Acute inactivation of the medial forebrain bundle imposes oscillations in the SNr: a challenge for the 6-OHDA model?

It has been recently shown that the substantia nigra pars reticulata (SNr) of 6-hydroxydopamine (6-OHDA)-lesioned rats, under urethane anaesthesia, manifests a prominent low frequency oscillation (LFO) of around 1Hz, synchronized with cortical slow wave activity (SWA). Nevertheless, it is poorly understood whether these electrophysiological alterations are correlated only with severe dopamine depletion or may also play a relevant pathogenetic role in the early stages of the dopamine denervation. Hence, here we recorded SNr single units and electrocorticogram (ECoG) in two models of dopamine denervation: (i) acute dopamine denervated rats, obtained by injection of tetrodotoxin (TTX), (ii) chronic dopamine depleted rats, 2 weeks after 6-OHDA lesioning. Both TTX and 6-OHDA were infused into the medial forebrain bundle (MFB). The acute TTX-mediated dopamine depletion caused a fast developing occurrence of a SNr/ECoG coherence, peaking between 0.48 and 1.22 Hz, parallel with a consistent decrease of firing rate (from 22.61 \ub1 7.04 to 15.35 \ub1 9.04 Hz) homolateraly to the infusion. Strikingly, this abnormal 1 Hz synchronization, TTX-mediated was qualitatively similar to the ECoG/SNr synchronization detectable in the 6-OHDA lesioned hemisphere (LH). In addition, TTX infusion in the un-lesioned hemispheres (UH) of 6-OHDA treated rats, produced ECoG/SNr synchronization qualitatively similar to that recordable in the LH. Hence, our data support the proposition that LFO, is tightly correlated to cortex, and represent a critical hallmark of a basal ganglia (BG) failure from the early stages of dopamine denervation

Successful subthalamic stimulation, but levodopa-induced dystonia, in a genetic Parkinson's disease

Recently, it is under scrutiny the possibility to anticipate the stereotactic implantation of the subthalamic nucleus (STN) even in relatively mild Parkinson's disease (PD) patients with an unsatisfying response to drugs. In addition, it is debated whether levodopa (LD) and deep brain stimulation (DBS) are congruent or, instead, mutually exclusive. A 56-year-old LRRK2-positive PD patient, with 7 years of disease history, dominated by severe left resting tremor, was submitted to bilateral implantation of the subthalamic nucleus (STN). Before surgery, the combination of LD and dopamine agonists failed to handle tremor unless administered at doses, which induced undesirable adverse events. STN deep brain stimulation (DBS) abolished tremor but did not provide satisfying control of hypokinetic-rigid symptoms. The condition STIM-ON plus LD, albeit transiently beneficial, installed a painful dystonia developing slowly after 24-36 h. Only a chronic therapy combining rotigotine plus STN-DBS proved effective without side effects. This case report, based upon the surprising difference between the therapeutic response to the combination of LD and dopamine agonist (before surgery) and the combination of DBS and agonist after surgery, emphasizes how STIM and LD target different motor domains through mechanisms with differential plasticity and confirms the efficacy of STN-DBS in LRKK2 patient

An attempt to dissect a peripheral marker based on cell pathology in Parkinson's disease

Peripheral markers in Parkinson’s disease (PD) represent a hot issue to provide early diagnosis and assess disease progression. The gold standard marker of PD should feature the same reliability as the pathogenic alteration, which produces the disease itself. PD is foremost a movement disorder produced by a loss of nigrostriatal dopamine innervation, in which striatal dopamine terminals are always markedly reduced in PD patients to an extent, which never overlaps with controls. Similarly, a reliable marker of PD should possess such a non-overlapping feature when compared with controls. In the present study, we provide a novel pathological hallmark, the autophagosome, which in each PD patient was always suppressed compared with each control subject. Autophagosomes were counted as microtubule-associated proteins 1A/1B light chain 3B (LC3)-positive vacuoles at ultrastructural morphometry within peripheral (blood) blood mononuclear cells (PBMC). This also provides the gold standard to assess the autophagy status. Since autophagy may play a role in the pathogenesis of PD, autophagosomes may be a disease marker, while participating in the biology of the disease. Stoichiometric measurement of α-synuclein despite significantly increased in PD patients, overlapped between PD and control patients. Although the study need to be validated in large populations, the number of autophagy vacuoles is neither related with therapy (the amount was similarly suppressed in a few de novo patients), nor the age in PD or controls

Homovanillic acid in CSF of mild stage Parkinson's disease patients correlates with motor impairment.

In Parkinson's disease (PD), several efforts have been spent in order to find biochemical parameters able to identify the progression of the pathological processes at the basis of the disease. It is already known that advanced PD patients manifesting dyskinesia are featured by the high homovanillic acid (HVA)/dopamine (DA) ratio, suggesting the increased turnover of DA in these patients. Less clear is whether similar changes affect mild and moderate stages of the disease (between 1 and 2.5 of Hoehn & Yahr -H&Y- stage). Hence, here we tested whether cerebrospinal fluid (CSF) concentrations of DA and its major metabolites, either 3,4-dihydroxyphenylacetic acid (DOPAC) or HVA, correlate with motor performance in mild and moderate PD patients. CSF samples were collected after 2 days of anti-PD drugs washout, via lumbar puncture (LP) performed 130 min following administration of oral levodopa (LD) dose (200 mg). LP timing was determined in light of our previous tests clarifying that 2 h after oral LD administration CSF DA concentration reaches a plateau, which was un-respective of PD stage or duration. DA, DOPAC and HVA were assayed by high performance liquid chromatography in a group of 19 patients, distributed in two groups on the basis of the H&Y stage with a cut-off of 1.5. In these PD patients, HVA was correlated with DOPAC (R = 0,56, p < 0,01) and both HVA and DOPAC CSF levels increased in parallel with the motor impairment. More importantly, HVA correlated with motor impairment measured by the Unified Parkinson's Disease Score -III (UPDRS) (R = 0.61; p < 0.0001). The present findings showed the early alteration of the DA pre-synaptic machinery, as documented by the progressive increase of CSF HVA concentrations, which also correlated with PD motor impairment. Therefore, we suggest the potential use of measuring the CSF HVA level as a possible biomarker of PD stage changes in order to monitor the effectiveness of PD-modifying pharmacological therapies

Deep Impression: Audiovisual Deep Residual Networks for Multimodal Apparent Personality Trait Recognition

Here, we develop an audiovisual deep residual network for multimodal apparent personality trait recognition. The network is trained end-to-end for predicting the Big Five personality traits of people from their videos. That is, the network does not require any feature engineering or visual analysis such as face detection, face landmark alignment or facial expression recognition. Recently, the network won the third place in the ChaLearn First Impressions Challenge with a test accuracy of 0.9109

How do you say ‘hello’? Personality impressions from brief novel voices

On hearing a novel voice, listeners readily form personality impressions of that speaker. Accurate or not, these impressions are known to affect subsequent interactions; yet the underlying psychological and acoustical bases remain poorly understood. Furthermore, hitherto studies have focussed on extended speech as opposed to analysing the instantaneous impressions we obtain from first experience. In this paper, through a mass online rating experiment, 320 participants rated 64 sub-second vocal utterances of the word ‘hello’ on one of 10 personality traits. We show that: (1) personality judgements of brief utterances from unfamiliar speakers are consistent across listeners; (2) a two-dimensional ‘social voice space’ with axes mapping Valence (Trust, Likeability) and Dominance, each driven by differing combinations of vocal acoustics, adequately summarises ratings in both male and female voices; and (3) a positive combination of Valence and Dominance results in increased perceived male vocal Attractiveness, whereas perceived female vocal Attractiveness is largely controlled by increasing Valence. Results are discussed in relation to the rapid evaluation of personality and, in turn, the intent of others, as being driven by survival mechanisms via approach or avoidance behaviours. These findings provide empirical bases for predicting personality impressions from acoustical analyses of short utterances and for generating desired personality impressions in artificial voices

Do demographic and clinical features and comorbidities affect the risk of spread to an additional body site in functional motor disorders?

The aim of this study is&nbsp;to assess changes in the body distribution and the semeiology of functional motor disorder (FMD) in patients who reported only one or more than one body site affected at FMD onset. Data were obtained from the Italian Registry of Functional Motor Disorders, which included patients with a diagnosis of clinically definite FMDs. The relationship between FMD features and spread to other body sites was estimated by multivariate Cox regression analysis. We identified 201 (49%) patients who reported only one body site affected at FMD onset and 209 (51%) who reported multiple body sites affected at onset. FMD spread from the initial site to another site in 43/201 (21.4%) patients over 5.7 ± 7.1&nbsp;years in those with only one site affected at FMD onset; FMD spread to an another body site in 29/209 (13.8%) over 5.5 ± 6.5&nbsp;years. The spread of FMD was associated with non-motor functional symptoms and psychiatric comorbidities only in the patients with one body site affected at FMD onset. Our findings provide novel insight into the natural history of FMD. The number of body sites affected at onset does not seem to have a consistent influence on the risk of spread. Furthermore, our findings suggest that psychiatric comorbidities and non-motor functional symptoms may predict the spread of FMD symptoms, at least in patients with one body site affected at onset

The Gettier Intuition from South America to Asia

This article examines whether people share the Gettier intuition (viz. that someone who has a true justified belief that p may nonetheless fail to know that p) in 24 sites, located in 23 countries (counting Hong Kong as a distinct country) and across 17 languages. We also consider the possible influence of gender and personality on this intuition with a very large sample size. Finally, we examine whether the Gettier intuition varies across people as a function of their disposition to engage in “reflective” thinking

Nothing at Stake in Knowledge

In the remainder of this article, we will disarm an important motivation for epistemic contextualism and interest-relative invariantism. We will accomplish this by presenting a stringent test of whether there is a stakes effect on ordinary knowledge ascription. Having shown that, even on a stringent way of testing, stakes fail to impact ordinary knowledge ascription, we will conclude that we should take another look at classical invariantism. Here is how we will proceed. Section 1 lays out some limitations of previous research on stakes. Section 2 presents our study and concludes that there is little evidence for a substantial stakes effect. Section 3 responds to objections. The conclusion clears the way for classical invariantism