Investigations of motor performance with neuromodulation and exoskeleton using leader-follower modality: a tDCS study.

This study investigates how the combination of robot-mediated haptic interaction and cerebellar neuromodulation can improve task performance and promote motor skill development in healthy individuals using a robotic exoskeleton worn on the index finger. The authors propose a leader-follower type of mirror game where participants can follow a leader in a two-dimensional virtual reality environment while the exoskeleton tracks the index finger motion using an admittance filter. The game requires two primary learning phases: the initial phase focuses on mastering the pinching interface, while the second phase centers on predicting the leader's movements. Cerebral transcranial direct current stimulation (tDCS) with anodal polarity is applied to the subjects during the game. It is shown that the subjects' performance improves as they play the game. The combination of tDCS with finger exoskeleton significantly enhances task performance. Our research indicates that modulation of the cerebellum during the mirror game improves the motor skills of healthy individuals. The results also indicate potential uses for motor neurorehabilitation in hemiplegia patients.

Low-threshold spiking interneurons perform feedback inhibition in the lateral amygdala.

Amygdala plays crucial roles in emotional learning. The lateral amygdala (LA) is the input station of the amygdala, where learning related plasticity occurs. The LA is cortical like in nature in terms of its cellular make up, composed of a majority of principal cells and a minority of interneurons with distinct subtypes defined by morphology, intrinsic electrophysiological properties and neurochemical expression profile. The specific functions served by LA interneuron subtypes remain elusive. This study aimed to elucidate the interneuron subtype mediating feedback inhibition. Electrophysiological evidence involving antidromic activation of recurrent LA circuitry via basolateral amygdala stimulation and paired recordings implicate low-threshold spiking interneurons in feedback inhibition. Recordings in somatostatin-cre animals crossed with tdtomato mice have revealed remarkable similarities between a subset of SOM+ interneurons and LTS interneurons. This study concludes that LTS interneurons, most of which are putatively SOM+, mediate feedback inhibition in the LA. Parallels with cortical areas and potential implications for information processing and plasticity are discussed.

Ionic current correlations are ubiquitous across phyla.

Ionic currents, whether measured as conductance amplitude or as ion channel transcript numbers, can vary many-fold within a population of identified neurons. In invertebrate neuronal types multiple currents can be seen to vary while at the same time their magnitudes are correlated. These conductance amplitude correlations are thought to reflect a tight homeostasis of cellular excitability that enhances the robustness and stability of neuronal activity over long stretches of time. Although such ionic conductance correlations are well documented in invertebrates, they have not been reported in vertebrates. Here we demonstrate with two examples, identified mouse hippocampal granule cells (GCs) and cholinergic basal forebrain neurons, that the correlation of ionic conductance amplitudes between different ionic currents also exists in vertebrates, and we argue that it is a ubiquitous phenomenon expressed by many species across phyla. We further demonstrate that in dentate gyrus GCs these conductance correlations are likely regulated in a circadian manner. This is reminiscent of the known conductance regulation by neuromodulators in crustaceans. However, in GCs we observe a more nuanced regulation, where for some conductance pairs the correlations are completely eliminated while for others the correlation is quantitatively modified but not obliterated.

The Validity and Reliability of Turkish Version of the Jenkins Sleep Evaluation Scale in Rheumatoid Arthritis.

OBJECTIVES: This study aims to assess the validity and reliability of the Jenkins Sleep Evaluation Scale (JSS) when applied to a Turkish population with rheumatoid arthritis. PATIENTS AND METHODS: The Turkish version of JSS (JSS-TR) was obtained after translation from English into Turkish, according to standard guidelines. The study included 61 patients of rheumatoid arthritis (13 males, 48 females; mean age 50.5 years; range 19 to 72 years) as defined by the American College of Rheumatology 2010 criteria. The internal consistency (Cronbach's alpha) was assessed for reliability. Content and construct validity (convergent and divergent validities) were evaluated. The relationships between the JSS-TR and the Pittsburgh Sleep Quality Index, the Multidimensional Assessment of Fatigue scale, subgroups of the Nottingham Health Profile, and the Stanford Health Assessment Questionnaire were assessed for convergent validity. In addition, the relationships between the JSS-TR and age, disease duration, visual analog scale patient global score, and disease activity score 28 were assessed for divergent validity. RESULTS: The Cronbach's alpha of JSS-TR was 0.80. All questions and the answer choices for the scale were understood well and related to some dimension of sleep demonstrating good content validity. The JSS-TR had good correlations with functional parameters (which are convergent), and poor or insignificant correlations with non-functional parameters (which are divergent). This implies that the JSS-TR had good construct validity in the context of this study. Overall, the JSS-TR had the best correlation with the Pittsburgh Sleep Quality Index (Spearman's rank correlation coefficient=0.76). CONCLUSION: The JSS-TR is a valid and reliable instrument. It is a simple and effective tool which can be used to evaluate sleep disturbances in rheumatoid arthritis patients in both daily practice and clinical research.

Fatigue in familial Mediterranean fever and its relations with other clinical parameters.

Fatigue is a common problem in patients with rheumatic disease. It may cause disability and poor quality of life. The aim of this study is to investigate fatigue in FMF patients as a disabling symptom and its associations with clinical and demographic variables. FMF patients were recruited into the study according to FMF Tel Hashomer criteria. Control group is composed of healthy individuals. Demographic and clinical features of the patients including PRAS scores were noted. Visual analogue score of pain (VAS-pain) and VAS-fatigue were used as clinical parameters. Pittsburgh Sleep Quality Index (PSQI), Multidimensional Assessment of Fatigue (MAF), Nottingham Health Profile (NHP), Fatigue Severity Scale (FSS), Fatigue Impact Scale (FIS) and Hospital Anxiety and Depression Scale (HADS) were filled out by both control and study group. Sixty-one FMF patients and 61 age and gender (44 female, 17 male in each group)-matched controls were enrolled into the study. Mean age of FMF and control group were 35.5 ± 11.8 and 35.8 ± 11.7 years, respectively. The mean disease duration was 82.5 ± 81.7 months. Difference between mean of VAS-pain, VAS-fatigue, PSQI total score, MAF, all subsets of NHP, FSS, FIS, and HADS scores of FMF patients was significantly higher than of control group (p = 0.0001). This study has shown that fatigue in FMF is associated with a number of psychological, sleep, quality of life and disease-related factors. FMF group had increased pain, fatigue, sleep disturbance and decreased quality of life compared to control group. FMF patients with fatigue may benefit from pharmacological and psychological interventions which target these factors.

Impact of basal forebrain cholinergic inputs on basolateral amygdala neurons.

In addition to innervating the cerebral cortex, basal forebrain cholinergic (BFc) neurons send a dense projection to the basolateral nucleus of the amygdala (BLA). In this study, we investigated the effect of near physiological acetylcholine release on BLA neurons using optogenetic tools and in vitro patch-clamp recordings. Adult transgenic mice expressing cre-recombinase under the choline acetyltransferase promoter were used to selectively transduce BFc neurons with channelrhodopsin-2 and a reporter through the injection of an adeno-associated virus. Light-induced stimulation of BFc axons produced different effects depending on the BLA cell type. In late-firing interneurons, BFc inputs elicited fast nicotinic EPSPs. In contrast, no response could be detected in fast-spiking interneurons. In principal BLA neurons, two different effects were elicited depending on their activity level. When principal BLA neurons were quiescent or made to fire at low rates by depolarizing current injection, light-induced activation of BFc axons elicited muscarinic IPSPs. In contrast, with stronger depolarizing currents, eliciting firing above ∼ 6-8 Hz, these muscarinic IPSPs lost their efficacy because stimulation of BFc inputs prolonged current-evoked afterdepolarizations. All the effects observed in principal neurons were dependent on muscarinic receptors type 1, engaging different intracellular mechanisms in a state-dependent manner. Overall, our results suggest that acetylcholine enhances the signal-to-noise ratio in principal BLA neurons. Moreover, the cholinergic engagement of afterdepolarizations may contribute to the formation of stimulus associations during fear-conditioning tasks where the timing of conditioned and unconditioned stimuli is not optimal for the induction of synaptic plasticity.

Adult mouse basal forebrain harbors two distinct cholinergic populations defined by their electrophysiology.

We performed whole-cell recordings from basal forebrain (BF) cholinergic neurons in transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the choline acetyltransferase promoter. BF cholinergic neurons can be differentiated into two electrophysiologically identifiable subtypes: early and late firing neurons. Early firing neurons (∼70%) are more excitable, show prominent spike frequency adaptation and are more susceptible to depolarization blockade, a phenomenon characterized by complete silencing of the neuron following initial action potentials. Late firing neurons (∼30%), albeit being less excitable, could maintain a tonic discharge at low frequencies. In voltage clamp analysis, we have shown that early firing neurons have a higher density of low voltage activated (LVA) calcium currents. These two cholinergic cell populations might be involved in distinct functions: the early firing group being more suitable for phasic changes in cortical acetylcholine release associated with attention while the late firing neurons could support general arousal by maintaining tonic acetylcholine levels.

Synaptic correlates of fear extinction in the amygdala.

Anxiety disorders such as post-traumatic stress are characterized by an impaired ability to learn that cues previously associated with danger no longer represent a threat. However, the mechanisms underlying fear extinction remain unclear. We found that fear extinction in rats was associated with increased levels of synaptic inhibition in fear output neurons of the central amygdala (CEA). This increased inhibition resulted from a potentiation of fear input synapses to GABAergic intercalated amygdala neurons that project to the CEA. Enhancement of inputs to intercalated cells required prefrontal activity during extinction training and involved an increased transmitter release probability coupled to an altered expression profile of ionotropic glutamate receptors. Overall, our results suggest that intercalated cells constitute a promising target for pharmacological treatment of anxiety disorders.

Long-lasting dysregulation of gene expression in corticostriatal circuits after repeated cocaine treatment in adult rats: effects on zif 268 and homer 1a.

Human imaging studies show that psychostimulants such as cocaine produce functional changes in several areas of cortex and striatum. These may reflect neuronal changes related to addiction. We employed gene markers (zif 268 and homer 1a) that offer a high anatomical resolution to map cocaine-induced changes in 22 cortical areas and 23 functionally related striatal sectors, in order to determine the corticostriatal circuits altered by repeated cocaine exposure (25 mg/kg, 5 days). Effects were investigated 1 day and 21 days after repeated treatment to assess their longevity. Repeated cocaine treatment increased basal expression of zif 268 predominantly in sensorimotor areas of the cortex. This effect endured for 3 weeks in some areas. These changes were accompanied by attenuated gene induction by a cocaine challenge. In the insular cortex, the cocaine challenge produced a decrease in zif 268 expression after the 21-day, but not 1-day, withdrawal period. In the striatum, cocaine also affected mostly sensorimotor sectors. Repeated cocaine resulted in blunted inducibility of both zif 268 and homer 1a, changes that were still very robust 3 weeks later. Thus, our findings demonstrate that cocaine produces robust and long-lasting changes in gene regulation predominantly in sensorimotor corticostriatal circuits. These neuronal changes were associated with behavioral stereotypies, which are thought to reflect dysfunction in sensorimotor corticostriatal circuits. Future studies will have to elucidate the role of such neuronal changes in psychostimulant addiction.