Cerebellum to motor cortex paired associative stimulation induces bidirectional STDP-like plasticity in human motor cortex

The cerebellum is crucially important for motor control and adaptation. Recent non-invasive brain stimulation studies have indicated the possibility to alter the excitability of the cerebellum and its projections to the contralateral motor cortex, with behavioral consequences on motor control and adaptation. Here we sought to induce bidirectional spike-timing dependent plasticity (STDP)-like modifications of motor cortex (M1) excitability by application of paired associative stimulation (PAS) in healthy subjects. Conditioning stimulation over the right lateral cerebellum (CB) preceded focal transcranial magnetic stimulation (TMS) of the left M1 hand area at an interstimulus interval of 2 ms (CB→M1 PAS(2 ms)), 6 ms (CB→M1 PAS(6 ms)) or 10 ms (CB→M1 PAS(10 ms)) or randomly alternating intervals of 2 and 10 ms (CB→M1 PAS(Control)). Effects of PAS on M1 excitability were assessed by the motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar-motor cortex inhibition (CBI) in the first dorsal interosseous muscle of the right hand. CB→M1 PAS(2 ms) resulted in MEP potentiation, CB→M1 PAS(6 ms) and CB→M1 PAS(10 ms) in MEP depression, and CB→M1 PAS(Control) in no change. The MEP changes lasted for 30-60 min after PAS. SICI and CBI decreased non-specifically after all PAS protocols, while ICF remained unaltered. The physiological mechanisms underlying these MEP changes are carefully discussed. Findings support the notion of bidirectional STDP-like plasticity in M1 mediated by associative stimulation of the cerebello-dentato-thalamo-cortical pathway and M1. Future studies may investigate the behavioral significance of this plasticity

Paired Associative Electroacupuncture and Transcranial Magnetic Stimulation in Humans

Pairing transcutaneous electric nerve stimulation (TENS) and transcranial magnetic stimulation (TMS) with specific stimulus-intervals induces associative motor plasticity at the primary motor cortex (M1). Electroacupuncture (EA) is an established medical technique in the eastern countries. This study investigates whether EA paired with TMS induces distinct M1 motor plasticity. Fifteen healthy, right-handed subjects (aged 23.6 ± 2.0 years, eight women) were studied. Two-hundred and twenty-five pairs of TMS of the left M1 preceded by right EA at acupoint “Neiguan” [Pericardium 6 (PC6), located 2 decimeters proximal from the wrist wrinkle] were respectively applied with the interstimulus interval (ISI) of individual somatosensory evoked potential (SSEP) N20 latency plus 2 ms (N20+2) and minus 5 ms (N20-5) with at least 1-week interval. The paired stimulation was delivered at a rate of 0.25 Hz. Sham TMS with a sham coil was adopted to examine the low-frequency EA influence on M1 in eleven subjects. M1 excitability was assessed by motor-evoked potential (MEP) recruitment curve with five TMS intensity levels, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar inhibition (CBI) at the abductor pollicis brevis (APB) muscle of the right hand before and after the EA-M1 paired associative stimulation (PAS). In addition, median nerve SSEPs and H-reflex were respectively measured to monitor somatosensory and spinal excitability. The MEP showed significantly facilitated after the sham EA-M1 PAS while tested with 80% of the TMS intensity producing on average 1 mV amplitude (i.e., MEP1 mV) in the resting APB muscle. It was also facilitated while tested with 90% MEP1 mV irrespective of the stimulation conditions. The SSEP showed a higher amplitude from the real EA-M1 PAS compared to that from the sham EA-M1 PAS. No significant change was found on SICI, ICF, CBI and H-reflex. Findings suggest that repetitive low frequency EA paired with real TMS did not induce spike-timing dependent motor plasticity but EA paired with sham TMS induced specific M1 excitability change. Complex sensory afferents with dispersed time locked to the sensorimotor cortical area could hamper instead of enhancing the induction of the spike-timing dependent plasticity (STDP) in M1

Degraded Impairment of Emotion Recognition in Parkinson's Disease Extends from Negative to Positive Emotions

Because of dopaminergic neurodegeneration, patients with Parkinson's disease (PD) show impairment in the recognition of negative facial expressions. In the present study, we aimed to determine whether PD patients with more advanced motor problems would show a much greater deficit in recognition of emotional facial expressions than a control group and whether impairment of emotion recognition would extend to positive emotions. Twenty-nine PD patients and 29 age-matched healthy controls were recruited. Participants were asked to discriminate emotions in Experiment 1 and identify gender in Experiment 2. In Experiment 1, PD patients demonstrated a recognition deficit for negative (sadness and anger) and positive faces. Further analysis showed that only PD patients with high motor dysfunction performed poorly in recognition of happy faces. In Experiment 2, PD patients showed an intact ability for gender identification, and the results eliminated possible abilities in the functions measured in Experiment 2 as alternative explanations for the results of Experiment 1. We concluded that patients' ability to recognize emotions deteriorated as the disease progressed. Recognition of negative emotions was impaired first, and then the impairment extended to positive emotions

P2-30: Discrimination of Facial Expressions in Patients with Parkinson's Disease

Besides movement disorder, patients with Parkinson's disease (PD) are revealed to have non-motor deficits. To fast detect or discriminate emotion stimuli is the basic ability of a human, and this ability implies adaptive value. There were two purposes in this study. The first goal was to investigate the discrimination of facial expressions in PD. The second goal was to investigate whether the fast discrimination of facial expressions in PD related to the level of their motor severities. Twenty-eight PDs and 28 age-matched healthy controls were recruited in this study, and they were asked to discriminate between positive (happiness) and negative (sadness, fear, anger) faces. The results revealed that PD discriminated all faces longer than healthy controls did, and PD also had less accuracy in the condition of happy and sad faces compared with healthy controls. We had further analysis to separate PDs into two subgroups by the cut-off score “35” of UPDRS motor examination (part 3). PDs with lower motor severity performed worse in the condition of sad faces than healthy controls did. Beside the deficits in perceiving negative emotions, the PDs with higher motor severity had dysfunctions in processing happy faces. We concluded that PDs had selective deficits in discriminating facial expressions, and this discriminating ability would be getting worse along with the progress of motor severity

Degraded Impairment of Emotion Recognition in Parkinson’s Disease Extends from Negative to Positive Emotions

Because of dopaminergic neurodegeneration, patients with Parkinson’s disease (PD) show impairment in the recognition of negative facial expressions. In the present study, we aimed to determine whether PD patients with more advanced motor problems would show a much greater deficit in recognition of emotional facial expressions than a control group and whether impairment of emotion recognition would extend to positive emotions. Twenty-nine PD patients and 29 age-matched healthy controls were recruited. Participants were asked to discriminate emotions in Experiment  1 and identify gender in Experiment  2. In Experiment  1, PD patients demonstrated a recognition deficit for negative (sadness and anger) and positive faces. Further analysis showed that only PD patients with high motor dysfunction performed poorly in recognition of happy faces. In Experiment  2, PD patients showed an intact ability for gender identification, and the results eliminated possible abilities in the functions measured in Experiment  2 as alternative explanations for the results of Experiment  1. We concluded that patients’ ability to recognize emotions deteriorated as the disease progressed. Recognition of negative emotions was impaired first, and then the impairment extended to positive emotions

Combining Neuropsychological Assessment with Neuroimaging to Distinguish Early-Stage Alzheimer’s Disease from Frontotemporal Lobar Degeneration in Non-Western Tonal Native Language-Speaking Individuals Living in Taiwan: A Case Series

Neuropsychological tests (NPTs), which are routinely used in clinical practice for assessment of dementia, are also considered to be essential for differential diagnosis of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD), especially the behavioral variants of frontotemporal dementia (bvFTD) and primary progressive aphasia (PPA) at their initial clinical presentations. However, the heterogeneous features of these diseases, which have many overlapping signs, make differentiation between AD and FTLD highly challenging. Moreover, NPTs were primarily developed in Western countries and for native speakers of non-tonal languages. Hence, there is an ongoing dispute over the validity and reliability of these tests in culturally different and typologically diverse language populations. The purpose of this case series was to examine which of the NPTs adjusted for Taiwanese society may be used to distinguish these two diseases. Since AD and FTLD have different effects on individuals’ brain, we combined NPTs with neuroimaging. We found that participants diagnosed with FTLD had lower scores in NPTs assessing language or social cognition than AD participants. PPA participants also had lower measures in the Free and Cued Selective Reminding Test than those diagnosed with bvFTD, while bvFTD participants showed poorer performances in the behavioral measures than PPA participants. In addition, the initial diagnosis was supported by the standard one-year clinical follow-up