Working memory in ALS patients: preserved performance but marked changes in underlying neuronal networks.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease which affects the motor system but also other frontal brain regions. In this study we investigated changes in functional neuronal networks including posterior brain regions that are not directly affected by the neurodegenerative process. To this end, we analyzed the contralateral delay activity (CDA), an ERP component considered an online marker of memory storage in posterior cortex, while 23 ALS patients and their controls performed a delayed-matching-to-sample working memory (WM) task. The task required encoding of stimuli in the cued hemifield whilst ignoring stimuli in the other hemifield. Despite their unimpaired behavioral performance patients displayed several changes in the neuronal markers of the memory processes. Their CDA amplitude was smaller; it showed less load-dependent modulation and lacked the reduction observed when controls performed the same task three months later. The smaller CDA in the patients could be attributed to more ipsilateral cortical activity which may indicate that ALS patients unnecessarily processed the irrelevant stimuli as well. The latter is presumably related to deterioration of the frontal cortex in the patient group which was indicated by slight deficits in tests of their executive functions that increased over time. The frontal pathology presumably affected their top-down control of memory storage in remote regions in the posterior brain. In sum, the present results demonstrate functional changes in neuronal networks, i.e. neuroplasticity, in ALS that go well beyond the known structural changes. They also show that at least in WM tasks, in which strategic top-down control demands are relatively low, the frontal deficit can be compensated for by intact low level processes in posterior brain regions.

Non-invasive alternating current stimulation improves vision in optic neuropathy.

PURPOSE: Partial blindness after visual system damage is considered irreversible, yet the brain has residual visual capacities and considerable plasticity potential. We now applied non-invasive alternating current stimulation (ACS) to the visual system of patients with optic nerve damage with the aim to induce recovery of visual functions. METHODS: In a prospective, double-blind, randomized, placebo-controlled clinical trial patients with several year old partial optic nerve lesions were treated with ACS (n = 12) or placebo-stimulation (n = 10). ACS was delivered transorbitally for 40 minutes on 10 days. Visual outcome measures and EEG were measured before and after treatment. RESULTS: ACS, but not placebo, led to significant improvement of a visual field detection deficit by 69%, and also significantly improved temporal processing of visual stimuli, detection performance in static perimetry, and visual acuity. These changes were associated with alpha-band changes in the EEG power spectra. Visual improvements were stable for at least 2-months. CONCLUSIONS: ACS can induce vision restoration many years after optic neuropathy. Though the mechanism is still unclear, EEG changes indicate increased synchronization in posterior brain regions. The present study provides Class Ib evidence that non-invasive transorbital ACS is well tolerated and improves visual function in optic neuropathy.

Auditory event-related response in visual cortex modulates subsequent visual responses in humans.

Growing evidence from electrophysiological data in animal and human studies suggests that multisensory interaction is not exclusively a higher-order process, but also takes place in primary sensory cortices. Such early multisensory interaction is thought to be mediated by means of phase resetting. The presentation of a stimulus to one sensory modality resets the phase of ongoing oscillations in another modality such that processing in the latter modality is modulated. In humans, evidence for such a mechanism is still sparse. In the current study, the influence of an auditory stimulus on visual processing was investigated by measuring the electroencephalogram (EEG) and behavioral responses of humans to visual, auditory, and audiovisual stimulation with varying stimulus-onset asynchrony (SOA). We observed three distinct oscillatory EEG responses in our data. An initial gamma-band response around 50 Hz was followed by a beta-band response around 25 Hz, and a theta response around 6 Hz. The latter was enhanced in response to cross-modal stimuli as compared to either unimodal stimuli. Interestingly, the beta response to unimodal auditory stimuli was dominant in electrodes over visual areas. The SOA between auditory and visual stimuli--albeit not consciously perceived--had a modulatory impact on the multisensory evoked beta-band responses; i.e., the amplitude depended on SOA in a sinusoidal fashion, suggesting a phase reset. These findings further support the notion that parameters of brain oscillations such as amplitude and phase are essential predictors of subsequent brain responses and might be one of the mechanisms underlying multisensory integration.

Gamma in motion: pattern reversal elicits stronger gamma-band responses than motion.

Previous studies showed higher gamma-band responses (GBRs, ≈40 Hz) of the electroencephalogram (EEG) for moving compared to stationary stimuli. However, it is unclear whether this modulation by motion reflects a special responsiveness of the GBR to the stimulus feature "motion," or whether GBR enhancements of similar magnitude can be elicited also by a salient change within a static stimulus that does not include motion. Therefore, we measured the EEG of healthy subjects watching stationary square wave gratings of high contrast that either started to move or reversed their black and white pattern shortly after their onset. The strong contrast change of the pattern reversal represented a salient but motionless change within the grating that was compared to the onset of the stationary grating and the motion onset. Induced and evoked GBRs were analyzed for all three display conditions. In order to assess the influence of fixational eye movements on the induced GBRs, we also examined the time courses of microsaccade rates during the three display conditions. Amplitudes of both evoked and induced GBRs were stronger for pattern reversal than for motion onset. There was no significant amplitude difference between the onsets of the stationary and moving gratings. However, mean frequencies of the induced GBR were ~10 Hz higher in response to the onsets of moving compared to stationary gratings. Furthermore, the modulations of the induced GBR did not parallel the modulations of microsaccade rate, indicating that our induced GBRs reflect neuronal processes. These results suggest that, within the gamma-band range, the encoding of moving gratings in early visual cortex is primarily based on an upward frequency shift, whereas contrast changes within static gratings are reflected by amplitude enhancement.

Anticipation of natural stimuli modulates EEG dynamics: physiology and simulation.

In everyday life we often encounter situations in which we can expect a visual stimulus before we actually see it. Here, we study the impact of such stimulus anticipation on the actual response to a visual stimulus. Participants were to indicate the sex of deer and cattle on photographs of the respective animals. On some trials, participants were cued on the species of the upcoming animal whereas on other trials this was not the case. Time frequency analysis of the simultaneously recorded EEG revealed modulations by this cue stimulus in two time windows. Early [Formula: see text] spectral responses [Formula: see text] displayed strongest stimulus-locking for stimuli that were preceded by a cue if they were sufficiently large. Late [Formula: see text] responses displayed enhanced amplitudes in response to large stimuli and to stimuli that were preceded by a cue. For late responses, however, no interaction between cue and stimulus size was observed. We were able to explain these results in a simulation by prestimulus gain modulations (early response) and by decreased response thresholds (late response). Thus, it seems plausible, that stimulus anticipation results in a pretuning of local neural populations.

Auditory memory: a comparison between humans and starlings.

In this study, we compare the processing of acoustic signals in European starlings (Sturnus vulgaris) and in human listeners by observing the decay of short-term auditory memory in delayed non-matching-to-sample experiments. A series of identical "sample" stimuli and a final "test" stimulus were separated by variable delays (1 to 180.1 s). Subjects had to classify sample and test stimuli as being either the same or different. Test stimuli were pure tones that differed in a single signal feature, i.e., frequency, and song motifs that differed in multiple signal characteristics. We have tested several predictions concerning the memory performance of starlings and humans and we obtained the following outcome: (1) In contrast to our expectation, signal complexity had no effect. The overall analysis of the starling data did not show differences in memory performance for signals differing in single or multiple signal features. (2) Starling and human data supported the hypothesis that auditory memory impairs with increasing delay. This was also seen when interfering noise was added to the delay periods in an additional series with human subjects. (3) The starling data showed that the repetition of sample stimuli improved memory performance, compared to only a single presentation. Human memory performance, however, was similar for a single and for the repeated presentation of signals. (4) Differences in salience between sample and test stimuli were positively related to memory performance only for tonal stimuli but not for song motifs. Results are discussed with respect to a model based on signal detection theory and to requirements for the analysis of natural communication signals.

Human EEG very high frequency oscillations reflect the number of matches with a template in auditory short-term memory.

Auditory perception comprises bottom-up as well as top-down processes. While research in the past has revealed many neural correlates of bottom-up processes, less is known about top-down modulation. Memory processes have recently been associated with oscillations in the gamma-band of human EEG (30 Hz and above) which are enhanced when incoming information matches a stored memory template. Therefore, we investigated event-related potentials (ERPs) and gamma-band activity in 17 healthy participants in a Go/NoGo-task. They listened to four frequency-modulated (FM) sounds which varied regarding the frequency range traversed and the direction of frequency modulation. One sound was defined as target and required a button press. The results of ERPs (N1, P2, N2, and P3) were consistent with previous studies. Analysis of evoked gamma-band responses yielded no significant task-dependent modulation, but we observed a stimulus dependency, which was also present in a control experiment: The amplitude of evoked gamma responses showed an inverted U-shape as a function of stimulus frequency. Investigation of total gamma activity revealed functionally relevant responses at high frequencies (90 Hz to 250 Hz), which showed significant modulations by matches with STM: Complete matches led to the strongest enhancements (starting around 100 ms after stimulus onset) and partial matches resulted in intermediate ones. The results support the conclusion that very high frequency oscillations (VHFOs) are markers of active stimulus discrimination in STM matching processes and are attributable to higher cognitive functions.