Simultaneous CBF and BOLD mapping of high frequency acupuncture induced brain activity.

This study mapped brain activity elicited by high frequency electroacupuncture by simultaneously using blood oxygenation level dependent (BOLD) and cerebral blood flow (CBF) contrasts. Forty subjects participated in the study, in which twenty ones were imaged during electrical acupoint stimulation (EAS) to the left LI4 acupoint at a maximal intensity without pain, and the others were with a minimal-EAS at a just detectible intensity. Both BOLD and CBF data were acquired simultaneously during alternating blocks of rest and stimulation. The results showed that the minimal-EAS mostly induced the activities in somatosensory region, including those in inferior parietal lobule, SII, insula, and thalamus. On the other hand, EAS activated more including also posterior middle cingulate cortex (pMCC), and deactivated superior temporal gyrus. Moreover, deactivation was found in posterior cingulated cortex (PCC), precuneus from BOLD and in culmen of cerebellum, caudate from CBF. The comparison between EAS and minimal-EAS revealed deactivation in the default mode network in both BOLD and CBF signals, activation in thalamus, insula, and caudal anterior cingulate cortex (ACC) in the CBF signal alone, and deactivation in putamen, rostral ACC and parahippocampal gyrus in the BOLD signal alone. This study provides, for the first time, simultaneous CBF and BOLD responses to high frequency EAS at the LI4 acupoint, revealing concordant and complementary insights into the neural effects of EAS, including modulation of subcortical structures and limbic system.

Common limbic and frontal-striatal disturbances in patients with obsessive compulsive disorder, panic disorder and hypochondriasis.

BACKGROUND: Direct comparisons of brain function between obsessive compulsive disorder (OCD) and other anxiety or OCD spectrum disorders are rare. This study aimed to investigate the specificity of altered frontal-striatal and limbic activations during planning in OCD, a prototypical anxiety disorder (panic disorder) and a putative OCD spectrum disorder (hypochondriasis). METHOD: The Tower of London task, a 'frontal-striatal' task, was used during functional magnetic resonance imaging measurements in 50 unmedicated patients, diagnosed with OCD (n=22), panic disorder (n=14) or hypochondriasis (n=14), and in 22 healthy subjects. Blood oxygen level-dependent (BOLD) signal changes were calculated for contrasts of interest (planning versus baseline and task load effects). Moreover, correlations between BOLD responses and both task performance and state anxiety were analysed. RESULTS: Overall, patients showed a decreased recruitment of the precuneus, caudate nucleus, globus pallidus and thalamus, compared with healthy controls. There were no statistically significant differences in brain activation between the three patient groups. State anxiety was negatively correlated with dorsal frontal-striatal activation. Task performance was positively correlated with dorsal frontal-striatal recruitment and negatively correlated with limbic and ventral frontal-striatal recruitment. Multiple regression models showed that adequate task performance was best explained by independent contributions from dorsolateral prefrontal cortex (positive correlation) and amygdala (negative correlation), even after controlling for state anxiety. CONCLUSIONS: Patients with OCD, panic disorder and hypochondriasis share similar alterations in frontal-striatal brain regions during a planning task, presumably partly related to increased limbic activation.

Fronto-limbic abnormalities in a patient with compulsive hoarding: a 99mTc-ECD SPECT study.

Little is known about the neuronal mechanism underpinning the pathophysiology of compulsive hoarding. We report the cerebral blood flow changes in an obsessive-convulsive patient with severe hoarding. The patient showed hyperperfusion of the fronto-temporal region and hypoperfusion of the striatal, the middle cingulate and the medial temporal regions during the stage with severe symptoms. Following improvement from the hoarding behaviors, the extent of hypoperfusion was expanded in the bilateral striatum, the anterior and middle cingulate gyrus. The result may substantiate evidence of the fronto-limbic abnormality involved in the pathophysiology of compulsive hoarding.

Acupuncture, the limbic system, and the anticorrelated networks of the brain.

The study of the mechanism of acupuncture action was revolutionized by the use of functional magnetic resonance imaging (fMRI). Over the past decade, our fMRI studies of healthy subjects have contributed substantially to elucidating the central effect of acupuncture on the human brain. These studies have shown that acupuncture stimulation, when associated with sensations comprising deqi, evokes deactivation of a limbic-paralimbic-neocortical network, which encompasses the limbic system, as well as activation of somatosensory brain regions. These networks closely match the default mode network and the anti-correlated task-positive network described in the literature. We have also shown that the effect of acupuncture on the brain is integrated at multiple levels, down to the brainstem and cerebellum. Our studies support the hypothesis that the effect of acupuncture on the brain goes beyond the effect of attention on the default mode network or the somatosensory stimulation of acupuncture needling. The amygdala and hypothalamus, in particular, show decreased activation during acupuncture stimulation that is not commonly associated with default mode network activity. At the same time, our research shows that acupuncture stimulation needs to be done carefully, limiting stimulation when the resulting sensations are very strong or when sharp pain is elicited. When acupuncture induced sharp pain, our studies show that the deactivation was attenuated or reversed in direction. Our results suggest that acupuncture mobilizes the functionally anti-correlated networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response. In this work we also discuss multiple avenues of future research, including the role of neurotransmitters, the effect of different acupuncture techniques, and the potential clinical application of our research findings to disease states including chronic pain, major depression, schizophrenia, autism, and Alzheimer's disease.

The salient characteristics of the central effects of acupuncture needling: limbic-paralimbic-neocortical network modulation.

Human and animal studies suggest that acupuncture produces many beneficial effects through the central nervous system. However, the neural substrates of acupuncture actions are not completely clear to date. fMRI studies at Hegu (LI4) and Zusanli (ST36) indicated that the limbic system may play an important role for acupuncture effects. To test if this finding applies to other major classical acupoints, fMRI was performed on 10 healthy adults during manual acupuncture at Taichong (LV3), Xingjian (LV2), Neiting (ST44), and a sham point on the dorsum of the left foot. Although certain differences could be observed between real and sham points, the hemodynamic response (BOLD signal changes) and psychophysical response (sensory experience) to acupuncture were generally similar for all four points. Acupuncture produced extensive deactivation of the limbic-paralimbic-neocortical system. Clusters of deactivated regions were seen in the medial prefrontal cortex (frontal pole, pregenual cingulate), the temporal lobe (amygdala, hippocampus, and parahippocampus) and the posterior medial cortex (precuneus, posterior cingulate). The sensorimotor cortices (somatosensory cortices, supplementary motor cortex), thalamus and occasional paralimbic structures such as the insula and anterior middle cingulate cortex showed activation. Our results provide additional evidence in support of previous reports that acupuncture modulates the limbic-paralimbic-neocortical network. We hypothesize that acupuncture may mediate its antipain, antianxiety, and other therapeutic effects via this intrinsic neural circuit that plays a central role in the affective and cognitive dimensions of pain as well as in the regulation and integration of emotion, memory processing, autonomic, endocrine, immunological, and sensorimotor functions.

Cerebral blood flow changes in man by wake-promoting drug, modafinil: a randomized double blind study.

To investigate the effects of a wake-promoting drug, modafinil on regional cerebral blood flow (rCBF) in healthy volunteers, we performed (99m)Tc-ethylcysteinate dimer single photon emission computed tomography (SPECT) before and after modafinil or placebo administration. Twenty-one healthy subjects received single doses of 400 mg modafinil or placebo in a double blind randomized crossover study design. Administrations of modafinil or placebo in a subject were separated by a 2-week washout. Brain SPECT was performed twice before and 3 h after modafinil or placebo administration. For statistical parametric mapping analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 12-mm full width at half-maximum Gaussian kernel. The paired t-test was used to compare pre- versus post-modafinil and pre- versus post-placebo SPECT images. Differences in rCBF between post-modafinil and post-placebo conditions were also tested. Modafinil decreased Epworth and Stanford sleepiness scales whereas placebo did not. The post-modafinil condition was associated with increased rCBF in bilateral thalami and dorsal pons, whereas the post-placebo condition showed increased rCBF in a smaller area of the dorsal pons when compared with the drug naïve baseline condition. Compared with the post-placebo condition, the post-modafinil condition showed higher rCBF in bilateral frontopolar, orbitofrontal, superior frontal, middle frontal gyri, short insular gyri, left cingulate gyrus, left middle/inferior temporal gyri, left parahippocampal gyrus, and left pons. In healthy volunteers, modafinil increased wakefulness and rCBF in the arousal-related systems and in brain areas related to emotion and executive function.

[NADPH-diaphorase neurons and their interrelationship with microvascular vessels in the basal forebrain limbic structures and hypothalamus].

NADPH-diaphorase histochemistry was used to study the distribution and density of labeled neurons in the limbic structures and hypothalamus in intact rat. NADPH-diaphorase positive neurons were registered in the basal forebrain-medial septal nucleus (MS), the nuclei of the diagonal band of Broca (VDB, HDB), substancia innominata (SI) and the nucleus basalis of Meynert (B). These areas largely overlap with the cholinergic CH1-CH4 forebrain system of the rodent brain. The order of density of labeled neurons in different regions of the basal forebrain was as following sequence: HDB > VDB > SI > B. The highest densities of the reactive neurons (> 1000 labeled neurons per section 200x200 microm2) was found in the islands of Calleja (ICjs). In the supraoptic (SO) and paraventricular (Pa) nuclei of hypothalamus were recorded > 130 and > 100 labeled units, respectively. The lowest density of labeled neurons was recorded within the SI-B complex: < 10 reactive units. Reactive neurons, their dendrites and axon-like processes within the ICjs, SO, Pa, the lateral nucleus hypothalamus (LH) often surround arterioles which traverse the structures. We suggest that NADPH-diaphorase-reactive (NO-generating) neurons within the ICjs and hypothalamus are involved in regulation of the regional, blood flow (RBF) that is important to adapt the blood flow to changes in neuronal activity of the basal forebrain structures.

Aggressive behavior and posterior cerebral artery stroke.

OBJECTIVE: To describe the mechanisms leading to aggressive behavior among patients with acute posterior cerebral artery stroke. DESIGN, SETTING, AND PATIENTS: We prospectively included all of the patients with posterior cerebral artery stroke and aggressive behavior admitted to our department from January 1, 2003, to December 31, 2004. Patients with history of stroke, cognitive impairment, or prior history of psychiatric disease were excluded. RESULTS: Aggressive behavior was found in 3 patients (7.3%) among 41 patients with posterior cerebral artery stroke. One patient had right occipitotemporal and ventrolateral thalamic stroke. The second patient had left occipitotemporal and lateral thalamic stroke. The third patient had right isolated occipital stroke. In addition to a contralateral homonymous hemianopsia, the patients, who were physically and emotionally balanced before the stroke, suddenly manifested an acute, unusual, aggressive behavior. The patients became agitated and aggressive when they were stimulated by the environment, and they responded to solicitation by their relatives or medical personnel by shouting obscenities and hitting and biting others. In all of the 3 cases, temporary physical restraint was required and neuroleptics were administered. This unusual behavioral pattern resolved within 2 weeks after stroke. CONCLUSIONS: Aggressive behavior is a rare presentation of acute posterior cerebral artery stroke, which may be difficult to diagnose in patients presenting with hemianopsia as the only concomitant neurological sign. The postulated mechanisms include dysfunction of the limbic or serotoninergic system.

Motor cortex stimulation for intractable pain.

Effective management of neuropathic pain is one of the more challenging endeavors for even the most experienced and skilled pain specialist. Pharmacological therapy is frequently ineffective and/or poorly tolerated, especially in elderly patients. Many if not most surgical procedures have yielded limited success in the treatment of these pain conditions. Motor cortex stimulation (MCS) has emerged as a promising technique for the management of pain in patients with difficult neuropathic and central pain conditions. Although MCS has proven most successful for patients with trigeminal neuropathic/deafferentation pain and central poststroke pain, other conditions are now emerging as potential targets for this therapy. Based on previous as well as ongoing work, it would appear that the future of MCS is indeed bright. Hopefully, as work continues in this area, investigators will be able to develop a better understanding of the mechanisms underlying this modality and be able to further refine the technique of MCS. It is also possible that with the use of noninvasive tools such as transcranial magnetic stimulation, practitioners will be able to predict with accuracy which patients are likely to respond favorably to MCS.

The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI.

Clinical and experimental data indicate that most acupuncture clinical results are mediated by the central nervous system, but the specific effects of acupuncture on the human brain remain unclear. Even less is known about its effects on the cerebellum. This fMRI study demonstrated that manual acupuncture at ST 36 (Stomach 36, Zusanli), a main acupoint on the leg, modulated neural activity at multiple levels of the cerebro-cerebellar and limbic systems. The pattern of hemodynamic response depended on the psychophysical response to needle manipulation. Acupuncture stimulation typically elicited a composite of sensations termed deqi that is related to clinical efficacy according to traditional Chinese medicine. The limbic and paralimbic structures of cortical and subcortical regions in the telencephalon, diencephalon, brainstem and cerebellum demonstrated a concerted attenuation of signal intensity when the subjects experienced deqi. When deqi was mixed with sharp pain, the hemodynamic response was mixed, showing a predominance of signal increases instead. Tactile stimulation as control also elicited a predominance of signal increase in a subset of these regions. The study provides preliminary evidence for an integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 that correlates with the psychophysical response.

Neuroanatomic correlates of psychopathologic components of major depressive disorder.

BACKGROUND: The Hamilton Depression Rating Scale (HDRS) is widely used to measure the severity of depression in mood disorders. Total HDRS score correlates with brain metabolism as measured by fludeoxyglucose F 18 ([(18)F]-FDG) positron emission tomography. The HDRS comprises distinct symptom clusters that may be associated with different patterns of regional brain glucose metabolism. OBJECTIVE: To examine associations between HDRS component psychopathologic clusters and resting glucose cerebral metabolism assessed by [(18)F]-FDG positron emission tomography. Patients We evaluated 298 drug-free patients who met the DSM-III-R criteria for major depressive disorder. MAIN OUTCOME MEASURES: Five principal components were extracted from the 24-item HDRS for all subjects and ProMax rotated: psychic depression, loss of motivated behavior, psychosis, anxiety, and sleep disturbance. The [(18)F]-FDG scans were acquired in a subgroup of 43 drug-free patients in twelve 5-minute frames. Voxel-level correlation maps were generated with HDRS total and factor scores. RESULTS: Total HDRS score correlated positively with activity in a large bilateral ventral cortical and subcortical region that included limbic, thalamic, and basal ganglia structures. Distinct correlation patterns were found with the 3 individual HDRS factors. Psychic depression correlated positively with metabolism in the cingulate gyrus, thalamus, and basal ganglia. Sleep disturbance correlated positively with metabolism in limbic structures and basal ganglia. Loss of motivated behavior was negatively associated with parietal and superior frontal cortical areas. CONCLUSIONS: Different brain regions correlate with discrete symptom components that compose the overall syndrome of major depression. Future studies should extend knowledge about specific regional networks by identifying responsible neurotransmitters related to specific psychopathologic components of mood disorders.

Corticolimbic blood flow in posttraumatic stress disorder during script-driven imagery.

BACKGROUND: Functional neuroimaging experiments targeting personal recall of emotional events may help elucidate neural substrates underlying posttraumatic stress disorder (PTSD). Studies suggest that limbic and paralimbic function might be altered in PTSD, as compared with trauma-exposed control subjects; however, little is known about functional changes resulting from traumatic experience itself. The present study examined both PTSD-specific and trauma-specific regional cerebral blood flow (rCBF) patterns during script-driven imagery. METHODS: Sixteen combat veterans with PTSD (PP); 15 combat veterans without PTSD (CC); and 14 healthy, aged-matched noncombat control subjects (NC) underwent [15O] H20 positron emission tomography (PET) scanning during script-driven imagery of emotionally evocative and neutral autobiographic events. RESULTS: Differential patterns of activation were detected in amygdala and medial frontal cortex. Past trauma experience was associated with decreased amygdala activity (i.e., less activity than healthy control subjects); however, combat control subjects deactivated this region (i.e., greater activity to neutral scripts). All subjects deactivated medial frontal cortex; PTSD patients had greater rostral anterior cingulate (rACC) deactivation compared with control groups, who deactivated ventromedial prefrontal cortex (vmPFC). CONCLUSIONS: Trauma-specific patterns may represent potential compensatory changes to traumatic reminders, while patterns observed only in the PTSD group may reflect neural substrates specific to PTSD pathophysiology.

GABAergic function in Alzheimer's disease: evidence for dysfunction and potential as a therapeutic target for the treatment of behavioural and psychological symptoms of dementia.

Alzheimer's disease (AD) is characterized by disruptions in multiple major neurotransmitters. While many studies have attempted to establish whether GABA is disrupted in AD patients, findings have varied. We review evidence for disruptions in GABA among patients with AD and suggest that the variable findings reflect subtypes of the disease that are possibly manifested clinically by differing behavioural symptoms. GABA, the major inhibitory neurotransmitter, has long been a target for anxiolytics, hypnotic sedatives, and anticonvulsants. We review the clinical use of GABAergic agents in treating persons with AD symptoms. While newer generation GABAergic medications are now available, they have yet to be evaluated among patients with AD.

Correlation between cerebral blood flow and items of the Hamilton Rating Scale for Depression in antidepressant-naive patients.

BACKGROUND: The purpose of this study was to correlate the basal cerebral blood flow (CBF) in patients with major depressive disorder (MDD) with the score for each of the 21 questions in the Hamilton Rating Scale for Depression (HRSD), in order to determine the cerebral regions associated with each item. METHODS: Fourteen antidepressant-naive patients with unipolar depression (DSM-IV criteria for MDD) participated in this study with a HRSD score of >/=20 points. CBF images obtained by SPECT were analyzed by SPM99 software. The significant correlation threshold for a priori regions (frontocortical and limbic regions) was a Z value of at least 2.25 and clusters formed by more than 10 voxels. RESULTS: Items 1, 6, 11 and 20 were positively correlated with right medial frontal gyrus; item 7 was negatively correlated with bilateral medial frontal gyrus. Items 2 and 10 were positively correlated with right anterior and medial cingulate, respectively. Item 5 was negatively correlated with the left amygdala. Item 9 was negatively correlated with bilateral insula, and item 16 with right insula. Items 12 and 14 were positively correlated with right and left precentral frontal gyrus, respectively. LIMITATIONS: The small sample size and only out-patients included in the study. CONCLUSIONS: The frontal cortex plays an important role in the expression of MDD symptoms. Not all the symptoms evaluated correlated with one single structure, which may explain the diverse results reported in the literature. These preliminary results support the necessity of further analyses by symptoms that could provide more specific information on the pathophysiology of MDD.

Investigation into the mechanisms of vagus nerve stimulation for the treatment of intractable epilepsy, using 99mTc-HMPAO SPET brain images.

Vagus nerve stimulation (VNS) has gained recognition as a treatment for refractory epilepsies where surgical treatment is not possible. While it appears that this treatment is effective in some patients, the mechanism of action is not clearly understood. The purpose of this study was to clarify findings of other positron emission tomography and single-photon emission tomography (SPET) investigations by measuring the acute effect of VNS on patients who have normal cerebral anatomy on magnetic resonance imaging and who have not previously been exposed to VNS. We investigated six subjects (two males and four females, mean age 29.5 years, range 21-39 years) with intractable epilepsy. One patient had primary generalised epilepsy causing generalised tonic-clonic seizures; the remaining five patients had localisation-related epilepsy causing complex partial seizures. SPET imaging was performed using 250 MBq of (99m)Tc-HMPAO and a four-scan paradigm - two with and two without stimulation. The stimulation began at VNS current levels of 0.25 mA and was increased according to the limit of patients' tolerance, usually defined by coughing or discomfort. The stimulating waveform was of continuous square wave pulses of 500 micro s duration at 30 Hz. Image analysis was by SPM99. Reduced perfusion during stimulation was observed in the ipsilateral brain stem, cingulate, amygdala and hippocampus and contralateral thalamus and cingulate. The study provides further evidence of the involvement of the limbic system in the action of vagal nerve stimulation.

3D MRI studies of neuroanatomic changes in unipolar major depression: the role of stress and medical comorbidity.

Increasing evidence has accumulated for structural brain changes associated with unipolar recurrent major depression. Studies of neuroanatomic structure in early-onset recurrent depression have only recently found evidence for depression-associated structural change. Studies using high-resolution three-dimensional magnetic resonance imaging (MRI) are now available to examine smaller brain structures with precision. Brain changes associated with early-onset major depression have been reported in the hippocampus, amygdala, caudate nucleus, putamen, and frontal cortex, structures that are extensively interconnected. They comprise a neuroanatomic circuit that has been termed the limbic-cortical-striatal-pallidal-thalamic tract. Of these structures, volume loss in the hippocampus is the only consistently observed change to persist past the resolution of the depression. Possible mechanisms for tissue loss include neuronal loss through exposure to repeated episodes of hypercortisolemia; glial cell loss, resulting in increased vulnerability to glutamate neurotoxicity; stress-induced reduction in neurotrophic factors; and stress-induced reduction in neurogenesis. Many depressed patients, particularly those with late-onset depression, have comorbid physical illnesses producing a high rate of hyperintensities in deep white matter and subcortical gray matter and brain damage to key structures involved in the modulation of emotion. Combining MRI studies with functional studies has the potential to localize abnormalities in blood flow, metabolism, and neurotransmitter receptors and provide a better integrated model of depression.

Consequences of the anatomy of deep venous outflow from the brain.

The deep venous system is best defined as the entire territory served by the great vein of Galen and the basal veins. This comprises not only the choroid plexuses and the deep grey matter of the thalamus and striatum, but also the periventricular white matter and corpus callosum, hippocampus and the cortical areas of the limbic lobe including the cingulate and parahippocampal gyri, the visual cortex, the diencephalon and rostral brain stem, and part of the cerebellum. The superficial venous system comprises the remaining neocortex (with the cortex of the entire convexity) together with a layer of subcortical white matter, separated from the periventricular white matter by a venous watershed. Outflow towards the great vein of Galen and straight sinus can be substituted by collateral channels towards the basal vein. The basal vein in turn is connected not only to the great vein of Galen, but also to the superior petrosal sinus (via the lateral mesencephalic vein), and in the adult configuration to the cavernous sinus and pterygoid plexus (via the deep and superficial sylvian veins). Evidence from pathological anatomy indicates that the venous watershed exists not only in the white matter of the hemispheres, but between the entire territories of the deep and superficial venous systems. Because of their anastomotic interconnections, only simultaneous obstruction of veins of Galen and basal veins wil effectively obstruct deep venous outflow. This can occur in the tentorial incisura, from swelling or displacement of the midbrain due to brain oedema, haematoma or tumour. Complete obstruction of great vein of Galen and basal veins leads to rapid death. In patients who survive incomplete obstruction, various combinations of damage to parts of the deep venous territory exist. This is possible because very many tributaries of the deep system unite below and sometimes above the tentorial incisura. The hallmarks these varying deep venous obstructions have in common are sparing of the subcortical white matter of the convexity, and cortical involvement limited to the limbic lobe and visual cortex. Obstruction of cerebral venous outflow explains many pathological phenomena. Treatment must aim at relieving this obstacle to blood flow.

Neuroanatomic correlates of CCK-4-induced panic attacks in healthy humans: a comparison of two time points.

BACKGROUND: Several functional imaging studies have demonstrated increases of brain activity in the temporofrontal, cingulate, and claustrum regions during a pharmacologically induced panic attack when scanning was done at a single point in time. However, no study has evaluated changes in brain activity at two time points during a panic attack. We hypothesized that in response to a single bolus injection of the panicogen cholecystokinin-4 (CCK-4) in healthy volunteers, changes in regional cerebral blood flow (rCBF) might be different if scanning were done at two different time points. METHODS: To test this hypothesis, we conducted a single-blind study, using positron emission tomography (PET). To determine the time effect of panic attack on brain activity, we performed either early scan or late scan covering the first or the second minute after CCK-4 bolus injection, respectively. The PET images were analyzed by statistical parametric mapping (SPM) followed by region of interest (ROI) analysis. RESULTS: The results showed significant differences between the early and the late scan. The early effects of CCK-4 are accompanied by increases in rCBF in the hypothalamic region, whereas the late scan showed an increase in rCBF in the claustrum-insular region. Reductions in rCBF were observed for both time groups in the medial frontal region. A separate scan for anticipatory anxiety demonstrated rCBF increases in the anterior cingulate region and decreases in the occipital regions. CONCLUSIONS: These results may support the hypothesis that changes in rCBF as a function of time during CCK-4-induced panic might correspond to a neurocircuitry involved in panic attacks.

Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: A PET investigation.

OBJECTIVE: The purpose of this study was to determine whether anterior limbic and paralimbic regions of the brain are differentially activated during the recollection and imagery of traumatic events in trauma-exposed individuals with and without posttraumatic stress disorder (PTSD). METHOD: Positron emission tomography (PET) was used to measure normalized regional cerebral blood flow (CBF) in 16 women with histories of childhood sexual abuse: eight with current PTSD and eight without current PTSD. In separate script-driven imagery conditions, participants recalled and imagined traumatic and neutral autobiographical events. Psychophysiologic responses and subjective ratings of emotional state were measured for each condition. RESULTS: In the traumatic condition versus the neutral control conditions, both groups exhibited regional CBF increases in orbitofrontal cortex and anterior temporal poles; however, these increases were greater in the PTSD group than in the comparison group. The comparison group exhibited regional CBF increases in insular cortex and anterior cingulate gyrus; increases in anterior cingulate gyrus were greater in the comparison group than in the PTSD group. Regional CBF decreases in bilateral anterior frontal regions were greater in the PTSD group than in the comparison group, and only the PTSD group exhibited regional CBF decreases in left inferior frontal gyrus. CONCLUSIONS: The recollection and imagery of traumatic events versus neutral events was accompanied by regional CBF increases in anterior paralimbic regions of the brain in trauma-exposed individuals with and without PTSD. However, the PTSD group had greater increases in orbitofrontal cortex and anterior temporal pole, whereas the comparison group had greater increases in anterior cingulate gyrus.

Brain blood flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: I. Acute effects at high and low levels of stimulation.

PURPOSE: Left cervical vagus nerve stimulation (VNS) decreases complex partial seizures (CPS) by unknown mechanisms of action. We hypothesized that therapeutic VNS alters synaptic activities at vagal afferent terminations and in sites that receive polysynaptic projections from these medullary nuclei. METHODS: Ten patients with partial epilepsy underwent positron emission tomographic (PET) measurements of cerebral blood flow (BF) three times before and three times during VNS. Parameters for VNS were at high levels for 5 patients and at low levels for 5. Resting BF measurements were subtracted from measurements during VNS in each subject. Subtraction data were averaged in each of 2 groups of 5 patients. t Tests were applied to BF changes in brain regions that receive vagal afferents and projections (significant at p < 0.05, corrected for repeated measures). RESULTS: In both the low- and high-stimulation groups during VNS, brain BF was (a) increased in the rostral, dorsal-central medulla; (b) increased in the right postcentral gyrus, (c) increased bilaterally in the hypothalami, thalami, and insular cortices, and in cerebellar hemispheres inferiorly; and (d) decreased bilaterally in hippocampus, amygdala, and posterior cingulate gyri. The high-stimulation group had greater volumes of activation and deactivation sites. CONCLUSIONS: Our findings suggest that left cervical VNS acutely increases synaptic activity in structures directly innervated by central vagal structures and areas that process left-sided somatosensory information, but VNS also acutely alters synaptic activity in multiple limbic system structures bilaterally. These findings may reflect sites of therapeutic actions of VNS.