Effects of 4-aminopyridine on attention and executive functions of patients with multiple sclerosis: Randomized, double-blind, placebo-controlled clinical trial. Preliminary report.

BACKGROUND: A high percentage of patients with multiple sclerosis present cognitive alterations. Because 4-aminopyridine improves nerve conduction and efficient synaptic connection could improve cognitive dysfunction. OBJECTIVE: To evaluate the efficacy on cognitive performance and safety of 4-aminopyridine administered to patients with relapsing-remitting multiple sclerosis. METHODS: A randomized, double-blind, placebo controlled clinical trial was conducted in patients with relapsing-remitting multiple sclerosis diagnosis according to the McDonald criteria. At the beginning and at the end of the treatment different tests were used to assess cognitive performance. Subsequently, patients were randomized 1:1 to receive treatment or placebo. A bootstrap-t test was proposed to test the effectiveness of cognitive performance, considering a p-value < 0.05 as statistically significant. RESULTS: Twenty-four patients were recruited of which 21 completed the trial, 11 with 4-aminopyridine and 10 with placebo treatment. No significant differences between groups in the initial assessments were observed. In terms of efficacy, the experimental group achieved significantly higher scores in attention span, verbal fluency, planning and graphics and constructive motion. CONCLUSIONS: 4-aminopyridine proved to be an effective treatment on cognitive aspects in patients with relapsing-remitting multiple sclerosis. Drug doses were shown to be safe with mild to moderate adverse events (ClinicalTrials.gov number, NCT02280096).

EEG changes during word and figure categorization.

OBJECTIVE: To analyze whether the EEG changes observed during figure and word categorization are compatible with either the dual, the common amodal, or the alternative model (modality-specific codes for words and pictures, where meaning is represented for both in a higher-order amodal system) for semantic knowledge. METHODS: EEG was recorded during word and figure categorization of animals or non-animals in a group of 28 children 8-10 years old. Computation of EEG sources in the frequency domain using variable resolution electrical tomography (VARETA) and their statistical evaluation by statistical parametric mapping were carried out. RESULTS: At all frequencies, there were significant changes between EEG segments prior to the presentation of the stimuli and EEG segments recorded after the stimuli. Post-segments showed more power from 1.56 to 7.02 Hz, and less power than pre-segments from 8 to 12.48 Hz. EEG changes were only observed in the word task at: 3.9 (left occipital), 4.68, 5.46, and 6.24 Hz (temporo-occipital regions). These changes may be associated with visual encoding of words. Frequencies 7.8 and 17.94 Hz increased in prefrontal, anterior cingulate, and anterior temporal regions only during figure categorization. The prefrontal region may be related to object working memory. Thus, these frequencies might be related to figure codification. No significant differences between tasks were observed at 3.12 and 7.02 Hz in very wide brain areas (all lobes except occipital), suggesting that the amodal semantic system storage could be the model compatible with figure and word categorization. CONCLUSIONS: Thus, our results support the modified amodal semantic hypothesis, which advocates that the meanings of both kinds of stimuli are represented in a conceptual memory that receives input from the logogen and iconogen systems.

Delayed P300 during Sternberg and color discrimination tasks in poor readers.

The P300 ERP component was studied in poor and normal readers, using Sternberg and color discrimination (Spaceships) tasks. During the first one, subjects must decide if a probe item belongs or not to a set of digits previously presented. In the second one, the participants must shoot violet spaceships with one key and other than violet spaceships with another key. There were no significant differences between groups with respect to reaction times, but a larger proportion of errors was observed in poor readers. Longer P300 latencies were recorded for poor readers than controls in both tasks. P300 amplitudes showed topographical differences between the two groups: Poor readers' P300 is larger frontally during the Sternberg task, but smaller at posterior sites during the Spaceships task. These results suggest that poor readers may have deficiencies during the early processing stage, such as visual stimulus evaluation. Poor readers also appear to have deficits for classifying and memorizing visual stimuli.

Sources of abnormal EEG activity in brain infarctions.

EEGs from 16 patients with stroke in three different stages of evolution were recorded. EEG sources were calculated every 0.39 Hz by frequency domain VARETA. The main source was within the delta band in 2 out of 4 chronic patients, and in 67% of the patients in the acute or subacute stages when edema (cytotoxic or vasogenic) was present. Moreover, all patients showed abnormal activity in the theta band. Sources of abnormal activity in cortical or corticosubcortical infarcts were located in the cortex, surrounding the lesion. At the site of the infarct, a decrease of EEG power was observed. Sources of abnormal theta power coincided with edema and/or ischemic penumbra.

Specific EEG frequencies at specific brain areas and performance.

In this study it was shown that in adults, the frequency characteristics of EEG preceding stimuli that were followed by incorrect responses were different from the characteristics of EEG preceding stimuli that were followed by correct responses. In the recording during three different tasks that explore different neuronal networks, higher values of current preceding incorrect performance in those areas directly related to the task were found in frequencies within the delta (1.56 and 3.12 Hz) and beta bands (13.26, 14.04, 14.82, 15.6, 17.16 and 17.94 Hz), suggesting that these frequencies signal inhibition. Frequencies within the alpha band (9.36 and 12.48 Hz) showed greater energy preceding correct responses in task-specific areas, supporting previous results observed in children.

Primary task demands modulate P3a amplitude.

Auditory event-related brain potentials (ERPs) were recorded from 10 subjects in two different conditions: (1) subjects were required to reorder five visually presented letters in order to form a word and provide a verbal response (task condition); (2) subjects were presented with a control stimulus with the same physical characteristics as the experimental stimulus, but containing just one type of letter (i.e., AAAAA). Subjects had to verbally respond to such stimuli by saying "A" (control condition). Tones of 1000 Hz (standard) and 1050 Hz (deviant) were also presented to the subjects in a 85%-15% probability paradigm 2 s before, during and 8 s after the presentation of the visual stimuli. Recordings were obtained from Fpz, Fz, Cz and Pz vs. linked ears. Auditory ERPs to the auditory stimuli after the presentation of the visual letter string and during the performance of the task were averaged for the standard and deviant tones in both conditions. Only correct responses were considered for the averages. The N100 was affected by stimulus type (standard vs. deviant) but not by condition (task vs. control); however, larger P3a waves were observed during the control than during the task condition. No significant differences between conditions were observed in the mismatch negativity (MMN) latency range. These results suggest that primary task demands modulate involuntary attention processing.

N400 and lexical decisions: automatic or controlled processing?

OBJECTIVE: To investigate whether the N400 effect is sensitive to automatic or controlled processes. METHODS: Two experiments were performed. In one experiment, directly related word pairs were used. In the other experiment, mediated-related word pairs were used. In order to reduce controlled processes, each experiment consisted of 3 tasks: Low- and high-proportion of related pairs, and single presentation lexical decision task. RESULTS: In the first experiment, the amount of priming was equivalent for the 3 tasks. The N400 effect appeared in the high and low proportion of directly related words, but not in the single presentation task. In the second experiment, behavioral priming was also found in the 3 tasks. However, the N400 effect was observed only in the task with low proportion of related pairs. CONCLUSION: These results suggest that the N400 effect may be related to controlled processes.