Depressive symptoms and cerebral microvascular disease in adults with Type 1 diabetes mellitus.

AIM: To assess the prevalence of, and risk factors for, depressive symptoms, comparing a sample of middle-aged adults with and without juvenile-onset Type 1 diabetes mellitus, and to determine if depressive symptoms were associated with white matter hyperintensity volume among those with Type 1 diabetes. METHODS: Depressive symptoms and white matter hyperintensities were compared between adults (age range 30-65 years) with juvenile-onset Type 1 diabetes (n=130) and adults without Type 1 diabetes (n=133). The association of Type 1 diabetes with depression was computed before and after adjustment for white matter hyperintensities. Among the Type 1 diabetes group, the primary associations of interest were between depressive symptoms (Beck Depression Inventory score ≥10) and white matter hyperintensities (n=71), hyperglycaemia and physical activity. Associations between depressive symptoms and diabetes-related complications, cognitive impairment, smoking and self-reported disability were examined. Analyses were controlled for education, sex, age and antidepressant use. RESULTS: Depressive symptoms were more prevalent among those with vs those without Type 1 diabetes (28% vs 3%; P<0.001). White matter hyperintensities explained 40% of the association of Type 1 diabetes with depressive symptoms, while Type 1 diabetes had a direct effect of 68% on depressive symptoms. Among those with Type 1 diabetes, depressive symptoms were related to white matter hyperintensity volume, a 16-year average HbA1c ≥58 mmol/mol (7.5%), and lower physical activity levels. Associations with other characteristics were not significant. CONCLUSION: These findings suggest a cerebrovascular origin for depressive symptoms in adults with Type 1 diabetes, perhaps triggered by hyperglycaemia. Future longitudinal studies should investigate whether targeting hyperglycaemia and physical inactivity alleviates depressive symptoms, possibly by slowing the development of cerebral microvascular disease, in people with Type 1 diabetes.

Regional grey matter shrinks in hypertensive individuals despite successful lowering of blood pressure.

The aim of the study was to determine whether the reduction in brain grey matter volume associated with hypertension persisted or was remediated among hypertensive patients newly treated over the course of a year. A total of 41 hypertensive patients were assessed over the course of a 1-year successful anti-hypertensive treatment. Brain areas identified previously in cross-sectional studies differing in volume between hypertensive and normotensive individuals were examined with a semi-automated measurement technique (automated labelling pathway). Volumes of grey matter regions were computed at baseline after a year of treatment and compared with archival data from normotensive individuals. Reductions in regional grey matter volume over the follow-up period were observed despite successful treatment of blood pressure (BP). The comparison group of older, but normotensive, individuals showed no significant changes over a year in the regions tested in the treated hypertensive group. These novel results suggest that essential hypertension is associated with regional grey matter shrinkage, and successful reduction of BP may not completely counter that trend.

Preparing hearts and minds: cardiac slowing and a cortical inhibitory network.

Preparing for a cued, speeded response induces a set of physiological changes. A review of the psychophysiology of preparation suggested that inhibition of action was an important process among the constellation of changes constituting attentive preparation. The current experiment combined event-related functional magnetic resonance imaging and cardiac inter-beat interval measures in an experiment that compared preparing for a response, watching stimuli without responding, and responding in the absence of preparation. Ten college-aged participants were tested in an initial psychophysiological experiment followed by two scanning sessions during which reverse spiral imaging was performed concurrent with inter-beat interval measurement. Two analytic approaches were used to confirm blood oxygenation level dependent responses during preparation, and these converged to show inferior prefrontal and related subthalamic nuclei activity in the context of other known changes related to brain attentional networks. Subthalamic nuclei changes were related to the depth of preparatory cardiac deceleration. This pattern of findings suggests that preparation involves the activation of a complex inhibitory neural network implicating brain and autonomic nervous systems.

Cognitive requirements for vestibular and ocular motor processing in healthy adults and patients with unilateral vestibular lesions.

This study investigated the role of cognition in the vestibulo-ocular reflex (VOR) and ocular pursuit using a dual-task paradigm in patients with unilateral peripheral vestibular loss and healthy adults. We hypothesized that cognitive resources are involved in successful processing and integration of vestibular and ocular motor sensory information, and this requirement would be greater in patients with vestibular dysfunction. Sixteen well-compensated patients with surgically confirmed absent unilateral peripheral vestibular function and 16 healthy age- and sex-matched controls underwent seven combinations of vestibular-only, visual-only, and visual-vestibular stimuli while performing three different information processing tasks. Visual-vestibular stimuli included a semicircular canal and an otolith stimulus provided through seated chair rotations; fixation on a laser target and sinusoidal smooth pursuit while still; and fixation on a head-fixed laser target during chair rotations. The information processing tasks were three different auditory reaction time (RT) tasks: (1) simple RT, (2) disjunctive RT, and (3) choice RT. Our results showed increases in RTs in both patients and controls under all vestibular-only stimulation conditions and during ocular pursuit. Patients showed greater increases in RTs during vestibular stimulation and the more complex disjunctive and choice RT tasks. No differences between the groups were found during the visual-only or visual-vestibular interaction conditions. These results reveal interference between vestibulo-ocular processing and a concurrent RT task, suggesting that the VOR and the ocular motor system are dependent upon cognitive resources to some extent, and thus, are not fully automatic systems. We speculate that this interference with cognition occurs as a result of the sensory integration required for resolving inputs from multiple sensory streams. The particularly large decrement in information processing task performance of the patients compared with controls during vestibular stimulation suggests that compensation for unilateral vestibular loss requires continued cognitive resources.

Reduced cerebral blood flow response and compensation among patients with untreated hypertension.

OBJECTIVE: To determine whether memory performance in hypertensive subjects induces diminished parietal and prefrontal blood flow activation relative to normotensive subjects but compensatory amygdala/hippocampal activation. METHODS: Thirty-seven untreated hypertensive subjects and 59 normotensive control subjects performed in two memory and one sensorimotor task while global and regional cerebral blood flow (rCBF) was assessed with [15O]water and PET. Neuropsychological, carotid artery ultrasound, and MRI assessments were obtained. RESULTS: When they were engaged in memory tasks, increases of CBF in hypertensive subjects were less than in normotensive subjects in the posterior parietal area, as expected; blunted responses were also shown within the middle posterior arterial watershed and thalamus. Relative to all other participants, hypertensive subjects that performed relatively well on verbal memory showed an enhanced rCBF response in the right amygdala/hippocampus. Furthermore, hypertensive, but not normotensive, subjects showed task-induced rCBF in the amygdala/hippocampal area that was significantly correlated with task-induced prefrontal rCBF. No confounding influences were identified from carotid artery or MRI measures. CONCLUSIONS: Memory performance in hypertensive individuals is related to a blunted regional cerebral blood flow (rCBF) response, particularly in parietal cortex. Potentially compensatory rCBF responses appear to occur in midbrain and correlate with prefrontal rCBF.

Sleep deprivation influences some but not all processes of supervisory attention.

Does one night of sleep deprivation alter processes of supervisory attention in general or only a specific subset of such processes? Twenty college-aged volunteers, half female, performed a choice reaction time task. A cue indicated that compatible (e.g., right button, right-pointing arrow) or incompatible (e.g., left button, right-pointing arrow) responses were to be given to a stimulus that followed 50 or 500 ms later. The paradigm assessed response inhibition, task-shifting skill, and task strategy-processes inherent in supervisory attention. Performance, along with heart rate, was assessed for 12 hr following normal sleep or a night of complete sleep deprivation. Sleep deprivation altered neither preparation for task shifting nor response inhibition. The ability to use preparatory bias to speed performance did decrease with sleep deprivation. Sleep deprivation appears to selectively affect this supervisory attention process, which is perceived as an active effort to cope with a challenging task.

A psychophysiological analysis of inhibitory motor control in the stop-signal paradigm.

We examined two potential inhibitory mechanisms for stopping a motor response. Participants performed a standard visual two-choice task in which visual stop signals and no-go signals were presented on a small proportion of the trials. Psychophysiological measures were taken during task performance to examine the time course of response activation and inhibition. The results were consistent with a horse race model previously proposed to account for data obtained using a stop-signal paradigm. The pattern of psychophysiological responses was similar on stop-signal and no-go trials suggesting that the same mechanism may initiate inhibitory control in both situations. We found a distinct frontal brain wave suggesting that inhibitory motor control is instigated from the frontal cortex. The results are best explained in terms of a single, centrally located inhibition mechanism. Results are discussed in terms of current neurophysiological knowledge.

Attention influences sensory integration for postural control in older adults.

This study investigated the influence of attention on the sensory integration component of postural control in young and older adults. Eighteen young and 18 older healthy subjects performed information-processing tasks during different postural challenge conditions. Postural conditions included seated, standing on a firm surface, standing on a sway-referenced floor, and standing on a sway-referenced floor while viewing a sway-referenced scene. During each condition, reaction time (RT) was measured during two simple and one inhibitory RT tasks. For the inhibitory task, the time required to inhibit an action was derived, termed the inhibitory time (IT). Performing a RT task was associated with increased postural sway in older subjects, but not in young subjects. The greatest influence of RT task on sway of older subjects was found during the sway-referenced floor/sway-referenced scene condition. Conversely, postural condition had an influence on RT task performance in both young and older subjects. The IT was increased in both young and older subjects only during the sway-referenced floor/scene condition. These results suggest that the sensory integration component of postural control in particular seems to require attention. Further, our data suggest that attentional processes related to inhibitory control are engaged when sensory integration requirements are high.

Selective attention and response inhibition alter phase-dependent cardiac slowing.

This study examined the effects of visual selective attention and stimulus discriminability on phasic heart rate changes. Grating stimuli consisting of four vertical bars were presented left or right from fixation. Participants attended to one side of the screen and responded with a button press to attended target stimuli that were defined by shorter middle bars. Stimulus discriminability was manipulated by increasing the length of the middle bars of targets. To examine the time course of response inhibition, participants had to respond to auditory probe stimuli that were presented occasionally and unpredictably at varying intervals following the visual stimulus. Responses to targets and probes following attended nontargets were slower in the difficult condition. Heart rate slowed in anticipation of a target and accelerated back to baseline afterwards. Phase-dependent cardiac slowing was larger for attended nontargets compared to unattended nontargets and was more pronounced in the difficult condition. These findings were interpreted vis-à-vis inhibition accounts of phase-dependent cardiac slowing.

Evaluation of treatment efficacy of Raynaud phenomenon by digital blood pressure response to cooling. Raynaud's Treatment Study Investigators.

Our previous studies have suggested that digital blood pressure response to cooling could provide a measure of the efficacy of treatments that are administered to patients with Raynaud phenomenon (RP). This method was used on 158 primary RP patients participating in a multicenter, randomized clinical trial that compared the efficacy of sustained-release nifedipine with temperature biofeedback in the treatment of RP. A pill placebo and electromyography served as controls. The response to local finger cooling was measured at 30 degrees, 20 degrees, 15 degrees and 10 degrees C in a temperature-controlled room under standardized conditions. The results showed that, at the 15 degrees C and 10 degrees C local cooling temperatures, the patients in the nifedipine group had a higher mean digital systolic blood pressure, a higher relative digital systolic blood pressure (RDSP), a smaller proportion of subjects with RDSP < 70% and a smaller proportion of subjects with a zero reopening pressure than the patients in the three other treatment groups. These results were statistically significant at 10 degrees C, the nifedipine group being significantly different from all others (p < 0.05); no significant difference was found between the three other treatment groups.

Selective inhibition is indexed by heart rate slowing.

This study examined the hypothesis that global and selective inhibition are mediated by distinct mechanisms: respectively, a peripheral mechanism, indexed by heart rate slowing, and a central mechanism, indexed by cortical but not autonomic measures. Three varieties of a Go-NoGo task were presented in which the Go signal required an index finger response rapidly followed by a middle finger response. The NoGo signal required the inhibition of (a) both responses (global inhibition), (b) the middle finger response (simple selective inhibition), or (c) the index finger response of one hand and the middle finger response of the other hand (complex selective inhibition). As anticipated, global inhibition was indexed by heart rate slowing. Most importantly, heart rate slowing was also elicited by selective inhibition and was more pronounced for complex than simple selective inhibition. These findings suggest that global and selective inhibition are mediated by one rather than two mechanisms and that heart rate is sensitive to the demands placed on this inhibition mechanism.

Developmental change in auditory selective attention as reflected by phasic heart rate changes.

Heart rate was recorded from five different groups of children (ages 7, 10, 12, 14, and 20 years) while they were performing an auditory selective attention task. The participants were instructed to count rare tone pips embedded in a series of standard tone pips presented at one (attended) ear while ignoring rare and standard stimuli presented at the other (unattended) ear. A pattern of anticipatory heart rate deceleration followed by acceleration was associated with rare tone pips at the attended ear but not with rare tone pips that should be ignored. The absence of differential sensitivity of heart rate responses to rare tone pips presented at the unattended ear was observed for all age groups. These findings were interpreted to suggest that the ability to ignore irrelevant target stimuli has reached mature levels during middle childhood. The depth of anticipatory deceleration increased until age 14, suggesting that the ability to maintain attentional set continues to develop beyond childhood.

Anticipatory blood pressure responses to exercise are associated with left ventricular mass in Finnish men: Kuopio Ischemic Heart Disease Risk Factor Study.

BACKGROUND: Exaggerated cardiovascular reactivity to psychological demands may contribute to the development of left ventricular (LV) hypertrophy. We examined the cross-sectional association between anticipatory blood pressure (BP) responses to bicycle exercise and LV mass in the Kuopio Ischemic Heart Disease Risk Factor Study, a population-based epidemiological sample. METHODS AND RESULTS: Among 876 men from 4 age cohorts (ages 42, 48, 58, and 64 years), we collected echocardiographic assessments of LV mass along with measures of BP response taken before bicycle ergometry testing. Anticipatory BP responses were positively associated with LV mass, with significant associations only among younger (age <50 years) subjects with elevated resting pressures (3-way interactions for anticipatory BP x age x resting pressure for systolic and diastolic BP, all P:<0.05; for younger subjects with elevated systolic BP, P:<0. 01; and for younger subjects with elevated diastolic BP, P:<0.001). Among these subgroups, exaggerated anticipatory BP responses (top quartile) were associated with an incremental increase in LV mass of 10% or greater, corrected for body surface area. Results remained significant after adjusting for age, education, salt consumption, and resting BP, and the pattern of findings was maintained among men with no previous history of cardiovascular disease. CONCLUSIONS: The tendency to show exaggerated pressor responses to psychological demands may be a significant independent correlate of LV mass, especially among young men with high resting pressures. This is the first study to examine such associations in a middle-aged population sample.

Dissociation of response conflict, attentional selection, and expectancy with functional magnetic resonance imaging.

Two different attentional networks have been associated with visuospatial attention and conflict resolution. In most situations either one of the two networks is active or both are increased in activity together. By using functional magnetic resonance imaging and a flanker task, we show conditions in which one network (anterior attention system) is increased in activity whereas the other (visuospatial attention system) is reduced, showing that attentional conflict and selection are separate aspects of attention. Further, we distinguish between neural systems involved in different forms of conflict. Specifically, we dissociate patterns of activity in the basal ganglia and insula cortex during simple violations in expectancies (i.e., sudden changes in the frequency of an event) from patterns of activity in the anterior attention system specifically correlated with response conflict as evidenced by longer response latencies and more errors. These data provide a systems-level approach in understanding integrated attentional networks.

Wisconsin Card Sorting in adolescents: analysis of performance, response times and heart rate.

Forty-nine adolescents performed the Wisconsin Card Sorting Test (WCST). A main PCA component of WCST performance was identified as 'efficiency of reasoning'. This factor was related to feedback processing. From the WCST, a perseveration score can be derived. Perseveration is the continued application of a rule, after it has been disconfirmed. We compared more and less perseverating subjects in relation to stimulus-response (SR) time, feedback inspection time and cardiac acceleration and deceleration. Less perseverating subjects responded faster, and had longer and more adaptive inspection times of error feedback. We examined the switch from rule application to rule search, and the difference between correct and error responses. A transient cardiac deceleration at the initiation of rule search was interpreted as a change in supervisory attention. An error-related deceleration to negative feedback was interpreted as a disturbance of higher control processing. Previous trial feedback influenced current processing time, feedback inspection time, and the cardiac acceleration and deceleration responses.

Behaviorally-evoked plasma catecholamine response and 24-hour excretion of urinary catecholamines among cardiac and vascular reactors.

Individuals differ in the cardiac and vascular processes that underlie blood pressure elevations evoked by environmental stimuli; such differences may reflect variability in sympathoadrenal response. We separated 108 healthy, young-adult males into those with predominant elevations in either cardiac output or peripheral resistance when exposed to psychological challenges. We then asked if they differed on other measures of cardiovascular response, concomitant plasma catecholamine reactions or 24-h urinary excretion of catecholamines. Cardiac reactors, relative to vascular reactors, showed reduced cardiac pre-ejection period, a smaller reduction in stroke volume, and elevated plasma epinephrine response and 24-h urinary epinephrine excretion. Vascular reactors, relative to cardiac reactors, responded to mental stress with more elevated diastolic blood pressure, a rise in peripheral resistance and pulse wave velocity, and a greater reduction in stroke volume. Vascular reactors, however, did not show plasma norepinephrine response or 24-h urinary norepinephrine excretion that was greater than cardiac reactors. The results provide partial support for the hypothesis that variability in sympathoadrenal activity contributes to individual differences in cardiac and vascular reactivity, and extend prior observations by demonstrating covariation of behaviorally-elicited cardiac reactivity with the 24-h excretion of epinephrine.

A thermal vascular test for distinguishing between patients with Raynaud's phenomenon and healthy controls. Raynaud's Treatment Study Investigators.

This study tested the reliability and validity of a diagnostic thermal vascular test (TVT) for patients with Raynaud's Phenomenon (RP). The TVT examined digital blood pressure responses to combined cooling and occlusion and was developed as part of the Raynaud's Treatment Study, a multicenter clinical trial comparing the efficacy of biofeedback and pharmacological treatment. A computerized system permitted efficient, accurate, and uniform testing at different geographical sites. A comparison of 199 patients with RP and 52 healthy controls is reported. The TVT showed a sensitivity of 79% and a specificity of 88%. Test-retest reliability was acceptable (r = .80). Addition of a psychological challenge failed to improve the discrimination between patients with RP and controls. The TVT separated patients with RP and controls as well as or better than existing tests and did so with enhanced ease of operation.

Changes in heart beat timing: reactivity, resetting, or perturbation?

A widely held hypothesis within behavioral medicine is that cardiovascular reactivity is a risk factor for cardiovascular disease. The measurement model for this cardiovascular reactivity is rather simple. A basal level of function is seen to increase while the organism is stressed and then return to basal function. We argue that this model is incomplete and that other forms of 'reactivity' may be relevant to pathophysiology. A pathophysiological hypothesis is discussed which assumes a cyclic heart beat generation mechanism that is sensitive to stimulation only at certain phases of its cycle. Implications of this hypothesis for measurement are developed to illustrate the point that models of normal function can determine the measures most relevant to pathophysiology.

Cerebral blood flow in hypertensive patients: an initial report of reduced and compensatory blood flow responses during performance of two cognitive tasks.

We asked whether the altered cerebral vasculature associated with essential hypertension might dampen or redirect the regional cerebral blood flow (rCBF) response to cognitive work. Relative rCBF was assessed with [(15)O]water positron emission tomography during a working memory task, a memory span task, and two perceptual control tasks. Unmedicated hypertensive patients and control subjects differed in rCBF response during both memory tasks. Hypertensives showed relatively diminished rCBF responses in right hemisphere areas combined with compensatory activation of homologous areas in the left cerebral cortex. Essential hypertension appears to selectively influence the circulatory reserve of portions of cerebral cortex and secondarily induce recruitment of other cortical areas to process certain tasks.

Postural control, attention and sleep deprivation.

We investigated the effect of sleep deprivation on postural control during a simple reaction time task (SRT), during a task requiring the intermittent inhibition of a reaction (IRT), and in the absence of a concurrent information processing task. Postural sway, i.e. changes in center of pressure on a force platform, was recorded in three increasingly difficult standing conditions (fixed platform, sway-referenced platform and sway-referenced platform with sway-referenced visual scene) during the three information-processing task conditions. Five healthy subjects performed the tasks either after normal sleep or following 24 h of sustained wakefulness. As hypothesized, sleep deprivation significantly increased postural sway only in the IRT condition. Within the IRT condition, sleep deprivation significantly increased sway across all postural conditions.