Casandra I. Montoro

Patterns of Cerebral Blood Flow Modulation During Painful Stimulation in Fibromyalgia: A Transcranial Doppler Sonography Study

OBJECTIVE This study analyzed the temporal dynamics of cerebral blood flow (CBF) modulations, during painful stimulation in fibromyalgia syndrome (FMS), using functional transcranial Doppler sonography. METHOD Blood flow velocities were recorded bilaterally in the anterior (ACA) and middle (MCA) cerebral arteries of 24 FMS patients and 20 healthy individuals during exposure to painful pressure stimulation. Participants were presented with two stimulation blocks: a) fixed pressure (2.4 kg) and b) stimulation pressure, individually calibrated to produce equal subjective and moderate pain intensity in all participants. RESULTS A complex pattern of CBF modulations arose, comprising four main components: an anticipatory increase before stimulation onset, an early increase, a transient decrease to baseline or below, and a final increase. Group differences were observed in all components. The anticipatory component only arose in FMS patients, specifically in the ACA. Patients exhibited a greater early CBF increase under the fixed pressure condition, predominantly in the right ACA. A stronger CBF decrease after the early component was observed in patients during the equal pain condition, in the ACA and MCA. Significant associations were found between clinical pain severity and CBF responses in the MCA. CONCLUSIONS The results demonstrate that acute pain processing is associated with a complex pattern of CBF modulation, where FMS patients exhibited alterations in all phases of the response. The aberrances may be ascribed to psychophysiological phenomena, including central nervous nociceptive sensitization and protective-defensive reflex mechanisms. The anticipatory CBF response in patients may relate to various cognitive, emotional, and behavioral mechanisms involved in pain chronification.

The effect of baroreceptor stimulation on pain perception depends on the elicitation of the reflex cardiovascular response: Evidence of the interplay between the two branches of the baroreceptor system

We examined the impact of baroreceptor stimulation on pain and cardiovascular responses in 39 healthy participants. Carotid baroreceptors were stimulated with external suction (-50 mmHg, stimulation) or pressure (+8 mmHg, control). Pain was induced by pressure to the nail of the left-index finger and quantified by a visual analog scale. Pain decreased heart rate (HR) and increased blood pressure (BP). Baroreceptor stimulation further decreased HR and reduced the BP increase. Pain experience failed to differ between baroreceptor stimulation conditions. However, significant results were obtained when trials were categorized according to the magnitude of the HR deceleration elicited by baroreceptor stimulation. In trials with strong baroreceptor-elicited HR deceleration pain intensity was lower than in trials both with inactive baroreceptor stimulation (pressure trials) or trials with small baroreceptor-elicited HR responses. Anti-nociceptive effects of baroreceptor stimulation depend on the activation of the reflex cardiovascular response. Central nervous inhibition due to baroreceptor stimulation only occurs if the peripheral cardiovascular response is engaged.

Reaction time, cerebral blood flow, and heart rate responses in fibromyalgia: Evidence of alterations in attentional control

The study investigated cerebral blood flow (CBF) and heart rate (HR) responses during a cued reaction time (RT) task in patients with fibromyalgia syndrome (FMS). CBF velocities in the middle (MCA) and anterior (ACA) cerebral arteries of both hemispheres were recorded in 46 patients and 32 healthy control participants using functional transcranial Doppler sonography (fTCD). Patients exhibited markedly longer RT than healthy participants. Group differences in CBF responses were mainly observed for both ACAs, with greater right hemispherical increases but lower left hemispherical increases in FMS patients than in healthy participants. HR deceleration around the imperative stimulus was more pronounced in healthy participants. RT was inversely related to increases in CBF in both right arteries and in the left ACA in the FMS group, but was positively associated with CBF responses in all four arteries in healthy participants. The magnitude of task-induced HR deceleration correlated negatively with RT in both groups. Patients’ clinical pain severity was positively associated with RT and CBF responses; trait anxiety and insomnia were secondary negative predictors of CBF responses. The study provided evidence of a deficit in the alertness component of attention in FMS at behavioral, CBF, and autonomic levels. These results may be interpreted in terms of the neural efficiency hypothesis of intelligence (i.e., less efficient brain activation during cognition in FMS) and the interfering effect of clinical factors on cognition. Clinical factors such as pain, anxiety, and sleep disturbances can affect cognition in FMS by interfering with CBF adjustment to cognitive demands.

Breath‐Holding During Exhalation as a Simple Manipulation to Reduce Pain Perception

OBJECTIVE Baroreceptor stimulation yields antinociceptive effects. In this study, baroreceptors were stimulated by a respiratory maneuver, with the effect of this manipulation on pain perception subsequently measured. METHODS Thirty-eight healthy participants were instructed to inhale slowly (control condition) and to hold the air in lungs after a deep inhalation (experimental condition). It was expected that breath-holding would increases blood pressure (BP) and thus stimulate the baroreceptors, which in turn would reduce pain perception. Pain was induced by pressure algometry on the nail of the left-index finger, at three different pressure intensities, and quantified by visual analogue scales. Heart rate (HR) and BP were continuously recorded. RESULTS Pain perception was lower when pain pressure was administered during the breath-holding phase versus the slow inhalation phase, regardless of the pressure intensity. During breath-holding, a rapid increase in BP and decrease in HR were observed, demonstrating activation of the baroreceptor reflex. CONCLUSION Pain perception is reduced when painful stimulation is applied during breath-holding immediately following a deep inhalation. These results suggest that a simple and easy-to-perform respiratory maneuver could be used to reduce acute pain perception.

Variability in cerebral blood flow velocity at rest and during mental stress in healthy individuals: Associations with cardiovascular parameters and cognitive performance

This study analyzed variability in cerebral blood flow velocity (CBFV) and possible underlying physiological mechanisms during rest and a mental arithmetic task. Blood flow velocities were bilaterally recorded by transcranial Doppler sonography in the anterior and middle cerebral arteries of 43 participants. Electrocardiography, continuous blood pressure (BP) and respiratory recordings were additionally obtained. Fast Fourier transformation revealed a spectral profile with two main components in CBFV, one in the very low frequency (VLF, 0.01-0.025 Hz), and the other in the low frequency band (LF, 0.075-0.11 Hz). During the task, CBFV variability decreased. While heart rate variability and respiration had only weak impacts, BP variability was closely associated with CBFV variability. LF CBFV variability correlated negatively with task performance. The findings indicate a connection between peripheral and cerebral hemodynamics, presumably mediated by the passive pressure-flow relationship and neural mechanisms. LF CBFV variability may constitute a suitable marker of mental effort load.

Cerebral blood flow variability in fibromyalgia syndrome: Relationships with emotional, clinical and functional variables

Objective This study analyzed variability in cerebral blood flow velocity (CBFV) and its association with emotional, clinical and functional variables and medication use in fibromyalgia syndrome (FMS). Methods Using transcranial Doppler sonography, CBFV were bilaterally recorded in the anterior (ACA) and middle (MCA) cerebral arteries of 44 FMS patients and 31 healthy individuals during a 5-min resting period. Participants also completed questionnaires assessing pain, fatigue, insomnia, anxiety, depression and health-related quality of life (HRQoL). Results Fast Fourier transformation revealed a spectral profile with four components: (1) a first very low frequency (VLF) component with the highest amplitude at 0.0024 Hz; (2) a second VLF component around 0.01-to-0.025 Hz; (3) a low frequency (LF) component from 0.075-to-0.11 Hz; and (4) a high frequency (HF) component with the lowest amplitude from 0.25-to-0.35 Hz. Compared to controls, FMS patients exhibited lower LF and HF CBFV variability in the MCAs (p < .005) and right ACA (p = .03), but higher variability at the first right MCA (p = .04) and left ACA (p = .005) VLF components. Emotional, clinical and functional variables were inversely related to LF and HF CBFV variability (r≥-.24, p≤.05). However, associations for the first VLF component were positive (r≥.28, p≤.05). While patients´ medication use was associated with lower CBFV variability, comorbid depression and anxiety disorders were unrelated to variability. Conclusions Lower CBFV variability in the LF and HF ranges were observed in FMS, suggesting impaired coordination of cerebral regulatory systems. CBFV variability was differentially associated with clinical variables as a function of time-scale, with short-term variability being related to better clinical outcomes. CBFV variability analysis may be a promising tool to characterize FMS pathology and it impact on facets of HRQoL.

Cognitive deficits in fibromyalgia syndrome are associated with pain responses to low intensity pressure stimulation

Background Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread musculoskeletal pain and diffuse tenderness, accompanied by complaints including morning stiffness, fatigue, insomnia and affective symptoms. In addition, affected patients frequently experience cognitive impairments such as concentration difficulties, forgetfulness or problems in planning and decision-making. These deficits are commonly ascribed to interference between nociceptive and cognitive processing. Method The present study investigated the association of cognitive performance with (a) pain responses to low intensity pressure stimulation (0.45–2.25 kg/cm2), (b) responses to stronger (above-threshold) stimulation (2.70 kg/cm2), and (c) pain threshold and tolerance in 42 women with FMS. Tests of attention, memory, processing speed, and executive functions were applied. Results While no significant correlations were seen for pain threshold and pain tolerance, inverse associations arose between pain intensity ratings during pressure stimulation and performance in all evaluated cognitive domains. The magnitude of the correlations increased with decreasing stimulus intensity. Conclusions It may be concluded that pain experience during somatosensory stimulation of low intensity is more closely related to attention, memory and executive functions in FMS than the traditional measures of pain threshold and pain tolerance. Considering that pain responses to low intensity stimulation reflect the hyperalgesia and allodynia phenomena characterizing FMS, it may be hypothesized that central nervous pain sensitization is involved in cognitive impairments in the disorder.

Cerebral blood flow modulations during cognitive control in major depressive disorder

BACKGROUND This study investigated cerebral blood flow modulations during proactive and reactive cognitive control in major depressive disorder (MDD). Proactive control refers to preparatory processes during anticipation of a behaviorally relevant event; reactive control is activated after such an event to ensure goal attainment. METHODS Using functional transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries of both hemispheres were recorded in 40 MDD patients and 40 healthy controls during a precued Stroop task. The font color of color words, which appeared 5 s after an acoustic warning signal, had to be indicated while ignoring word meaning. RESULTS Patients, as compared to controls, exhibited smaller bilateral blood flow increases during task preparation and larger increases after color word presentation. Response time was longer in patients irrespective of the match or mismatch between font color and word meaning. The blood flow increase after word presentation correlated positively with response time. LIMITATIONS Potential effects of psychotropic medication on cognition and cerebral blood flow could not be controlled. CONCLUSIONS The study revealed evidence of reduced cortical activity during proactive and elevated activity that occurs during reactive control in MDD. Deficient implementation of proactive control in MDD may lead to increased reliance on reactive control. The association between the blood flow increase after color word presentation and poorer performance indicates that deficient response preparation cannot be compensated for by reactive strategies. The findings are clinically relevant, as they may contribute to our understanding of the mechanisms relevant to cognitive impairments in MDD.

Cerebral blood flow modulations during preparatory attention and proactive inhibition

This study investigated cerebral blood flow modulations during task preparation in a precued saccade paradigm. Bilateral blood flow velocities in the middle cerebral arteries were recorded in 48 subjects using functional transcranial Doppler sonography. Video-based eye-tracking was applied for ocular recording. Antisaccade and prosaccade trials were presented in both block-wise and interleaved order. A right dominant flow response arose during task preparation. While the response was stronger during antisaccade than prosaccade trials, the degree of lateralisation did not differ between the two trial types. Direction error rates were higher and latencies were longer for antisaccades than prosaccades. There were no differences between block-wise and interleaved trials in blood flow or performance. The stronger blood flow increases during antisaccade than prosaccade preparation reflects the complexity of the upcoming task demands as well as proactive inhibition. The right hemispheric lateralisation may be attributed to preparatory attention independent of demands on inhibitory control.

Autonomic Cardiovascular Dysregulation at Rest and During Stress in Chronically Low Blood Pressure

Chronic low blood pressure (hypotension) is accompanied by symptoms such as fatigue, reduced drive, faintness, dizziness, cold limbs, and concentration difficulties. The study explored the involvement of aberrances in autonomic cardiovascular control in the origin of this condition. In 40 hypotensive and 40 normotensive subjects, impedance cardiography, electrocardiography, and continuous blood pressure recordings were performed at rest and during stress induced by mental calculation. Parameters of cardiac sympathetic control (i.e., stroke volume, cardiac output, pre-ejection period, total peripheral resistance), parasympathetic control (i.e., heart rate variability), and baroreflex function (i.e., baroreflex sensitivity) were obtained. The hypotensive group exhibited markedly lower stroke volume, heart rate, and cardiac output, as well as higher pre-ejection period and baroreflex sensitivity than the control group. Hypotension was furthermore associated with a smaller blood pressure response during stress. No group differences arose in total peripheral resistance and heart rate variability. While reduced beta-adrenergic myocardial drive seems to constitute the principal feature of the autonomic impairment that characterizes chronic hypotension, baroreflex-related mechanisms may also contribute to this state. Insufficient organ perfusion due to reduced cardiac output and deficient cardiovascular adjustment to situational requirements may be involved in the manifestation of bodily and mental symptoms.