Visually guided associative learning in pediatric and adult migraine without aura.

INTRODUCTION: The Rutgers Acquired Equivalence Test is a visually guided equivalence learning paradigm that involves rule acquisition and generalization. Earlier we found impaired performance in this paradigm among adult migraine patients without aura. The aim of the study was to investigate if similar impairments can be found already in the pediatric form of the disease and to compare the performance of the pediatric study population with that of an adult study population. We hypothesized that the deficits observed in adults would be observable already in the pediatric population. METHODS: Twenty-seven children and adolescents newly diagnosed with migraine without aura and 27 age- and sex-matched healthy controls were tested with the Rutgers Acquired Equivalence Test. Their performance data were compared to each other and those of an earlier adult study population involving 22 patients and 22 age- and sex-matched healthy controls. Four parameters characterizing performance in the two main phases of the paradigm were calculated for each of the four groups. Performance parameters were compared with Mann-Whitney U test. RESULTS: In contrast to the decreased performance of the adult patients in the Rutgers Acquired Equivalence Test, no significant difference was found between pediatric patients and controls in any phase of the paradigm. CONCLUSION: Children living with migraine without aura do not exhibit the same cognitive deficits in the Rutgers Acquired Equivalence Test as their adult counterparts. It can be hypothesized that the deficit of equivalence learning is not an inherent feature of the migrainous cognitive profile, rather the result of the interference of the disease with normal development.

Maintained Visual-, Auditory-, and Multisensory-Guided Associative Learning Functions in Children With Obsessive-Compulsive Disorder.

Sensory-guided acquired equivalence learning, a specific kind of non-verbal associative learning, is associated with the frontal cortex-basal ganglia loops and hippocampi, which seem to be involved in the pathogenesis of obsessive-compulsive disorder (OCD). In this study, we asked whether visual-, auditory-, and multisensory-guided associative acquired equivalence learning is affected in children with OCD. The first part of the applied learning paradigm investigated association building between two different sensory stimuli (where feedback was given about the correctness of the choices), a task that critically depends upon the basal ganglia. During the test phases, which primarily depended upon the hippocampi, the earlier learned and hitherto not shown but predictable associations were asked about without feedback. This study involved 31 children diagnosed with OCD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria and 31 matched healthy control participants. The children suffering from OCD had the same performance as the control children in all phases of the applied visual-, auditory-, and multisensory-guided associative learning paradigms. Thus, both the acquisition and test phases were not negatively affected by OCD. The reaction times did not differ between the two groups, and the applied medication had no effect on the performances of the OCD patients. Our results support the findings that the structural changes of basal ganglia and hippocampi detected in adult OCD patients are not as pronounced in children, which could be the explanation of the maintained associative equivalence learning functions in children suffering from OCD.

Predicting Stimulus Modality and Working Memory Load During Visual- and Audiovisual-Acquired Equivalence Learning.

Scholars have extensively studied the electroencephalography (EEG) correlates of associative working memory (WM) load. However, the effect of stimulus modality on EEG patterns within this process is less understood. To fill this research gap, the present study re-analyzed EEG datasets recorded during visual and audiovisual equivalence learning tasks from earlier studies. The number of associations required to be maintained (WM load) in WM was increased using the staircase method during the acquisition phase of the tasks. The support vector machine algorithm was employed to predict WM load and stimulus modality using the power, phase connectivity, and cross-frequency coupling (CFC) values obtained during time segments with different WM loads in the visual and audiovisual tasks. A high accuracy (>90%) in predicting stimulus modality based on power spectral density and from the theta-beta CFC was observed. However, accuracy in predicting WM load was higher (≥75% accuracy) than that in predicting stimulus modality (which was at chance level) using theta and alpha phase connectivity. Under low WM load conditions, this connectivity was highest between the frontal and parieto-occipital channels. The results validated our findings from earlier studies that dissociated stimulus modality based on power-spectra and CFC during equivalence learning. Furthermore, the results emphasized the importance of alpha and theta frontoparietal connectivity in WM load.

Power-spectra and cross-frequency coupling changes in visual and Audio-visual acquired equivalence learning.

The three phases of the applied acquired equivalence learning test, i.e. acquisition, retrieval and generalization, investigate the capabilities of humans in associative learning, working memory load and rule-transfer, respectively. Earlier findings denoted the role of different subcortical structures and cortical regions in the visual test. However, there is a lack of information about how multimodal cues modify the EEG-patterns during acquired equivalence learning. To test this we have recorded EEG from 18 healthy volunteers and analyzed the power spectra and the strength of cross-frequency coupling, comparing a unimodal visual-guided and a bimodal, audio-visual-guided paradigm. We found that the changes in the power of the different frequency band oscillations were more critical during the visual paradigm and they showed less synchronized activation compared to the audio-visual paradigm. These findings indicate that multimodal cues require less prominent, but more synchronized cortical contribution, which might be a possible biomarker of forming multimodal associations.

Multisensory guided associative learning in healthy humans.

Associative learning is a basic cognitive function by which discrete and often different percepts are linked together. The Rutgers Acquired Equivalence Test investigates a specific kind of associative learning, visually guided equivalence learning. The test consists of an acquisition (pair learning) and a test (rule transfer) phase, which are associated primarily with the function of the basal ganglia and the hippocampi, respectively. Earlier studies described that both fundamentally-involved brain structures in the visual associative learning, the basal ganglia and the hippocampi, receive not only visual but also multisensory information. However, no study has investigated whether there is a priority for multisensory guided equivalence learning compared to unimodal ones. Thus we had no data about the modality-dependence or independence of the equivalence learning. In the present study, we have therefore introduced the auditory- and multisensory (audiovisual)-guided equivalence learning paradigms and investigated the performance of 151 healthy volunteers in the visual as well as in the auditory and multisensory paradigms. Our results indicated that visual, auditory and multisensory guided associative learning is similarly effective in healthy humans, which suggest that the acquisition phase is fairly independent from the modality of the stimuli. On the other hand, in the test phase, where participants were presented with acquisitions that were learned earlier and associations that were until then not seen or heard but predictable, the multisensory stimuli elicited the best performance. The test phase, especially its generalization part, seems to be a harder cognitive task, where the multisensory information processing could improve the performance of the participants.

Cortical Power-Density Changes of Different Frequency Bands in Visually Guided Associative Learning: A Human EEG-Study.

The computer-based Rutgers Acquired Equivalence test (RAET) is a widely used paradigm to test the function of subcortical structures in visual associative learning. The test consists of an acquisition (pair learning) and a test (rule transfer) phase, associated with the function of the basal ganglia and the hippocampi, respectively. Obviously, such a complex task also requires cortical involvement. To investigate the activity of different cortical areas during this test, 64-channel EEG recordings were recorded in 24 healthy volunteers. Fast-Fourier and Morlet wavelet convolution analyses were performed on the recordings. The most robust power changes were observed in the theta (4-7 Hz) and gamma (>30 Hz) frequency bands, in which significant power elevation was observed in the vast majority of the subjects, over the parieto-occipital and temporo-parietal areas during the acquisition phase. The involvement of the frontal areas in the acquisition phase was remarkably weaker. No remarkable cortical power elevations were found in the test phase. In fact, the power of the alpha and beta bands was significantly decreased over the parietooccipital areas. We conclude that the initial acquisition of the image pairs requires strong cortical involvement, but once the pairs have been learned, neither retrieval nor generalization requires strong cortical contribution.

The effect of simultaneous flickering light stimulation on global form and motion perception thresholds.

The question regarding the exact function of the primary visual cortex (V1) in vision has been around ever since the description of residual vision after damage to this cortical area by Riddoch in 1917. In 2002, Schoenfeld and colleagues proposed that V1 can be saturated by flashes of light, by which the function of V1-bypassing visual pathways can be "unmasked". The Schoenfeld group found that light flashes applied on stimulus onset led to the elevation of brightness increment detection thresholds, but left motion detection thresholds unaltered. Although the proposed method (i.e. the use of light flashes to induce refractoriness in V1) could be a simple, cheap and elegant way of exploring V1 functions, no study has followed up on this. Therefore it is not known if it works at all with other types of stimuli. For that reason, we decided to revisit the idea in a modified form. Global form and motion perception thresholds were assessed with static Glass pattern stimuli and random dot kinematograms, with and without 12Hz flickering light stimulation. Global motion thresholds were almost unaltered by flickering stimulation, while a significant threshold elevation was caused in the global form perception task. The strongest conclusion allowed by our data is that simultaneous flickering photostimulation elevates global form perception thresholds but not global motion perception thresholds. This is in some way related to the refractoriness generated in an unsatisfactorily defined part of V1. We suggest that this does not necessarily reflect the activity of V1-bypassing pathways, and propose that the application of light flashes is a method that deserves more attention in the exploration of the V1-dependent and independent elements of visual consciousness in human subjects.