Investigation of Autonomic Dysfunction in Alzheimer's Disease-A Computational Model-Based Approach.

(1) Background and Objective: Alzheimer's disease (AD) is commonly accompanied by autonomic dysfunction. Investigating autonomic dysfunction's occurrence patterns and severity may aid in making a distinction between different dementia subtypes, as cardiac autonomic dysfunction and AD severity are correlated. Heart rate variability (HRV) allows for a non-invasive assessment of the autonomic nervous system (ANS). AD is characterized by cholinergic depletion. A computational model of ANS based on the kinetics of acetylcholine and norepinephrine is used to simulate HRV for various autonomic states. The model has the flexibility to suitably modulate the concentration of acetylcholine corresponding to different autonomic states. (2) Methods: Twenty clinically plausible AD patients are compared to 20 age- and gender-matched healthy controls using HRV measures. Statistical analysis is performed to identify the HRV parameters that vary significantly in AD. By modulating the acetylcholine concentration in a controlled manner, different autonomic states of Alzheimer's disease are simulated using the ANS model. (3) Results: In patients with AD, there is a significant decrease in vagal activity, sympathovagal imbalance with a dominant sympathetic activity, and change in the time domain, frequency domain, and nonlinear HRV characteristics. Simulated HRV features corresponding to 10 progressive states of AD are presented. (4) Conclusions: There is a significant difference in the HRV features during AD. As cholinergic depletion and autonomic dysfunction have a common neurological basis, autonomic function assessment can help in diagnosis and assessment of AD. Quantitative models may help in better comprehending the pathophysiology of the disease and assessment of its progress.

Quality of life assessment in the first episode of acute coronary syndrome.

Background: Assessment of health-related quality of life (HRQoL) is an important measure of a patient's recovery after an illness. However, HRQoL among acute coronary syndrome (ACS) survivors has not been extensively studied following cardiac management. Aim: The purpose of this study was to assess the quality of life (QoL) among ACS patients who have undergone percutaneous coronary intervention (PCI). Methods: This cohort study included 145 consecutive male ACS patients between March 2021 and May 2022. Of these patients, 138 (mean age 54.3 ± 10.7 years) completed the QoL assessment using the short form-12 (SF-12) health survey questionnaire. Seventy (51%) of them presented with ST-segment elevation myocardial infarction (STEMI), 18 (13%) had non-STEMI, 39 (28%) had evolved MI, and 11 (8%) had unstable angina. Recruited patients' QoL data were assessed at various time points post-PCI. Results: At the end of the 12 months of follow-up, major clinical events (MCE) defined as death, sudden death, or re-acute myocardial infarction occurred in 54.9% of patients. Out of 7 MCE, four deaths and three re-AMIs had occurred. SF-12 physical component score was found to be significantly improved when compared to the mental component score, which seems to improve without reaching statistical significance over time. Among event-free ACS patients, we found a significant positive correlation between left ventricular ejection fraction and HRQoL. Conclusion: Improvement in HRQoL (physical component) was seen among ACS patients post-PCI. Relevance for Patients: QoL assessment outcomes should be considered in clinical settings, practice guidelines, and treatment modality post-PCI to improve QoL in post-ACS survivors.

Effects of an 18-Week Integrated Yoga Program on Cardiac Autonomic Function in Breast Cancer Patients Undergoing Adjuvant Chemotherapy: A Randomized Controlled Trial.

BACKGROUND: Cardiotoxicity is a commonly observed adverse effect seen in breast cancer (BC) patients undergoing chemotherapy with attributes toward cardiac autonomic dysfunction (CAD). Yoga, a mind-body system of medicine that has been shown to improve cardiac autonomic nervous system (ANS) activity in various health conditions, could be an effective adjuvant approach in addressing CAD. OBJECTIVE: This study aims to investigate the protective effects of Integrated Yoga Therapy (IYT) on ANS functioning, assessed using Heart rate variability (HRV) in breast cancer patients undergoing chemotherapy. METHODS: A total of 68 (stage I-III) BC patients were randomly assigned into 2 groups: Treatment as Usual group (TAU) and TAU with Yoga Therapy group (TAUYT). All patients underwent anthracycline-based adjuvant chemotherapy for a total of 6 cycles with 21 days/cycle. During chemotherapy, the TAUYT group received IYT 5 days a week for 18 weeks, compared with usual care alone in the TAU group. Resting heart rate (RHR) and HRV, measured in both the time and frequency domains, were used to assess the cardiac ANS function of each patient before and after 6 cycles of chemotherapy. RESULTS: A total of 30 subjects in the TAU group and 29 subjects in the TAUYT group were included in the analysis. At baseline (before chemotherapy), there were no significant differences between the TAU and TAUYT groups in terms of RHR and HRV indices. However, after chemotherapy, patients in the TAU group had a significantly higher average RHR (P < .02) and lower HRV indices with reduced parasympathetic indices: RMSSD (P < .01), pNN50% (P < .04), high-frequency power (P < .001) and increased sympathetic indices: low-frequency power (P < .001) with sympathovagal imbalance: LF/HF (P < .001) compared with patients in the TAUYT group. CONCLUSION: The study showed the protective effects of yoga therapy on CAD in patients receiving anthracycline-based chemotherapy for BC, proposing yoga as a potential adjuvant intervention in improving cardiac health and preventing cardiovascular-related morbidities. TRIAL REGISTRATION: This trial is registered with the Clinical Trials Registry-India (CTRI) database (CTRI/2020/10/028446; October 16, 2020).

Evaluation of Cardiac, Autonomic Functions in Ambulant Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder caused by dystrophin gene mutation resulting in muscle weakness, motor delays, difficulty in standing, and inability to walk by 12 years. As disease progresses, it leads to cardiac and respiratory failure. Evaluation of cardiac autonomic status and echocardiography in DMD patients at a young age can be a potential biomarker to assess disease progression. This study aimed to investigate the younger DMD population of 5-11years of age with mild to moderate cardiac involvement for early detection using non-invasive and cost-effective tools. Genetically confirmed male DMD patients, aged 5-11 years (n = 47), screened from the outpatient department of a tertiary neuroscience institution were subjected to heart rate variability and echocardiographic analysis, and values were correlated with their clinical variables. DMD patients showed a significantly higher difference in HR, interventricular septum, E m/s, and E-wave to A-wave (E/A) ratio than normal values (p < 0.001). Significantly higher HR indicates initial sinus tachycardia and decreased IVD (d), and increased E m/s and E/A ratio mark the onset of cardiac symptoms in DMD patients even though its chamber dimension remains normal and are associated with cardiac muscle fibrosis.

Neuro-Cardio-Autonomic Modulations in Children with Duchenne Muscular Dystrophy.

BACKGROUND AND OBJECTIVE: Duchenne muscular dystrophy (DMD) is a degenerative X-linked muscle disease. Death frequently results from complications in cardiopulmonary systems. Preclinical/early diagnosis of cardiac autonomic abnormalities may aid initiate cardioprotective therapy and enhance prognosis. METHODS: A cross sectional, prospective study of 38 DMD boys compared with 37 age-matched healthy controls was conducted. Lead II electrocardiography and beat-to-beat blood pressure were recorded to assess heart rate variability (HRV), blood pressure variability (BPV), and baroreceptor sensitivity (BRS) in a standardized environment. Data were analysed and correlated with disease severity and genotype. RESULTS: In the DMD group, the median age at assessment was 8 years [IQR 7-9 years], the median age at disease onset was 3 years [IQR, 2-6 years], and the mean duration of illness was 4 years [IQR, 2.5-5]. DNA sequencing showed deletions in 34/38 (89.5 %) and duplications in 4/38 (10.5%) patients. The median heart rate in DMD children was significantly higher [101.19 (Range, 94.71-108.49)] /min compared to controls [81 (Range, 76.2-92.76)] /min (p < 0.05). All the assessed HRV and BPV parameters were significantly impaired in DMD cases except for the coefficient of variance of systolic blood pressure. Further, BRS parameters were also significantly reduced in DMD, excluding alpha-LF. A positive correlation was found between alpha HF with age at onset and duration of illness. CONCLUSION: This study demonstrates a distinct early impairment of neuro-cardio-autonomic regulation in DMD. Simple yet effective non-invasive techniques such as HRV, BPV, and BRS may help identify cardiac dysfunction in a pre-clinical state, paving the way for early cardio-protective therapies and limiting disease progression in DMD patients.

Long-Term Recording of Subthalamic Aperiodic Activities and Beta Bursts in Parkinson's Disease.

BACKGROUND: Local field potentials (LFPs) represent the summation of periodic (oscillations) and aperiodic (fractal) signals. Although previous studies showed changes in beta band oscillations and burst characteristics of the subthalamic nucleus (STN) in Parkinson's disease (PD), how aperiodic activity in the STN is related to PD pathophysiology is unknown. OBJECTIVES: The study aimed to characterize the long-term effects of STN-deep brain stimulation (DBS) and dopaminergic medications on aperiodic activities and beta bursts. METHODS: A total of 10 patients with PD participated in this longitudinal study. Simultaneous bilateral STN-LFP recordings were conducted in six separate visits during a period of 18 months using the Activa PC + S device in the off and on dopaminergic medication states. We used irregular-resampling auto-spectral analysis to separate oscillations and aperiodic components (exponent and offset) in the power spectrum of STN-LFP signals in beta band. RESULTS: Our results revealed a systematic increase in both the exponent and the offset of the aperiodic spectrum over 18 months following the DBS implantation, independent of the dopaminergic medication state of patients with PD. In contrast, beta burst durations and amplitudes were stable over time and were suppressed by dopaminergic medications. CONCLUSIONS: These findings indicate that oscillations and aperiodic activities reflect at least partially distinct yet complementary neural mechanisms, which should be considered in the design of robust biomarkers to optimize adaptive DBS. Given the link between increased gamma-aminobutyric acidergic (GABAergic) transmission and higher aperiodic activity, our findings suggest that long-term STN-DBS may relate to increased inhibition in the basal ganglia. © 2022 International Parkinson and Movement Disorder Society.

Resting heart rate variability as a diagnostic marker of cardiovascular dysautonomia in postural tachycardia syndrome.

OBJECTIVES: Postural orthostatic tachycardia syndrome (POTS) is a disorder of the autonomic nervous system characterised by orthostatic intolerance and orthostatic tachycardia without hypotension. Heart rate variability (HRV) is the most reliable and objective tool for assessing autonomic dysfunction severity. In the present study, we aimed to investigate HRV changes in resting supine position, predicting severity and cardiovascular risk in patients with POTS. METHODS: We compared 100 POTS patients with 160 healthy controls matched for age and gender in a case-control design. Along with clinical characterization, heart rate variability was evaluated using ambulatory 5 min ECG in lead II and expressed in frequency and time-domain measures. RESULTS: The resting heart rate of patients with POTS was significantly higher than that of healthy controls. In HRV measures, root mean square successive difference of RR intervals (RMSSD), total and high frequency (HF) powers were statistically lower with an increased low frequency (LF) to high-frequency ratio in patients with POTS compared to healthy controls. Further, stepwise logistic regression analysis showed increased basal HR and LF/HF as significant predictors of POTS and its severity. CONCLUSIONS: This is the first study on a large cohort of patients with POTS from India wherein HRV was assessed. The study showed reduced parasympathetic activity and increased sympathetic activity in patients with POTS compared to healthy controls. These findings of increased resting heart rate and LF/HF were found to be potential predictors of POTS and future cardiovascular risks, which need to be replicated in a larger and more homogenized cohort.

Prognostic value of heart rate variability in acute coronary syndrome.

OBJECTIVES: To assess the predictive value of pre-discharge heart rate variability (HRV) parameters in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI). METHODS: 145 consecutive male patients with ACS (aged 57.12 ± 10.81 years) were included in this study. Fifteen minutes electrocardiogram recording was done to measure time-domain [standard deviation of N-N intervals (SDNN), root-mean square differences of successive R-R intervals (rMSSD)] and frequency-domain [low-frequency (LF) power, high-frequency (HF) power and total power (TP)] HRV parameters before and after PCI. The primary end point was the occurrence of major clinical events (MCE) defined as death, sudden death or re-acute myocardial infarction at the end of 3 months follow-up. RESULTS: At a follow-up of 3 months, MCE occurred in 06 patients (4.14%) (Cardiac death was 3.01%, while that of sudden death was 1.13%). Out of six-MCE, four deaths and two re-AMIs occurred. Pre-discharge HRV values (SDNN, rMSSD, TP, LF and HF) were significantly lower in patients with ACS without MCE. Only total power HRV index (AUC=0.748; p=0.040) showed greater prognostic accuracy. CONCLUSIONS: In conclusion, study showed an increase in SDNN, rMSSD, LF, HF and TP after successful revascularization with PCI in patients who had MCE. The resultant sensitivity, specificity of HRV is still limited in the present study. Particularly, its sensitivity is higher (33-83%) with a modest specificity (61-72%).

Impact of integrated yoga therapy on cognitive impairment and cardiac dysfunction in relation to quality of life in breast cancer patients undergoing chemotherapy: Study protocol for a two-arm randomized controlled trial.

Background: Chemotherapy-related cognitive impairment (CRCI) and cardiac dysfunction (CRCD) are common adverse effects seen in breast cancer patients undergoing chemotherapy. Even though these effects significantly influence daily functioning and overall quality of life, effective strategies to avoid and/or mitigate these adverse effects remain elusive. Yoga as a Mind-body intervention has been used increasingly by cancer patients and has undergone empirical investigations as a potential intervention for patients with cancer. Furthermore, yoga is associated with improved cognition and cardiac functioning in healthy older adults and subjects with cognitive and cardiac impairments. Accordingly, in the current study, yoga holds promise as an intervention to prevent/manage CRCI and CRCD with improved overall QOL in women receiving chemotherapy for breast cancer. Methods: The study is a two-arm, randomized controlled trial. Women diagnosed with stage I-III breast cancer and awaiting neo-adjuvant or adjuvant chemotherapy will be recruited from a tertiary care center in Bangalore, India. Following recruitment, subjects are randomized to the intervention group (integrated yoga therapy intervention during chemotherapy) or the control group (standard care during chemotherapy). The study's primary outcome is to measure the quality of life (cognitive domain) using European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The other primary objectives will include cognitive functioning using neuropsychological test battery and cardiac autonomic function testing using heart rate variability. Secondary outcomes are Brain-derived neurotrophic factor (BDNF), brain function (functional MRI), Echocardiography, serum cortisol, Functional assessment of cancer therapy-cognition (FACT-Cog V3), perceived stress scale and Ryff Scales of Psychological Well-Being. Assessments take place before, during and after chemotherapy; 16-weeks post chemotherapy and 1-year post-baseline. Discussion: Yoga is a promising intervention for preventing and/or managing chemotherapy-related adverse effects (CRAE) and enhancing the quality of life among breast cancer patients. The findings from this study may also help understand the inner mechanisms involved in the protective and restorative effects of yoga on CRAE and support the use of yoga prophylactically for breast cancer patients. In addition, the results of this study could help chemotherapy-exposed individuals with other solid cancer types who have cognitive and cardiac issues. Ethics and Dissemination: The study is approved by the ethics committee of the HealthCare Global Enterprises Ltd. Hospital (EC/434/19/01) and National Institute of Mental Health and Neurosciences (NIMH/DO/ETHICS SUB-COMMITTEE (BS&NS) 9th MEETING/2018). Clinical Trial Registration: http://ctri.nic.in/Clinicaltrials/advancesearchmain.php, identifier CTRI/2020/10/028446.

Cardiac autonomic dysfunctions in type 2 diabetes mellitus: an investigative study with heart rate variability measures.

Cardiac autonomic neuropathy (CAN) is a common yet underdiagnosed complication of Type 2 diabetes mellitus (T2DM). Heart rate variability (HRV), a sensitive diagnostic marker of cardiovascular risk, could help detect CAN at its earliest stage. However, the progression of CAN based on age and disease duration in T2DM is lacking. In this study, we propose to explore the occurrence of CAN in patients with varying stages and duration of T2DM. This cross-sectional study involves participants with T2DM (n = 160) and healthy volunteers (n = 40) with an age range of 30-60 years of both genders. Patients in the T2DM group were further subdivided into four subgroups based on their disease duration [Prediabetes, disease duration <5 yrs (D1), 5-10 yrs (D2), and >10 yrs (D3)]. All participants underwent short-term HRV recording for 20 minutes and analyzed for both time and frequency domain measures. The study results showed a significant increase in Heart Rate (HR) in D1 (P = 0.031) and D3 (P = 0.001) groups compared to healthy controls. The time-domain measures of HRV were significantly reduced in the T2DM group compared to the healthy controls. Furthermore, this reduction is more intense in the D3 group than in D2 and D1. Correspondingly, in frequency domain parameters: total power, high-frequency power, and low-frequency power were significantly reduced in all the T2DM groups compared to healthy controls. The study concludes that the overall HRV (as determined by total power), sympathetic activity (low frequency power) and parasympathetic activity (time domain measures and high frequency power) were significantly reduced in all the diabetic subgroups except prediabetes as compared to the healthy controls, implying that both sympathetic and parasympathetic limbs are symmetrically affected in T2DM patients even in the earliest stages (<5 yrs) implying subclinical cardiac autonomic dysfunction in the earliest stages.

Variation of cerebrospinal fluid in specific regions regulates focality in transcranial direct current stimulation.

Background: Conventionally, transcranial direct current stimulation (tDCS) aims to focalize the current reaching the target region-of-interest (ROI). The focality can be quantified by the dose-target-determination-index (DTDI). Despite having a uniform tDCS setup, some individuals receive focal stimulation (high DTDI) while others show reduced focality ("non-focal"). The volume of cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) underlying each ROI govern the tDCS current distribution inside the brain, thereby regulating focality. Aim: To determine the regional volume parameters that differentiate the focal and non-focal groups. Methods: T1-weighted images of the brain from 300 age-sex matched adults were divided into three equal groups- (a) Young (20 ≤ × < 40 years), (b) Middle (40 ≤ × < 60 years), and (c) Older (60 ≤ × < 80 years). For each group, inter and intra-hemispheric montages with electrodes at (1) F3 and right supraorbital region (F3-RSO), and (2) CP5 and Cz (CP5-Cz) were simulated, targeting the left- Dorsolateral Prefrontal Cortex (DLPFC) and -Inferior Parietal Lobule (IPL), respectively. Both montages were simulated for two current doses (1 and 2 mA). For each individual head simulated for a tDCS configuration (montage and dose), the current density at each region-of-interest (ROI) and their DTDI were calculated. The individuals were categorized into two groups- (1) Focal (DTDI ≥ 0.75), and (2) Non-focal (DTDI < 0.75). The regional volume of CSF, GM, and WM of all the ROIs was determined. For each tDCS configuration and ROI, three 3-way analysis of variance was performed considering- (i) GM, (ii) WM, and (iii) CSF as the dependent variable (DV). The age group, sex, and focality group were the between-subject factors. For a given ROI, if any of the 3 DV's showed a significant main effect or interaction involving the focality group, then that ROI was classified as a "focal ROI." Results: Regional CSF was the principal determinant of focality. For interhemispheric F3-RSO montage, interaction effect (p < 0.05) of age and focality was observed at Left Caudate Nucleus, with the focal group exhibiting higher CSF volume. The CSF volume of focal ROI correlated positively (r ∼ 0.16, p < 0.05) with the current density at the target ROI (DLPFC). For intrahemispheric CP5-Cz montage, a significant (p < 0.05) main effect was observed at the left pre- and post-central gyrus, with the focal group showing lower CSF volume. The CSF volume correlated negatively (r ∼ -0.16, p < 0.05) with current density at left IPL. The results were consistent for both current doses. Conclusion: The CSF channels the flow of tDCS current between electrodes with focal ROIs acting like reservoirs of current. The position of focal ROI in the channel determines the stimulation intensity at the target ROI. For focal stimulation in interhemispheric F3-RSO, the proximity of focal ROI reserves the current density at the target ROI (DLPFC). In contrast, for intrahemispheric montage (CP5-Cz), the far-end location of focal ROI reduces the current density at the target (IPL).

Efficacy of Non-contact BallistocardiographySystem to Determine Heart Rate Variability.

Background: Functions of the autonomic nervous system have cardinal importance in day-to-day life. Heart rate variability (HRV) has been shown to estimate the functioning of the autonomic nervous system. Imbalance in the functioning of the autonomic nervous system is seen to be associated with chronic conditions such as chronic kidney disease, cardiovascular diseases, diabetes mellitus, and so on. Purpose: To evaluate the efficacy of a non-contact ballistocardiography (BCG) system to calculate HRV parameters by comparing them to the parameters derived from a standard commercial software that uses an electrocardiogram (ECG). Methods: Current study captured an ECG signal using a three-channel ECG Holter machine, whereas the BCG signal was captured using a BCG sensor sheet consisting of vibroacoustic sensors placed under the mattress of the participants of the study. Results: The study was conducted on 24 subjects for a total of 54 overnight recordings. The proposed method covered 97.92% epochs of the standard deviation of NN intervals (SDNN) and 99.27% epochs of root mean square of successive differences (RMSSD) within 20 ms and 30 ms tolerance, respectively, whereas 98.84% of two-min intervals for low-frequency (LF) to high-frequency (HF) ratio was covered within a tolerance of 1. Kendall's coefficient of concordance was also calculated, giving a P < .001 for all the three parameters and coefficients 0.66, 0.55, and 0.44 for SDNN, RMSSD, and LF/HF, respectively. Conclusion: The results show that HRV parameters captured using unobtrusive and non-invasive BCG sensors are comparable to HRV calculated using ECG.

Clinical neurophysiology of Parkinson's disease and parkinsonism.

This review is part of the series on the clinical neurophysiology of movement disorders. It focuses on Parkinson's disease and parkinsonism. The topics covered include the pathophysiology of tremor, rigidity and bradykinesia, balance and gait disturbance and myoclonus in Parkinson's disease. The use of electroencephalography, electromyography, long latency reflexes, cutaneous silent period, studies of cortical excitability with single and paired transcranial magnetic stimulation, studies of plasticity, intraoperative microelectrode recordings and recording of local field potentials from deep brain stimulation, and electrocorticography are also reviewed. In addition to advancing knowledge of pathophysiology, neurophysiological studies can be useful in refining the diagnosis, localization of surgical targets, and help to develop novel therapies for Parkinson's disease.

Immediate Effects of OM Chanting on Heart Rate Variability Measures Compared Between Experienced and Inexperienced Yoga Practitioners.

Background: Chanting "OM" is a form of meditation that has numerous health benefits. However, the neurophysiological mechanisms underpinning its effect are surprisingly scarce. The present study aimed to investigate the effect of OM chanting on autonomic modulation, using heart rate variability (HRV), on experienced yoga practitioners and yoga naïve persons. Methods: This prospective study included 19 yoga practitioners (9 females and 10 males; group mean age ± standard deviation [SD]; 25.9 ± 3.2 years) and 17 yoga naïve persons (8 females and 9 males; group mean age ± SD; 24.8 ± 3.6 years) of both sexes and similar age range. Both the groups were assessed for HRV indices (time and frequency domain measures) before and after loud OM chanting for 5 min. Results: Baseline comparison using Mann-Whitney U test between groups showed yoga practitioners had significantly increased high frequency (HF) power (P < 0.029) than nonyoga practitioners, signifying a state of tranquility before the chanting of OM. After 5 min of loud chanting of OM, a comparison between groups assessed using Wilcoxon Signed Ranks test revealed: HF Power, a component of the parasympathetic nervous system, was further amplified with a significantly increase (P < 0.001) in the yoga practitioners group compared to nonyoga practitioners. Furthermore, this increase in HF power was positively correlated with the years of experience in yoga. Conclusion: The present study showed that a brief chanting of OM (5 min) might enhance parasympathetic nervous system activity, promote relaxation, and provide calmness. Further, this experience may be achieved effectively in individuals experienced in yoga than nonyoga practitioners.

Parkinson's disease: Alterations of motor plasticity and motor learning.

This chapter reviews the alterations in motor learning and motor cortical plasticity in Parkinson's disease (PD), the most common movement disorder. Impairments in motor learning, which is a hallmark of basal ganglia disorders, influence the performance of motor learning-related behavioral tasks and have clinical implications for the management of disturbance in gait and posture, and for rehabilitative management of PD. Although plasticity is classically induced and assessed in sliced preparation in animal models, in this review we have concentrated on the results from non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS), transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS) in patients with PD, in addition to a few animal electrophysiologic studies. The chapter summarizes the results from different cortical and subcortical plasticity investigations. Plasticity induction protocols reveal deficient plasticity in PD and these plasticity measures are modulated by medications and deep brain stimulation. There is considerable variability in these measures that are related to inter-individual variations, different disease characteristics and methodological considerations. Nevertheless, these pathophysiologic studies expand our knowledge of cortical excitability, plasticity and the effects of different treatments in PD. These tools of modulating plasticity and motor learning improve our understanding of PD pathophysiology and help to develop new treatments for this disabling condition.

An Overview of Noninvasive Brain Stimulation: Basic Principles and Clinical Applications.

The brain has the innate ability to undergo neuronal plasticity, which refers to changes in its structure and functions in response to continued changes in the environment. Although these concepts are well established in animal slice preparation models, their application to a large number of human subjects could only be achieved using noninvasive brain stimulation (NIBS) techniques. In this review, we discuss the mechanisms of plasticity induction using NIBS techniques including transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), random noise stimulation (RNS), transcranial ultrasound stimulation (TUS), vagus nerve stimulation (VNS), and galvanic vestibular stimulation (GVS). We briefly introduce these techniques, explain the stimulation parameters and potential clinical implications. Although their mechanisms are different, all these NIBS techniques can be used to induce plasticity at the systems level, to examine the neurophysiology of brain circuits and have potential therapeutic use in psychiatric and neurological disorders. TMS is the most established technique for the treatment of brain disorders, and repetitive TMS is an approved treatment for medication-resistant depression. Although the data on the clinical utility of the other modes of stimulation are more limited, the electrical stimulation techniques (tDCS, tACS, RNS, VNS, GVS) have the advantage of lower cost, portability, applicability at home, and can readily be combined with training or rehabilitation. Further research is needed to expand the clinical utility of NIBS and test the combination of different modes of NIBS to optimize neuromodulation induced clinical benefits.

Exploring the connections between basal ganglia and cortex revealed by transcranial magnetic stimulation, evoked potential and deep brain stimulation in dystonia.

We review the findings for motor cortical excitability, plasticity and evoked potentials in dystonia. Plasticity can be induced and assessed in cortical areas by non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and the invasive technique of deep brain stimulation (DBS), which allows access to deep brain structures. Single-pulse TMS measures have been widely studied in dystonia and consistently showed reduced silent period duration. Paired pulse TMS measures showed reduced short and long interval intracortical inhibition, interhemispheric inhibition, long-latency afferent inhibition and increased intracortical facilitation in dystonia. Repetitive transcranial magnetic stimulation (rTMS) of the premotor cortex improved handwriting with prolongation of the silent period in focal hand dystonia patients. Continuous theta-burst stimulation (cTBS) of the cerebellum or cTBS of the dorsal premotor cortex improved dystonia in some studies. Plasticity induction protocols in dystonia demonstrated excessive motor cortical plasticity with the reduction in cortico-motor topographic specificity. Bilateral DBS of the globus pallidus internus (GPi) improves dystonia, associated pain and functional disability. Local field potentials recordings in dystonia patients suggested that there is increased power in the low-frequency band (4-12 Hz) in the GPi. Cortical evoked potentials at peak latencies of 10 and 25 ms can be recorded with GPi stimulation in dystonia. Plasticity induction protocols based on the principles of spike timing dependent plasticity that involved repeated pairing of GPi-DBS and motor cortical TMS at latencies of cortical evoked potentials induced motor cortical plasticity. These studies expanded our knowledge of the pathophysiology of dystonia and how cortical excitability and plasticity are altered with different treatments such as DBS.

Focality-Oriented Selection of Current Dose for Transcranial Direct Current Stimulation.

Background: In transcranial direct current stimulation (tDCS), the injected current becomes distributed across the brain areas. The objective is to stimulate the target region of interest (ROI) while minimizing the current in non-target ROIs (the 'focality' of tDCS). For this purpose, determining the appropriate current dose for an individual is difficult. Aim: To introduce a dose-target determination index (DTDI) to quantify the focality of tDCS and examine the dose-focality relationship in three different populations. Method: Here, we extended our previous toolbox i-SATA to the MNI reference space. After a tDCS montage is simulated for a current dose, the i-SATA(MNI) computes the average (over voxels) current density for every region in the brain. DTDI is the ratio of the average current density at the target ROI to the ROI with a maximum value (the peak region). Ideally, target ROI should be the peak region, so DTDI shall range from 0 to 1. The higher the value, the better the dose. We estimated the variation of DTDI within and across individuals using T1-weighted brain images of 45 males and females distributed equally across three age groups: (a) young adults (20 ≤ x ˂ 40 years), (b) mid adults (40 ≤ x ˂ 60 years), and (c) older adults (60 ≤ x ˂ 80 years). DTDI's were evaluated for the frontal montage with electrodes at F3 and the right supraorbital for three current doses of 1 mA, 2 mA, and 3 mA, with the target ROI at the left middle frontal gyrus. Result: As the dose is incremented, DTDI may show (a) increase, (b) decrease, and (c) no change across the individuals depending on the relationship (nonlinear or linear) between the injected tDCS current and the distribution of current density in the target ROI. The nonlinearity is predominant in older adults with a decrease in focality. The decline is stronger in males. Higher current dose at older age can enhance the focality of stimulation. Conclusion: DTDI provides information on which tDCS current dose will optimize the focality of stimulation. The recommended DTDI dose should be prioritized based on the age (>40 years) and sex (especially for males) of an individual. The toolbox i-SATA(MNI) is freely available.

Adjunct yoga therapy: Influence on heart rate variability in major depressive disorder - A randomized controlled trial.

HRV is inversely proportional to severity of depression. Effect of 12-weeks adjunct yoga therapy on HRV in patients with MDD was assessed through a randomized controlled trial. Sixty-eight subjects (40 females) with mean age 31.58 ± 8.79 years, scoring ≥ 18 on HDRS were randomized to either (YG; n = 35) or (WG; n = 33). Linear mixed model analysis showed no significant difference between groups. On comparing change in mean percentage, substantial more decrease could be elicited only for LF/HF ratio in YG compared to WG, while being comparable for other variables across the groups. Findings suggest Yoga therapy may help in bringing parasympathetic dominance in patients with MDD.