The insula is a brain structure implicated in disparate cognitive, affective, and regulatory functions, including interoceptive awareness, emotional responses, and empathic processes. While classically considered a limbic region, recent evidence from network analysis suggests a critical role for the insula, particularly the anterior division, in high-level cognitive control and attentional processes. The crucial insight and view we present here is of the anterior insula as an integral hub in mediating dynamic interactions between other large-scale brain networks involved in externally oriented attention and internally oriented or self-related cognition. The model we present postulates that the insula is sensitive to salient events, and that its core function is to mark such events for additional processing and initiate appropriate control signals. The anterior insula and the anterior cingulate cortex form a “salience network” that functions to segregate the most relevant among internal and extrapersonal stimuli in order to guide behavior. Within the framework of our network model, the disparate functions ascribed to the insula can be conceptualized by a few basic mechanisms: (1) bottom–up detection of salient events, (2) switching between other large-scale networks to facilitate access to attention and working memory resources when a salient event is detected, (3) interaction of the anterior and posterior insula to modulate autonomic reactivity to salient stimuli, and (4) strong functional coupling with the anterior cingulate cortex that facilitates rapid access to the motor system. In this manner, with the insula as its integral hub, the salience network assists target brain regions in the generation of appropriate behavioral responses to salient stimuli. We suggest that this framework provides a parsimonious account of insula function in neurotypical adults, and may provide novel insights into the neural basis of disorders of affective and social cognition.

/pdf/saliency-switching-attention-and-control-a-network-model-of-4nzu8lqybn.pdf

Saliency, switching, attention and control: a network model of insula function

Cognitively demanding tasks that evoke activation in the brain's central-executive network (CEN) have been consistently shown to evoke decreased activation (deactivation) in the default-mode network (DMN). The neural mechanisms underlying this switch between activation and deactivation of large-scale brain networks remain completely unknown. Here, we use functional magnetic resonance imaging (fMRI) to investigate the mechanisms underlying switching of brain networks in three different experiments. We first examined this switching process in an auditory event segmentation task. We observed significant activation of the CEN and deactivation of the DMN, along with activation of a third network comprising the right fronto-insular cortex (rFIC) and anterior cingulate cortex (ACC), when participants perceived salient auditory event boundaries. Using chronometric techniques and Granger causality analysis, we show that the rFIC-ACC network, and the rFIC, in particular, plays a critical and causal role in switching between the CEN and the DMN. We replicated this causal connectivity pattern in two additional experiments: (i) a visual attention "oddball" task and (ii) a task-free resting state. These results indicate that the rFIC is likely to play a major role in switching between distinct brain networks across task paradigms and stimulus modalities. Our findings have important implications for a unified view of network mechanisms underlying both exogenous and endogenous cognitive control.

https://www.pnas.org/content/pnas/105/34/12569.full.pdf

A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks

Inhibition and the right inferior frontal cortex: one decade on.

Inhibition and impulsivity: Behavioral and neural basis of response control

K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients.

For clinical trials of acupuncture, it would be desirable to have a sham procedure that is indistinguishable from the real treatment, yet inactive. A sham needle has been designed which telescopes instead of penetrating the skin. The Park Sham Device involves an improved method of supporting the sham needle and requires validation. The objective of these studies was to test whether the sham procedure using the new device was 1) indistinguishable from the same procedure using real needles in acupuncture naive subjects, and 2) inactive, where the specific needle sensation (de qi) is taken as a surrogate measure of activity. The studies were designed as subject and assessor blind, randomised controlled trials. Study 1) included 58 patients enrolled in a clinical trial of acupuncture for acute stroke. Study 2) included 63 healthy, acupuncture naive, adult volunteers. The interventions used were real or sham acupuncture using the Park Sham Device. Study 1) was set in a district general hospital, and study 2) in a university laboratory. The outcome measure in study 1) was the form of treatment that patients believed they had received. In study 2) the outcome measure was experience of de qi, as judged by three acupuncture experts. No patient in either group(study 1) believed he or she had been treated with the sham needle. In 40 volunteers (study 2) for whom experts achieved consensus, the relative risk of experiencing de qi with real acupuncture to that with sham acupuncture was 15.38 (95% CI 2.26 to 104.86). The inter-rater reliability of all 13 experts (study 2), calculated from their judgements on 10 subjects selected by randomisation, was 0.52 (95% CI 0.19 to 0.61). In conclusion, the results suggest that the procedure using the new device is indistinguishable from the same procedure using real needles in acupuncture naive subjects, and is inactive, where the specific needle sensation (de qi) is taken as a surrogate measure of activity. It is therefore a valid control for acupuncture trials. The findings also lend support to the existence of de qi, a major concept underlying traditional Chinese acupuncture.

Validating a new non-penetrating sham acupuncture device: two randomised controlled trials

Background and Purpose The blood pressure (BP) fall and increased BP variability after acute stroke have been previously described. The underlying pathophysiological mechanisms producing these findings are unclear but may include abnormalities of cardiac baroreceptor reflex arc and/or changes in sympathetic nervous system activity. To date, evidence of impaired cardiac baroreceptor sensitivity (BRS) after stroke is limited to patients with chronic disease as determined by invasive methodology. Therefore, it was proposed to assess cardiac BRS and sympathovagal balance with the use of novel noninvasive techniques after acute stroke.

Methods Thirty-seven acute stroke patients underwent simultaneous surface electrocardiographic and noninvasive beat-to-beat BP recording. Cardiac BRS was assessed by power spectral analysis techniques, and sympathovagal balance was determined from the ratio of the low- to high-frequency powers for pulse interval variability. The responses were compared with a control group matched for age, sex, and BP.

Results Median cardiac BRS was significantly lower in stroke patients than in control subjects (high-frequency α-index, 4.89 versus 6.50 ms/mm Hg; P =.007; combined α-index, 4.65 versus 5.46 ms/mm Hg; P =.02). Median normalized high- but not low-frequency power of systolic BP variability was significantly greater in stroke patients (11.0 versus 6.7 normalized units; P <.001), probably reflecting differences in the mechanical effects of respiration on BP in stroke patients. No significant differences were observed in the power spectrum of pulse interval variability between stroke patients and control subjects. Patients with right hemisphere strokes, however, had a significant reduction in median high-frequency pulse interval power compared with patients with left hemisphere strokes (8 versus 20 normalized units; P =.03), which may reflect a change in sympathovagal balance in favor of increased sympathetic tone in this group.

Conclusions The impairment of cardiac BRS may be important in explaining the increased BP variability after stroke. There was no significant difference in surrogate measures of sympathovagal activity between acute stroke patients and control subjects, but right hemisphere stroke patients had a significant alteration in the sympathovagal balance of pulse interval variability compared with left hemisphere stroke patients. This sympathetic predominance in right hemisphere strokes may be important in the development of cardiac arrhythmias after stroke. The prognostic implications of these findings need to be further explored.

Cardiac Baroreceptor Sensitivity Is Impaired After Acute Stroke

There has been recent interest in the possibility that resistance vessel structural adaptation in hypertension may be more closely related to pulse pressure than to other blood pressure parameters. We investigated the relation between blood pressure and resistance vessel structure in a group of subjects from an age group (older than 60 years) in which a widening of pulse pressure is a typical finding and characterized blood pressure parameters using 24-hour ambulatory blood pressure monitoring. We studied resistance vessels retrieved from biopsies of skin and subcutaneous fat taken from the gluteal region of 32 subjects under local anesthesia (age, 70±1 years [mean±SEM]), 21 of whom were hypertensive and 11 normotensive. Media-lumen ratio was higher in the hypertensive than the normotensive subjects (18.6±1.6% versus 12.8±1.2%, P r =.44, P r =.35, P r =.40, P r =.56, P R 2 =41%, P

Pulse Pressure and Resistance Artery Structure in the Elderly

It has been proposed that the inferior/ventrolateral frontal cortex plays a critical role in the inhibitory control of action during cognitive tasks. However, the contribution of this region to the control of eye movements has not been clearly established. Here, we describe the performance of a group of 23 frontal lobe damaged patients in an oculomotor rule switching task for which the association between a centrally presented visual cue and the direction of a saccade could change from trial to trial. A subset of 16 patients also completed the standard antisaccade task. Ventrolateral damage was found to be a significant predictor of errors in both tasks. Analysis of the rate at which patients corrected errors in the rule switching task also revealed an important dissociation between left and right hemisphere damaged patients. Whilst patients with left ventrolateral damage usually corrected response errors with secondary saccades, those with right hemisphere lesions often failed to do so. The results suggest that the inferior frontal cortex forms part of a wider frontal network mediating inhibitory control over stimulus elicited eye movements. The critical role played by the right ventrolateral region in cognitive tasks may arise due to an additional functional specialization for the monitoring and updating of task rules.

/pdf/the-role-of-the-ventrolateral-frontal-cortex-in-inhibitory-23d74dbb9m.pdf

The role of the ventrolateral frontal cortex in inhibitory oculomotor control

Background: orthostatic hypotension in elderly people is often attributed to diminished afferent baroreflex sensitivity, but this has not been demonstrated. We examined the hypothesis that postural change in blood pressure is related to baroreflex sensitivity, independent of the confounding effect of baseline blood pressure. Methods: we studied 25 active, untreated elderly subjects free of postural symptoms (mean age 70 6 1 years): 16 with hypertension (clinic blood pressure 194 6 6/98 6 3 mmHg) and nine normotensive controls (clinic blood pressure 134 6 3/77 6 3 mmHg). We assessed baroreflex sensitivity from the heart rate and blood pressure responses to the Valsalva manoeuvre and a pressor and depressor stimulus (bolus phenylephrine injection or sodium nitroprusside infusion respectively). Subjects were then passively tilted to 608 and maximum changes in systolic blood pressure, heart rate, forearm blood flow and forearm vascular resistance recorded. Results: maximum change in systolic blood pressure with head-up tilt was correlated with supine systolic blood pressure (r = 0.60, P = 0.001). Maximum change in systolic blood pressure with orthostasis was greater in the hypertensive subjects (45 6 4 mmHg versus 29 6 6, P = 0.04) and the heart rate increment was less (16 6 2 bpm versus 24 6 4, P = 0.02). The increase in forearm vascular resistance with tilt was similar in the two groups (47 6 11 versus 38 6 7 units, P = 0.52). All three methods of assessing baroreflex sensitivity showed a reduction in the hypertensive subjects (all P # 0.02). Lower values of baroreflex sensitivity were related to greater falls in systolic blood pressure with tilt, after adjustment for the baseline level of systolic blood pressure. Conclusions: we found a relationship between baroreflex sensitivity and the systolic blood pressure fall with orthostasis, even after adjustment for prevailing systolic blood pressure. Despite equivalent changes in forearm vascular resistance with tilt, greater falls in systolic blood pressure were seen in hypertensive subjects than in normotensive controls, due in part to an inadequate baroreflex-mediated heart rate response. The postural fall in blood pressure often observed in elderly hypertensive subjects may be related to the reduced baroreflex sensitivity seen in this condition.

http://www.luzimarteixeira.com.br/wp-content/uploads/2010/08/age-and-ageing_1999_orthostatic-blood-pressure-change-arterial-baroreflex-sensitivity-in-elderly-subject.pdf

Martin A. James

Papers

Validating a new non-penetrating sham acupuncture device: two randomised controlled trials

Cardiac Baroreceptor Sensitivity Is Impaired After Acute Stroke

Pulse Pressure and Resistance Artery Structure in the Elderly

The role of the ventrolateral frontal cortex in inhibitory oculomotor control

Orthostatic blood pressure changes and arterial baroreflex sensitivity in elderly subjects.