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Post-perceptual cues can enhance visual short term memory encoding even after the offset of the visual stimulus. However, both the mechanisms by which the sensory stimulus characteristics are buffered as well as the mechanisms by which post-perceptual selective attention enhances short term memory encoding remain unclear. We analyzed late post-perceptual event-related potentials (ERPs) in visual change detection tasks (100ms stimulus duration) by high-resolution ERP analysis to elucidate these mechanisms. The effects of early and late auditory post-cues (300ms or 850ms after visual stimulus onset) as well as the effects of a visual interference stimulus were examined in 27 healthy right-handed adults. Focusing attention with post-perceptual cues at both latencies significantly improved memory performance, i.e. sensory stimulus characteristics were available for up to 850ms after stimulus presentation. Passive watching of the visual stimuli without auditory cue presentation evoked a slow negative wave (N700) over occipito-temporal visual areas. N700 was strongly reduced by a visual interference stimulus which impeded memory maintenance. In contrast, contralateral delay activity (CDA) still developed in this condition after the application of auditory post-cues and was thereby dissociated from N700. CDA and N700 seem to represent two different processes involved in short term memory encoding. While N700 could reflect visual post processing by automatic attention attraction, CDA may reflect the top-down process of searching selectively for the required information through post-perceptual attention.

Increased intra-subject variability (ISV) in reaction times (RTs) is a candidate endophenotype for several psychiatric and neurological conditions, including schizophrenia. ISV reflects the degree of variability in RTs and is thought to be an index of the stability of cognition. It is generally assumed to have the same underlying physiological basis across conditions, but recent evidence raises the possibility that the neural underpinnings of ISV vary with aetiology. Combining genetics with single-trial event-related potentials is an ideal method for investigating the neural basis of ISV in groups where ISV may vary for relatively homogenous reasons. Here we examine the association between P3b latency variability and a polymorphism on the ZNF804A gene associated with psychosis. Ninety-one healthy volunteers genotyped for rs1344706, a polymorphism on ZNF804A, had electroencephalographic data recorded while carrying out three n-back tasks. Data were analysed with a single-trial approach and latency variability of the P3b was compared between the AA homozygous risk group (N=30) and C allele carriers (N=61). P3b latencies were more variable for AA carriers than C carriers. Behavioural ISV, however, was not associated with genotype. The increase in neurophysiological variability, unaccompanied by increased behavioural variability, suggests that this risk gene is associated with an attenuated form of an endophenotype associated with the psychosis phenotype. The increase in both stimulus and response-locked variability also contrasts with previous work into attention-deficit hyperactivity disorder, where only response-locked P3b variability was elevated, suggesting that increased ISV may not signify the same underlying processes in all conditions with which it is associated.

Intra-subject variability in reaction times (ISV) is a promising endophenotype for several psychiatric conditions, but its neural underpinnings are not yet established. Converging evidence from neuroimaging, molecular genetics, and psychopharmacology suggests that ISV could index catecholaminergically-mediated neural noise. The fine-grained temporal resolution of electroencephalography is ideal for investigating ISV, but only if potential neural correlates of ISV can be assessed in single trials. Based on evidence that ISV is associated with dopaminergic functioning, we apply a recently developed method of single-trial P3b analysis to investigate the association of COMT Val(158)Met genotype with measures of ISV on the behavioural and neural levels at different working memory loads. Greater number of Met alleles was associated with poorer and more intra-individually variable performance on the tasks, and greater latency jitter in single-trial P3bs. These converging results at the behavioural and neurophysiological levels confirm previous observations that prefrontal dopamine availability is associated with stability and accuracy of cognitive performance. Together with previous studies, these data imply pleiotropic cognitive effects of COMT genotype.

This study examined whether the memory encoding and short term maintenance of olfactory stimuli is associated with neurophysiological activation patterns which parallel those described for sensory modalities such as vision and auditory. We examined olfactory event-related potentials in an olfactory change detection task in twenty-four healthy adults and compared the measured activation to that found during passive olfactory stimulation. During the early olfactory post-processing phase, we found a sustained negativity over bilateral frontotemporal areas in the passive perception condition which was enhanced in the active memory task. There was no significant lateralization in either experimental condition. During the maintenance interval at the end of the delay period, we still found sustained activation over bilateral frontotemporal areas which was more negative in trials with correct - as compared to incorrect - behavioural responses. This was complemented by a general significantly stronger frontocentral activation. Summarizing, we were able to show that olfactory short term memory involves a parallel sequence of activation as found in other sensory modalities. In addition to olfactory-specific frontotemporal activations in the memory encoding phase, we found slow cortical potentials over frontocentral areas during the memory maintenance phase indicating the activation of a supramodal memory maintenance system. These findings could represent the neurophysiological underpinning of the 'olfactory flacon', the olfactory counter-part to the visual sketchpad and phonological loop embedded in Baddeley's working memory model.

The ventrolateral prefrontal cortex (VLPFC) is implicated in contingency detection and the evaluation of emotionally significant stimuli. However, the mechanisms whereby an individual can effectively avoid painful or unpleasant events are not well understood. We therefore examined whether the absence of an unpleasant somatosensory stimulus could evoke a response in the human VLPFC as a correlate of contingency detection (the feeling that “I am safe”) without any immediately preceding stimulus. In a differential trace-conditioning paradigm, the unpleasant stimulus followed the partially reinforced stimulus in 50% of trials after 3 s; it never occurred after the nonreinforced stimulus. High-resolution DC electroencephalography, current source density mapping, and spatio-temporal source analysis were performed. After the nonreinforced stimulus, a highly significant negativity over the VLPFC began about a second after the time for the unpleasant stimulus to occur had passed. We concluded that the VLPFC can be activated merely by a sequence of stimuli (with long interstimulus intervals) without any directly preceding stimulus, provided that this sequence creates the expectation that at a certain time an unpleasant stimulus might occur. This mechanism might allow for the detection of conditions under which harmful events could be avoided. Moreover, in reinforced trials, we found a highly significantly lateralized negativity (N700) that outlasted the strong, unpleasant somatosensory stimulus for about a second. Topography and source analysis pointed to prolonged activation of the somatosensory system. This processing stage preceded activation of the VLPFC. We concluded that N700 might provide important insights into the time course of somatosensory memory traces.

During motor learning in goal-directed reactions, a specific movement has to be associated with feedback about the movement's success. Such feedback often follows when the movement is already over. We investigated the time-course of post-movement cortical motor processing by high-resolution analysis of lateralized post-movement potentials in forewarned and simple reaction time tasks. In both paradigms we could separate a post-movement component (motor postimperative negative variation-mPINV) peaking about 500 ms after the button press (confirmed by electromyogram and accelerometer). mPINV could not be sufficiently explained by motor cortex activity related to EMG output and/or by sensory feedback. mPINV was enhanced by long intertrial intervals and its lateralization changed with response movement side. Its scalp potential distribution resembled (pre-)motor cortex activity during preceding movement stages and differed from the frontal motor potential peak (proprioceptive and somatosensory reafferent feedback); suggesting post-movement activation of pre-/primary motor cortex. Dipole source analysis yielded a single radial source near premotor cortex which explained lateralized mPINV almost completely. mPINV was present in simple reaction time tasks, indicating that mPINV is an independent component and does not represent delayed resolution of pre-movement negativity. An equivalent of "classical" PINV (cPINV) occurred later over prefrontal and anterior temporal sites in simple and forewarned reaction time tasks. Our results suggest that high-resolution analysis of lateralized movement-related potentials allows to image post-movement motor cortex activity and might provide insights into basic mechanisms of motor learning: A characteristic sequence might involve motor cortex activation (mPINV) before "higher order associative areas" come into play (cPINV).