Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Word-specific cortical activity as revealed by the mismatch negativity

Neurophysiological brain activity evoked by individual spoken words and pseudowords was recorded and the mismatch negativity (MMN), an automatic index of experience-dependent auditory memory traces, was calculated. Consistent with earlier reported results, the MMN response to word-final syllables was enhanced compared with that elicited by the same syllables placed in a pseudoword context. Here we now demonstrate that the enhancement of the MMN elicited by two individual words showed different scalp topographies. The early word-specific brain activity is consistent with the assumption that the memory traces activated by individual words are carried by large neuronal ensembles that differ in their distributions over the cortex. Current source estimates localized the between-word differences in the right hemisphere and in parieto-occipital left-hemispheric areas. The differential brain responses to individual words appeared as early as ∼100 ms after the recognition points of the words, suggesting that their specific memory traces become active almost immediately after the information in the acoustic input is sufficient for word identification.     

Attention to Color: An Analysis of Selection, Controlled Search, and Motor Activation, Using Event-Related Potentials

In this study the organization of information processing in a selective search task was examined by analyzing event-related potentials. This task consisted of searching for target letters in a relevant (attended) color. The ERPs revealed two different effects of attention: an early occipital negativity (+/- 150 ms) reflecting feature-specific attention, and a later, central N2b component (+/- 240 ms) reflecting covert orienting of attention. A later, prolonged negativity (search-related negativity) (+/- 300 ms), maximal at Cz, was related to controlled search to letters in the attended color. Detection of relevant targets resulted in a parietal P3b component. Depending on stimulus presentation conditions an earlier response to both attended and unattended targets was found: an N2 component (+/- 250 ms). In these same conditions, C'3-C'4 asymmetries (Corrected Motor Asymmetries--CMA) suggested motor activation at +/- 300 ms, in the same time range as search-related negativity. It was argued that N2 and CMA suggest the existence of a preattentive target detection system, operating in parallel with a slower serial attentive system, as reflected by N2b and search negativity.     

Large B-cell lymphomas: fine-needle aspiration plays an important role in initial diagnosis of cases which are falsely negative by flow cytometry

Large B-cell lymphomas (LBCLs) have significant false-negative results when immunophenotyped by flow cytometry (FC). To clarify the role fine-needle aspiration (FNA) in reducing this false-negative rate, 28 cases ultimately diagnosed as LBCL that had FNA as part of the workup and a negative FC were identified. We examined their clinical and cytologic features, in comparison with cases of LBCL with FNAs that were positive by FC. In 24/28 FC-negative cases (86%) a cytologic diagnosis of suspicious or positive for malignancy was rendered. We conclude that cytologic analysis is more sensitive than FC in the diagnosis of malignancy in FNA of LBCL, particularly in aspirates with low cellularity and/or low viability. Examination of cytospin preparations of the actual material analyzed by FC may provide an indication that an FC result is falsely negative. It is important to recognize the potential of false-negativity by FC of LBCLs when interpreting FNAs with features suggesting lymphoma.     

Effects of information and reward on stimulus-preceding negativity prior to feedback stimuli

The purpose of the present study was to investigate the effects of informational and motivational level of feedback stimuli on the stimulus-preceding negativity (SPN). In the time estimation task, in which a visual stimulus was presented 3 s after a voluntary movement, (a) the information level (high information and low information) and (b) the motivation level (reward and no-reward) for feedback stimuli were manipulated. Under the high-information condition, subjects received feedback information about (1) correctness (correct or incorrect), (2) direction of error (under- or overestimate), and (3) degree of accuracy (accurate or less accurate) of their time estimation. In the low-information condition, however, they received information about the correctness only. In the reward condition, they received a monetary reward for accurate time estimations but received nothing in the no-reward condition. The results demonstrated a significant interaction of information by motivation level, showing that the SPN amplitude under the reward/high-information was larger than that in the no-reward/high-information condition. The results are discussed in terms of emotional anticipation, taking into consideration the result of self-report that subjects felt to be more motivated when they received precise information.     

The effect of erroneous responses on response monitoring in patients with major depressive disorder: a study with event-related potentials

Perceived failure is reported to have detrimental effects on subsequent performance in patients with major depressive disorder. We investigated the error-related negativity (ERN)/error negativity (Ne), an electrophysiological correlate of response monitoring, using a 64-channel EEG. Sixteen patients with DSM-IV major depressive disorder and 16 matched controls participated in an Eriksen flanker task with continuous performance feedback that signaled monetary reward. Compared to controls, patients with major depressive disorder showed a less negative ERN/Ne in error trials following error trials. This result might reflect impaired response monitoring processes in major depressive disorder resulting from an underactivity in a central reward pathway and/or a deficit in strategic reasoning.     

A Negative Slow Wave Related to Conceptual Load Which Vanishes if the Amount of Load is Increased? A Reply to Ruchkin and Johnson

Ruchkin and Johnson (1991) claim that the mode of responding used by Rösler & Heil (1991) may have camouflaged effects of a negative slow wave that Ruckin et al. (1988) had found to be related to the difficulty of mental calculation problems. This criticism is addressed by three arguments which support the interpretation of Rösler and Heil (1991). According to this view, the negative slow wave in question is more likely related to unspecific processing factors, such as effort and event expectation, than to specific processing demands such as these induced by mental arithmetic.     

The Effect of Small Variation of the Frequent Auditory Stimulus on the Event-Related Brain Potential to the Infrequent Stimulus

We investigated whether the mismatch process between a rare stimulus and the trace of frequent stimulus, which generates the mismatch-negativity component of the event-related potential, can tolerate a small variation in the intensity of the frequent stimulus. Series of short tone pips were presented to 10 subjects while they were reading a book and ignoring the auditory stimuli. The intensity (mean 80dB) of the frequent stimulus (600 Hz) varied within a range that was different in different blocks. The probability of the infrequent stimuli which were, in different blocks, either intensity deviants (600 Hz/70dB) or frequency deviants (650 Hz/80dB) was 10%. Both deviant stimuli elicited mismatch negativity even when the intensity of the frequent stimulus varied, although the amplitude of this component decreased with the increasing variability of the frequent stimulus. These results show that the generator process of mismatch negativity tolerates some variation in the repetitive stimulus, thus indicating that this process is also activated in ecologically more valid conditions. This is crucial to the interpretation of the generator process of mismatch negativity as a biologically vital warning mechanism.     

On the ERN and the significance of errors

The error-related negativity (ERN) is an event-related brain potential observed when subjects commit errors. To examine whether the ERN is sensitive to the value of errors, the motivational significance of errors was manipulated in two experiments. In Experiment 1, low and high monetary value errors were compared to evaluate the effect of trial value on the ERN. In Experiment 2, subjects performed a flanker task both while their performance was being evaluated and during a control condition. Consistent with the notion that the error-detection system is sensitive to the significance of errors, the ERN was significantly larger on high-value trials in Experiment 1 and during evaluation in Experiment 2. There were no corresponding effects on the correct response negativity, and no behavioral differences between conditions were evident in either experiment. These results are discussed in terms of the functional role of the ERN in response monitoring.     

Strategic control and medial frontal negativity: beyond errors and response conflict

Errors in timed choice tasks typically produce an error-related negativity (ERN) in the event-related potential (ERP). The error specificity of the ERN has been challenged by studies showing a correct response negativity (CRN). Forty-five participants engaged in a flanker task in which both compatibility between flankers and target and the probability of compatible flankers were manipulated. Correct responses elicited a CRN, the amplitude of which increased with the degree of mismatch between the presence of conflict and conflict probability, even on low-conflict (compatible) trials. The fronto-central N2 component was larger on high-conflict (incompatible) correct response trials. However, in contrast to some recent accounts, this N2 was largest for highly probable stimuli. These findings suggest revision to models of the effects of conflict on response-related negativity to account for strategic adjustments made in preparation for the response.