Altered neural processing of reward and punishment in adolescents with Major Depressive Disorder.

BACKGROUND: Altered reward and punishment function has been suggested as an important vulnerability factor for the development of Major Depressive Disorder (MDD). Prior ERP studies found evidence for neurophysiological dysfunctions in reinforcement processes in adults with MDD. To date, only few ERP studies have examined the neural underpinnings of reinforcement processing in adolescents diagnosed with MDD. The present event-related potential (ERP) study aimed to investigate neurophysiological mechanisms of anticipation and consumption of reward and punishment in adolescents with MDD in one comprehensive paradigm. METHOD: During ERP recording, 25 adolescents with MDD and 29 healthy controls (12-17 years) completed a Monetary Incentive Delay Task comprising both a monetary reward and a monetary punishment condition. During anticipation, the cue-P3 signaling attentional allocation was recorded. During consumption, the feedback-P3 and Reward Positivity (RewP) were recorded to capture attentional allocation and outcome evaluation, respectively. RESULTS: Compared to controls, adolescents with MDD showed prolonged cue-P3 latencies to reward cues. Furthermore, unlike controls, adolescents with MDD displayed shorter feedback-P3 latencies in the reward versus punishment condition. RewPs did not differ between groups. LIMITATIONS: It remains unanswered whether the observed alterations in adolescent MDD represent a state or trait. CONCLUSIONS: Delayed neural processing of reward cues corresponds to the clinical presentation of adolescent MDD with reduced motivational tendencies to obtain rewards. Relatively shorter feedback-P3 latencies in the reward versus punishment condition could indicate a high salience of performance-contingent reward. Frequent exposure of negatively biased adolescents with MDD to performance-contingent rewards might constitute a promising intervention approach.

Auditory selective attention in adolescents with major depression: An event-related potential study.

BACKGROUND: Major depression (MD) is associated with deficits in selective attention. Previous studies in adults with MD using event-related potentials (ERPs) reported abnormalities in the neurophysiological correlates of auditory selective attention. However, it is yet unclear whether these findings can be generalized to MD in adolescence. Thus, the aim of the present ERP study was to explore the neural mechanisms of auditory selective attention in adolescents with MD. METHODS: 24 male and female unmedicated adolescents with MD and 21 control subjects were included in the study. ERPs were collected during an auditory oddball paradigm. RESULTS: Depressive adolescents tended to show a longer N100 latency to target and non-target tones. Moreover, MD subjects showed a prolonged latency of the P200 component to targets. Across groups, longer P200 latency was associated with a decreased tendency of disinhibited behavior as assessed by a behavioral questionnaire. LIMITATIONS: To be able to draw more precise conclusions about differences between the neural bases of selective attention in adolescents vs. adults with MD, future studies should include both age groups and apply the same experimental setting across all subjects. CONCLUSIONS: The study provides strong support for abnormalities in the neurophysiolgical bases of selective attention in adolecents with MD at early stages of auditory information processing. Absent group differences in later ERP components reflecting voluntary attentional processes stand in contrast to results reported in adults with MD and may suggest that adolescents with MD possess mechanisms to compensate for abnormalities in the early stages of selective attention.

The temporal dynamics of coherent motion processing in autism spectrum disorder: evidence for a deficit in the dorsal pathway.

Individuals with autism spectrum disorder (ASD) show impairments in processing coherent motion which have been proposed to be linked to a general deficit in the dorsal visual pathway. However, few studies have investigated the neural mechanisms underlying coherent motion processing in ASD. Thus, the aim of this study was to further test the hypothesis of a dorsal pathway deficit in ASD using visual evoked potentials (VEPs). 16 children and adolescents with ASD and 12 typically developing controls were examined with VEPs elicited by a random dot kinematogram. After an initial experimental sequence, where subjects were presented randomly moving dots, a fraction of the dots moved coherently (dependent on the level of coherence, 20%, 40%, or 60% of the dots) to the left or right side. Subjects were asked to detect the direction of coherent motion via button press. On the behavioural level, no significant group differences emerged. On the neural level, coherently moving dots elicited a N200 followed by a late positive potential (P400). ASD subjects exhibited a reduced N200 amplitude compared to controls. Moreover, in the ASD group, a trend for a negative relationship between N200 amplitude and a measure of autistic pathology was revealed. The present study provides strong support of a dorsal stream deficiency in the disorder and renders alternative explanations for impaired coherent motion processing in ASD less likely. Together with findings from related research fields, our data indicate that deviances in the N200 during coherent motion perception might be fundamental to ASD.

First genome-wide association scan on neurophysiological endophenotypes points to trans-regulation effects on SLC2A3 in dyslexic children.

Dyslexia is one of the most common learning disorders affecting about 5% of all school-aged children. It has been shown that event-related potential measurements reveal differences between dyslexic children and age-matched controls. This holds particularly true for mismatch negativity (MMN), which reflects automatic speech deviance processing and is altered in dyslexic children. We performed a whole-genome association analysis in 200 dyslexic children, focusing on MMN measurements. We identified rs4234898, a marker located on chromosome 4q32.1, to be significantly associated with the late MMN component. This association could be replicated in an independent second sample of 186 dyslexic children, reaching genome-wide significance in the combined sample (P = 5.14e-08). We also found an association between the late MMN component and a two-marker haplotype of rs4234898 and rs11100040, one of its neighboring single nucleotide polymorphisms (SNPs). In the combined sample, this marker combination withstands correction for multiple testing (P = 6.71e-08). Both SNPs lie in a region devoid of any protein-coding genes; however, they both show significant association with mRNA-expression levels of SLC2A3 on chromosome 12, the predominant facilitative glucose transporter in neurons. Our results suggest a possible trans-regulation effect on SLC2A3, which might lead to glucose deficits in dyslexic children and could explain their attenuated MMN in passive listening tasks.

EEG responses to tonic heat pain.

The aim of the present study was to characterize the EEG response pattern specific for tonic pain which is an experimental pain model resembling clinical pain more closely than phasic pain. Tonic experimental pain was produced by a series of heat pulses 1 degree C above pain threshold over 10 min. A series of heat pulses 0.3 degree C below pain threshold and a constant temperature of 37 degrees C served as non-painful heat control and as baseline condition, respectively. The level of attention was experimentally manipulated by instruction and by a distraction task. Twenty male, pain-free subjects had to rate the sensation intensity and sensation unpleasantness during thermal stimulation. Furthermore, a German version of the McGill Pain Questionnaire was to be filled out after tonic painful heat stimulation. The EEG was recorded via 10 leads according to 10/20 convention. Power density was calculated for the usual frequency bands. The ratings showed that tonic painful heat was experienced clearly distinct from tonic non-painful heat. An EEG response pattern emerged characterized by a rather generalized increased delta(2) activity, a left-biased fronto-temporally diminished theta activity, a fronto-temporal decrease in the alpha(1) activity and a left-sided temporal increase in the beta(1) activity. This observation agrees well with the findings of others. However, there was no evidence in our data that these EEG changes are specific to tonic heat pain as opposed to changes observed during tonic non-painful heat stimulation. Accordingly, the repeatedly reported EEG patterns are also likely to be produced by other forms of strong somatosensory stimuli and to be not specific for pain.

Spatial-frequency- and contrast-dependent visible persistence and reading disorder: no evidence for a basic perceptual deficit.

The aetiology of dyslexia is still unclear, the most widely and controversially discussed theory is the magnocellular deficit hypothesis. One of the first and most influential paradigms used to investigate this visual deficit in dyslexia is the visible persistence (VP). However results on VP are decisively influenced by the method measuring VP. Lovegrove et al. (1986) repeatedly found a longer VP in reading disabled children which is significantly influenced by spatial frequency and contrast. However, these results were not investigated with the same method to date. Seventy-six unselected 2nd grade students (41 boys, 35 girls) of a rural primary school were investigated with an identical experimental design comparable to the Lovegrove et al. (1986) studies. Comparing reading disabled (n = 17) with controls (n = 34) no evidence for a longer VP in the reading disabled group was found. Additionally, correlation analysis revealed no evidence for a significance of VP for spelling, phoneme awareness and speech discrimination. This study does not encourage either a magnocellular nor parvocellular deficit in dyslexia.

Neurophysiological correlates of word recognition in dyslexia.

The neurobiological basis of learning word spellings and recognition of recently learned words was assessed in a learning experiment in 9 dyslexics and 9 controls male adolescents. In a recognition paradigm previously learned pseudowords and graphic symbols were presented 50 times each interspersed pseudo-randomly between 3 unlearned items which were repeated 50 times and 150 filler pseudowords. The electrophysiological correlate of recognition of learned pseudowords and graphic symbols was a positivity around 600 ms. For pseudowords the amplitude of this ERP component was significantly attenuated in the dyslexic group, no differences between the groups were found for recognition of graphic material. These data suggest that dyslexic children are able to learn the spelling of simple words, however, the neurophysiological correlate of recognition of these learned words is significantly attenuated. This result strengthens the view that dyslexic children are not generally impaired in recognition memory but specific for linguistic material like words.

Visual information processing in dyslexic children.

OBJECTIVE: Several studies presented evidence for magnocellular deficits in dyslexics both in behavioural as well as in electrophysiological data of local electrode sites. We investigated two well-known paradigms (motion-onset and random-dot-kinematogram) with regard to global electrophysiological parameters. METHODS: Twenty-one-channel event-related potentials (ERPs) of 16 dyslectic and 15 control children were analyzed with reference-independent methods. For each paradigm quasi stable microstates were identified by means of a data-driven segmentation procedure and compared between both groups. RESULTS: Differences in global ERP responses between dyslexic and control children could be found for rapid moving gratings but not for the dot coherence. CONCLUSIONS: Dyslexic children seem to have some highly specific visual deficits in processing moving stimuli. These deficits can be related to the magnocellular system.

Speech perception deficit in dyslexic adults as measured by mismatch negativity (MMN).

Deficits in phonological processing are known to play a major role in the aetiology of dyslexia, and speech perception is a prerequisite condition for phonological processing. Significant group differences between dyslexics and controls have been found in the categorical perception of synthetic speech stimuli. In a previous work, we have demonstrated that these group differences are already present at an early pre-attentive stage of signal processing in dyslexic children: the late component of the MMN elicited by passive speech perception was attenuated in comparison to a control group. In this study, 12 dyslexic adults and 13 controls were assessed using a passive oddball paradigm. Mismatch negativity (MMN) was determined for both tone and speech stimuli. The tone stimuli yielded two MMN components, but no group differences. Three components were found for the speech stimuli. Multivariate testing for group differences yielded a significant result, and univariate P values revealed significant differences between dyslexics and controls in two of the three time windows. This suggests that speech perception as measured on an early, pre-attentive level plays a major role in dyslexia not only in children (as shown in our previous study) but also in adults.

Pre-attentive processing of auditory patterns in dyslexic human subjects.

It has been hypothesized that auditory temporal processing plays a major role in the aetiology of dyslexia. Event-related brain potentials (mismatch negativity, MMN) of auditory temporal processing were assessed in 15 dyslectic adults and 20 controls. A complex tonal pattern was used where the difference between standard and deviant stimuli was the temporal, not the frequency structure. Dyslexics had a significantly smaller MMN in the time window of 225-600 ms. This result shows that dyslexics have a significant pre-attentive deficit in processing of rapid temporal patterns suggesting that it may be the temporal information embedded in speech sounds, rather than phonetic information per se, that resulted in the attenuated MMN found in dyslexics in previous studies. MMN scalp topographies were similar for both groups, showing a maximum over fronto-central leads.

The role of phonological awareness, speech perception, and auditory temporal processing for dyslexia.

There is strong evidence that auditory processing plays a major role in the etiology of dyslexia. Auditory temporal processing of non-speech stimuli, speech perception, and phonological awareness have been shown to be influential in reading and spelling development. However, the relationship between these variables remains unclear. In order to analyze the influence of these three auditory processing levels on spelling, 19 dyslexic and 15 control children were examined. Significant group differences were found for all speech variables, but not for any non-speech variable. Structural equation modeling resulted in a fairly simple model with direct paths to the respective next lower level. One additional path from preattentive speech processing to spelling had to be included in order to improve the model fit. These results strengthen the role of speech and phonological processing for the etiology in dyslexia.

Attenuated hemispheric lateralization in dyslexia: evidence of a visual processing deficit.

There is controversial evidence that deficits in the processing of low contrast and low spatial frequency stimuli are of importance in the pathogenesis of dyslexia. Fifteen adult dyslexics and 19 controls were examined using visual evoked potentials (VEP) at varying spatial frequencies (2 and 11.33 cpd) and contrasts (0.2, 0.4, 0.6, 0.8). Our results show that the amplitude of VEPs following different spatial frequencies and contrasts did not differentiate between dyslexics and controls. Further, we found significantly higher amplitudes of the P1 and P2 over the right occipital cortex. For the P2, this hemispheric asymmetry was not found in the dyslexic group suggesting a specific low level visual processing deficit in the right occipital region in dyslexia.

Role of auditory temporal processing for reading and spelling disability.

The role of auditory temporal processing in reading and spelling was investigated in a sample of 30 children and one of 31 adults, using a gap-detection task with nonspeech stimuli. There was no evidence for a relationship between reading and spelling disability (dyslexia) and the gap-detection threshold. The results were discussed regarding the relevance for the popular hypothesis of an auditory temporal processing deficit underlying dyslexia.

Auditory processing and dyslexia: evidence for a specific speech processing deficit.

In order to investigate the relationship between dyslexia and central auditory processing, 19 children with spelling disability and 15 controls at grades 5 and 6 were examined using a passive oddball paradigm. Mismatch negativity (MMN) was determined for tone and speech stimuli. While there were no group differences for the tone stimuli, we found a significantly attenuated MMN in the dyslexic group for the speech stimuli. This finding leads to the conclusion that dyslexics have a specific speech processing deficit at the sensory level which could be used to identify children at risk at an early age.