Gamma-patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease.

Non-invasive sensory stimulation in the range of the brain's gamma rhythm (30-100 Hz) is emerging as a new potential therapeutic strategy for the treatment of Alzheimer's disease (AD). Here, we investigated the effect of repeated combined exposure to 40 Hz synchronized sound and light stimuli on hippocampal long-term potentiation (LTP) in vivo in three rat models of early AD. We employed a very complete model of AD amyloidosis, amyloid precursor protein (APP)-overexpressing transgenic McGill-R-Thy1-APP rats at an early pre-plaque stage, systemic treatment of transgenic APP rats with corticosterone modelling certain environmental AD risk factors and, importantly, intracerebral injection of highly disease-relevant AD patient-derived synaptotoxic beta-amyloid and tau in wild-type animals. We found that daily treatment with 40 Hz sensory stimulation for 2 weeks fully abrogated the inhibition of LTP in all three models. Moreover, there was a negative correlation between the magnitude of LTP and the level of active caspase-1 in the hippocampus of transgenic APP animals, which suggests that the beneficial effect of 40 Hz stimulation was dependent on modulation of pro-inflammatory mechanisms. Our findings support ongoing clinical trials of gamma-patterned sensory stimulation in early AD.

The development of visuotactile congruency effects for sequences of events.

Sensitivity to the temporal coherence of visual and tactile signals increases perceptual reliability and is evident during infancy. However, it is not clear how, or whether, bidirectional visuotactile interactions change across childhood. Furthermore, no study has explored whether viewing a body modulates how children perceive visuotactile sequences of events. Here, children aged 5-7 years (n = 19), 8 and 9 years (n = 21), and 10-12 years (n = 24) and adults (n = 20) discriminated the number of target events (one or two) in a task-relevant modality (touch or vision) and ignored distractors (one or two) in the opposing modality. While participants performed the task, an image of either a hand or an object was presented. Children aged 5-7 years and 8 and 9 years showed larger crossmodal interference from visual distractors when discriminating tactile targets than the converse. Across age groups, this was strongest when two visual distractors were presented with one tactile target, implying a "fission-like" crossmodal effect (perceiving one event as two events). There was no influence of visual context (viewing a hand or non-hand image) on visuotactile interactions for any age group. Our results suggest robust interference from discontinuous visual information on tactile discrimination of sequences of events during early and middle childhood. These findings are discussed with respect to age-related changes in sensory dominance, selective attention, and multisensory processing.

Decreased Theta Power Reflects Disruption in Postural Control Networks of Fragile X Premutation Carriers.

FRM1 premutation carriers exhibit various subtle deficits in balance and stability, prior to the development of the movement disorder Fragile X Associated Tremor/Ataxia Syndrome (FXTAS). Force plate posturography has increasingly been combined with the temporal sensitive imaging methods such as EEG to offer insight into the neural mechanisms which govern postural control. This study investigated cortical theta power during continuous balance and its relationship to balance performance in Fragile X premutation carriers. Eight premutation carriers and 6 controls stood on a force platform under altered sensory and cognitive conditions while postural sway and high-density EEG data were simultaneously recorded. Carriers exhibited greater sway area when sensory input was reduced (p=0.01) and cognitive load was increased (p=0.01), as well as significantly reduced frontal theta power compared to the Control Group. The relationship between theta power and postural control seen in the control group may indicate an increase in error detection caused by reduced visual input and greater discrepancies between expected and actual balance state. While the lower theta power in frontal regions of carriers may indicate a disruption in neural networks underpinning postural control. Such results provide new insight into the neural correlates of balance control in Fragile X premutation carriers.

Quantification of Neural Activity in FMR1 Premutation Carriers during a Dynamic Sway Task using Source Localization.

Fragile X-associated Tremor/Ataxia Syndrome is a genetic neurodegenerative disorder affecting carriers of the FMR1 premutation. Not all carriers develop the condition and the age of onset is somewhat variable. A greater understanding of disease progression would be beneficial. Eight carriers and five controls matched by age, sex, and dominant hand volunteered to perform a sway task on a force platform while EEG was simultaneously recorded. Sway parameters were extracted from the movement data at important timepoints throughout their sway cycles and matched to their EEG activity. Distributed source analysis was applied. While there initially appeared to be differences in neural activity between the two groups in the anterior lobe, the right posterior lobe, the right superior parietal lobule and the right parietal lobe, these differences did not survive correction for multiple comparisons.

Cortical Theta Activity and Postural Control in Non-Visual and High Cognitive Load Tasks: Impact for Clinical Studies.

Due to the major role of balance in our everyday lives and the unsatisfying understanding of the role of neural mechanism on balance control, the focus of this study was to explore the role of the cerebral cortex and its effects on stability. We investigated the effects of non-visual and cognitive tasks on balance performance and cortical theta response in a small, convenient sample. The cognitive tasks were N-back and Sustained Attention Response Task (SART). Cortical theta activity showed strong correlations with balance performance metrics. Particularly, central regions showed an increase in theta power in more cognitively challenging tasks but not statistically significant. Parietal theta power had a statistically significant increase in tasks that led to a heavier reliance on proprioception and vestibular information. This study shows the efficacy of EEG recording during balance control tasks. Future studies on neurodegenerative diseases that affect neuromotor control could investigate these outcomes.