Regional Cerebral Blood Flow Responses Research Articles

Regional cerebral blood flow responses to rapid reductions in blood pressure after high level spinal cord injury: the effect of alpha1‐agonist (1068.8)

Spinal cord injury (SCI) above the T6 level frequently results in orthostatic intolerance, but how cerebral blood flow (CBF) responds to an orthostatic challenge in SCI is poorly understood. It is also unclear how alpha1 agonists, meant to improve orthostatic tolerance, influence the CBF response. This study examined: 1) the acute regional CBF velocity (CBFv) response to acute blood pressure (BP) reductions secondary to orthostatic stress in SCI, compared to able‐bodied controls (AB), and 2) the effect of Midodrine (alpha1‐agonist) on orthostatic tolerance and CBFv regulation in SCI. Ten individuals with SCI >T6, and 10 age‐and sex‐matched controls had beat‐by‐beat BP, as well as middle and posterior cerebral artery blood velocity (MCAv, PCAv) recorded during a progressive tilt‐test to quantify the acute CBF response and orthostatic tolerance. Dynamic CBFv‐BP relationships were evaluated from the first 60s after tilt. The SCI group was tested again after administration of an alpha1‐agonist (10 mg midodrine) in order to elevate BP. The acute (i.e., 0‐30s after tilt) MCAv and PCAv responses were similar in SCI and AB. In contrast, Midodrine led to improved PCAv responses 30‐60 s (10±3 vs. 4±2 %decline; p<0.05) after tilt, and a 59% improvement in orthostatic tolerance (p<0.01). The vertebrobasilar region may be particularly susceptible to hypoperfusion in SCI, leading to increased orthostatic intolerance.Grant Funding Source: Supported by HSFC, NSERC, MSFHR & CNF

Perturbed and spontaneous regional cerebral blood flow responses to changes in blood pressure after high-level spinal cord injury: the effect of midodrine

Individuals with spinal cord injury (SCI) above the T6 spinal segment suffer from orthostatic intolerance. How cerebral blood flow (CBF) responds to orthostatic challenges in SCI is poorly understood. Furthermore, it is unclear how interventions meant to improve orthostatic tolerance in SCI influence CBF. This study aimed to examine 1) the acute regional CBF responses to rapid changes in blood pressure (BP) during orthostatic stress in individuals with SCI and able-bodied (AB) individuals; and 2) the effect of midodrine (alpha1-agonist) on orthostatic tolerance and CBF regulation in SCI. Ten individuals with SCI >T6, and 10 age- and sex-matched AB controls had beat-by-beat BP and middle and posterior cerebral artery blood velocity (MCAv, PCAv, respectively) recorded during a progressive tilt-test to quantify the acute CBF response and orthostatic tolerance. Dynamic MCAv and PCAv to BP relationships were evaluated continuously in the time domain and frequency domain (via transfer function analysis). The SCI group was tested again after administration of 10 mg midodrine to elevate BP. Coherence (i.e., linearity) was elevated in SCI between BP-MCAv and BP-PCAv by 35% and 22%, respectively, compared with AB, whereas SCI BP-PCAv gain (i.e., magnitudinal relationship) was reduced 30% compared with AB (all P < 0.05). The acute (i.e., 0-30 s after tilt) MCAv and PCAv responses were similar between groups. In individuals with SCI, midodrine led to improved PCAv responses 30-60 s following tilt (10 ± 3% vs. 4 ± 2% decline; P < 0.05), and a 59% improvement in orthostatic tolerance (P < 0.01). The vertebrobasilar region may be particularly susceptible to hypoperfusion in SCI, leading to increased orthostatic intolerance.

Ischemic pretreatment delays ischemic brain vasospasm injury in gerbils.

Three experiments were conducted for the present study. First, to elucidate the mechanism and functional significance underlying ischemic vasoconstriction, we investigated the relationship between arteriolar constriction and tissue energy metabolism during bilateral common carotid artery occlusion in gerbils. Second, to identify differences in the postischemic recovery of physiologic parameters between short and prolonged brain ischemia, we measured changes in regional cerebral blood flow, microvessel diameter, brain temperature, and electrophysiologic response. Third, to explore the physiological mechanism of ischemic tolerance, we studied vascular response and intracerebral oxygenation states after acute global ischemia with and without pretreatment by mild ischemic stress. Here, we identify one of the physiologic mechanisms of the ischemic tolerance caused by brief ischemic pretreatment.

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The catechol-o-methyltransferase Val158Met polymorphism modulates organization of regional cerebral blood flow response to working memory in adults

This study examined the effect of catechol-o-methyltransferase (COMT) Val158Met genotypes on the co-activation of brain areas involved in cognition during a working memory (WM) task. The pattern of concomitant region of interest (ROI) activation during WM performance varied by genotype: Val/Val showing the least and Met/Met the most covariance. There were no differences of performance on the WM task between the COMT genotypes. However, relatively better performance was associated with less concomitance of dorsolateral prefrontal cortex (DLPFC) and cingulate cortex for Val/Val, but more concomitance of DLPFC with AH for Met/Met. Within genotypes WM performance was significantly correlated with rCBF to the amygdala/hippocampus (AH) for Val/Val (r=0.44, p=0.009), to the parietal lobe for Val/Met (r=0.29, p=0.03), and to the thalamus for Met/Met (r=0.32, p=0.04). Different genotypes showed different regional specificity and concomitant activation patterns suggesting that varying dopamine availability induces different brain processing pathways to achieve similar WM performance.

Neurobiological insight into hyperbaric hyperoxia

Hyperbaric hyperoxia (HBO) is known to modulate aerobic metabolism, vasoreactivity and blood flow in the brain. Nevertheless, mechanisms underlying its therapeutic effects, especially in traumatic brain injury (TBI) and stroke patients, are debated. The present study aimed at investigating regional cerebral blood flow (rCBF) distribution during acute HBO exposure. Regional cerebral blood flow response was investigated in seven healthy subjects exposed to either normobaric normoxia or HBO with ambient pressure/inspired oxygen pressure of 101/21 and 250/250 kPa respectively. After 40 min at the desired pressure, they were injected a perfusion tracer and subsequently underwent brain single photon emission computed tomography. rCBF distribution changes in the whole brain were assessed by Statistical Parametric Mapping. During HBO, an increased relative rCBF distribution was found in sensory-motor, premotor, visual and posterior cingulate cortices as well as in superior frontal gyrus, middle/inferior temporal and angular gyrus and cerebellum, mainly in the dominant hemisphere. During normobaric normoxia, a higher (99m) Tc-HMPAO distribution in the right insula and subcortical structures as well as in bilateral hippocampi and anterior cingulated cortex was found. The present study firstly confirmed the rCBF distribution increase during HBO in sensory-motor and visual cortices, and it showed for the first time a higher perfusion tracer distribution in areas encompassed in dorsal attention system and in default mode network. These findings unfold both the externally directed cognition performance improvement related to the HBO and the internally directed cognition states during resting-state conditions, suggesting possible beneficial effects in TBI and stroke patients.

Differences in regional cerebral blood flow response to a 5HT3 antagonist in early‐ and late‐onset cocaine‐dependent subjects

5-hydroxytryptamine 3 (5HT3) receptors are important modulators of mesostriatal dopaminergic transmission and have been implicated in the pathophysiology of cocaine reward, withdrawal and self-administration. In addition, the 5HT3 antagonist ondansetron is effective in treating early-onset, but not late-onset, alcohol-dependent subjects. To explore the role of 5HT3 receptor systems in cocaine addiction using functioning imaging, we administered ondansetron to 23 abstinent, treatment-seeking cocaine-addicted and 22 sex-, age- and race-matched healthy control participants. Differences between early- (first use before 20 years, n = 10) and late-onset (first use after 20 years, n = 10) cocaine-addicted subjects were also assessed. On two separate days, subjects were administered ondansetron (0.15 mg/kg intravenously over 15 minutes) or saline. Regional cerebral blood flow (rCBF) was measured following each infusion with single photon emission computed tomography. No significant rCBF differences between the cocaine-addicted and control participants were observed following ondansetron relative to saline. Early-onset subjects, however, showed increased (P < 0.001) right posterior parahippocampal rCBF following ondansetron. In contrast, late-onset subjects showed decreased rCBF following ondansetron in an overlapping region of the right parahippocampal/hippocampal gyrus. Early-onset subjects also displayed increased rCBF in the left anterior insula and subthalamic nucleus following ondansetron; late-onset subjects showed decreased rCBF in the right anterior insula. These findings suggest that the age of drug use onset is associated with serotonergic biosignatures in cocaine-addicted subjects. Further clarification of these alterations may guide targeted treatment with serotonergic medications similar to those successfully used in alcohol-dependent patients.

Effects of arterial cannulation stress on regional cerebral blood flow in major depressive disorder

Individuals with major depressive disorder (MDD) display abnormal neurophysiological responses to psychological stress but little is known about their neurophysiological responses to physiological stressors. Using [15O-H2O] positron emission tomography we assessed whether the regional cerebral blood flow (rCBF) response to arterial cannulation differed between patients with MDD and healthy controls (HCs). Fifty-one MDD patients and 62 HCs were scanned following arterial cannulation and 15 MDD patients and 17 HCs were scanned without arterial cannulation. A region-of-interest analysis showed that a significantly increased rCBF of the anterior cingulate cortex and right amygdala was associated with arterial cannulation in MDD. A whole brain analysis showed increased rCBF of the right post-central gyrus, left temporopolar cortex, and right amygdala during arterial cannulation in MDD patients. The rCBF in the right amygdala was significantly correlated with depression severity. Conceivably, the limbic response to invasive physical stress is greater in MDD subjects than in HCs.

Neural Bases of Hypoactive Sexual Desire Disorder in Women: An Event‐Related fMRI Study

Although there is an abundant debate regarding the mechanisms sustaining one of the most common sexual complaints among women, i.e., female hypoactive sexual desire disorder (HSDD), little remains known about the specific neural bases of this disorder. The main goal of this study was to determine whether women with HSDD showed differential patterns of activation within the brain network that is active for sexual desire in subjects without HSDD. A total of 28 right-handed women participated in this study (mean age 31.1±7.02 years). Thirteen out of the 28 women had HSDD (HSDD participants), while 15 women reported no hypoactive sexual desire disorder (NHSDD participants). Using event-related functional magnetic resonance imaging (fMRI), we compared the regional cerebral blood flow responses between these two groups of participants, while they were looking at erotic vs. non-erotic stimuli. Blood-oxygenation level dependent (BOLD) signal changes in response to erotic stimuli (compared with non-erotic stimuli). Statistical Parametric Mapping was used to identify brain regions that demonstrated significant differential activations between stimuli and between groups. As expected, behavioral results showed that NHSDD participants rated erotic stimuli significantly higher than HSDD participants did on a 10-point desirable scale. No rating difference was observed for the non-erotic stimuli between NHSDD and HSDD participants. Our functional neuroimaging results extended these data by demonstrating two distinct types of neural changes in participants with and without HSDD. In comparison with HSDD participants, participants without HSDD demonstrated more activation in brain areas involved in the processing of erotic stimuli, including intraparietal sulcus, dorsal anterior cingulate gyrus, and ento/perirhinal region. Interestingly, HSDD participants also showed additional activations in brain areas associated with higher order social and cognitive functions, such as inferior parietal lobule, inferior frontal gyrus, and posterior medial occipital gyrus. Together, these findings indicate that HSDD participants do not only show a hypo activation in brain areas mediating sexual desire, but also a different brain network of hyper activation, which might reflect differences in subjective, social, and cognitive interpretations of erotic stimuli. Collectively, these data are in line with the incentive motivation model of sexual functioning.

Regional cerebral blood flow responses to hyperventilation during sevoflurane anaesthesia studied with PET

Arterial carbon dioxide tension (PaCO(2)) is an important factor controlling cerebral blood flow (CBF) in neurosurgical patients. It is still unclear whether the hypocapnia-induced decrease in CBF is a general effect on the brain or rather linked to specific brain regions. We evaluated the effects of hyperventilation on regional cerebral blood flow (rCBF) in healthy volunteers during sevoflurane anaesthesia measured with positron emission tomography (PET). Eight human volunteers were anaesthetized with sevoflurane 1 MAC, while exposed to hyperventilation. During 1 MAC sevoflurane at normocapnia and 1 MAC sevoflurane at hypocapnia, one H(2)(15)O scan was performed. Statistical parametric maps and conventional regions of interest analysis were used for estimating rCBF differences. Cardiovascular parameters were maintained constant over time. During hyperventilation, the mean PaCO(2) was decreased from 5.5 + or - 0.7 to 3.8 + or - 0.9 kPa. Total CBF decreased during the hypocapnic state by 44%. PET revealed wide variations in CBF between regions. The greatest values of vascular responses during hypocapnia were observed in the thalamus, medial occipitotemporal gyrus, cerebellum, precuneus, putamen and insula regions. The lowest values were observed in the superior parietal lobe, middle and inferior frontal gyrus, middle and inferior temporal gyrus and precentral gyrus. No increases in rCBF were observed. This study reports highly localized and specific changes in rCBF during hyperventilation in sevoflurane anaesthesia, with the most pronounced decreases in the sub cortical grey matter. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve during hypocapnia.

Cerebral Blood Flow, Blood Volume, and Mean Transit Time Responses to Propofol and Indomethacin in Peritumor and Contralateral Brain Regions

The regional cerebral blood flow (CBF) response to propofol and indomethacin may be abnormal in patients with brain tumors. First, the authors tested the hypothesis that during propofol anesthesia alone and combined with indomethacin, changes in CBF, cerebral blood volume (CBV), and plasma mean transit time (MTT) differ in the peritumoral tissue compared with the contralateral normal brain region. Second, the authors tested the hypothesis that CBF and CBV are reduced and MTT is prolonged, in both regions during propofol anesthesia and indomethacin administration compared with propofol alone. The authors studied eight patients subjected to craniotomy under propofol-fentanyl anesthesia for supratentorial brain tumors. Magnetic resonance imaging, including perfusion- and diffusion-weighted and structural sequences, was performed (1) on the day before surgery, (2) before and (3) after administration of indomethacin in the propofol-fentanyl anesthetized patient, and (4) 2 days after surgery. Maps of CBF, CBV, and MTT were calculated. The regions of interest were peritumoral gray matter and opposite contralateral gray matter. Analysis of variance was used to analyze flow data. Propofol anesthesia was associated with a median 32% (range, 3-61%) and 47% (range, 17-67%) reduction in CBF in the peritumoral and contralateral regions, respectively.The interaction between intervention with propofol and indomethacin and region of interest was not significant for any flow modalities. Neither intervention nor region was significant for MTT, CBF, and CBV (P > 0.05). The CBF, CBV, and MTT responses to propofol and indomethacin are not different in the peritumoral region compared with contralateral brain tissue. Indomethacin did not further influence regional CBF, CBV, and MTT during propofol anesthesia.

Low-dose Propofol–induced Amnesia Is Not due to a Failure of Encoding

Propofol may produce amnesia by affecting encoding. The hypothesis that propofol weakens encoding was tested by measuring regional cerebral blood flow during verbal encoding. Seventeen volunteer participants (12 men; aged 30.4 +/- 6.5 yr) had regional cerebral blood flow measured using H2O positron emission tomography during complex and simple encoding tasks (deep vs. shallow level of processing) to identify a region of interest in the left inferior prefrontal cortex (LIPFC). The effect of either propofol (n = 6, 0.9 microg/ml target concentration), placebo with a divided attention task (n = 5), or thiopental at sedative doses (n = 6, 3 microg/ml) on regional cerebral blood flow activation in the LIPFC was tested. The divided attention task was expected to decrease activation in the LIPFC. Propofol did not impair encoding performance or reaction times, but impaired recognition memory of deeply encoded words 4 h later (median recognition of 35% [interquartile range, 17-54%] of words presented during propofol vs. 65% [38-91%] before drug; P < 0.05). Statistical parametric mapping analysis identified a region of interest of 6.6 cm in the LIPFC (T = 7.44, P = 0.014). Regional cerebral blood flow response to deep encoding was present in this region of interest in each group before drug (T > 4.41, P < 0.04). During drug infusion, only the propofol group continued to have borderline significant activation in this region (T = 4.00, P = 0.063). If the amnesic effect of propofol were solely due to effects on encoding, activation in the LIPFC should be minimal. Because LIPFC activation was not totally eliminated by propofol, the amnesic action of propofol must be present in other brain regions and/or affect other memory processes.

Cerebrovascular Support for Cognitive Processing in Hypertensive Patients Is Altered by Blood Pressure Treatment

Hypertension is associated with mild decrements in cognition. In addition, regional cerebral blood flow responses during memory processing are blunted in parietal and thalamic areas among untreated hypertensive adults, who, compared with normotensive subjects, manifest greater correlation in blood flow response across task-related brain regions. Here, we test whether pharmacological treatment of hypertension normalizes regional cerebral blood flow responses and whether it does so differentially according to drug class. Treatment with lisinopril, an angiotensin-converting enzyme blocker, known to enhance vasodilative responsivity, was compared with treatment with atenolol, a beta-blocker. Untreated hypertensive volunteers (n=28) were randomly assigned and treated for 1 year. Whole brain and regional cerebral flow responses to memory processing and acutely administered acetazolamide, a vasodilator, were assessed pretreatment and posttreatment. Peripheral brachial artery dilation during reactive hyperemia was also measured. Quantitative blood flow measures showed no difference in the magnitude of regional cerebral blood flow responses pretreatment and posttreatment to either memory tasks or acetazolamide injection. Brachial artery flow-mediated dilation increased with treatment. No differences between medications were observed. In brain regions active in memory processing, however, regional cerebral blood flow responses were more highly correlated after treatment. Specificity of cerebral blood flow to different regions appears to decline with treatment of hypertension. This greater correlation among active brain regions, which is present as well in untreated hypertensive relative to normotensive volunteers, may represent compensation in the face of less region-specific responsivity in individuals with hypertension.

Effect of aging on regional cerebral blood flow responses associated with osmotic thirst and its satiation by water drinking: a PET study.

Levels of thirst and ad libitum drinking decrease with advancing age, making older people vulnerable to dehydration. This study investigated age-related changes in brain responses to thirst and drinking in healthy men. Thirst was induced with hypertonic infusions (3.1 ml/kg 0.51M NaCl) in young (Y) and older (O) subjects. Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET). Thirst activations were identified by correlating rCBF with thirst ratings. Average rCBF was measured from regions of interest (ROI) corresponding to activation clusters in each group. The effects of drinking were examined by correlating volume of water drunk with changes in ROI rCBF from maximum thirst to postdrinking. There were increases in blood osmolality (Y, 2.8 +/- 1.8%; O, 2.2 +/- 1.4%) and thirst ratings (Y, 3.1 +/- 2.1; O, 3.7 +/- 2.8) from baseline to the end of the hypertonic infusion. Older subjects drank less water (1.9 +/- 1.6 ml/kg) than younger subjects (3.9 +/- 1.9 ml/kg). Thirst-related activation was evident in S1/M1, prefrontal cortex, anterior midcingulate cortex (aMCC), premotor cortex, and superior temporal gyrus in both groups. Postdrinking changes of rCBF in the aMCC correlated with drinking volumes in both groups. There was a greater reduction in aMCC rCBF relative to water drunk in the older group. Aging is associated with changes in satiation that militate against adequate hydration in response to hyperosmolarity, although it is unclear whether these alterations are due to changes in primary afferent inflow or higher cortical functioning.

Effects of a sedative antihistamine, D‐chlorpheniramine, on regional cerebral perfusion and performance during simulated car driving

The sedative side effects of antihistamines have been recognized to be potentially dangerous in car driving, but the mechanism underlying these effects has not yet been elucidated to date. The aim of the present study is to examine regional cerebral blood flow (rCBF) responses during a simulated car-driving task following oral administration of D-chlorpheniramine using positron emission tomography (PET) and [15O]H2O, based on a single-blind cross-over study-design. Right-handed, healthy male volunteers (n = 14) drove a car in a simulated environment following oral administration of D-chlorpheniramine repetab 6 mg or placebo. Their rCBF was measured using PET with [15O]H2O in the following three conditions: (1) resting, (2) active driving, and (3) passive driving. All 'in-car' views during the simulated driving were videotaped and used for rating driving performance. Performance evaluation revealed that the number of lane deviations significantly increased in the D-chlorpheniramine condition compared with the placebo condition (p < 0.01). Subjective sleepiness was not significantly different between the two drug conditions. The regions of diminished brain responses following D-chlorpheniramine treatment were detected in the parietal, temporal and visual cortices, and in the cerebellum. The regions of augmented rCBF responses were found in the orbitofrontal cortex and cerebellar vermis. These results suggest that D-chlorpheniramine tends to suppress visuo-spatial cognition and visuo-motor coordinating functions rather than attention and motor functions during car driving.

Gray matter blood flow change is unevenly distributed during moderate isocapnic hypoxia in humans

Hypoxia increases cerebral blood flow (CBF), but it is unknown whether this increase is uniform across all brain regions. We used H(2)(15)O positron emission tomography imaging to measure absolute blood flow in 50 regions of interest across the human brain (n = 5) during normoxia and moderate hypoxia. Pco(2) was kept constant ( approximately 44 Torr) throughout the study to avoid decreases in CBF associated with the hypocapnia that normally occurs with hypoxia. Breathing was controlled by mechanical ventilation. During hypoxia (inspired Po(2) = 70 Torr), mean end-tidal Po(2) fell to 45 +/- 6.3 Torr (means +/- SD). Mean global CBF increased from normoxic levels of 0.39 +/- 0.13 to 0.45 +/- 0.13 ml/g during hypoxia. Increases in regional CBF were not uniform and ranged from 9.9 +/- 8.6% in the occipital lobe to 28.9 +/- 10.3% in the nucleus accumbens. Regions of interest that were better perfused during normoxia generally showed a greater regional CBF response. Phylogenetically older regions of the brain tended to show larger vascular responses to hypoxia than evolutionary younger regions, e.g., the putamen, brain stem, thalamus, caudate nucleus, nucleus accumbens, and pallidum received greater than average increases in blood flow, while cortical regions generally received below average increases. The heterogeneous blood flow distribution during hypoxia may serve to protect regions of the brain with essential homeostatic roles. This may be relevant to conditions such as altitude, breath-hold diving, and obstructive sleep apnea, and may have implications for functional brain imaging studies that involve hypoxia.

Perfusion fMRI detects deficits in regional CBF during memory-encoding tasks in MCI subjects

To determine how memory-encoding tasks elicit functional perfusion change in subjects with amnestic mild cognitive impairment (aMCI). Twelve subjects with aMCI and 14 age-matched cognitively normal (CN) subjects were recruited for this study. Arterial spin-labeling perfusion MRI (ASL-MRI) was employed to measure regional cerebral blood flow (CBF) during both control and encoding task conditions. Experimental results demonstrated that hypoperfusion occurred in the right precuneus and cuneus in the aMCI group, and not the CN group, during the control state. During the memory-task performance, the difference in these regional hypoperfusion areas extended to the posterior cingulate. These regional perfusion rates correlated with the Mini-Mental State Examination and the Rey Auditory Verbal Learning Test scores. In addition, a CBF percentage increase (22.7%) occurred in the right parahippocampus region during the memory-encoding task performance in the CN group, with approximately no change in the aMCI group. Subjects with amnestic mild cognitive impairment had significant regional cerebral hypoperfusion and lacked the dynamic capability to modulate their regional cerebral blood flow responses to the challenge of the functional tasks.

Converged surface roughness parameters A new tool to quantify rock surface morphology and reactivity alteration

The neural correlates of identification and name retrieval have proved difficult to characterise because both occur highly automatically in normal language processing. Thus, although some evidence points to the left anterior temporal cortex (ATC) as a brain region underlying these functions, its relative role in semantic and lexical retrieval processes is still a matter of debate. Positron emission tomography (PET) was used to measure regional cerebral blood flow responses to famous and non-famous visually presented faces and buildings in a severely anomic patient and in six control subjects, while they were performing a same-different matching task. Because the patient was able to identify the stimuli that he could not name, it was possible to investigate whether the left ATC would respond when identification occurred without name retrieval. Both the patient and the controls activated the left ATC when famous stimuli were compared with non-famous stimuli. This result supports the hypothesis of a predominantly semantic function of the left ATC.

Effects of long-term methylphenidate treatment: A pilot follow-up clinical and SPECT study

Background Although abnormalities in the regional cerebral blood flow (rCBF) responses to methylphenidate (MPH) treatment have been reported in children with attention deficit hyperactivity disorder (ADHD), there are few prospective longitudinal studies assessing the long-term effects of MPH and discontinuation effects after chronic treatment. Methods The authors studied ten drug-naive children (2 girls, 8 boys, mean age ± S.D. = 9.60 ± 1.96) diagnosed with ADHD by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnostic criteria, using 99mTc-HMPAO-single photon emission computed tomography (SPECT). Patients were studied at baseline (visit 1), after 2 months of MPH treatment (visit 2) and after a drug-free period of 2 months following 12 months of MPH treatment (visit 3) at doses of 1 mg/kg/day. We evaluated SPECT data visually and semi-quantitatively. Results Two months of chronic MPH treatment resulted in visually detectable improvement in hypoperfusion in the right frontal cortex and all areas of temporal cortex with the exception of left lateral temporal cortex. This improvement was still detectable on visual evaluations of SPECT data after 2 months of treatment discontinuation. The treatment effects that were detected visually were not statistically significant in semi-quantitative analyses. Conclusions Treatment effects of chronic MPH treatment may persist long after the discontinuation of the treatment.

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

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. 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. 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. 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.