Low-intensity ultrasound restores long-term potentiation and memory in senescent mice through pleiotropic mechanisms including NMDAR signaling

Advanced physiological aging is associated with impaired cognitive performance and the inability to induce long-term potentiation (LTP), an electrophysiological correlate of memory. Here, we demonstrate in the physiologically aged, senescent mouse brain that scanning ultrasound combined with microbubbles (SUS+MB), by transiently opening the blood–brain barrier, fully restores LTP induction in the dentate gyrus of the hippocampus. Intriguingly, SUS treatment without microbubbles (SUSonly), i.e., without the uptake of blood-borne factors, proved even more effective, not only restoring LTP, but also ameliorating the spatial learning deficits of the aged mice. This functional improvement is accompanied by an altered milieu of the aged hippocampus, including a lower density of perineuronal nets, increased neurogenesis, and synaptic signaling, which collectively results in improved spatial learning. We therefore conclude that therapeutic ultrasound is a non-invasive, pleiotropic modality that may enhance cognition in elderly humans.

Individual Alpha Frequency Predicts Perceived Visuotactile Simultaneity

Temporal encoding is a key feature in multisensory processing that leads to the integration versus segregation of perceived events over time. Whether or not two events presented at different offsets are perceived as simultaneous varies widely across the general population. Such tolerance to temporal delays is known as the temporal binding window (TBW). It has been recently suggested that individual oscillatory alpha frequency (IAF) peak may represent the electrophysiological correlate of TBW, with IAF also showing a wide variability in the general population (8–12 Hz). In our work, we directly tested this hypothesis by measuring each individual's TBW during a visuotactile simultaneity judgment task while concurrently recording their electrophysiological activity. We found that the individual's TBW significantly correlated with their left parietal IAF, such that faster IAF accounted for narrower TBW. Furthermore, we found that higher prestimulus alpha power measured over the same left parietal regions accounted for more veridical responses of non-simultaneity, which may be explained either by accuracy in perceptual simultaneity or, alternatively, in line with recent proposals by a shift in response bias from more conservative (high alpha power) to more liberal (low alpha power). We propose that the length of an alpha cycle constrains the temporal resolution within which perceptual processes take place.

Deficits in monitoring self-produced speech in Parkinson’s disease

ObjectiveSpeech deficits are common in Parkinson’s disease, and behavioural findings suggest that the deficits may be due to impaired monitoring of self-produced speech. The neural mechanisms of speech deficits are not well understood. We examined a well-documented electrophysiological correlate of speech self-monitoring in patients with Parkinson’s disease and control participants.MethodsWe measured evoked electroencephalographic responses to self-produced and passively heard sounds (/a/ phonemes) in age-matched controls (N=18), and Parkinson’s disease patients who had minor speech impairment, but reported subjectively experiencing no speech deficits (N=17).ResultsDuring speaking, auditory evoked activity 100 ms after phonation (N1 wave) was less suppressed in Parkinson’s disease than controls when compared to the activity evoked by passively heard phonemes. This difference between the groups was driven by increased amplitudes to self-produced phonemes, and reduced amplitudes passively heard phonemes in Parkinson’s disease.ConclusionsThe finding indicates that auditory evoked activity is abnormally modulated during speech in Parkinson’s patients who do not subjectively notice speech impairment. This mechanism could play a role in producing speech deficits in as the disease progresses.

Prediction errors indexed by the P3 track the updating of complex long-term memory schemas

Memory schemas are higher-level knowledge structures that store an abstraction of multiple previous experiences. They allow us to retain a multitude of information without the cost of storing every detail. Schemas are believed to be relatively stable, but occasionally have to be updated to remain useful in the face of changing environmental conditions. Once a schema is consolidated, schema updating has been proposed to be the result of a prediction-error (PE) based learning mechanism, similar to the updating of less complex knowledge. However, for schema memory this hypothesis has been difficult to test because no sufficiently sensitive tools to track modifications to complex memory schemas existed so far. Current research on the updating of less complex beliefs and at much shorter time scales has identified the P3 as an electrophysiological correlate of PE-induced updating of beliefs. In this study, I recorded electroencephalography and continuous memory measures during the encoding of schema consistent vs. inconsistent material to test the behavioural and neural correlates of schema updating. I observed that PEs predicted the updating of a schema after a 24-hour delay, especially when participants were faced with inconsistent compared to consistent material. Moreover, the P3 amplitude tracked both the PE at the time of learning as well as the updating of the memory schema in the inconsistent condition. These results demonstrate that schema updating in the face of inconsistent information is driven by PE-based learning, and that similar neural mechanisms underlie the updating of consolidated long-term memory schemas and short-term belief structures.

Neurological Worsening After Implantable Pulse Generator Replacement

ABSTRACT:Background:Most of the implantable pulse generators (IPGs) in deep brain stimulation (DBS) used to date are non-rechargeable requiring regular replacements. IPG replacement is a minor surgical procedure, but adverse events including neurological worsening have been reported. In this study, we determine the possibility of neurological worsening after IPG replacement in Parkinson’s disease (PD) cases on chronic DBS therapy (CDT) and its electrophysiological basis along with the therapeutic interventions used to alleviate them.Methods:This study is a retrospective chart review of PD cases on CDT followed at London Movement Disorders Centre from January 2010 to December 2016. Included cases were those who underwent one or more IPG replacement.Results:A total of 45 PD cases on CDT underwent 62 IPG replacements involving 121 channels. Neurological worsening was observed in 16 (35.5%) cases following 17 (27.4%) IPG replacements, all following dual-channel IPG replacements. Tremor (41.2%), speech (35.3%), and gait (23.5%) worsened most commonly. Deviation from the pre-replacement parameters including voltage and impedance resulting in change in total electrical energy delivered (TEED) was the most common electrophysiological correlate, observed in 82.4% (14/17) IPGs having neurological worsening. This included switched laterality in a dual-channel IPG. Neurological worsening in the remaining 17.6% cases was hardware-related.Conclusion:Neurological worsening followed 27.4% of IPG replacements in PD cases on CDT with approximately 82.4% of these being avoidable by carefully monitoring stimulation parameters to match pre-replacement TEED values.

Movement-Related Potentials and Event-Related Potentials

Movement-related cortical potentials (MRCPs) are EEG potentials that occur with movement and are recorded using surface scalp electrodes. A technique termed “EEG-EMG back-averaging” is used to obtain MRCPs. The earliest recordable MRCP is the Bereitschaftspotential or readiness potential. Special EEG averaging techniques may also be used to study the cortical processes underlying cognition. Event-related potentials (ERPs) record the cortical activity evoked by a stimulus charged with cognitive significance. The P300 is the most commonly recorded ERP, elicited in an oddball technique of auditory stimulation; the subject is instructed to attend to a rare stimulus presented among a string of frequent stimuli. Only trials triggered by this rare event are averaged. The P300 may be the electrophysiological correlate of selected attention. The N400, another ERP, is assessed during semantic comprehension of language. The chapter discusses normal variants of MRCPs and ERPs, as well as disruptions secondary to neurological disease.

Sensory Ganglionopathy and the Blink Reflex: Electrophysiological Features

Background: Sensory ganglionopathy (SG) is characterised by asymmetrical sensory fibre degeneration, with the primary pathology occurring at the level of the dorsal root ganglion. It is seen in the context of autoimmune, paraneoplastic, and degenerative disorders. There is limited literature examining the electrophysiological correlate of the trigeminal ganglion and associated pathways, the blink reflex (BR), in cases of SG. Previous work has suggested that the BR is preserved in cases of SG associated with paraneoplasia. Methods: The local clinical neurophysiology database was searched for patients diagnosed with SG from peripheral nerve conduction studies in whom the BR was performed. Twenty-six patients were included in the final analysis. Results: Sjögren’s syndrome constituted the most common SG aetiology (8/26), followed by idiopathic cases (7/26) and paraneoplasia (5/26). BR abnormalities were seen in 9 of the 26 patients (34.6%) across all aetiologies. No patients reported sensory disturbance in the distribution of the trigeminal nerve, indicating that the changes noted are subclinical. Three patients showed abnormality of the R1 response; in the remaining six patients, only R2 responses were affected. Conclusions: Subclinical abnormalities of both R1 and R2 can be seen in the context of SG of varying aetiologies, including paraneoplasia. Performing the BR in patients with suspected of having SG may be helpful in providing additional evidence of patchy sensory fibre involvement that is characteristic of the disease.