Investigating the Effects of Auditory and Vibrotactile Rhythmic Sensory Stimulation on Depression: An EEG Pilot Study.

Background Major depressive disorder (MDD) is a persistent psychiatric condition and one of the leading causes of global disease burden. In a previous study, we investigated the effects of a five-week intervention consisting of rhythmic gamma frequency (30-70 Hz) vibroacoustic stimulation in 20 patients formally diagnosed with MDD. In that study, the findings suggested a significant clinical improvement in depression symptoms as measured using the Montgomery-Asberg Depression Rating Scale (MADRS), with 37% of participants meeting the criteria for clinical response. The goal of the present research was to examine possible changes from baseline to posttreatment in resting-state electroencephalography (EEG) recordings using the same treatment protocol and to characterize basic changes in EEG related to treatment response. Materials and methods The study sample consisted of 19 individuals aged 18-70 years with a clinical diagnosis of MDD. The participants were assessed before and after a five-week treatment period, which consisted of listening to an instrumental musical track on a vibroacoustic device, delivering auditory and vibrotactile stimulus in the gamma-band range (30-70 Hz, with particular emphasis on 40 Hz). The primary outcome measure was the change in Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to posttreatment and resting-state EEG. Results Analysis comparing MADRS score at baseline and post-intervention indicated a significant change in the severity of depression symptoms after five weeks (t = 3.9923, df = 18, p = 0.0009). The clinical response rate was 36.85%. Resting-state EEG power analysis revealed a significant increase in occipital alpha power (t = -2.149, df = 18, p = 0.04548), as well as an increase in the prefrontal gamma power of the responders (t = 2.8079, df = 13.431, p = 0.01442). Conclusions The results indicate that improvements in MADRS scores after rhythmic sensory stimulation (RSS) were accompanied by an increase in alpha power in the occipital region and an increase in gamma in the prefrontal region, thus suggesting treatment effects on cortical activity in depression. The results of this pilot study will help inform subsequent controlled studies evaluating whether treatment response to vibroacoustic stimulation constitutes a real and replicable reduction of depressive symptoms and to characterize the underlying mechanisms.

A monoclonal antibody acts as a migratory cue via Ca2+ re-wiring.

As monoclonal antibodies have two epitopes for their target ligand, they should theoretically dimerize target receptors upon binding. In particular, the dimerization of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) stimulates early events occurring within minutes (e.g. Ca2+ signal generation) and late events occurring over hours and days (e.g. cell migration in angiogenesis). Although studies have noted that antibodies targeting VEGFR2 (anti-VEGFR2) inhibited cell migration in angiogenesis, we show in this paper that an anti-VEGFR2 stimulus nevertheless triggered a Ca2+ signal in VEGFR2 expressing cells. This Ca2+ signal was then re-wired to promote cell migration by co-expressing an engineered Ca2+ activated RhoA (called CaRQ), thereby engineering the opposite anticipated effect of an anti-VEGFR2 antibody. In these cells, the anti-VEGFR2 antibody stimulus induced cellular blebbing, migration across a membrane, and in vitro scratch wound healing. This work expands the utility of monoclonal antibodies to induce tailored responses in engineered cells such as changes in cell fluorescence via Ca2+ reporters or migration patterns via CaRQ.

Genetically Encoded Circuit for Remote Regulation of Cell Migration by Magnetic Fields.

Magnetoreception can be generally defined as the ability to transduce the effects of a magnetic field into a cellular response. Magnetic stimulation at the cellular level is particularly attractive due to its ability for deep penetration and minimal invasiveness, allowing remote regulation of engineered biological processes. Previously, a magnetic-responsive genetic circuit was engineered using the transient receptor potential vanilloid 1 (TRPV1) and the iron containing ferritin protein (i.e., the TF circuit). In this study, we combined the TF circuit with a Ca2+ activated RhoA protein (CaRQ) to allow a magnetic field to remotely regulate cell migration. Cells expressing the TF circuit and CaRQ exhibited consistent dynamic protrusions, leading to migration along a porous membrane, directed spreading in response to a magnetic field gradient, as well as wound healing. This work offers a compelling interface for programmable electrical devices to control the migration of living systems for potential applications in cell-based therapy.

Ca2+-mediated rewiring of cell homing and fusion to VEGF sources.

Challenges of cell-based cancer therapy include effectively homing therapeutic cells to the disease site and producing a controlled response in recognition of the microenvironment. While stem cells have been intensively studied for treating cancer as they naturally home towards sites of injury, they have drawbacks due to their pluripotency. In this paper we have shown that a stable HEK293 cell line expressing VEGFR2 and CarQ (an engineered Ca2+-sensitive RhoA) can home towards a cell colony expressing VEGF. Upon VEGF binding to VEGFR2, a Ca2+ signal is produced that in turn activates CarQ-mediated cell blebbing. With the addition of VSVG, these homing cells can further initiate pH-dependent fusion upon reaching the cell colony. This protein system can form the basis of engineering cells for therapeutic intervention by homing and inhibiting tumour growth by pH-dependent fusion.

Restless leg syndrome: a risk factor of higher prevalence of anxiety and depression in Parkinson's disease patients.

BACKGROUND: Many studies have assessed the relationship of depression and anxiety with Parkinson's disease (PD), as well as examining restless leg syndrome (RLS) with depression and anxiety. Nonetheless, there has not been an extensive effort to show how the prevalence of RLS affects both depression and anxiety in PD patients. The objective of this study was to examine how the prevalence of RLS in PD patients affects the prevalence and severity of depression and anxiety and how they compare with each other. This study is the first of its kind that examines the effects of the combination of the two neurological conditions with depression and anxiety as well as comparing their prevalence and severity to each other. METHODS: The study included 27 PD patients who also suffered from RLS, 27 PD patients not suffering from RLS, and 27 gender-matched healthy individuals. All were evaluated for caseness and severity of both anxiety and depression using the Hospital Anxiety and Depression Scale (HADS); HADS-A and HADS-D, respectively. RESULTS: PD patients with RLS reported having the highest prevalence of both anxiety and depression. The least reported cases for both anxiety and depression were in the control group. In comparison, the results for severity of anxiety and depression within the three groups showed that PD patients with and without RLS had significantly higher severity scores for both anxiety and depression than the control group, but the scores did not significantly differ between the two PD patient groups. CONCLUSION: The presence of RLS in PD patients may increase the occurrence of both anxiety and depression, but the severity of the symptoms is not significant in the two groups of the PD patients.

An Engineered Split Intein for Photoactivated Protein Trans-Splicing.

Protein splicing is mediated by inteins that auto-catalytically join two separated protein fragments with a peptide bond. Here we engineered a genetically encoded synthetic photoactivatable intein (named LOVInC), by using the light-sensitive LOV2 domain from Avena sativa as a switch to modulate the splicing activity of the split DnaE intein from Nostoc punctiforme. Periodic blue light illumination of LOVInC induced protein splicing activity in mammalian cells. To demonstrate the broad applicability of LOVInC, synthetic protein systems were engineered for the light-induced reassembly of several target proteins such as fluorescent protein markers, a dominant positive mutant of RhoA, caspase-7, and the genetically encoded Ca2+ indicator GCaMP2. Spatial precision of LOVInC was demonstrated by targeting activity to specific mammalian cells. Thus, LOVInC can serve as a general platform for engineering light-based control for modulating the activity of many different proteins.

Is action tremor in Parkinson's disease related to resting tremor?

OBJECTIVE: Action tremor (AT) and resting tremor (RT) have been widely cited in many studies with Parkinson's disease (PD) patients, but studies looking at the association between the two tremor types are few and show inconsistent results. This study will look at the prevalence and association of AT and RT in a large sample of idiopathic PD patients, and will put the results into context with the literature. METHODS: A retrospective chart review analysis of 332 patients with idiopathic PD was performed. Prevalence rates of particular tremor types were noted. The presence of AT was analyzed relative to the presence and severity of RT. RESULTS: Nearly all individuals with AT also had RT. The concurrence of the two tremor types was found to be highly significant by statistical analysis (P < 0.0001). The severity of RT, measured by its laterality, may also be of importance, albeit to a much smaller extent if at all. Neither presence of tremor nor type of tremor present was influenced by patient gender, age, or Hoehn and Yahr stage of PD. CONCLUSIONS: The results indicate that AT has extensive presence in PD. This and its seemingly close relationship to RT suggest that AT may be considered a variant of RT, particularly in PD patients. The degree of association between RT and AT needs to be further analyzed in PD, as well as in essential tremor (ET) and ET-PD.