates

Space-oriented segmentation can decompose multi-channel EEG map series into time segments characterized by quasi-stationary field map configurations. This assesses the dynamics of the underlying processes as activities of different neural generator ensembles. Our method of space-oriented segmentation describes the scalp field at times of maximal field strength (Global Field Power) by the locations of the centroids of positive and negative map areas. A quantitative measure of the simultaneous distance of the centroid locations evaluates the similarity between consecutive maps. A segment is defined as a sequence of maps that do not differ from each other by more than a present value. Finally, the average centroid locations for each segment are entered into an agglomerative clustering procedure to obtain a set of distinct classes of field configurations. Four records of 16 s of 42-channel resting EEG (band-pass filtered 2-16 Hz) from six subjects were analyzed. Average segment duration was 157.9 ms. Most segments belonged to a small number of classes (from 2 to 6, mean 3.7 classes for 90% of analysis time). The most frequent class showed an anterior-posterior field orientation and covered from 45 to 74% (mean 55% across subjects) of total time, with an average duration of 265 ms. The procedure was also tested using temporally and spatially unstructured data (white noise and randomly shuffled EEG) to ascertain that the methods reflect the spatio-temporal structure of the EEG processes.

Motor symptoms and schizophrenia.

Classical schizophrenia literature reports motor symptoms as characteristic of the disorder. After the introduction of neuroleptic drugs, the existence of genuine motor disorders was challenged. Renewed interest arose as symptoms were found in never-medicated patients. Reports focused on abnormal involuntary movements, parkinsonism, neurological soft signs, catatonia, negative symptoms, or psychomotor slowing. Since these syndromes refer to different concepts, however, the definitions are not congruent and the symptoms overlap. The prevalence rates of motor symptoms in schizophrenia are surprisingly high, and recent studies indicate a possible pathobiology. In particular, the development and maturation of the human motor system appears to be closely linked to the emergence of motor symptoms observed in schizophrenia. Post-mortem and neuroimaging results demonstrated aberrant structure and function of premotor and motor cortices, basal ganglia, thalamus, and the connecting white matter tracts. Animal models have focused on aberrant neurotransmission and genetic contributions. Findings of localized abnormal oligodendrocyte function and myelination point to the special role of the white matter in schizophrenia, and recent studies specifically found an association between motor abnormalities and white matter structure in schizophrenia. This review of the literature supports the idea that motor symptoms are closely related to the neurodevelopmental disturbances of schizophrenia and a distinct syndromal dimension with its own pathophysiology.

A robust assessment of the NoGo-anteriorisation of P300 microstates in a cued Continuous Performance Test.

SummaryThe Continuous Performance Test (CPT) is successfully applied in clinical routine to evaluate attentional performance. The aim of the present study was to investigate the features of the ERPs related to the conditions of a cued CPT, in particular the Go-and the NoGo-condition demanding either the execution or the inhibition of a prepared motor response. For that purpose, 21-channel-ERPs of ten healthy subjects elicited by the Go, NoGo, primer and distractor cues were analyzed with reference-independent methods. The P300 microstates were identified by means of a data-driven segmentation of the ERPs based on the individual peaks of the Global Field Power (GFP). The topographical assessment of the P300 fields yielded an extraordinarily robust result consisting of a more anterior location of the positive centroid in the NoGo compared to the Go condition in every single subject. In conclusion, this result is an impressive validation of the applied reference-independent spatial analysis which reveals the rapid changes of the brain electrical field configurations related to the execution/inhibition paradigm within the cued CPT. Because of the stability of the NoGo anteriorisation we propose to use this parameter as a topographical standard index, analogous to the amplitude effect between oddball targets and nontargets which defines the classical P300.

Frontal brain activation during the Wisconsin Card Sorting Test assessed with two-channel near-infrared spectroscopy

Abstract Near-infrared spectroscopy (NIRS) is a new non-invasive optical technique suitable to assess the concentration changes of oxygenated (O2HB) and deoxygenated (HHB) hemoglobin in brain tissue. Previous NIRS studies showed distinct patterns of blood oxygenation changes during different cognitive tasks. In particular, bilateral frontal hypo-oxygenation was found during reading, right frontal hyper-oxygenation during the Continuous Performance Test, and left frontal hyper-oxygenation during the Verbal Fluency Test. The Wisconsin Card Sorting Test (WCST) is a neuropsychological test which is presumed to activate prevalently the frontal lobes. This was demonstrated by lesion studies and functional imaging (single photon emission computed tomography and positron emission tomography). In the present study, a two-channel NIRS system was applied to investigate frontal brain areas of ten healthy subjects during performance of the WCST. A significant bilateral increase of O2HB in frontal brain regions without hemispheric differences was found during the WCST compared with a baseline at rest. This result indicates an enhanced perfusion of the frontal lobes consistent with local activation. The findings add further evidence that the NIRS technique is sensitive enough to detect physiological blood oxygenation changes. Furthermore, a comparison with previous studies revealed an activation pattern distinct from those observed during other cognitive tasks. It is concluded that the results reflect local responses to specific task demands of the WCST.

Loss of functional hemispheric asymmetry in Alzheimer's dementia assessed with near-infrared spectroscopy.

In a total of 10 patients with dementia of the Alzheimer-type (DAT) and in 10 healthy controls near-infrared spectroscopy (NIRS), a new non-invasive optical method, was used to measure the changes of concentrations of oxy- (O2HB) and deoxyhemoglobin (HHB) in left and right hemispheric prefrontal brain tissue areas during performance of the Verbal Fluency Test (VFT). On a neuropsychological level, the healthy subjects performed better in the VFT than patients with DAT. Statistical analysis of the relative concentrations of O2HB and HHB measured with NIRS during performance of the VFT revealed a significant interaction of the hemispheric effects with the diagnosis. A possible interpretation of this finding is that a good performance in the VFT relies on a predominantly left hemispheric activation observed in controls, whereas a low number of correct responses is associated with a loss of this asymmetric activation in patients with DAT. Although both, patients and controls, performed better in the category version of the VFT, the metabolic effects of this task were significantly less pronounced than in the letter version. This indicates that different energy demands, according to the type of access to the memory stores, may be interpreted as the result of a less energy-demanding access to categorically stored information and adds further evidence to the view that memory departments in humans are organized according to categorical principles.

The effect of appraisal level on processing of emotional prosody in meaningless speech

In visual perception of emotional stimuli, low- and high-level appraisal processes have been found to engage different neural structures. Beyond emotional facial expression, emotional prosody is an important auditory cue for social interaction. Neuroimaging studies have proposed a network for emotional prosody processing that involves a right temporal input region and explicit evaluation in bilateral prefrontal areas. However, the comparison of different appraisal levels has so far relied upon using linguistic instructions during low-level processing, which might confound effects of processing level and linguistic task. In order to circumvent this problem, we examined processing of emotional prosody in meaningless speech during gender labelling (implicit, low-level appraisal) and emotion labelling (explicit, high-level appraisal). While bilateral amygdala, left superior temporal sulcus and right parietal areas showed stronger blood oxygen level-dependent (BOLD) responses during implicit processing, areas with stronger BOLD responses during explicit processing included the left inferior frontal gyrus, bilateral parietal, anterior cingulate and supplemental motor cortex. Emotional versus neutral prosody evoked BOLD responses in right superior temporal gyrus, bilateral anterior cingulate, left inferior frontal gyrus, insula and bilateral putamen. Basal ganglia and right anterior cingulate responses to emotional versus neutral prosody were particularly pronounced during explicit processing. These results are in line with an amygdala-prefrontal-cingulate network controlling different appraisal levels, and suggest a specific role of the left inferior frontal gyrus in explicit evaluation of emotional prosody. In addition to brain areas commonly related to prosody processing, our results suggest specific functions of anterior cingulate and basal ganglia in detecting emotional prosody, particularly when explicit identification is necessary.