Short-term plasticity of the motor cortex compensates for bradykinesia in Parkinson's disease

Patients with Parkinson's disease (PD) show impaired short-term potentiation (STP) mechanisms in the primary motor cortex (M1). However, the role played by this neurophysiological abnormality in bradykinesia pathophysiology is unknown. In this study, we used a multimodal neuromodulation approach to test whether defective STP contributes to bradykinesia. We evaluated STP by measuring motor-evoked potential facilitation during 5 Hz-repetitive transcranial magnetic stimulation (rTMS) and assessed repetitive finger tapping movements through kinematic techniques. Also, we used transcranial alternating current stimulation (tACS) to drive M1 oscillations and experimentally modulate bradykinesia. STP was assessed during tACS delivered at beta (β) and gamma (γ) frequency, and during sham-tACS. Data were compared to those recorded in a group of healthy subjects. In PD, we found that STP was impaired during sham- and γ-tACS, while it was restored during β-tACS. Importantly, the degree of STP impairment was associated with the severity of movement slowness and amplitude reduction. Moreover, β-tACS-related improvements in STP were linked to changes in movement slowness and intracortical GABA-A-ergic inhibition during stimulation, as assessed by short-interval intracortical inhibition (SICI). Patients with prominent STP amelioration had greater SICI reduction (cortical disinhibition) and less slowness worsening during β-tACS. Dopaminergic medications did not modify β-tACS effects. These data demonstrate that abnormal STP processes are involved in bradykinesia pathophysiology and return to normal levels when β oscillations increase. STP changes are likely mediated by modifications in GABA-A-ergic intracortical circuits and may represent a compensatory mechanism against β-induced bradykinesia in PD

Investigating the effects of transcranial alternating current stimulation on primary somatosensory cortex

Near-threshold tactile stimuli perception and somatosensory temporal discrimination threshold (STDT) are encoded in the primary somatosensory cortex (S1) and largely depend on alpha and beta S1 rhythm. Transcranial alternating current stimulation (tACS) is a non-invasive neurophysiological technique that allows cortical rhythm modulation. We investigated the effects of tACS delivered over S1 at alpha, beta, and gamma frequencies on near-threshold tactile stimuli perception and STDT, as well as phase-dependent tACS effects on near-threshold tactile stimuli perception in healthy subjects. In separate sessions, we tested the effects of different tACS montages, and tACS at the individualised S1 μ-alpha frequency peak, on STDT and near-threshold tactile stimuli perception. We found that tACS applied over S1 at alpha, beta, and gamma frequencies did not modify STDT or near-threshold tactile stimuli perception. Moreover, we did not detect effects of tACS phase or montage. Finally, tACS did not modify near-threshold tactile stimuli perception and STDT even when delivered at the individualised μ-alpha frequency peak. Our study showed that tACS does not alter near-threshold tactile stimuli or STDT, possibly due to the inability of tACS to activate deep S1 layers. Future investigations may clarify tACS effects over S1 in patients with focal dystonia, whose pathophysiology implicates increased STDT

Painful stimulation increases spontaneous blink rate in healthy subjects

Spontaneous blink rate is considered a biomarker of central dopaminergic activity. Recent evidence suggests that the central dopaminergic system plays a role in nociception. In the present study, we aimed to investigate whether pain modulates spontaneous blink rate in healthy subjects. We enrolled 15 participants. Spontaneous blink rate was quantified with an optoelectronic system before and after: (1) a painful laser stimulation, and (2) an acoustic startling stimulation. In control experiments, we investigated whether laser stimulation effects depended on stimulation intensity and whether laser stimulation induced any changes in the blink reflex recovery cycle. Finally, we investigated any relationship between spontaneous blink rate modification and pain modulation effect during the cold pressor test. Laser, but not acoustic, stimulation increased spontaneous blink rate. This effect was independent of stimulation intensity and negatively correlated with pain perception. No changes in trigeminal-facial reflex circuit excitability were elicited by laser stimulation. The cold pressor test also induced an increased spontaneous blink rate. Our study provides evidence on the role of dopamine in nociception and suggests that dopaminergic activity may be involved in pain modulation. These findings lay the groundwork for further investigations in patients with pathological conditions characterized by dopaminergic deficit and pain

Energetics of running in top level marathon runners from Kenya.

On ten top-level Kenyan marathon runners (KA) plus nine European controls (EC, equivalent to KA), we measured maximal oxygen consumption ( _V O2max) and the energy cost of running (Cr) on track during training camps at moderate altitude, to better understand the KA dominance in the marathon. At each incremental running speed, steady-state oxygen consumption ( _V O2) was measured by telemetric metabolic cart, and lactate by electroenzymatic method. The speed requiring _V O2 ¼ _V O2max provided the maximal aerobic velocity (vmax). The energy cost of running was calculated by dividing net _V O2 by the corresponding speed. The speed at lactate threshold (vHAN)was computed from individual Laˆb versus speed curves. The sustainable _V O2max fraction (Fd) at vHAN (FHAN) was computed dividing vHAN by vmax. The Fd for the marathon (Fmar) was determined as Fmar = 0.92 FHAN. Overall, _VO2max (64.9 ± 5.8 vs. 63.9 ± 3.7 ml kg-1 min-1), vmax (5.55 ± 0.30 vs. 5.41 ± 0.29 m s-1) and Cr (3.64 ± 0.28 vs. 3.63 ± 0.31 J kg-1 m-1) resulted the same in KA as in EC. In both groups, Cr increased linearly with the square of speed. FHAN was 0.896 ± 0.054 in KA and 0.909 ± 0.068 in EC; Fmar was 0.825 ± 0.050 in KA and .836 ± 0.062 in EC (NS). Accounting for altitude, running speed predictions from present data are close to actual running performances, if FHAN instead of Fmar is taken as index of Fd. In conclusion, both KA and EC did not have a very high _V O2max, but had extremely high Fd, and low Cr, equal between them. The dominance of KA over EC cannot be explained on energetic grounds

Plasticity Induced in the Human Spinal Cord by Focal Muscle Vibration

The spinal cord spinal cord has in the past been considered a hardwired system which responds to inputs in a stereotyped way. A growing body of data have instead demonstrated its ability to retain information and modify its effector capabilities, showing activity-dependent plasticity. Whereas, plasticity in the spinal cord is well documented after different forms of physical exercise, whether exogenous stimulation can induce similar changes is still a matter of debate. This issue is both of scientific and clinical relevance, since at least one form of stimulation, i.e., focal muscle vibration (fMV), is currently used as a treatment for spasticity. The aim of the present study was to assess whether fMV can induce plasticity at the SC level when applied to different muscles of the upper limb. Changes in different electrophysiological measures, such as H-reflex testing homonymous and heteronymous pathways, reciprocal inhibition and somatosensory evoked potentials were used as outcomes. We found that fMV was able to induce long-term depression-like plasticity in specific spinal cord circuits depending on the muscle vibrated. These findings helped understand the basic mechanisms underlying the effects of fMV and might help to develop more advanced stimulation protocols

The role of demoralization and hopelessness in suicide risk in schizophrenia: a review of the literature

Background and Objectives: Demoralization has been defined by hopelessness and helplessness attributable to a loss of purpose and meaning in life. Demoralization is a meaningful mental health concern, frequently associated with suicide risk in medical and psychiatric patients. The aim of this systematic review was to synthesize the recent empirical evidence on demoralization in patients with schizophrenia and to better understand the relationship between demoralization and suicide risk in patients with schizophrenia. Methods: A comprehensive literature search using key words and subject headings was performed following PRISMA guidelines with several bibliographic databases, resulting in the identification of 27 studies. Results: The findings suggested that demoralization is prevalent in patients with schizophrenia and supported the hypothesis that the association between depression and suicide is moderated by hopelessness. In clinical practice, it is important to recognize symptoms of demoralization using appropriate psychological tools to better understand the suffering of patients with schizophrenia and to implement suicide prevention programs

“Hard to say, hard to understand, hard to live”: possible associations between neurologic language impairments and suicide risk

In clinical practice, patients with language impairments often exhibit suicidal ideation (SI) and suicidal behavior (SB, covering the entire range from suicide attempts, SA, to completed suicides). However, only few studies exist regarding this subject. We conducted a mini-review on the possible associations between neurologic language impairment (on the motor, comprehension, and semantic sides) and SI/SB. Based on the literature review, we hypothesized that language impairments exacerbate psychiatric comorbidities, which, in turn, aggravate language impairments. Patients trapped in this vicious cycle can develop SI/SB. The so-called “affective prosody” provides some relevant insights concerning the interaction between the different language levels and the world of emotions. This hypothesis is illustrated in a clinical case that we reported, consisting of the case of a 74-year old woman who was admitted to a psychiatric emergency department (ED) after a failed SA. Having suffered an ischemic stroke two years earlier, she suffered from incomplete Broca’s aphasia and dysprosody. She also presented with generalized anxiety and depressive symptoms. We observed that her language impairments were both aggravated by the exacerbations of her anxiety and depressive symptoms. In this patient, who had deficits on the motor side, these exacerbations were triggered by her inability to express herself, her emotional status, and suffering. SI was fluctuant, and—one year after the SA—she completed suicide. Further studies are needed to ascertain possible reciprocal and interacting associations between language impairments, psychiatric comorbidities, and SI/SB. They could enable clinicians to better understand their patient’s specific suffering, as brought on by language impairment, and contribute to the refining of suicide risk detection in this sub-group of affected patients

a transverse and longitudinal mr imaging voxel based morphometry study in patients with primary cervical dystonia

BACKGROUND AND PURPOSE: Findings of standard MR imaging examinations are usually normal in primary CD. These findings are now increasingly challenged by studies using advanced neuroimaging techniques detecting abnormalities in brain areas that may be functionally involved in the pathophysiology of CD. Our purpose was to evaluate GM volumes in patients with CD at baseline and 5 years later. MATERIALS AND METHODS: We enrolled 19 patients (F/M = 15:4, mean age = 53.2 + 11.2 years), 12 of whom were studied at baseline and again approximately 5 years later. Twenty-eight healthy volunteers acted as controls (F/M = 17:11, mean age = 47.5 + 15.6 years). The subjects were imaged with a 1.5T scanner by using a 3D T1-weighted sequence on 150 contiguous axial 1-mm-thick sections to apply VBM. RESULTS: At entry, VBM analysis disclosed significantly lower GM volumes in the left caudate head and putamen and in the premotor and primary sensorimotor cortices bilaterally in patients than in controls. No correlation was found between decreased GM volumes and patient age, severity of dystonia, or disease duration. At the 5-year follow-up, GM volumes in the left primary sensorimotor cortex in patients had decreased significantly from baseline. CONCLUSIONS: The findings obtained at entry and after a 5-year follow-up consistently showed decreased caudate, putamen, and sensorimotor cortex GM volumes in patients with CD, and they probably play a pathophysiologic role in CD

Botulinum toxin A treatment for primary hemifacial spasm - A 10-year multicenter study

BACKGROUND: Botulinum toxin A (BTX) is the currently preferred symptomatic treatment for primary hemifacial spasm (HFS), but its long-term efficacy and safety are not known. OBJECTIVE: To assess the long-term effectiveness and safety of BTX in the treatment of primary HFS. DESIGN: Retrospective review of medical records of the 1st and 10th years of treatment. SETTING: Outpatient clinics of 4 Italian university centers in the Italian Movement Disorders Study Group. PARTICIPANTS: A series of 65 patients with primary HFS who had received BTX injections regularly for at least 10 years. MAIN OUTCOME MEASURES: Mean duration of improvement and quality of the effect induced by the preceding treatment (measured using a patient self-evaluation scale) and occurrence and duration of adverse effects in the 1st and 10th years of treatment. RESULTS: Using a mean BTX dose per treatment session similar to that used by others, we obtained a 95% response rate and an overall mean duration of improvement of 12.6 weeks during year 1. The effectiveness of BTX in relieving the symptoms of primary HFS, as measured by the response rate and average duration of improvement, remained unchanged in the 1st and 10th years. Patients needed statistically similar BTX doses in the 1st and 10th years. The rate of local adverse effects (including upper lid ptosis, facial weakness, and diplopia) diminished significantly in the 10th year of treatment. CONCLUSION: Treatment with BTX effectively induces sustained relief from symptoms of HFS in the long term, with only minimal and transient adverse reactions

The effect of stimulation frequency on transcranial evoked potentials

Introduction - Transcranial magnetic stimulation-evoked electroencephalography potentials (TEPs) have been used to study motor cortical excitability in healthy subjects and several neurological conditions. However, optimal recording parameters for TEPs are still debated. Stimulation rates could affect TEP amplitude due to plasticity effects, thus confounding the assessment of cortical excitability. We tested whether short interpulse intervals (IPIs) affect TEP amplitude.Methods - We investigated possible changes in TEP amplitude and global mean field amplitude (GMFA) obtained with stimulation of the primary motor cortex at IPIs of 1.1-1.4 s in a group of healthy subjects.Results - We found no differences in TEP amplitude or GMFA between the first, second and last third of trials.Discussion - Short IPIs do not affect TEP size and can be used without the risk of confounding effects due to short-term plasticity