Hyperintensities on T2-weighted images in the basal ganglia of patients with major depression: cerebral perfusion and clinical implications.

White matter hyperintensities on T2-weighted images (WMH T2-WI) are prevalent in depressed, particularly elderly, patients. In an earlier study we used structural magnetic resonance imaging (MRI) to study 37 depressed and 27 healthy control subjects to show that prevalence of WMH T2-WI is higher in depressed patients and that severity of depression and cognitive impairment is associated with presence of WMH T2-WI in basal ganglia. The occurrence of WMH T2-WI in depression may also be associated with cerebrovascular deficiency, although this association has not been adequately studied. We therefore performed single photon emission computed tomography (SPECT) with Technetium-99m hexamethylpropyleneamineoxime (Tc-99m HMPAO) as tracer in this same sample to seek an association between presence/location of WMH T2-WI and cerebral perfusion deficits. In addition, we examined the relationship between presence/location of WMH T2-WI and treatment response. We found that severely depressed, cognitively compromised patients with WMH T2-WI in the basal ganglia display more profuse cerebral perfusion deficits than less depressed patients with WMH T2-WI in other regions or with no WMH T2-WI but are not less responsive to antidepressant treatment. WMH T2-WI in depression are associated with cerebral perfusion deficits, although not necessarily located in the same regions as the MRI findings. Clinical symptoms are largely reversible even in depressed patients with WMH T2-WI in basal ganglia.

Brain imaging study of the acute effects of Delta9-tetrahydrocannabinol (THC) on attention and motor coordination in regular users of marijuana.

PROCEDURE: Twelve regular users of marijuana underwent two positron emission tomography (PET) scans using [18F] Fluorodeoxyglucose (FDG), one while subject to the effects of 17 mg THC, the other without THC. In both sessions, a virtual reality maze task was performed during the FDG uptake period. RESULTS: When subject to the effects of 17 mg THC, regular marijuana smokers hit the walls more often on the virtual maze task than without THC. Compared to results without THC, 17 mg THC increased brain metabolism during task performance in areas that are associated with motor coordination and attention in the middle and medial frontal cortices and anterior cingulate, and reduced metabolism in areas that are related to visual integration of motion in the occipital lobes. CONCLUSION: These findings suggest that in regular marijuana users, the immediate effects of marijuana may impact on cognitive-motor skills and brain mechanisms that modulate coordinated movement and driving.

99mTc-HMPAO SPECT study of cerebral perfusion after treatment with medication and electroconvulsive therapy in major depression.

UNLABELLED: Compromised regional cerebral blood flow (rCBF) in major depressive disorder may be partly reversed by successful antidepressant treatment. However, it is not known if the reversal of rCBF compromise is dependent on the mode of antidepressant treatment. The current study aimed to address this question. METHODS: Thirty-three patients (19 women and 14 men; mean age +/- SD, 53 +/- 16 y) with moderate major depressive disorder were studied before 6 wk of treatment with tricyclic antidepressants, selective serotonin reuptake inhibitors, or a course of electroconvulsive therapy, and 31 of these patients were also studied afterward. A comparison group of 25 healthy volunteers (13 women and 12 men; mean age, 49 +/- 15 y) were studied once. rCBF was assessed using 99mTc-hexamethylpropyleneamine oxime SPECT. Images were analyzed using globally normalized statistical parametric mapping localized to the Montreal Neurologic Institute brain atlas. RESULTS: Baseline rCBF was lower in depressed patients than in controls in the frontal cortex and subcortical nuclei bilaterally. A response to medication was associated with normalization of rCBF deficits, whereas a response to electroconvulsive therapy was associated with an additional rCBF decrease in the parietotemporal and cerebellar regions bilaterally. CONCLUSION: Hypoperfusion in major depressive disorder largely normalizes after a response to pharmacotherapy. Perfusion changes after a response to electroconvulsive therapy may follow a different course.

Cerebral glucose utilization and platelet mitochondrial complex I activity in schizophrenia: A FDG-PET study.

Altered cerebral energy metabolism and mitochondrial dysfunction in periphery and in brain are implicated in the pathophysiology of schizophrenia. This study investigated whether cerebral glucose metabolism (rCGM) abnormalities are linked to altered mitochondrial complex I activity in the periphery, in schizophrenia. Sixteen schizophrenic patients, 8 with total positive PANSS score >or=20 (high positive schizophrenics; HPS), and 8 with total positive score

In vivo measurement of brain monoamine oxidase B occupancy by rasagiline, using (11)C-l-deprenyl and PET.

UNLABELLED: In recent years, monoamine oxidase B (MAO-B) inhibitors have become widely used in the treatment of early-stage Parkinson's disease. (11)C-l-deprenyl PET has been used by others to characterize MAO-B ligands in terms of their in vivo potency toward MAO-B and duration of action. In this study, we used (11)C-l-deprenyl PET to demonstrate the specific binding characteristics of the new irreversible selective MAO-B inhibitor rasagiline in 3 healthy volunteers. METHODS: The healthy volunteers received 1 mg of rasagiline daily for 10 d. Dynamic (11)C-l-deprenyl PET brain scans were acquired before the first treatment (scan 1) and immediately (scan 2), 2-3 wk (scan 3), and 4-6 wk (scan 4) after the final treatment. RESULTS: On scan 1, all subjects showed the highest l-deprenyl uptake in the thalamus and basal ganglia, with fairly high activity also in the cortex and cerebellum and much lower activity in the white matter. The areas of high uptake were absent from scan 2, on which activity throughout the brain was comparable to that in white matter, presumably because of blocking of MAO-B binding sites by rasagiline. Gradual recovery toward the baseline state was observed in the weeks after termination of treatment (scans 3 and 4). CONCLUSION: (11)C-l-deprenyl PET showed binding of rasagiline to MAO-B, confirming blocking of MAO-B sites after 10 d of treatment with 1 mg of rasagiline per day, with immediate post-rasagiline treatment tracer uptake and metabolism in the basal ganglia compatible only with nonspecific binding. Subsequent gradual recovery was also seen, with return to near-baseline uptake. This finding is compatible with the known rate of de novo synthesis of MAO-B, confirming the irreversible binding of rasagiline.

Functional connectivity of the prefrontal cortex and the amygdala in posttraumatic stress disorder.

BACKGROUND: Persistent, intrusive re-experiencing in posttraumatic stress disorder (PTSD) is commonly construed as a failure of cingulate inhibition (i.e., extinction) over a hyperresponsive amygdala, based primarily on animal research of fear conditioning and the finding of cingulate hypoperfusion in PTSD. METHODS: We examined functional connectivity in patients with PTSD and healthy trauma survivors during repeated symptom provocation using H(2)O(15) positron emission tomography. RESULTS: Memory retrieval networks (right prefrontal cortex, hippocampus, and visual cortex) were common to both groups. Networks supporting autonomic and emotional control and preparatory motor action (amygdala, anterior cingulate, subcallosal gyrus, and premotor cortex) differed between the two groups and became progressively disparate with successive presentations of the traumatic script. Patterns of effective connectivity demonstrated the predominance of direct influences of the amygdala on visual cortex, subcallosal gyrus, and anterior cingulate in PTSD but not in control subjects. There was little evidence for failure of inhibition of cingulate or subcallosal cortex over the amygdala. CONCLUSIONS: These patterns might represent excessive influences of the amygdala over regions involved in autonomic, and higher-order visual memory processing in PTSD. The present data suggest that inferences of direct correspondence between animal studies and pathophysiology of PTSD should be made with caution.

Resting regional cerebral perfusion in recent posttraumatic stress disorder.

BACKGROUND: Brain imaging research in posttraumatic stress disorder has been largely performed on patients with chronic disease, often heavily medicated, with current or past alcohol and substance abuse. Additionally, virtually only activation brain imaging paradigms have been done in posttraumatic stress disorder, whereas in other mental disorders both resting and activation studies have been performed. METHODS: Twenty-eight (11 posttraumatic stress disorder) trauma survivors underwent resting state hexamethylpropyleneamineoxime single photon emission computed tomography and magnetic resonance imaging 6 months after trauma. Eleven nontraumatized subjects served as healthy controls. RESULTS: Regional cerebral blood flow in the cerebellum was higher in posttraumatic stress disorder than in both control groups. Regional cerebral blood flow in right precentral, superior temporal, and fusiform gyri in posttraumatic stress disorder was higher than in healthy controls. Cerebellar and extrastriate regional cerebral blood flow were positively correlated with continuous measures of depression and posttraumatic stress disorder. Cortisol level in posttraumatic stress disorder was negatively correlated with medial temporal lobe perfusion. Anterior cingulate perfusion and cortisol level were positively correlated in posttraumatic stress disorder and negatively correlated in trauma survivors without posttraumatic stress disorder. CONCLUSIONS: Recent posttraumatic stress disorder is accompanied by elevated regional cerebral blood flow, particularly in the cerebellum. This warrants attention because the cerebellum is often used as a reference region in regional cerebral blood flow studies. The inverse correlation between plasma cortisol and medial temporal lobe perfusion may herald hippocampal damage.

Regional cerebral blood flow in patients with mild hypothyroidism.

UNLABELLED: Emotional and cognitive abnormalities are common in adult hypothyroidism. Few studies, however, have evaluated cerebral perfusion and metabolism in this disorder. The aims of this study were to compare regional cerebral blood flow (rCBF) between hypothyroid patients and healthy subjects and assess flow during the euthyroid state after treatment. METHODS: Ten mildly hypothyroid patients, before and after thyroxine treatment, and 10 healthy controls underwent 99mTc-hexamethylpropyleneamine oxime brain SPECT, MRI, and psychometric testing. SPECT images were analyzed using statistical parametric mapping. RESULTS: Compared with controls, rCBF in patients before treatment was lower in right parietooccipital gyri, cuneus, posterior cingulate, lingual gyrus, fusiform, insula, and pre- and postcentral gyri. Perfusion did not normalize on a return to the euthyroid state. CONCLUSION: Decreased rCBF in mild hypothyroidism is found in regions mediating attention, motor speed, memory, and visuospatial processing, faculties affected in hypothyroidism. Follow-up studies are needed to determine the longer-term persistence of perfusion abnormalities in this disorder.

Does streaming affect the cerebral distribution of infraophthalmic intracarotid chemotherapy?

BACKGROUND AND PURPOSE: The development of new non-ocular-toxic drugs has enabled infraophthalmic chemotherapeutic infusion. We assessed whether streaming occurs with infraophthalmic, high cervical internal carotid artery (ICA) delivery of chemotherapeutic agents by means of conventional angiographic catheters. METHODS: Six patients with high-grade gliomas treated with monthly carotid intraarterial chemotherapy were studied. Chemotherapy delivery and distribution was modeled by technetium 99m hexylmethyl-propyleneamine oxine (HMPAO), a first-pass agent. Each patient received 0.5 mCi (18.5 MBq) of (99m)Tc-HMPAO in 50-mL of saline intraarterially in the ICA at the C1-C2 level. Injections were given twice, at two different injection rates: 0.08 mL/s at one therapeutic session and 6 mL/s a month later. The slow injection rate modeled the slowest rate used in the delivery of chemotherapy into the ICA. The higher rate was selected to avoid any possibility of uneven mixing, by replacing intracarotid blood completely and by using a turbulent injection rate that destroys laminar flow and intraarterial streaming. Single photon emission CT (SPECT) was performed 2 hours after injection. For each patient, the corresponding SPECT sections at the two injection rates were compared. RESULTS: No differences were noted in (99m)Tc-HMPAO distribution between the two injection rates in any of the patients. However, some of the rapid injection rate SPECT scans showed extension of the (99m)Tc-HMPAO uptake into adjacent watershed territories. CONCLUSION: There was no evidence, in humans, of substantial streaming during slow infraophthalmic intracarotid injections. Slow rates of infusion are as good as high rates for infraophthalmic intracarotid drug delivery. This is of special importance for drugs that are not tolerated at high injection rates. Moreover, infraophthalmic intracarotid chemotherapeutic infusion does not require special injectors or catheters.

Cerebral blood flow in chronic symptomatic mild traumatic brain injury.

Patients with mild traumatic brain injury (MTBI) challenge physicians' skills and test their patience. Their manifold symptomatology is often not supported by objective neurological findings. We sought to compare regional cerebral blood flow (rCBF) between symptomatic subjects with longstanding MTBI and healthy controls, and to examine the correspondence between neuropsychological deficit and rCBF compromise. Twenty-eight clinically symptomatic male subjects with MTBI and twenty matched controls underwent neuropsychological testing and Tc-99m-HMPAO brain SPECT imaging. Neuropsychological test data were used to categorize subjects into sub-groups according to the presumed location of lesions based on their neurobehavioral deficits. Image subtraction comparisons were made between controls, all MTBI subjects and sub-groups. MTBI patients demonstrated regions of hypoperfusion in frontal, pre-frontal and temporal cortices, and sub-cortical structures. Hypoperfusion in 'frontal', 'left posterior' and to a lesser extent 'sub-cortical' sub-groups was concordant with neuropsychological localization. This was not the case for the 'right posterior' group, where no concordance was found. The rCBF is reduced in symptomatic patients with longstanding MTBI and unremarkable structural brain imaging. Although group analysis is appropriate for the generation of statistically significant differences, the clinical application of brain SPECT imaging in MTBI calls for a capability to associate clinical examination, neuropsychological assessment and cerebral perfusion at the individual subject level. Such competence is still to be attained.

Brain activation and heart rate during script-driven traumatic imagery in PTSD: preliminary findings.

Patients with posttraumatic stress disorder (PTSD) experience psychological and physiological distress. However, imaging research has mostly focused on the psychological aspects of the disorder. Considered an expression of distress, heart rate (HR) in PTSD is often elevated. In the current study, we sought to identify brain regions associated with increased HR in PTSD. Nine patients with PTSD and six healthy trauma survivors were scanned while resting, clenching teeth, and listening to neutral and traumatic scripts. Brain function was evaluated using H2O15 positron emission tomography (PET). HR was monitored by electrocardiogram. Data were analyzed using statistical parametric mapping (SPM). Subjects with PTSD exhibited a significant increase in HR upon exposure to traumatic scripts, while trauma survivors did not. Correlations between regional cerebral blood flow and HR were found only in patients with PTSD, in orbitofrontal, precentral and occipital regions. Neither group showed correlation between rCBF and HR in the amygdala or hippocampus. These preliminary results indicate that "top down" central nervous system regulation of autonomic stress response in PTSD may involve associative, sensory and motor areas in addition to regions commonly implicated in fear conditioning.

Cerebral perfusion after a 2-year remission in major depression.

Although patients suffering from major depression respond to antidepressant treatment within several weeks, full reinstatement of premorbid capabilities requires much longer. Nevertheless, most research in major depression seeking the pathophysiological correlates of remission has focused upon the acute post-treatment period. Brain imaging research offers no exception. We have recently shown that cerebral perfusion in depressed patients responding to 6-wk antidepressant medication increases in parieto/cerebellar regions and becomes similar to that of healthy control subjects. We now present technetium-99m hexamethylpropylene amine oxime single-photon emission computed tomography (99mTc-HMPAO SPECT) data collected from 11 of these patients 2 years in remission. Images were analysed using Statistical Parametric Mapping. After 2 years, perfusion normalization found immediately after treatment was maintained, with further increases in frontal and decreases in parieto/cerebellar regions. These findings suggest that perfusion increases in parieto/cerebellar regions may be involved in acute response to treatment whereas increases in frontal regions may be related to its consolidation.

Brain SPECT study of common ground between hypothyroidism and depression.

Hypothyroidism and major depressive disorder (MDD) share neuropsychiatric features. Cerebral perfusion deficits are found in both disorders. We compared regional cerebral blood flow (rCBF) in hypothyroidism and MDD to determine if clinical similarities are mediated by common neurocircuitry. Ten hypothyroid and 10 depressed patients underwent 99mTc-HMPAO-SPECT and clinical evaluation before and after response to respective treatments. Ten healthy controls underwent a similar, single, evaluation. Before treatment, rCBF in hypothyroid and depressed patients was lower than in controls, in posterior and anterior aspects of the brain respectively. rCBF in hypothyroidism was lower than in MDD in right posterior cingulate and parieto/occipital regions, and higher in frontal, prefrontal and sub-genual regions. Reduced rCBF in pre- and post-central gyri was found in both groups. Following treatment, rCBF in depressed patients increased and normalized, but remained unchanged in hypothyroidism. Affective symptoms in hypothyroidism may be mediated by neurocircuitry different from that of major depression.