Mesocorticolimbic hemodynamic response in Parkinson's disease patients with compulsive behaviors.

BACKGROUND: PD patients treated with dopamine therapy can develop maladaptive impulsive and compulsive behaviors, manifesting as repetitive participation in reward-driven activities. This behavioral phenotype implicates aberrant mesocorticolimbic network function, a concept supported by past literature. However, no study has investigated the acute hemodynamic response to dopamine agonists in this subpopulation. OBJECTIVES: We tested the hypothesis that dopamine agonists differentially alter mesocortical and mesolimbic network activity in patients with impulsive-compulsive behaviors. METHODS: Dopamine agonist effects on neuronal metabolism were quantified using arterial-spin-labeling MRI measures of cerebral blood flow in the on-dopamine agonist and off-dopamine states. The within-subject design included 34 PD patients, 17 with active impulsive compulsive behavior symptoms, matched for age, sex, disease duration, and PD severity. RESULTS: Patients with impulsive-compulsive behaviors have a significant increase in ventral striatal cerebral blood flow in response to dopamine agonists. Across all patients, ventral striatal cerebral blood flow on-dopamine agonist is significantly correlated with impulsive-compulsive behavior severity (Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease- Rating Scale). Voxel-wise analysis of dopamine agonist-induced cerebral blood flow revealed group differences in mesocortical (ventromedial prefrontal cortex; insular cortex), mesolimbic (ventral striatum), and midbrain (SN; periaqueductal gray) regions. CONCLUSIONS: These results indicate that dopamine agonist therapy can augment mesocorticolimbic and striato-nigro-striatal network activity in patients susceptible to impulsive-compulsive behaviors. Our findings reinforce a wider literature linking studies of maladaptive behaviors to mesocorticolimbic networks and extend our understanding of biological mechanisms of impulsive compulsive behaviors in PD. © 2017 International Parkinson and Movement Disorder Society.

Uncertainty increases pain: evidence for a novel mechanism of pain modulation involving the periaqueductal gray.

Predictions about sensory input exert a dominant effect on what we perceive, and this is particularly true for the experience of pain. However, it remains unclear what component of prediction, from an information-theoretic perspective, controls this effect. We used a vicarious pain observation paradigm to study how the underlying statistics of predictive information modulate experience. Subjects observed judgments that a group of people made to a painful thermal stimulus, before receiving the same stimulus themselves. We show that the mean observed rating exerted a strong assimilative effect on subjective pain. In addition, we show that observed uncertainty had a specific and potent hyperalgesic effect. Using computational functional magnetic resonance imaging, we found that this effect correlated with activity in the periaqueductal gray. Our results provide evidence for a novel form of cognitive hyperalgesia relating to perceptual uncertainty, induced here by vicarious observation, with control mediated by the brainstem pain modulatory system.

Common representation of pain and negative emotion in the midbrain periaqueductal gray.

Human neuroimaging offers a powerful way to connect animal and human research on emotion, with profound implications for psychological science. However, the gulf between animal and human studies remains a formidable obstacle: human studies typically focus on the cortex and a few subcortical regions such as the amygdala, whereas deeper structures such as the brainstem periaqueductal gray (PAG) play a key role in animal models. Here, we directly assessed the role of PAG in human affect by interleaving in a single fMRI session two conditions known to elicit strong emotional responses--physical pain and negative image viewing. Negative affect and PAG activity increased in both conditions. We next examined eight independent data sets, half featuring pain stimulation and half negative image viewing. In sum, these data sets comprised 198 additional participants. We found increased activity in PAG in all eight studies. Taken together, these findings suggest PAG is a key component of human affective responses.

Spumiform basement membrane aberrations in the microvasculature of the midbrain periaqueductal gray region in hamster: rostro-caudal pathogenesis?

Spumiform basement membrane degeneration (sbmd) is a specific kind of aberration present in the capillaries of the midbrain periaqueductal gray (PAG) region of the senescent hamster. These capillaries, separated by the ependymal cell layer, are bordering the Sylvian cerebral aqueduct. The aqueduct, connecting the 3rd and 4th ventricle, may be crucial for local homeostatic as well as general autonomic functions of the PAG. Local pressure effects of the flowing and pulsating cerebrospinal fluid on the PAG-vasculature are probably different for the rostral 'entrance' and the caudal 'exit' of the aqueduct. In view of the different functions of the various divisions of the PAG, the frequency and extent of the aberrations in the rostral, intermediate and caudal dl/vlPAG-microvasculature could shed some light on the causal factors involved in the regional distribution of the particular microvascular aberrations found in the PAG during aging. In the present study we investigated the ultrastructure of capillaries in dorsal and ventral subdivisions of anterior and posterior regions of the PAG of young and old female Syrian hamsters. Sbmds were classified into four stages of spumiform severity and for each stage the frequency was determined in the rostral PAG, at two levels in the intermediate PAG and in a dorsal and a ventral part of the caudal PAG. Results of our quantitative studies showed that in aged hamster PAG various stages of sbmd were present in 91.6 ± 0.6% of all capillaries. No clear evidence was found for regional differentiation between rostral, intermediate and caudal parts of the PAG. Next to sbmd, capillary split basement membrane (sbm) and vacuolization were common features at all five PAG locations. 84.3 ± 2.3% of all screened PAG capillaries displayed sbm. In agreement with our previous findings, several other types of microvascular aberrations were observed in addition to general aspects of aging and some ependymal structural peculiarities. We conclude that the presence of various forms of sbmds in the PAG of senescent hamsters is a phenomenon that appears to be specific to the PAG region, but causal factors for this type of capillary degeneration remain unclear. Sbmds in the PAG may have serious consequences not only for blood-brain barrier functioning, but also for vascular perfusion and blood supply with eventually serious consequences for adequate regulation of the autonomic and motor control functions of the PAG region.

The role of periaqueductal gray and cingulate cortex during suppression of pain in complex regional pain syndrome.

OBJECTIVE: Complex regional pain syndrome I (CRPS I) is a frequent and debilitating condition with unclear etiology. Hypothesizing that maladaptive central processes play a crucial role in CRPS, the current study set out to explore cerebral activation during a task to suppress the feeling of pain under constant painful stimulation. METHODS: Ten individuals with CRPS I with symptoms on their left hand were subjected to electrical stimulation of both index fingers subsequently in a functional magnetic resonance imaging experiment. Their data were compared with 15 healthy controls. RESULTS: Concerning psychophysical measures, patients succeeded similarly as healthy controls in suppressing the feeling of pain. However, during constant painful stimulation and with the task to suppress the feeling of pain, there were significant differences in the interaction analyses of the corresponding cortical activation. DISCUSSION: Patients differ from healthy controls by the activation pattern of cerebral areas that belong to the descending opioid pain suppression pathway: PAG and cingulate cortex are activated significantly less during suppression of pain, regardless of whether the symptomatic or asymptomatic hand was stimulated. Thus, there is a generalized functional change in individuals with CRPS I. However, it cannot be deducted whether the abnormality is causative or merely an effect, possibly maladaptive.

Vertical ophthalmoplegia due to a unilateral periaqueductal gray matter infarct in an adolescent.

Brainstem strokes affecting the periaqueductal gray matter of the midbrain can cause vertical ophthalmoplegia. Accompanying clinical features are frequently associated and reflect the involvement of other brainstem structures. We report on an adolescent presenting with vertical gaze palsy and left mydriatic pupil as the only clinical expression of a small infarct located in the left periaqueductal gray matter. Even when the lesion was strictly unilateral, vertical ophthalmoplegia affected both eyes.

fMRI study of acupuncture-induced periaqueductal gray activity in humans.

BOLD fMRI was used to study acupuncture-induced activation (increase in the BOLD signal from undetectable) of the periaqueductal gray (PAG) and two somatosensory cortical areas in seven healthy human subjects. Mechanical stimulation (push-pull) was given to the LI4 (Hoku) acupoint or to a non-acupoint. The stimulation paradigm consisted of 5 runs, each consisting of four 30 s On/30 s OFF periods over 30 min. The scan for each ON period was analyzed individually. The PAG and cortical areas showed different activity patterns. PAG activity was episodic and reliably demonstrated after 20-25 min of stimulation; both cortical areas, however, were active > 90% of the time. Stimulation of a non-acupoint (leg) resulted in reduced levels of PAG and cortical activity.

Role of nociceptin/orphanin FQ in age-dependent cerebral hemodynamic effects of brain injury.

This study was designed to compare the role of the newly described endogenous opioid nociceptin/orphanin FQ (NOC/oFQ) in the reductions of cerebral blood flow (CBF) and pial artery diameter observed following fluid percussion brain injury (FPI) in chloralose anesthetized newborn and juvenile pigs as a function of time postinsult. FPI elevated CSF NOC/oFQ concentration from 70 +/- 3 to 444 +/- 51 within 1 h and to 1,931 +/- 112 pg/mL (n = 7) within 8 h, whereas concentrations returned to control value within 168 h in the newborn. In contrast, FPI elevated CSF NOC/oFQ from 77 +/- 4 to 202 +/- 16 pg/mL (n = 7) within 1 h, while values returned to control value within 8 h in the juvenile. Topical NOC/oFQ (10(-8), 10(-6) M) induced vasodilation was reversed to vasoconstriction by FPI in the newborn while such responses were only attenuated in the juvenile at 1 h post insult (control, 9 +/- 1 and 16 +/- 1%; FPI newborn, -8 +/- 1 and -14 +/- 1%; FPI juvenile, 2 +/- 1 and 5 +/- 1%, n = 7). Such altered dilation returned to control value within 168 h in newborns and 8 h in juveniles. Blood flow in the cerebrum was reduced from 57 +/- 4 to 23 +/- 3 mL x min(-1) x 100 g(-1) (n = 7) within 1 h and returned to control value with 168 h post FPI in newborns. In animals pretreated with [F/G] NOC/oFQ (1-13) NH2 (1 mg/kg, i.v.), a NOC/oFQ antagonist, however, CBF only fell to 39 +/- 4 mL x min(-1) x 100 g(-1) (n = 7) at 1 h post insult in newborns. In contrast, CBF was only reduced from 57 +/- 6 to 32 +/- 2 in untreated and to 39 +/- 3 mL/min(-1) x 100 g(-1) (n = 7) in treated juveniles within 1 h post FPI. Similar observations for reductions in pial artery diameter were made in untreated and treated newborns and juveniles. These data suggest that an elevated CSF NOC/oFQ concentration and altered vascular responsiveness to this opioid contribute to reductions in CBF and pial artery diameter observed following FPI. Because such NOC/oFQ changes were greater in newborns versus juveniles, these data further suggest that NOC/oFQ contributes to age-related cerebral hemodynamic differences in the effects of FPI.

Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET: II. Normal values and gray matter blood flow response to visual activation.

One of the most limiting factors for the accurate quantification of physiologic parameters with positron emission tomography (PET) is the partial volume effect (PVE). To assess the magnitude of this contribution to the measurement of regional cerebral blood flow (rCBF), the authors have formulated four kinetic models each including a parameter defining the perfusable tissue fraction (PTF). The four kinetic models used were 2 one-tissue compartment models with (Model A) and without (Model B) a vascular term and 2 two-tissue compartment models with fixed (Model C) or variable (Model D) white matter flow. Furthermore, rCBF based on the autoradiographic method was measured. The goals of the study were to determine the following in normal humans: (1) the optimal model, (2) the optimal length of fit, (3) the model parameters and their reproducibility, and (4) the effects of data acquisition (2D or 3D). Furthermore, the authors wanted to measure the activation response in the occipital gray matter compartment, and in doing so test the stability of the PTF, during perturbations of rCBF induced by visual stimulation. Eight dynamic PET scans were acquired per subject (n = 8), each for a duration of 6 minutes after IV bolus injection of H2(15)O. Four of these scans were performed using 2D and four using 3D acquisition. Visual stimulation was presented in four scans, and four scans were during rest. Model C was found optimal based on Akaike's Information Criteria (AIC) and had the smallest coefficient of variance after a 6-minute length of fit. Using this model the average PVE corrected rCBF during rest in gray matter was 1.07 mL x min(-1) x g(-1) (0.11 SD), with an average coefficient of variance of 6%. Acquisition mode did not affect the estimated parameters, with the exception of a significant increase in the white matter rCBF using the autoradiographic method (2D: 0.17 mL x min(-1) x g(-1) (0.02 SD); 3D: 0.21 mL x min(-1) x g(-1) (0.02 SD)). At a 6-minute fit the average gray matter CBF using Models C and D were increased by 100% to 150% compared with Models A and B and the autoradiographic method. There were no significant changes in the perfusable tissue fraction by the activation induced rCBF increases. The largest activation response was found using Model C (median = 39.1%). The current study clearly demonstrates the importance of PVE correction in the quantitation of rCBF in normal humans. The potential use of this method is to cost-effectively deliver PVE corrected measures of rCBF and tissue volumes without reference to imaging modalities other than PET.

Quantitation of regional cerebral blood flow corrected for partial volume effect using O-15 water and PET: I. Theory, error analysis, and stereologic comparison.

Limited spatial resolution of positron emission tomography (PET) can cause significant underestimation in the observed regional radioactivity concentration (so-called partial volume effect or PVE) resulting in systematic errors in estimating quantitative physiologic parameters. The authors have formulated four mathematical models that describe the dynamic behavior of a freely diffusible tracer (H215O) in a region of interest (ROI) incorporating estimates of regional tissue flow that are independent of PVE. The current study was intended to evaluate the feasibility of these models and to establish a methodology to accurately quantify regional cerebral blood flow (CBF) corrected for PVE in cortical gray matter regions. Five monkeys were studied with PET after IV H2(15)O two times (n = 3) or three times (n = 2) in a row. Two ROIs were drawn on structural magnetic resonance imaging (MRI) scans and projected onto the PET images in which regional CBF values and the water perfusable tissue fraction for the cortical gray matter tissue (hence the volume of gray matter) were estimated. After the PET study, the animals were killed and stereologic analysis was performed to assess the gray matter mass in the corresponding ROIs. Reproducibility of the estimated parameters and sensitivity to various error sources were also evaluated. All models tested in the current study yielded PVE-corrected regional CBF values (approximately 0.8 mL x min(-1) x g(-1) for models with a term for gray matter tissue and 0.5 mL x min(-1) x g(-1) for models with a term for a mixture of gray matter and white matter tissues). These values were greater than those obtained from ROIs tracing the gray matter cortex using conventional H2(15)O autoradiography (approximately 0.40 mL x min(-1) x g(-1)). Among the four models, configurations that included two parallel tissue compartments demonstrated better results with regards to the agreement of tissue time-activity curve and the Akaike's Information Criteria. Error sensitivity analysis suggested the model that fits three parameters of the gray matter CBF, the gray matter fraction, and the white matter fraction with fixed white matter CBF as the most reliable and suitable for estimating the gray matter CBF. Reproducibility with this model was 11% for estimating the gray matter CBF. The volume of gray matter tissue can also be estimated using this model and was significantly correlated with the results from the stereologic analysis. However, values were significantly smaller compared with those measured by stereologic analysis by 40%, which can not be explained by the methodologic errors. In conclusion, the partial volume correction was essential in quantitation of regional CBF. The method presented in this article provided the PVE-corrected regional CBF in the cortical gray matter tissue. This study also suggests that further studies are required before using MRI derived anatomic information for PVE correction in PET.

Midbrain ptosis caused by periaqueductal infarct following cardiac catheterization: early detection with diffusion-weighted imaging.

Isolated infarcts in the periaqueductal region are rare but have been reported after cardiac catheterization. The authors report a case of dorsal midbrain infarct which caused bilateral ptosis, partial upgaze paresis, and internuclear ophthalmoplegia imaged within eight hours with diffusion-weighted imaging (DWI). The lesion was later confirmed on T2-weighted images. Diffusion-weighted imaging can rapidly confirm the diagnosis of this rare brain-stem infarct.

Volume expansion fails to normally activate neural pathways in the brain of conscious rabbits with heart failure.

Immunohistochemical detection of the protein, Fos, was used to identify neurons in the brain activated following a volume load in conscious rabbits with doxorubicin-induced congestive cardiomyopathy. The plasma expander, Haemaccel, was infused intravenously into rabbits for 60 min and significantly increased right atrial pressure, blood pressure and heart rate. The rabbits were perfusion fixed 90 min after the start of the infusion and the distribution of Fos-positive cell nuclei was examined. Compared to control rabbits with heart failure, there was a small significant increase in the number of Fos-positive cell nuclei in the organum vasculosum of the lamina terminalis following volume expansion. In other regions of the brain that were studied in detail, there were no significant increases in Fos production. These included the parvocellular paraventricular nucleus (PVN) of the hypothalamus, the midbrain periaqueductal gray, the nucleus tractus solitarius (NTS), area postrema and the ventrolateral medulla (VLM). In the supraoptic nucleus and the magnocellular PVN, no Fos-positive cell nuclei were present as expected. The median preoptic nucleus, the bed nucleus of the striae terminalis and the diagonal band of Broca contained some Fos but there was no marked difference between volume expanded and control animals. In the anterior cortical and medial subnuclei of the amygdala there was a high concentration of Fos but there was no consistent difference between the two groups. The present findings in heart failure rabbits suggest that most brain regions are not activated sufficiently by the stimulus to elicit Fos expression. The results are in accord with findings showing that sympathetic reflexes initiated by volume expansion are attenuated in heart failure.

Increased cerebral blood volume in HIV-positive patients detected by functional MRI.

OBJECTIVE: To study changes in cerebral hemodynamics related to HIV infection. BACKGROUND: Cerebral injury is a well-known manifestation of HIV infection. Physiologic changes in the HIV brain may precede structural changes and may be detected by functional MRI (fMRI). METHODS: Dynamic contrast fMRI was used to measure the cerebral blood volume (CBV) in 13 patients infected with HIV and in 7 healthy control subjects. RESULTS: Significant increases in dynamic CBV were found in the deep (p < 0.001) and cortical gray matter (p < 0.05) of HIV-positive (HIV+) patients. Patients with definite cognitive impairment showed significantly greater increases in CBV in the deep gray matter (DGM) compared with those without impairment. In one patient with rapidly progressive cognitive impairment, these abnormalities reversed and paralleled clinical improvement after initiation of zidovudine monotherapy. CONCLUSIONS: This study supports the hypothesis that HIV infection is associated with significant cerebral hemodynamic changes, particularly in the DGM, that may contribute to cognitive dysfunction in AIDS. Functional MRI may be useful for early detection of cerebral injury and for the assessment of novel therapies.

A PET study on brain control of micturition in humans.

Although the brain plays a crucial role in the control of micturition, little is known about the structures involved. Identification of these areas is important, because their dysfunction is though to cause urge incontinence, a major problem in the elderly. In the cat, three areas in the brainstem and diencephalon are specifically implicated in the control of micturition: the dorsomedial pontine tegmentum, the periaqueductal grey, and the preoptic area of the hypothalamus. PET scans were used to test whether these areas are also involved in human micturition. Seventeen right-handed male volunteers were scanned during the following four conditions: (i) 15 min prior to micturition during urine withholding: (ii) during micturition; (iii) 15 min after micturition; (iv) 30 min after micturition. Ten of the 17 volunteers were able to micturate during scanning. micuturition was associated with increased blood flow in the right dorsomedial pontine tegmentum, the periaqueductal grey, the hypothalamus and the right inferior frontal gyrus. Decreased blood flow was found in the right anterior cingulate gyrus when urine was withheld. The other seven volunteers were not able to micturate during scanning, although they had a full bladder and tried vigorously to do so. In this group, during these unsuccessful attempts to micturate, increased blood flow was found in the right ventral pontine tegmentum, which corresponds with the hypothesis, formulated from results in cats, that this area controls the motor neurons of the pelvic floor. Increased blood flow was also found in the right inferior frontal gyrus during unsuccessful attempts at micturition, and decreased blood flow in the right anterior cingulate gyrus was found during the withholding of urine. The results suggest that, as that of the cat, the human brainstem contains specific nuclei responsible for the control of micturition, and that the cortical and pontine micturition sites are predominantly on the right side.

Regional cerebral blood flow response in gray matter heterotopia during finger tapping: an activation study with positron emission tomography.

We examined regional cerebral blood flow response in a patient with gray matter heterotopia located beneath the sensorimotor cortex during a finger tapping task. We found regional cerebral blood flow was specifically increased during contralateral finger tapping. This indicated the possibility of functional differentiation of the ectopic neurons despite incomplete migration.

Traumatic nociceptive pain activates the hypothalamus and the periaqueductal gray: a positron emission tomography study.

The study was conducted to investigate which areas of the brain respond to a painful encounter of minor dermal injury (a model of clinical pain) elicited by intracutaneous injection of a minute amount of ethanol. Four healthy volunteers (27-46 years) were subjected to positron emission tomographic (PET) investigation of regional cerebral blood flow (rCBF), using [15O]butanol as tracer. The ethanol (20 microliters, 70%) and saline (20 microliters, 0.9%) were injected intracutaneously 3 times in a single-blinded, semi-randomised manner for the pain experiment. All the injections were performed, adjacent to each other, at the lateral aspect of the right upper arm. Subjective sensory intensity of pain, unpleasantness and anxiety were rated with separate 100-mm visual analogue scales together with the Spielberger's State Anxiety Inventory (Spielberger et al. 1970) and heart rate. Paired-subtraction (pixel-by-pixel) between ethanol and saline was performed. Traumatic pain significantly caused higher ratings of intensity and affect scales, i.e., pain intensity, unpleasantness and increased sympathetic activity (evidenced by tachycardia). In contrast the anxiety rating remained unchanged. Acute traumatic nociceptive pain prominently activated the hypothalamus and periaqueductal gray (PAG). In addition, activations of the prefrontal cortex (PFC), insular, anterior cingulate cortex (ACC), posterior parietal cortex (PPC), primary motor/somatosensory areas (MI/SI: face, upper arm), supplementary motor area (SMA), and cerebellum were also demonstrated. The central processing of the pain-relevant/anticipatory arousal also engaged the PAG. This study demonstrates the involvement of the human cerebral cortex in perception, arousal, cognitive evaluative processes, and, hence, affective reactions (somatic/ autonomic outflow) associated with pain. The pain stimulus of traumatic character may, by its very nature, evoke the central processing to involve both the hypothalamus and the PAG.

Simulation study of cerebral blood flow measurements in xenon-CT: evaluation of washin/washout procedures.

Simulation programs have been created that allow one to vary image pixel noise, the number and the distribution of scans with time, cerebral tissue parameters, and the type of xenon CT inhalation procedure in order to investigate CBF measurements with respect to accuracy and signal-to-noise ratio (SNR). In particular, standard washin studies were compared to washin/washout studies. Based on the results of these simulations, a new protocol is suggested; it consists of only 3 min of xenon inhalation (washin phase) and 3 min of washout, monitored by one reference and six enhancement scans taken at 1-min intervals. Compared with a standard 8-min washin study of equal total dose, flow standard deviation (s.d.) for an unconstrained least-squares algorithm is reduced by factors of 2.2 and 1.2 for gray and white matter, respectively; for flow distributed uniformly from 20 to 80 ml/min/100 g, an average s.d. reduction factor of 1.7 is achieved. This was confirmed experimentally in a volunteer study using noise power spectrum analysis. In addition, effects of tissue heterogeneity have been investigated; both the bias and s.d. of flow estimates due to varying proportions of white and gray matter in a given volume element are reduced in washin/washout protocols. When compared to a short washin-only study of 4.5 min, the 3-min washin/3-min washout study provides an improvement of flow s.d. by a factor of 1.6 and 1.9 for gray and white matter, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Trigeminovascular fibers increase blood flow in cortical gray matter by axon reflex-like mechanisms during acute severe hypertension or seizures.

Cerebral blood flow was measured and compared in 10 symmetrical brain regions following unilateral trigeminal ganglionectomy (n = 13), sham operation (n = 6), or trigeminal root section (rhizotomy) (n = 8) in cats. Multiple determinations were obtained in anesthetized and paralyzed animals using radiolabeled microspheres during (i) normocapnia-normotension, (ii) hypercapnia (5% CO2/95% room air), (iii) angiotensin-induced acute severe hypertension (190 greater than mean arterial blood pressure less than 210 mmHg), or (iv) bicuculline-induced seizures. Flow was symmetrical in all brain regions at rest and during increases induced by hypercapnia in the three groups. During severe hypertension or seizures, marked elevations developed bilaterally (approximately 93% and approximately 130%, respectively). In ganglionectomized animals, increases due to hypertension or seizures were attenuated by 28-32% on the denervated side within cortical gray matter regions corresponding to the anterior, middle, and posterior cerebral arteries. Flow was symmetrical within all brain regions in sham-operated animals and in the rhizotomy group, despite comparable increases in regional cerebral blood flow induced by angiotensin. Hence, the trigeminal nerve mediates blood flow adaptations during severe hypertension and seizures. Furthermore, since trigeminal cell bodies and peripheral axons are destroyed or degenerate following ganglionectomy but not following rhizotomy, local "axon reflex-like" mechanisms mediate these increases in cerebral blood flow.