Matthias Weisbrod

The time course of brain activations during response inhibition : evidence from event-related potentials in a go/no go task

THE cortical organization of executive control was investigated using event-related potentials (ERPs). ERPs were collected while subjects performed a go/no go task that required response inhibition. First, around 26ms after stimulus onset, an effect of response inhibition on ERPs was observed over inferior prefrontal areas. Generators in these regions were confirmed by source analysis. Later, between 300–60 ms after stimulus onset, a left lateralized fronto-central ERP effect was found which differed in topography from a non-specific effect of task difficulty. Source analysis indicated that generators in anterior cingulate and left premotor areas also contributed to this effect. Orchestrated activation of prefrontal areas and the anterior cingulate subserves executive function whereas relatively late activity of the left premotor cortex is involved in motor control.

Neural correlates of impaired cognitive-behavioral flexibility in anorexia nervosa

OBJECTIVE Impaired cognitive-behavioral flexibility is regarded as a trait marker in anorexia nervosa patients. The authors sought to investigate the neural correlates of this deficit in executive functioning in anorexia nervosa. METHOD Fifteen women with anorexia nervosa and 15 age-matched healthy comparison women underwent event-related functional MRI while performing a target-detection task. The task distinguished between shifts in behavioral response and shifts in cognitive set. It involved infrequent target and non-target distractor stimuli embedded in a sequence of prepotent standard stimuli. RESULTS Relative to comparison subjects, anorexia nervosa patients showed a significantly higher error rate in behavioral response shifting, independent of whether those runs also involved cognitive set shifting. During behavioral response shifting, patients showed reduced activation in the left and right thalamus, ventral striatum, anterior cingulate cortex, sensorimotor brain regions, and cerebellum that differed significantly from the comparison group but showed dominant activation in frontal and parietal brain regions. These differential activations in patients and comparison subjects were specific to shifts in behavioral response: except for thalamic activation, they were not observed in response to non-target distractor trials that required no alteration in behavioral response. CONCLUSION Impaired behavioral response shifting in anorexia nervosa seems to be associated with hypoactivation in the ventral anterior cingulate-striato-thalamic loop that is involved in motivation-related behavior. In contrast, anorexia nervosa patients showed predominant activation of frontoparietal networks that is indicative of effortful and supervisory cognitive control during task performance.

Executive control is disturbed in schizophrenia: evidence from event-related potentials in a Go/NoGo task

BACKGROUND Schizophrenic patients suffer from cognitive and attentional deficits, particularly from failure of executive control functions. METHODS This study investigated the cortical organization of executive control in schizophrenic patients and healthy control subjects using event-related potentials (ERPs). Event-related potentials were collected while subjects performed an auditory Go/NoGo task that required response inhibition. To exclude stimulus discriminability and early stimulus processing to confound results, stimuli were adjusted to the subjects individual discrimination ability and were presented in a simple and a difficult version. RESULTS Schizophrenic patients performed similar to control subjects in the Go condition but worse than control subjects in the NoGo condition that required response inhibition. Event-related potentials revealed the neurophysiological substrate of this dysfunction. In the Go conditions, both healthy control subjects and schizophrenic patients showed the same voltage pattern. In the NoGo condition, control subjects and patients showed similar cortical activation only during early processing (N2 time window). However, in later stages of processing (P3 time window), healthy subjects showed left lateralization of ERPs over frontal areas while schizophrenic patients did not. CONCLUSIONS We conclude that schizophrenic patients exhibit deficient processing in a neuronal network, including left frontal areas, that is involved in later stages of executive control function.

Executive control deficit in depression: event-related potentials in a Go/Nogo task

Growing evidence suggests an impairment of executive control functions in depression. The aim of this study was to investigate whether depressive patients show a specific impairment of executive control in a response inhibition task and to investigate its neurophysiological correlates using event-related potentials. We analyzed data from 16 patients with unipolar depression and 16 healthy controls using an auditory Go/Nogo task. High resolution event-related potentials (ERPs) were recorded. Depressive patients performed similar to controls in the Go task, but worse in the Nogo task, which required response inhibition. ERPs revealed the neurophysiological correlate of this deficit. Both groups showed the same voltage pattern in the Go task. However, in the Nogo task depressive patients showed a reduction of an early fronto-temporal positivity in the N2 time window, which was associated with response inhibition in healthy subjects. This effect could not be explained by increased task difficulty in the Nogo task. There was no difference between groups in later stages of processing as indexed by the P3 complex. Therefore, the findings suggest a specific deficit in response inhibition, which requires executive control. This deficit is thought to reflect dysfunctional activation of the network subserving executive control during an early stage of cortical processing.

Right hemisphere activation during indirect semantic priming: evidence from event-related potentials.

Healthy subjects performed a lexical decision task in a semantic priming paradigm while event-related potentials (ERPs) were recorded from 64 channels. Semantic distance between prime and target was varied by including directly, indirectly, and nonrelated word pairs. At centro-parietal electrodes an N400 to nonrelated pairs was elicited bilaterally which was sensitive only to direct, but not to indirect semantic priming. These N400 priming effects were mirrored by the RT data. At inferior fronto-temporal sites directly related words showed ERP priming effects over both hemispheres. However, indirectly related words only elicited ERP priming effects over the right hemisphere. These results support the hypothesis that the right hemisphere semantic system is involved in processing of remote semantic information.

Dopaminergic modulation of semantic network activation

In order to examine the effect of dopamine on semantic processing, we performed a double-blind, placebo-controlled study. Healthy volunteers (n = 31) were tested in a lexical decision paradigm after ingestion of either L-dopa 100 mg with benserazide 25 mg or placebo. While direct semantic priming was influenced only marginally by L-dopa, the indirect priming effects was reduced significantly. These data support the hypothesis that dopamine increases the signal-to-noise ratio in semantic networks by reducing the spread of semantic processing, thereby leading to a focussing of activation.

Intra-individual reaction time variability in schizophrenia, depression and borderline personality disorder

Intra-individual reaction time variability (IIV) in neuropsychological task performance reflects short term fluctuations in performance. Increased IIV has been reported in patients with schizophrenia and could be related to a deficient neural timing mechanism, but the role of IIV in adult patients with other psychiatric disorders has not been established. Therefore, we compared IIV measures obtained in a Go/Nogo task from patients with schizophrenia, major depression and borderline personality disorder. IIV was increased for patients with schizophrenia. When correcting for differences in mean reaction time, depressive and borderline patients also showed increased IIV. Importantly, all groups showed a strong association between IIV and accuracy of task performance. This suggests that increased IIV might be a sensitive marker for the efficiency of top-down attentional control in all diagnostic groups. Aside from these similarities, the complete results including measures of IIV, mean reaction time and accuracy show differential patterns for patients with schizophrenia compared to those with borderline personality disorder or depression. These results are discussed with respect to common versus disorder-specific neural mechanisms underlying increased IIV.

Is frontal lobe involved in the generation of auditory evoked P50

This study examined the functional substrate of P50 suppression. Auditory evoked potentials (AEPs) and magnetic fields (AEFs) were recorded from healthy subjects simultaneously and analyzed using spatio-temporal source analysis. The resulting equivalent dipole model for the AEP consisted of one source in the auditory cortex (AC) of each hemisphere and an radially oriented medial frontal source, both with maximum AEP activity around 50 ms. The frontal source was functionally separated from the AC sources since it peaked significantly later and showed significantly larger P50 amplitude suppression. P30m showed neither suppression nor substantial frontal activity. In sum, this study relates P50 suppression to reduction of AC source activity and is the first to yield direct evidence for frontal involvement in P50 suppression.

Automatic vs. controlled processes in semantic priming--differentiation by event-related potentials.

Semantic network models propose that automatic (e.g. spreading activation) and controlled processes are involved in semantic priming. Behavioural studies propose that the influence of each of these processes depends on the stimulus onset asynchrony (SOA). To investigate this hypothesis with a more sensitive method, we applied high-resolution event-related potential (ERP) measures to a word-pseudoword lexical decision task that contained direct, indirect, and non-related prime-target pairs. SOAs consisted of 150 or 700 ms. The results showed that independently of SOA, increasing semantic distance prolonged reaction times and enlarged N400 amplitudes. Furthermore, the word-pseudoword decision evoked a parieto-central late positive complex (LPC respectively delayed P300), which was sensitive for semantic relatedness in the short SOA only. In addition, we found two early frontal components: a P250 in the short SOA only and a N310 sensitive to semantic relatedness more prominent in the short SOA. We conclude that ERP-differences between both SOAs indicate two separate processes: (1) an access to semantic memory, which is facilitated by spreading activation in the short SOA only; and (2) an SOA-independent, controlled process, which integrates prime and target words into a semantic context.

Tracking the time course of object categorization using event-related potentials

Object categorization processes were investigated by measuring event-related potentials while subjects categorized objects at the superordinate (e.g. animal), basic (e.g. dog) and subordinate (e.g. beagle) levels of abstraction. An enhanced negative deflection (N1) was found at posterior recording sites for subordinate level categorizations compared with basic level categorizations and was interpreted as a marker of increased visual analysis. In contrast, superordinate level categorizations produced a larger frontal negativity relative to basic level categorizations and were interpreted as an indicator of increased semantic processing. These results suggest a neurophysiological basis for the separate cognitive processes responsible for subordinate and superordinate object categorizations.