Riccardo Bravi

Increased anxiety-like behavior and selective learning impairments are concomitant to loss of hippocampal interneurons in the presymptomatic SOD1(G93A) ALS mouse model.

Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease primarily characterized by motor neuron death, causes damages beyond motor‐related areas. In particular, cognitive impairments and hippocampal damage have been reported in ALS patients. We investigated spatial navigation learning and hippocampal interneurons in a mutant SOD1(G93A) mouse (mSOD1) model of ALS. Behavioral tests were performed by using presymptomatic mSOD1 mice. General motor activity was comparable to that of wild‐type mice in the open‐field test, in which, however mSOD1 exhibited increased anxiety‐like behavior. In the Barnes maze test, mSOD1 mice displayed a delay in learning, outperformed wild‐type mice during the first probe trial, and exhibited impaired long‐term memory. Stereological counts of parvalbumin‐positive interneurons, which are crucial for hippocampal physiology and known to be altered in other central nervous system regions of mSOD1 mice, were also performed. At postnatal day (P) 56, the population of parvalbumin‐positive interneurons in mSOD1 mice was already reduced in CA1 and in CA3, and at P90 the reduction extended to the dentate gyrus. Loss of parvalbumin‐positive hippocampal interneurons occurred mostly during the presymptomatic stage. Western blot analysis showed that hippocampal parvalbumin expression levels were already reduced in mSOD1 mice at P56. The hippocampal alterations in mSOD1 mice could at least partly account for the increased anxiety‐like behavior and deficits in spatial navigation learning. Our study provides evidence for cognitive alterations and damage to the γ‐aminobutyric acid (GABA)ergic system in the hippocampus of murine ALS, thereby revealing selective deficits antecedent to the onset of motor symptoms. J. Comp. Neurol. 523:1622–1638, 2015.

A little elastic for a better performance: kinesiotaping of the motor effector modulates neural mechanisms for rhythmic movements

A rhythmic motor performance is brought about by an integration of timing information with movements. Investigations on the millisecond time scale distinguish two forms of time control, event-based timing and emergent timing. While event-based timing asserts the existence of a central internal timekeeper for the control of repetitive movements, the emergent timing perspective claims that timing emerges from dynamic control of nontemporal movements parameters. We have recently demonstrated that the precision of an isochronous performance, defined as performance of repeated movements having a uniform duration, was insensible to auditory stimuli of various characteristics (Bravi et al., 2014). Such finding has led us to investigate whether the application of an elastic therapeutic tape (Kinesio® Tex taping; KTT) used for treating athletic injuries and a variety of physical disorders, is able to reduce the timing variability of repetitive rhythmic movement. Young healthy subjects, tested with and without KTT, have participated in sessions in which sets of repeated isochronous wrists flexion-extensions (IWFEs) were performed under various auditory conditions and during their recall. Kinematics was recorded and temporal parameters were extracted and analyzed. Our results show that the application of KTT decreases the variability of rhythmic movements by a 2-fold effect: on the one hand KTT provides extra proprioceptive information activating cutaneous mechanoreceptors, on the other KTT biases toward the emergent timing thus modulating the processes for rhythmic movements. Therefore, KTT appears able to render movements less audio dependent by relieving, at least partially, the central structures from time control and making available more resources for an augmented performance.

Neural plasticity and network remodeling: From concepts to pathology

Neuroplasticity has been subject to a great deal of research in the last century. Recently, significant emphasis has been placed on the global effect of localized plastic changes throughout the central nervous system, and on how these changes integrate in a pathological context. Specifically, alterations of network functionality have been described in various pathological contexts to which corresponding structural alterations have been proposed. However, considering the amount of literature and the different pathological contexts, an integration of this information is still lacking. In this paper we will review the concepts of neural plasticity as well as their repercussions on network remodeling and provide a possible explanation to how these two concepts relate to each other. We will further examine how alterations in different pathological contexts may relate to each other and will discuss the concept of plasticity diseases, its models and implications.

Modulation of isochronous movements in a flexible environment: links between motion and auditory experience.

The ability to perform isochronous movements while listening to a rhythmic auditory stimulus requires a flexible process that integrates timing information with movement. Here, we explored how non-temporal and temporal characteristics of an auditory stimulus (presence, interval occupancy, and tempo) affect motor performance. These characteristics were chosen on the basis of their ability to modulate the precision and accuracy of synchronized movements. Subjects have participated in sessions in which they performed sets of repeated isochronous wrist’s flexion–extensions under various conditions. The conditions were chosen on the basis of the defined characteristics. Kinematic parameters were evaluated during each session, and temporal parameters were analyzed. In order to study the effects of the auditory stimulus, we have minimized all other sensory information that could interfere with its perception or affect the performance of repeated isochronous movements. The present study shows that the distinct characteristics of an auditory stimulus significantly influence isochronous movements by altering their duration. Results provide evidence for an adaptable control of timing in the audio–motor coupling for isochronous movements. This flexibility would make plausible the use of different encoding strategies to adapt audio–motor coupling for specific tasks.

Effect of Direction and Tension of Kinesio Taping Application on Sensorimotor Coordination

The present study investigates whether different directions and tensions of Kinesio(®) Tex tape (KT) application differently influence the precision of sensorimotor synchronization, defined as the ability to coordinate actions with predictable external events. 10 healthy participants performed sets of repetitive wrist flexion-extensions synchronized to a series of paced audio stimuli with an inter-onset interval (IOI) of 500 and 400 ms. KT was applied over the wrist and finger extensor muscles. 2 facilitatory (light and moderate tension) and one inhibitory KT applications were used in different sessions. Standard deviation of the asynchrony (SDasy) and percentage difference of SDasy were calculated and compared across KT and the no-KT control cases. Direction and tension of KT application did not differently influence the ability to coordinate rhythmic movements to an auditory stimulus. However, compared with the no-KT control case, SDasy decreased significantly in all KT cases in both 500- and 400-ms IOI. Independent of direction/tension, the effect of KT on improving sensorimotor synchronization is likely associated with variations in the nature of the neuro-anatomical constraints determining the control of voluntary movement. KT is then proposed to be tested on sensorimotor disorders associated with intense repetitive exercise to check for regaining effective motor control.

Music, clicks, and their imaginations favor differently the event‑based timing component for rhythmic movements

The involvement or noninvolvement of a clock-like neural process, an effector-independent representation of the time intervals to produce, is described as the essential difference between event-based and emergent timing. In a previous work (Bravi et al. in Exp Brain Res 232:1663–1675, 2014a. doi:10.1007/s00221-014-3845-9), we studied repetitive isochronous wrist’s flexion–extensions (IWFEs), performed while minimizing visual and tactile information, to clarify whether non-temporal and temporal characteristics of paced auditory stimuli affect the precision and accuracy of the rhythmic motor performance. Here, with the inclusion of new recordings, we expand the examination of the dataset described in our previous study to investigate whether simple and complex paced auditory stimuli (clicks and music) and their imaginations influence in a different way the timing mechanisms for repetitive IWFEs. Sets of IWFEs were analyzed by the windowed (lag one) autocorrelation—wγ(1), a statistical method recently introduced for the distinction between event-based and emergent timing. Our findings provide evidence that paced auditory information and its imagination favor the engagement of a clock-like neural process, and specifically that music, unlike clicks, lacks the power to elicit event-based timing, not counteracting the natural shift of wγ(1) toward positive values as frequency of movements increase.

The effect of fidget spinners on fine motor control

Fidgeting, defined as the generation of small movements through nervousness or impatience, is one of cardinal characteristic of ADHD. While fidgeting is, by definition, a motor experience still nothing is known about the effects of fidgeting on motor control. Some forms of fidgeting involve also the manipulation of external objects which, through repetition, may become automatic and second nature. Both repetition and practice are important for the acquisition of motor skills and, therefore, it is plausible that the repetitive manipulation of objects may influence motor control and performance. As such, fidget spinners, by being diffuse and prone to repetitive usage, may represent interesting tool for improving motor control. In this study we examine the effect of fidget spinners on fine motor control, evaluated by a spiral-tracing task. We show that the use of fidget spinner indeed seems to have a favorable effect on fine motor control, at least in the short term, although this effect does not seem to be in any way inherent to fidget spinners themselves as much as to object manipulation in general. However, due to their widespread usage, fidget spinner may have the advantage of being an enjoyable means for improving fine motor control.

When Non-Dominant Is Better than Dominant: Kinesiotape Modulates Asymmetries in Timed Performance during a Synchronization-Continuation Task

There is a growing consensus regarding the specialization of the non-dominant limb (NDL)/hemisphere system to employ proprioceptive feedback when executing motor actions. In a wide variety of rhythmic tasks the dominant limb (DL) has advantages in speed and timing consistency over the NDL. Recently, we demonstrated that the application of Kinesio® Tex (KT) tape, an elastic therapeutic device used for treating athletic injuries, improves significantly the timing consistency of isochronous wrist’s flexion-extensions (IWFEs) of the DL. We argued that the augmented precision of IWFEs is determined by a more efficient motor control during movements due to the extra-proprioceptive effect provided by KT. In this study, we tested the effect of KT on timing precision of IWFEs performed with the DL and the NDL, and we evaluated the efficacy of KT to counteract possible timing precision difference between limbs. Young healthy subjects performed with and without KT (NKT) a synchronization-continuation task in which they first entrained IWFEs to paced auditory stimuli (synchronization phase), and subsequently continued to produce motor responses with the same temporal interval in the absence of the auditory stimulus (continuation phase). Two inter-onset intervals (IOIs) of 550-ms and 800-ms, one within and the other beyond the boundaries of the spontaneous motor tempo, were tested. Kinematics was recorded and temporal parameters were extracted and analyzed. Our results show that limb advantages in performing proficiently rhythmic movements are not side-locked but depend also on speed of movement. The application of KT significantly reduces the timing variability of IWFEs performed at 550-ms IOI. KT not only cancels the disadvantages of the NDL but also makes it even more precise than the DL without KT. The superior sensitivity of the NDL to use the extra-sensory information provided by KT is attributed to a greater competence of the NDL/hemisphere system to rely on sensory input. The findings in this study add a new piece of information to the context of motor timing literature. The performance asymmetries here demonstrated as preferred temporal environments could reflect limb differences in the choice of sensorimotor control strategies for the production of human movement.

Deletion of the endogenous TrkB.T1 receptor isoform restores the number of hippocampal CA1 parvalbumin-positive neurons and rescues long-term potentiation in pre-symptomatic mSOD1(G93A) ALS mice

ABSTRACT Amyotrophic lateral sclerosis (ALS) causes rapidly progressive paralysis and death within 5 years from diagnosis due to degeneration of the motor circuits. However, a significant population of ALS patients also shows cognitive impairments and progressive hippocampal pathology. Likewise, the mutant SOD1(G93A) mouse model of ALS (mSOD1), in addition to loss of spinal motor neurons, displays altered spatial behavior and hippocampal abnormalities including loss of parvalbumin‐positive interneurons (PVi) and enhanced long‐term potentiation (LTP). However, the cellular and molecular mechanisms underlying these morpho‐functional features are not well understood. Since removal of TrkB.T1, a receptor isoform of the brain‐derived neurotrophic factor, can partially rescue the phenotype of the mSOD1 mice, here we tested whether removal of TrkB.T1 can normalize the number of PVi and the LTP in this model. Stereological analysis of hippocampal PVi in control, TrkB.T1−/−, mSOD1, and mSOD1 mice deficient for TrkB.T1 (mSOD1/T1−/−) showed that deletion of TrkB.T1 restored the number of PVi to physiological level in the mSOD1 hippocampus. The rescue of PVi neuron number is paralleled by a normalization of high‐frequency stimulation‐induced LTP in the pre‐symptomatic mSOD1/T1−/− mice. Our experiments identified TrkB.T1 as a cellular player involved in the homeostasis of parvalbumin expressing interneurons and, in the context of murine ALS, show that TrkB.T1 is involved in the mechanism underlying structural and functional hippocampal degeneration. These findings have potential implications for hippocampal degeneration and cognitive impairments reported in ALS patients at early stages of the disease. HighlightsDeletion of TrkB.T1 (T1) increases parvalbumin‐positive interneurons (PVi) number in the CA3 hippocampal subfield.T1 contributes to the loss of PVi occurring in pre‐symptomatic mSOD1(G93A) ALS mice.Deletion of T1 restores physiological levels of high‐frequency stimulus‐induced LTP in pre‐symptomatic ALS mice.T1 may be involved in the mechanism causing cognitive impairments the mSOD1 mouse model of ALS.

Muscle shortening maneuver and not topical anti-inflammatory therapy is effective in reducing the width of subacromial-subdeltoid bursa in shoulder impingement syndrome

Aim of the study was to compare the efficacy of a muscle shortening maneuver (MSM) with the efficacy of a topical NSAID (flurbiprofen) in patients with subacromial impingement syndrome (SIS). The effects of these therapies were evaluated by sonographic exam (US). SIS was diagnosed by US in 78 patients with painful shoulder. Thirty patients (first group) were treated with topical flurbiprofen for 15 days. Forty-eight patients (second group) were treated with MSM, which was performed once. The shoulder was analyzed in all patients by US before and after treatment. Before treatment and 15 days after treatment, pain by Visual Analogue Scale (VAS), range of motion (ROM) and Neer’s Test were evaluated. Pain was decreased by both treatments. In only 8 patients of the first group, the encroachment of acromion into the rotator cuff was no more detectable by US after the treatment; ROM increased (> 45°) only in 11 patients (36%) and the width of subacromial-subdeltoid bursa (SSB) was not significantly reduced. At variance with the results obtained in the first group, in all patients of the second group the encroachment of acromion was no more detectable by US, ROM increased (> 45°) and the width of SSB was significantly reduced after the maneuver. Both topical flurbiprofen and MSM were helpful in pain control, but better results, with decrease of width of SSB assessed by US, were obtained by MSM.