Changes in regional cerebral blood flow following antidepressant treatment in late-life depression

OBJECTIVE: Reversible/irreversible abnormalities of regional cerebral blood flow (rCBF) are seen in patients with depression. However, in late-life depression there is little evidence of a longitudinal change in rCBF through remission. We examined whether the decreased rCBF in individuals with late-life depression resolves following treatment. METHODS: Twenty-five depressed patients older than 55 years completed the Hamilton Rating Scale for Depression and single photon emission computed tomography before and after a mean of 13.7 weeks of pharmacotherapy. Quantitative analyses were performed using the Statistical Parametric Mapping procedure. RESULTS: Patients with depression demonstrated decreased rCBF in the anterior ventral and dorsal medial prefrontal cortex (PFC), including anterior cingulate cortices, bilateral ventrolateral PFC to temporal cortices, and bilateral medial to lateral parieto-occipital lobes relative to healthy controls. No particular areas showed increased rCBF. Following pharmacotherapy, rCBF significantly increased in the left dorsolateral PFC to precentral areas and the right parieto-occipital regions. However, decreased rCBF at baseline in the anterior ventral/dorsal medial PFC, bilateral ventrolateral PFC, bilateral temporal lobes, and bilateral parietal lobes did not show significant improvement after treatment. CONCLUSIONS: Remarkable improvements in rCBF in the left dorsolateral PFC to precentral regions are consistent with the hypothesis that neuronetworks including the left frontal cortex may be functionally and reversibly involved in late-life unipolar major depression (state-dependent). In contrast, neural circuits including bilateral medial, dorsolateral, and parietal areas may reflect underlying and continuous pathognomonic brain dysfunction of depression (trait-dependent).     

Cerebral blood flow in corticobasal degeneration and progressive supranuclear palsy

To compare brain perfusion between corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP), we investigated regional cerebral blood flow (rCBF) semiquantitatively with single-photon emission computed tomography and [123I]iodoamphetamine in six patients with CBD and five with PSP. Compared with 12 age-matched control subjects, the average of the left and right rCBF values for the CBD patients was significantly reduced in the inferior prefrontal, anterior cingulate, medial premotor, sensorimotor, posterior parietal, and superior temporal cortices as well as in the basal ganglia and thalamus, whereas only the medial premotor cortex was significantly hypoperfused in the PSP patients. Compared with the PSP patients, the CBD patients showed significantly decreased rCBF in the inferior prefrontal, sensorimotor, and posterior parietal cortices, but not in the subcortical regions. Compared with the controls, interhemispheric differences of rCBF were significant in the inferior prefrontal, sensorimotor, and posterior parietal cortices of the CBD patients but in only the medial prefrontal cortex of the PSP patients. These results indicate that rCBF reductions are more extensive and asymmetric in CBD than in PSP, although the two diseases share medial frontal involvement.     

Regional cerebral glucose utilization in patients with a range of severities of unipolar depression.

BACKGROUND: Patients with unipolar depression are most often reported to have decreased regional cerebral glucose metabolism (rCMRglu) in dorsal prefrontal and anterior cingulate cortices compared with healthy control subjects, often correlating inversely with severity of depression. METHODS: We measured rCMRglu with fluorine-18 deoxyglucose positron emission tomography (PET) in 38 medication-free patients with unipolar depression and 37 healthy control subjects performing an auditory continuous performance task to further investigate potential prefrontal and anterior paralimbic rCMRglu abnormalities in patients attending to this task. RESULTS: Compared with control subjects, the subgroup of patients with Hamilton depression scores of 22 or greater demonstrated decreased absolute rCMRglu in right prefrontal cortex and paralimbic/amygdala regions as well as bilaterally in the insula and temporoparietal cortex (right > left); they also exhibited increased normalized metabolic activity bilaterally in the cerebellum, lingula/cuneus, and brain stem. Severity of depression negatively correlated with absolute rCMRglu in almost the entire extent of the right cingulate cortex as well as bilaterally in prefrontal cortex, insula, basal ganglia, and temporoparietal cortex (right > left). CONCLUSIONS: Areas of frontal, cingulate, insula, and temporal cortex appear hypometabolic in association with different components of the severity and course of illness in treatment-resistant unipolar depression.     

Retrosplenial cortical activation in the fibromyalgia syndrome

To study the CNS in chronic muscular pain typical of fibromyalgia we compared PET measures of regional cerebral blood flow (rCBF) in eight fibromyalgic patients and controls at rest. Higher rCBF for patients than controls was found bilaterally in the retrosplenial cortex. Lower rCBF for patients than controls were seen in the left frontal, temporal, parietal, and occipital cortices. The higher retroplenial rCBF in patients than controls may reflect increased attention towards sub-noxious somatosensory signaling, and agrees with the notion that fibromyalgic pain reflects secondary hyperalgesia. The brain regions with lower rCBF in fibromyalgic patients than controls participate in the normal cognitive processing of pain, which may be dysfunctional in fibromyalgia.     

A SPECT study of apathy in Alzheimer's disease

BACKGROUND/AIMS: To assess the association between regional cerebral blood flow (rCBF) and apathy in Alzheimer's Disease (AD). METHODS: SPECT and MRI scans were obtained from 51 nondepressed outpatients meeting criteria for probable AD (age 77.6 +/- 6.6 years; MMSE 22.3 +/- 5.1; 23 apathetic, 28 nonapathetic) and 23 healthy elderly (75.6 +/- 3.8 years) controls. The following regions of interest (ROIs) were compared between apathetic and nonapathetic AD patients and then referenced against aged controls: anterior cingulate, orbitofrontal cortex, middle medial temporal cortex, hippocampus, medial superior temporal cortex, thalamus/hypothalamus and pons. RESULTS: Apathetic and nonapathetic patients had significant differences in rCBF. Relative to nonapathetic AD patients, apathetic AD patients had lower perfusion in 2 ROIs (right orbitofrontal cortex and left anterior cingulate) and higher perfusion in 5 ROIs (right and left hippocampi, left medial superior temporal gyrus, and right and left middle medial temporal cortex). Comparison of rCBF in these 7 ROIs to healthy elderly controls confirmed hypoperfusion in the left anterior cingulate and right orbitofrontal cortex and suggested a relative sparing of perfusion among apathetic AD patients in the remaining 5 ROIs. CONCLUSIONS: In this group of nondepressed patients with AD, apathetic subjects displayed significant perfusion differences compared to nonapathetic subjects.     

SPECT study of visual fixation in schizophrenia and comparison subjects.

BACKGROUND: The consistent association of impaired eye movements and schizophrenia suggests a relationship between the neurobiology of the illness and visual pursuit systems. Visual fixation (VF), an eye "movement" task at zero velocity, is the simplest such abnormality in schizophrenia patients and their relatives. METHODS: We used a VF task for a functional imaging study. Six neuroleptic-free schizophrenia patients and eight gender and mean age matched comparison subjects had SPECT scans with 20 mCi of Tc99-HMPAO, during VF on a simple blue line intersection. MEDX data saved in ANALYZE format for SPM 95 was used to generate paired t-test statistical data for display in Talairach space, with rCBF changes given as Z-scores. RESULTS: Patients, compared to controls, had increased rCBF in both the parahippocampal gyrus (bilaterally) and in the right fusiform gyrus. They had decreased rCBF in the left frontal cortex, including medial and superior frontal gyri and anterior cingulate. Overall, compared to controls, patients had medial temporal lobe hyperperfusion along with left prefrontal hypoperfusion. CONCLUSIONS: These findings are consistent with the hypothesized imbalance between the medial temporal and frontal lobes that is postulated for schizophrenia. It was of interest that the relative rCBF differences between schizophrenia patients and controls in this small sample were observable with this cognitively non-demanding visual fixation task.     

Perfusion MRI detects rCBF abnormalities in early stages of HIV-cognitive motor complex

OBJECTIVE: To evaluate patients with early HIV-cognitive motor complex (HIV-CMC) for possible regional cerebral blood flow (rCBF) abnormalities on perfusion MRI (pMRI). BACKGROUND: Nuclear medicine techniques have demonstrated global and focal cerebral perfusion abnormalities in patients with HIV dementia. Ultrafast pMRI enables the measurement of rCBF throughout the brain without the need to apply radioactive tracers or ionizing radiation. METHODS: pMRI was used to measure the rCBF in 19 patients with early stages of HIV-CMC and 15 healthy seronegative control subjects. The rCBF maps were registered to high-resolution anatomic MRI scans and transformed into Talairach space. Statistical analysis of the rCBF maps was performed with SPM96. RESULTS: Compared with the control subjects, the patients with HIV had statistically significantly decreased rCBF bilaterally in the inferior lateral frontal cortices (right: -15%, p < 0.002; left: -12%, p < 0.005) and in the inferior medial parietal brain region (-15%, p < 0.0009). In contrast, rCBF was increased bilaterally in the posterior inferior parietal white matter (right: +19%, p < 0.0001; left: + 17%, p < 0.001). Furthermore, rCBF abnormalities correlated significantly with clinical disease severity as measured by CD4 count, plasma viral load, Karnofsky score, and HIV dementia scale. DISCUSSION: Our results are consistent with previous findings from PET and SPECT studies. Furthermore, pMRI can detect rCBF abnormalities that correlate with disease severity in HIV-CMC. Because pMRI is more cost-effective, faster, and safer than nuclear medicine techniques for monitoring rCBF changes, pMRI may be more feasible for monitoring the effects of therapy for HIV-CMC.     

State and trait influences on mood regulation in bipolar disorder: blood flow differences with an acute mood challenge.

BACKGROUND: Even in remission, patients with bipolar disorder (BD) remain sensitive to external stressors that can trigger new episodes. Imitating such stressors by the controlled transient exposure to an emotional stimulus may help to identify brain regions modulating this sensitivity. METHODS: Transient sadness was induced in 9 euthymic and in 11 depressed subjects with BD. Regional blood flow (rCBF) changes were measured using (15)O-water positron emission tomography. RESULTS: Common changes in both groups were increased rCBF in anterior insula and cerebellum and decreased rCBF in dorsal-ventral-medial frontal cortex, posterior cingulate, inferior parietal, and temporal cortices. Decreases in dorsal ventral medial frontal cortices occurred in both groups, but subjects in remission showed a greater magnitude of change. Unique to remitted subjects with BD were rCBF increases in dorsal anterior cingulate and in premotor cortex. Lateral prefrontal rCBF decreases were unique to depressed subjects with BD. At baseline, remitted subjects showed a unique increase in dorsal anterior cingulate and orbitofrontal cortex. CONCLUSIONS: Common rCBF changes in remitted and depressed subjects identifies potential sites of disease vulnerability. Unique cingulate and orbitofrontal changes both at baseline and with induced sadness seen in the absence of prefrontal rCBF decreases may identify regional interactions important to the euthymic state in this population.     

Altered anterior‐posterior connectivity through the arcuate fasciculus in temporal lobe epilepsy

How the interactions between cortices through a specific white matter pathway change during cognitive processing in patients with epilepsy remains unclear. Here, we used surface‐based structural connectivity analysis to examine the change in structural connectivity with Broca's area/the right Broca's homologue in the lateral temporal and inferior parietal cortices through the arcuate fasciculus (AF) in 17 patients with left temporal lobe epilepsy (TLE) compared with 17 healthy controls. Then, we investigated its functional relevance to the changes in task‐related responses and task‐modulated functional connectivity with Broca's area/the right Broca's homologue during a semantic classification task of a single word. The structural connectivity through the AF pathway and task‐modulated functional connectivity with Broca's area decreased in the left midtemporal cortex. Furthermore, task‐related response decreased in the left mid temporal cortex that overlapped with the region showing a decrease in the structural connectivity. In contrast, the region showing an increase in the structural connectivity through the AF overlapped with the regions showing an increase in task‐modulated functional connectivity in the left inferior parietal cortex. These structural and functional changes in the overlapping regions were correlated. The results suggest that the change in the structural connectivity through the left frontal–temporal AF pathway underlies the altered functional networks between the frontal and temporal cortices during the language‐related processing in patients with left TLE. The left frontal–parietal AF pathway might be employed to connect anterior and posterior brain regions during language processing and compensate for the compromised left frontal–temporal AF pathway. Hum Brain Mapp 37:4425–4438, 2016. © 2016 Wiley Periodicals, Inc.     

抑郁症患者局部脑血流的研究

目的：了解抑郁症患者局部脑血流灌注的特点：方法：应用单光子发射计算机断层扫描对20例抑郁症患者及18例正常对照者局部脑血流灌注进行对比分析。结果：抑郁症组双侧基底核、双侧额叶、左颞叶及左枕叶局部血流低灌注；抑郁症组与对照组左右大脑半球局部血流灌注无显著性差异：结论：抑郁症患者局部脑血流存在低灌注，但未发现局部脑血流低灌注有侧化现象。     

Psychiatric symptoms associated with cortical-subcortical dysfunction in Alzheimer's disease

Positron emission tomography was used to evaluate 3 Alzheimer's disease (AD) patients: 1 with major depression, 1 with emotional lability, and 1 with apathy. Compared with 5 non-mood-disordered AD patients, the patient with depression had diminished relative regional cerebral blood flow (rel-CBF) in the anterior cingulate and superior temporal cortices, bilaterally. This patient also showed diminished rel-CBF in the left dorsolateral prefrontal and right medial temporal and parietal cortices. The patient with emotional lability had diminished rel-CBF in the anterior cingulate and dorsolateral prefrontal cortices, bilaterally, and left basal ganglia. The patient with apathy had diminished rel-CBF in the basal ganglia and dorsolateral prefrontal cortex, bilaterally. Results are consistent with the hypothesis of a common frontal-temporal-subcortical substrate (e.g., involving aminergic nuclei) in the etiology of depression in AD. Frontal-subcortical dysfunction may also be associated with emotional lability and apathy in AD, although these may be related to a greater involvement of frontal-basal ganglia circuits.     

Changes in regional cerebral blood flow after body image exposure in eating disorders

Relationships of ‘perceptual distortion’ and ‘cognitive evaluation’ components of body image disturbances to brain activity were investigated. Changes in regional cerebral blood (rCBF) of nine patients with anorexia nervosa restrictive type (AN), 13 patients with bulimia nervosa purging type (BN) and 12 controls following three experiments with single photon emission computed tomography (SPECT) were compared: at rest, following a landscape video presentation (neutral stimulus), and after their filmed body image (positive stimulus) exposure. Body distortion was measured with the Silhouette test and body dissatisfaction with the Body Shape Questionnaire (BSQ). Patients with AN showed a hyperactivation of the left parietal and right superior frontal from neutral to positive stimulus. Patients with BN showed a hyperactivation of the right temporal and right occipital areas. Changes in BSQ responses were associated with changes in the right inferior frontal and right temporal rCBF, whereas changes in body distortion were related to the left parietal. The activation of the right temporal after the own body image exposure might be in accordance with the aversive events' response. Functional abnormalities in AN might be related to the storage of a distorted prototypical image of the body in the left parietal lobe.     

Cerebral blood flow patterns in Binswanger's disease: a SPECT study using three-dimensional stereotactic surface projections

We investigated regional cerebral blood flow (rCBF) patterns in Binswanger's disease (BD) patients using single photon emission computed tomography (SPECT). SPECT data on 22 patients with BD were analyzed using three-dimensional stereotactic surface projections (3D-SSP) and were compared with those of 22 patients with Alzheimer's disease (AD). rCBF patterns in patients with BD were different from those with AD. The BD group had greater CBF reduction in the frontal and anterior cingulate cortices, while the AD group had greater CBF reduction in the temporoparietal and posterior cingulate cortices. However, the rCBF pattern of each patient was more variable, and could be divided into three patterns: anterior cerebral hypoperfusion, posterior cerebral hypoperfusion, and diffuse cerebral hypoperfusion patterns. A distinct CBF reduction in the temporoparietal and/or posterior cingulate cortices, indistinguishable from the CBF pattern observed in AD, was demonstrated in 8 of 22 (36%) patients with BD, in particular there was bilateral hemispheric involvement with a diffuse hypoperfusion pattern. Although no pathological confirmation could be performed, some of the BD patients with CBF reduction in the posterior cerebral cortices may represent additional changes in the brain due to AD. In the future, a longitudinal study including pathology will be needed to determine whether these patients have coexisting AD pathology.     

Left frontotemporal hyperperfusion in a patient with post-stroke mania

A 78-year-old housewife with major depression developed a right-sided infarction in the territory of the middle cerebral arteries, followed by acute post-stroke mania. Comparison between pre- and post-stroke SPECT scans demonstrated a unique pattern of left orbitofrontal hyperperfusion with extensive right frontal hypoperfusion. A functional imbalance between right and left orbitofrontal cortices may be important in mania.     

Voxel-based analyses of gray/white matter volume and diffusion tensor data in major depression

The purpose of this study is to use voxel-based analysis to simultaneously elucidate regional changes in gray/white matter volume, mean diffusivity (MD), and fractional anisotropy (FA) in patients with unipolar major depressive disorder. We studied 21 right-handed patients and 42 age- and gender-matched right-handed normal subjects. Local areas showing significant gray matter volume reduction in depressive patients compared with controls were observed in the right parahippocampal gyrus, hippocampus, bilateral middle frontal gyri, bilateral anterior cingulate cortices, left parietal and occipital lobes, and right superior temporal gyrus. Local areas showing an increase of MD in depressive patients were observed in the bilateral parahippocampal gyri, hippocampus, pons, cerebellum, left frontal and temporal lobes, and right frontal lobe. There was no significant difference between the two groups for FA and white matter volume in the entire brain. Although there was no local area where brain volume and MD were significantly correlated with disease severity, FA tended to correlate negatively with total days depressed in the right anterior cingulate and the left frontal white matter. These results suggest that the frontolimbic neural circuit might play an important role in the neuropathology of patients with major depressive disorder.     

The regional cerebral blood flow changes in major depressive disorder with and without psychotic features

Depressive patients with psychotic features demonstrate distinct biological abnormalities in the hypothalamic-pituitary-adrenal axis (HPA), dopaminergic activity, electroencephalogram sleep profiles and measures of serotonergic function when compared to nonpsychotic depressive patients. However, very few functional neuroimaging studies were specifically designed for studying the effects of psychotic features on neuroimaging findings in depressed patients. The objective of the present study was to compare brain Single Photon Emission Tomography (SPECT) images in a group of unmedicated depressive patients with and without psychotic features. Twenty-eight patients who fully met DSM-IV criteria for major depressive disorder (MDD, 12 had psychotic features) were included in the study. They were compared with 16 control subjects matched for age, gender and education. Both psychotic and nonpsychotic depressed patients showed significantly lower regional cerebral blood flow (rCBF) values in the left and right superior frontal cortex, and left anterior cingulate cortex compared to those of controls. In comparison with depressive patients without psychotic features (DwoPF), depressive patients with psychotic features (DwPF) showed significantly lower rCBF perfusion ratios in left parietal cortex, left cerebellum but had higher rCBF perfusion ratio in the left inferior frontal cortex and caudate nucleus. The present study showed that DwPF have a different rCBF pattern compared to patients without psychotic features. Abnormalities involving inferior frontal cortex, striatum and cerebellum may play an important role in the generation of psychotic symptoms in depression.     

A Tc-99m HMPAO SPECT study of regional cerebral blood flow in drug-free schizophrenic patients with deficit and non-deficit syndrome

Twenty-nine patients with DSM-IV diagnoses of schizophrenia were categorized into deficit syndrome (n=14) and non-deficit syndrome (n=15) subgroups on the basis of the Schedule for the Deficit Syndrome. The patients, who had all been free of antipsychotic medication for at least 3 weeks, and 17 sex- and age-matched normal controls were studied with single-photon emission computed tomography with Tc-99m HMPAO. Age at onset, Brief Psychiatric Rating Scale (BPRS) total scores, BPRS positive symptom subscores and duration of illness were similar between the two schizophrenic subgroups. As expected, the deficit patients had more negative symptoms than the non-deficit patients. There were no statistically significant correlations between clinical parameters and regional cerebral blood flow (rCBF) values. The deficit syndrome subgroup showed diminished rCBF in the frontal regions bilaterally, right parietal regions and right superior temporal region compared with the control groups. Deficit patients showed significantly lower rCBF perfusion ratios in the right superior and inferior frontal cortex than did the non-deficit patients. No differences were detected between the controls and the non-deficit schizophrenic patients in terms of rCBF perfusion indices. The results of the present study confirm previous reports of different patterns of rCBF in deficit vs. non-deficit schizophrenic subgroups.     

Reduced regional cerebral blood flow in non-psychotic violent offenders

The present study was designed to replicate previously reported findings of abnormal frontal and/or temporal cerebral blood flow in violent offenders and to control for the influence of major mental disorder (MMD), substance abuse, and current medication. HMPAO-SPECT-CBF and MRI scans from pretrial forensic psychiatric investigations of 21 subjects convicted of impulsive violent crimes were retrospectively re-evaluated. In 16/21 subjects, visual assessment of SPECT scans showed some hypoperfusion in the temporal and/or frontal lobes. MRI showed no corresponding structural damage. Quantified regional cerebral blood flow (rCBF) in defined regions of interest was compared between index cases and 11 healthy control subjects. Index subjects had significant reductions in the right angular gyrus and the right medial temporal gyrus, bilaterally in the hippocampus, and in the left white frontal matter, but they had significantly increased rCBF in the parietal association cortex bilaterally. The aberrations were as frequent and severe among the subjects without MMD, substance abuse, and current medication (n=7) as in the entire group of index subjects.     

SPECT检测利培酮对精神分裂症患者脑血流灌注的影响

目的探讨利培酮对局部脑血流灌注(rCBF)的影响及疗效与rCBF之间的关系。方法研究组为24例未用过药的精神分裂症患者。男10例,女14例。正常对照组26例,男12例,女14例。用利培酮(3～6mg/d)治疗8周。患者在治疗前后进行基础状态及认知激活状态脑SPECT显像。结果与正常对照组相比,治疗前基础状态时,24例患者左右颞叶后下部血流灌注增加;激活状态时,左额叶外侧中部血流灌注显著下降。治疗后与治疗前相比,右颞叶外侧部、左右颞叶后上部基础状态的血流灌注显著下降;左右额叶中下部、左额叶外侧下部、左额颞上部及左额外侧上部认知激活状态的血流灌注显著增加。PANSS减分率与脑血流灌注的变化有关。结论利培酮治疗精神分裂症后,右颞外侧部、左右颞叶后上部、左右额叶中下部及左额叶外侧上下部的血流灌注变化显著。疗效与血流灌注变化有关。提示脑血流灌注对预测药物疗效具有重要意义。     

Regional cerebral blood flow abnormalities associated with apathy and depression in Alzheimer disease

The aim of this study was to identify brain areas related to apathy or depression in patients with Alzheimer disease (AD). Eighty-one AD patients were enrolled in this prospective study. (99m)Tc-HMPAO single photon emission computed tomography was performed to evaluate regional cerebral blood flow (rCBF). According to the Neuropsychiatric Inventory subscores of apathy and depression, 9 patients were classified as clinically significant (cs) depressed and non-cs-apathetic (D+) groups and 9 were classified as cs-apathetic and non-cs-depressed (A+) groups. In addition, 18 patients were classified as age-matched and Mini-Mental State Examination-matched disease control groups (D-, A-). The significance of rCBF differences between groups and the correlation between rCBF and subscores in 81 AD patients were estimated by SPM (uncorrected P < 0.005) analysis. D+ patients had significantly lower perfusion in the right orbitofrontal and inferior frontal gyri than D- patients, whereas A+ patients had this in the right amygdala, temporal, posterior cingulate, right superior frontal, postcentral, and left superior temporal gyri than A- patients. The negatively correlated areas with depression subscores included the left inferior frontal and the right middle frontal gyri and those with apathy subscores included the right temporal and right medial frontal gyri. We suggest that this finding may indicate that apathy and depression in AD patients involve distinct functional circuits.