Mark V. Kamath

Transcranial magnetic stimulation for migraine: clinical effects

The objective was to assess the impact of transcranial magnetic stimulation (TMS) on pain and the autonomic nervous system (ANS) in migraine. Fortytwo people [mean age 41.43±11.69 (SD) years, 36 females] were randomised into high vs. low TMS stimulation groups and received 2 brief pulses of TMS. Thirty-three (33/42) individuals had heart-rate variability assessed, before and after stimulation. No group effects were found. Pain decreased by 75%; 32% of people after 1 treatment reported no headache after 24 h. Mean heart rate decreased from 79.05±10.27 to 72.89±11.35 beats/min. The low-frequency (LF) and the high-frequency (HF) areas derived from power spectral analyses increased [mean 6522±1277 to 8315±1009 beats/min2 (LF) (p=0.001) and mean 5600±1568 to 8755±3071 beats/min2 (HF) (p=0.001)]. The LF:HF ratio decreased from mean 1.31±0.51 to 1.13±0.48 (NS). TMS produces immediate, sustained reductions in pain and modification of the ANS.

Abnormal cerebral processing of oesophageal stimuli in patients with noncardiac chest pain (NCCP).

In noncardiac chest pain (NCCP), altered visceral perception may result from abnormal cerebral processing of sensory input rather than abnormalities of afferent pathways. However, the interactions between symptoms, autonomic function and oesophageal stimuli are poorly studied. Oesophageal stimulation elicits reproducible cortical evoked potentials [CEP] and modulates heart rate variability via vagal pathways, as visible on power spectrum analysis of heart rate variability [PS‐HRV]. These methods are increasingly used to study the function of visceral afferent neural pathways in human. The aim of this study was to compare EP and PS‐HRV during oesophageal stimuli in NCCP and controls. Twelve healthy volunteers (one female, 11 male; aged 24–51 years; mean 32 ± 8 years), and eight NCCP patients (three female, five male; age range 26–58, mean 40.5 ± 10 years) were studied. Electrical oesophageal stimulation (EOS; 200 μs, 0.2 Hz, 25 stimuli) was applied to the oesophageal wall 5 cm above the lower oesophageal sphincter (LOS), and perception thresholds (measured in mA) determined. EP responses were recorded using 22 standard electroencephalogram scalp electrodes. Autonomic activity was assessed using PS‐HRV, before, during, and after oesophageal stimulation. Measured PS‐HRV indices included high frequency (HF; 0.15–0.5 Hz) and low frequency (LF; 0.06–0.15 Hz) power, respectively, assessing vagal and sympathetic activity, and the LF/HF ratio. EOS perception occurred at lower thresholds in NCCP than in controls (3.6 ± 1 vs. 7.8 ± 2 mA, P < 0.05). EP amplitude was greater (13 ± 2 vs. 6 ± 1 μV, P < 0.0001), and latency longer in controls vs. NCCP (191 ± 7 ms vs. 219 ± 6 ms, P < 0.001). In NCCP, EOS decreased sympathetic outflow (low frequency peak on PS‐HRV) and increased cardiovagal activity (high frequency peak, P < 0.02) to a significantly higher degree in comparison with controls. During EOS, heart rate decreased in NCCP from 68 vs. 62 beats min–1 (P < 0.003) but not in controls. In NCCP patients, EOS was perceived at lower intensities and was associated with a greater cardiovagal reflex response. EP responses associated with EOS were smaller in NCCP than in controls, suggesting that an increased perception of oesophageal stimuli results from an enhanced cerebral processing of visceral sensory input in NCCP, rather than from hyperalgesic responses in visceral afferent pathways.

Neurocardiac Responses to Vagoafferent Electrostimulation in Humans

To determine if cardiac vagal tone is enhanced by vagal electrostimulation (VES), we examined the heart rate autospectrum (HRA) in eight patients with implanted stimulators for complex partial seizures. In four patients the VES was activated at 30 Hz and 500‐msec pulse (HiStim group) compared to 2 Hz and 130‐msec pulse for the LoStim group (n = 4). Continuous ECG and respiratory waveforms were recorded for 45 minutes every 8 hours (7–8 AM; 3–4 PM 11–12 PM) during resting supine wakeful epochs both before and 15 days after surgical implantation. From the HRA cardiac sympathovagal balance was expressed as the ratio of the low frequency (LF) power to the high frequency (HF) power. RESULTS: There were no presurgical differences between the groups in heart rate, its variance, or the energies contained in any autospectral band. The LoStim group showed no significant change in heart rate (HR), HF peak power, or LF:HF ratios during 2 weeks of VES. Conversely, in the HiStim group, the LF:HF peak power ratio fan expression of sympathetic dominance) decreased from 2.5 ± 1.5 preimplant to 1.5 ± 0.49 (P < 0.02) with VES. During VES there was a significantly higher HF power in the HiStim compared to LoStim group. No diurnal variations in HRA values were seen for either group. CONCLUSIONS: (1) A relationship exists between selective vagal nerve electrostimulation and the HRA; and (2) high stimulation frequency of the vagus nerve in man is associated with sustained augmentation of cardiac vagal tone throughout a 24‐hour cycle.

The effects of body-weight supported treadmill training on cardiovascular regulation in individuals with motor-complete SCI

Study design:Four-month longitudinal within-subject exercise training study.Objective:Although body-weight supported treadmill training (BWSTT) has not shown promise as a means of improving ambulation in individuals with motor-complete spinal cord injury (SCI), it may still improve cardiovascular health and function in this population. The purpose of this study was to (i) investigate the effects of BWSTT on peripheral muscular and elastic artery dimension and function and measures of heart rate variability (HRV) and blood pressure variability (BPV) in individuals with motor-complete SCI, and (ii) to make a preliminary examination of what factors may predict favourable cardiovascular outcomes following BWSTT in this population.Setting:Centre for Health Promotion and Rehabilitation, McMaster University, Hamilton, Ontario, Canada.Methods:Six individuals (four male, two female; age 37.7±15.4 years) with chronic SCI (C4-T12; ASIA A-B; 7.6±9.4 years post-injury) were included in the present investigation. Doppler ultrasound was used to determine femoral (exercising; muscular), carotid (elastic) and brachial (nonexercising control; muscular) artery dimension and function before and after 4 months of BWSTT. Continuous heart rate and blood pressure were also recorded before and after 4-months of BWSTT to determine frequency domain measures of HRV and BPV; clinically valuable indices of neurocardiac and neurovascular control, respectively.Results:Two-way ANOVA (vessel × time) revealed no exercise-induced change in femoral or carotid artery cross-sectional area, blood flow or resistance and no change in carotid artery compliance following the 4 months of BWSTT compared to the nonexercising control brachial artery. However, there was a significant exercise-induced increase in femoral artery compliance. There were no exercise-induced changes in HRV or BPV when all participants were considered together. However, the results suggest that the subgroup of individuals who had a substantial heart rate response to BWSTT (n=3), experienced exercise-training induced changes in HRV reflective of a relative shift toward cardiac vagal predominance and reductions in BPV.Conclusions:BWSTT may cause an increase in femoral artery compliance in individuals with motor-complete SCI and therefore, should be encouraged as a means of improving cardiovascular health in this population. BWSTT may also cause modest improvements in measures of HRV and BPV in a select subgroup of individuals who respond to ambulation with moderate to large increases in HR. In the present study, factors associated with a substantial HR response to BWSTT were a propensity to orthostatic intolerance and muscular spasticity.

Vagal dysfunction in irritable bowel syndrome assessed by rectal distension and baroreceptor sensitivity

Abstract  Autonomic nervous system dysfunction has been implicated in the pathophysiology of irritable bowel syndrome (IBS). This study characterized the autonomic response to rectal distension in IBS using baroreceptor sensitivity (BRS), a measure of autonomic function. Rectal bag pressure, discomfort, pain, ECG, blood pressure and BRS were continuously measured before, during and after rectal distension in 98 healthy volunteers (34 ± 12 years old, 52 females) and 39 IBS patients (39 ± 11 years old, 35 females). In comparison with the healthy volunteers, IBS patients experienced significantly more discomfort (69 ± 2.2% vs 56 ± 3.6%; P < 0.05), but not pain (9 ± 1.4% vs 6 ± 2.4%; ns) with rectal distension despite similar distension pressures (51 ± 1.4 vs 54 ± 2.4 mmHg; ns) and volumes (394 ± 10.9 vs 398 ± 21.5 mL; ns). With rectal distension, heart rate increased in both healthy volunteers (66 ± 1 to 71 ± 1 bpm; P < 0.05) and IBS patients (66 ± 2 to 74 ± 3 bpm; P < 0.05). Systolic blood pressure also increased in both healthy volunteers (121 ± 2 to 143 ± 2 mmHg; P < 0.05) and patients (126 ± 3 to 153 ± 4 mmHg (P < 0.05) as did diastolic blood pressure, 66 ± 2 to 80 ± 2 mmHg (P < 0.05), compared with 68 ± 3 to 84 ± 3 mmHg (P < 0.05) in IBS patients. The systolic blood pressure increase observed in IBS patients was greater than that seen in healthy volunteers and remained elevated in the post distension period (139 ± 3 mmHg vs 129 ± 2 mmHg; P < 0.05). IBS patients had lower BRS (7.85 ± 0.4 ms mmHg−1) compared with healthy volunteers (9.4 ± 0.3; P < 0.05) at rest and throughout rectal distension. Greater systolic blood pressure response to rectal distension and associated diminished BRS suggests a compromise of the autonomic nervous system in IBS patients.

Reproducibility of heart rate variability and blood pressure variability in individuals with spinal cord injury

Individuals with spinal cord injury (SCI) are prone to orthostatic intolerance and an increased risk of cardiovascular disease. The use of heart rate variability (HRV) and blood pressure variability (BPV) as indices of cardiovascular regulation would be valuable in this population; however, their reproducibility has yet to be tested in those with SCI. The purpose of this study was to examine the day-to-day reproducibility of resting HRV and BPV in individuals with SCI. Ten individuals (age 35.9±13.2 yrs) with chronic (5.4±7.7 years post injury) SCI (C4-T12; ASIA A-C) participated. On two occasions within a two-week period, 10-minute supine electrocardiogram and Finapres blood pressure recordings were obtained during spontaneous breathing. Computer software calculated frequency domain measures of HRV and BPV (Low frequency (LF) power, High frequency (HF) power, and LF:HF ratio). Intraclass correlations coefficients (R) were used as an index of day-to-day reproducibility, and analyses were conducted on all participants and only those with tetraplegia. For HRV, measures of heart rate, LF, and LF:HF were found to be highly reproducible (R=0.82–0.88); however, the reproducibility of HF was found to be poor (all participants: R=0.53, tetraplegia: R=0.66). Measures of blood pressure as well as systolic BPV also showed high reproducibility (R=0.72–0.93). Measures of diastolic BPV were less reproducible but still acceptable (R=0.71–0.89) with the exception of LF:HFDBP (R=0.51). In conclusion, despite the autonomic dysfunction associated with SCI, measures of HRV and BPV may still be used as reproducible indices of autonomic cardiovascular regulation in this population.

A comparison of autonomic function in patients with inflammatory bowel disease and in healthy controls

Abstract We evaluated autonomic function, symptoms and psychological parameters in patients with ulcerative colitis (UC), Crohn’s disease (CD) and matched controls to assess whether UC patients have greater basal sympathetic autonomic activity. Outpatients with UC (n = 15), CD (n = 13) and healthy controls (n = 28) underwent spectral analysis of heart rate variability to assess cardiac autonomic function, a methacholine challenge to assess cholinergic pulmonary responsiveness, and questionnaires assessing disease severity, anxiety and depression. UC but not CD patients had greater sympathetic activity than controls with increased absolute (6600 vs 5884; P = 0.04) and relative (62.8%vs 54.8%; P = 0.02) low frequency areas. This was not because of increased overall autonomic nervous system (ANS) activation and was independent of disease activity. In UC patients, trait (personality‐related) anxiety correlated strongly with disease symptoms (R = 0.84; P < 0.001) and quality of life (R = −0.81; P < 0.001) while situational (state) anxiety did not. In CD patients, ANS measures were similar to controls and disease activity was unrelated to psychological measures. Cholinergic pulmonary responsiveness was normal in both UC and CD patients. UC patients have an increased sympathetic ANS activity which is independent of symptom severity. In these patients symptom severity is strongly associated with measures of personality related (but not current) anxiety.

Impaired Baroreflex Gain in Patients with Inappropriate Sinus Tachycardia

Introduction: The aim of this study was to determine the characteristics of heart rate variability (HRV), blood pressure variability (BPV), and baroreflex gain (BRG) at rest and during orthostatic stress in patients with clinical criteria of inappropriate sinus tachycardia (IST).

Clinical Applications Of Heart Rate Variability Power Spectra

Heart rate variability power spectra is explored in a number of clinical and experimental settings. our results indicate that PS/HRV provides a useful noninvasive window to measure neurocardiac control.

State space modeling of cardiovascular regulation

A linear state-space model (LSSM) of cardiovascular regulation was developed using measurements of instantaneous lung volume (ILV), heart rate (HR) and arterial blood pressure (APE) in 6 normal human volunteers (male, age: 22-30 yr., median 24 yr). The system order and an orthogonal basis for the state space of the system were estimated using the singular value decomposition (SVD) of a data matrix. The LSSM parameters were then found from the solution of an over-determined set of equations in least squares. The LSSM improves the phase function estimate and shows that (1) HR and ABP is most responsive to slow changes in ILV tidal volume when mean breathing frequency is 0.2-0.4 Hz (p>0.95) although system gain at these frequencies is reduced. (2) ANS responsiveness to changes in tidal volume increases linearly with frequency at slow (0.05-0.1 Hz) breathing rates (p>0.95). It is concluded that paced breathing system identification is a fast and non-invasive way to accurately characterize some of the physiological links between respiration, blood pressure and heart rate variability.