Regional cerebral blood flow changes in early-onset anorexia nervosa before and after weight gain

To investigate the changes of regional cerebral blood flow (rCBF) in early-onset anorexia nervosa (AN) before and after weight gain, we examined resting rCBF using single photon emission computed tomography (SPECT) with [¹²³I]iodoamphetamine (¹²³I-IMP). Ten female children with AN (mean age 13.2 years old) participated in this study. SPECT examinations were performed in all patients twice at the beginning of treatment and after weight gain. The mean body mass index (BMI) was changed from 13.1 to 16.6 during 4 months treatment period. Automatic voxel-based analysis of the images was carried out using statistical parametric mapping (SPM) software. Relatively increased rCBF in the bilateral parietal lobe and limbic lobe including the posterior cingulate cortex (PCC) were observed after weight gain in early-onset AN. There was no significant decrease in the rCBF after weight gain. A significant positive correlation was observed between BMI and rCBF in the right thalamus, right parietal lobe, and right cerebellum. These results suggested that weight gain during the process of recovery from early-onset AN might activate specific brain regions which are possibly relevant to the pathophysiological aspects of the disorder.     

Cerebral blood flow abnormalities in patients with neurally mediated syncope

The aim of this study is to investigate regional cerebral blood flow (rCBF) in patients with syncope. We compared brain single photon emission computed tomography (SPECT) images of neurally mediated syncope patients with those of age/sex matched healthy volunteers. ^99mTc-ethylcysteinate dimer (ECD) brain SPECT was performed in 35 patients (M/F = 17/18, mean 36.6 years) with syncope during the asymptomatic period, and in 35 healthy volunteers. For statistical parametric mapping (SPM) analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 14-mm full width at half maximum Gaussian kernel. The mean duration of syncope history was 4.9 years and the mean number of syncope episodes was 6.3. In all patients, syncope or presyncope episodes occurred during head-up tilt tests, and all were the vasodepressive type. SPM analysis of brain SPECT images showed significantly decreased rCBF in the right anterior insular cortex, left parahippocampal gyrus, bilateral fusiform gyri, bilateral middle and inferior temporal gyri, left lingual gyrus, bilateral precuneus and bilateral posterior lobes of the cerebellum in syncope patients at a false discovery rate corrected p < 0.05. There were no brain regions that showed increased rCBF in syncope patients. Furthermore, we found a negative correlation between the total number of syncopal episodes and the rCBF of the right prefrontal cortex, and between the duration of syncope history and the rCBF of the right cingulate gyrus at uncorrected p < 0.001. Decreases of rCBF in multiple brain regions may be responsible for autonomic dysregulation and improper processing of emotional stress in neurally mediated syncope patients, and frequent syncope episodes may lead to frontal dysfuction.     

Regional cerebral blood flow abnormalities in early-onset obsessive-compulsive disorder: an exploratory SPECT study

OBJECTIVE: Recent epidemiological and clinical data suggest that obsessive-compulsive disorder (OCD) may be subtyped according the age of onset of obsessive-compulsive symptoms. The regional cerebral blood flow (rCBF) single photon emission computed tomography (SPECT) technique was used to investigate whether the pathophysiology of OCD differs between early- and late-onset OCD subjects. METHOD: Resting rCBF was measured in 13 early-onset (<10 years) and 13 late-onset (>12 years) adult OCD subjects and in 22 healthy controls. Voxel-based rCBF comparisons were performed with statistical parametric mapping. RESULTS: Early-onset OCD cases showed decreased rCBF in the right thalamus, left anterior cingulate cortex, and bilateral inferior prefrontal cortex relative to late-onset subjects (p < .0005, uncorrected for multiple comparisons). Relative to controls, early-onset cases had decreased left anterior cingulate and right orbitofrontal rCBF, and increased rCBF in the right cerebellum, whereas late-onset subjects showed reduced right orbitofrontal rCBF and increased rCBF in the left precuneus. In early-onset subjects only, severity of obsessive-compulsive symptoms correlated positively with left orbitofrontal rCBF. CONCLUSIONS: rCBF differences in frontal-subcortical circuits between early-onset and late-onset OCD subjects were found, both in location and direction of changes. These results provide preliminary evidence that brain mechanisms in OCD may differ depending on the age at which symptoms are first expressed.     

Comparison of regional cerebral blood flow in patients with eating disorders

We used single photon emission computed tomography (SPECT) with Tc-99m-HMPAO to examine the characteristics of regional cerebral blood flow (rCBF) in five patients with bulimia nervosa (BN), eight patients with anorexia nervosa (AN), and in nine healthy controls. The SPECT examinations were performed before and attar food intake stimulus, and the values of the corrected ratio (R) for rCBF in 10 cerebral cortical regions before (R_before) and after eating (R_after) were calculated. The asymmetry indices (AI) of the R values for the left and right side of each cortical region and the percent change from R_before to R_after (%change) were computed. In comparison with the other two groups, BN patients showed significantly higher R_before values in the bilateral inferior frontal and left temporal regions. The AN patients showed significantly lower R_before values in the left parietal region than the control group. There were no significant differences in R_after values among the three groups. The %change values in the AN group showed the greatest increase in 9 out of the 10 regions. In contrast to the positive values obtained from the 10 regions observed in the AN group, 5 out of the 10 regions in the BN group showed negative values. Among the three groups, significant differences in %change were observed on both sides of the inferior frontal, temporal, parietal, and occipital regions. These findings indicate that differences in cerebral function of BN and AN patients can be characterized through SPECT imaging.     

Assessment of regional blood flow in cerebral motor and sensory areas in patients with spinal cord injury

We assessed the presence and the degree of alteration of the regional blood flow (rCBF) as visualized by Tc-99m HMPAO brain rest SPECT in the sensory motor cortex and subcortical structure in spinal cord injury (SCI) patients, who suffered from various levels of motor and sensory function loss. Twenty-two patients (mean age: 42.1+/-13.4 years, 18 M, 4 F) and 11 control subjects (mean age: 32.2+/-6.4 years, 8 M, 3 F) participated in this study. The spinal cord injury group was consisted of 2 groups (14 paraplegic and 8 tetraplegic patients). The corticocortical rCBF ratios were calculated by using region of interests obtained from 34 cortical areas on coronal slices. Significantly reduced rCBF were measured from 11 cortical areas in tetraplegic patients and 11 cortical areas in paraplegic patients. Some of these areas were different in each group. In the tetraplegic group, significant reduction was observed in the following rCBF areas: left anterior cingulate gyrus, left medial supplementary motor area, bilateral front and back aspects of posterior cingulate gyrus, right lateral primary motor area, right medial primary sensory area, bilateral putamen, and right cerebellum. In the paraplegic group, reduced rCBF areas were as follows: bilateral anterior cingulate gyrus, right lateral supplementary motor area, left front aspect of posterior cingulate gyrus, left lateral primary motor area, bilateral back aspects of posterior cingulate gyrus, right medial primary sensory area, left lateral primary sensory area and bilateral putamen. In conclusion, in some of the movement-cortical and subcortical areas having significantly reduced blood flow in SCI may be helpful to demonstrate the disrupted areas of rCBF by SPECT. We believe that it may be useful if these findings should be considered during the evaluations related to the reorganization in SCI cases.     

The relationship between 99mTc-HMPAO brain SPECT and the scores of real life rating scale in autistic children

Childhood autism is a developmental disability of unknown origin with probable multiple etiologies. The purpose of this study was to compare the changes of regional cerebral blood flow (rCBF) in autistic and non-autistic controls, and to determine the relationship between rCBF on 99mTc-hexamethylpropylene amine oxime (HMPAO) brain SPECT and the scores of the Ritvo-Freeman Real Life Rating Scale (RLRS), IQ levels, and age of autistic children. Eighteen autistic children (four girls, 14 boys; mean age: 6.13 +/- 1.99 years) and 11 non-autistic controls (five girls, six boys, mean age: 6.5 +/- 3.39 years) were examined using 99mTc-HMPAO brain SPECT. All the children satisfying DSM-IV criteria for autistic disorder were taken into evaluation, and scored by the Ritvo-Freeman RLRS. IQ levels of these children were determined by Goodenough IQ test. Six cortical regions of interest (ROIs; frontal (F), parietal (P), frontotemporal (FT), temporal (T), temporo-occipital (TO), and occipital (O)) were obtained on transaxial slices for count data acquisition. The ratio of average counts in each ROI to whole-slice counts for the autistic children was correlated with the scores of Ritvo-Freeman RLRS. Hypoperfusion in rCBF in autistic children compared with the control group were identified in bilateral F, FT, T, and TO regions. We found no relationship between rCBF on 99mTc-HMPAO brain SPECT and the scores of the Ritvo-Freeman RLRS. There was a relationship between bilateral F regions perfusion on 99mTc-HMPAO brain SPECT and the age of autistic children. There was also a negative correlation between IQ levels and the scores of sensory responses, social relationship to people, and sensory-motor responses. Our results suggest that 99mTc-HMPAO brain SPECT is helpful to locate the perfusion abnormalities but no correlation is found between rCBF on 99mTc-HMPAO brain SPECT and the scores of Ritvo-Freeman RLRS.     

Regional cerebral blood flow measured by99mTc-HMPAO SPECT differs in subgroups of Alzheimer's disease

Summary Alzheimer's disease (AD) is a heterogeneous entity. Identifying AD subtypes might have impact in patients' response to different treatment strategies. We designed a study to examine regional cerebral blood flow (rCBF) in AD subtypes. To identify AD subtypes, we performed a cluster analysis including performance on memory, language, visuospatial, praxis, and executive functions. The rCBF measured by^99mTc-HMPAO SPECT was referred to the cerebellum. We examined 35 patients fulfilling the NINCDS-ADRDA criteria of probable AD and 13 age and sex-matched healthy cognitively intact controls. AD patients were at the early stage of the disease, their mean Mini-Mental Status (MMS) score (S.D.) was 22.5 (3.6). The cluster analysis revealed two AD subgroups: AD1 (N=12) and AD2 (N=23). The subgroups did not differ in age, sex, or global clinical severity as assessed by MMS and Brief Cognitive Rating Scale (BCRS). Both subgroups had equally impaired memory. The AD2 group was inferior to the AD1 group on verbal, visuospatial, praxic, and executive functions. The AD1 group showed reduced rCBF ratios in the temporal and parietal cortices and the amygdala compared to controls. The AD2 group differed from controls in the rCBF ratios of frontal, temporal, parietal, occipital, basal ganglia, and amygdaloid regions bilateral and from AD1 in the rCBF ratios of frontal and temporal cortices. In AD patients, the rCBF ratios did not correlate with MMS or BCRS scores. In contrast, several significant correlations were found between decreases rCBF ratios and impairment of memory and other cognitive functions. In conclusion, a cluster analysis on neuropsychological test performance identified two AD subgroups that differed on the neuropsychological profile and on the rCBF in spite of similar global clinical severity.     

Interictal cerebral blood flow abnormality in cryptogenic West syndrome

Purpose: To elucidate the abnormality of interictal regional cerebral blood flow (rCBF) of West syndrome at the onset . Methods: Quantitative measurement of rCBF with an autoradiography method using N‐isopropyl‐(¹²³I) p‐iodoamphetamine single photon emission computed tomography (SPECT) was performed on 14 infants with cryptogenic West syndrome. Regions of interest (ROIs) for rCBF were placed automatically using an automated ROI analysis software (three‐dimensional stereotactic ROI template), and were grouped into 12 segments: callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus, hippocampus, and cerebellum. We compared rCBF between the patients and seven age‐matched infants with cryptogenic focal epilepsy as a control group. The patients were divided into two groups according to the duration from onset to SPECT, to compare rCBF. Results: Quantitative analysis revealed cerebral hypoperfusion in cryptogenic West syndrome with normal SPECT images under visual inspection. In bilateral central, posterior cerebral, pericallosal, lenticular nucleus, and hippocampus, and in the left parietal, temporal, and cerebellum, and in the right angular and thalamus segments there were statistical differences (p < 0.05). Compared with the duration from onset to SPECT, there were no significant differences of rCBF in all segments. Discussion: Broad cerebral hypoperfusion with posterior predominance involving the hippocampus and lenticular nucleus implies that even cryptogenic West syndrome has a widespread cerebral dysfunction at least transiently, which would correspond to clinical manifestations of hypsarrhythmia and epileptic spasms. Hippocampal hypoperfusion suggests the dysfunction of hippocampal circuitry in the brain adrenal axis, and may contribute to subsequent cognitive impairment of cryptogenic West syndrome.     

Ictal SPECT in supplementary motor area seizures

Abstract

Objectives: We used ictal single photon emission computed tomography (SPECT) to clarify the propagation pathways of epileptic discharges in patients with supplementary motor area (SMA) seizure.

Methods: In four patients (four males, age range, 18–27 years) with SMA seizures, SPECT studies by radioisotope 99mTc-ECD were performed as a preoperative evaluation. Two of the patients remained seizure-free after complete resection of the focal cortical dysplasia on magnetic resonance (MR) images including epileptic foci. In the other two patients, MR images were normal, but subdural electrode monitoring allowed for verifying the ictal onset in the left SMA. After partial resection of the SMA including epileptic foci, these patients experienced a significant (>90%) reduction of seizure frequency. Regional cerebral blood flow (rCBF) measurements obtained under ictal and interictal conditions were compared on a voxel-by-voxel basis by means of the SPM99 paired t-test option (uncorrected p<0.001).

Results: Significant increases in rCBF under ictal conditions were identified in the bilateral anterior cingulate cortex (ACC), the globus pallidus ipsilateral to epileptic foci and the contralateral cerebellar hemisphere. The right ACC included a cluster with a submaximum in the right primary sensorimotor area.

Discussion: In patients with SMA seizures, the hyperperfusion areas of ictal SPECT did not localize within the SMA but spread to the adjacent cortex such as the ACC and sensorimotor cortex ipsilateral to epileptic foci. Additionally, the epileptic discharges propagated to the remote areas such as the globus pallidus and cerebellum. We caution that ictal SPECT localization in patients with SMA seizures is not always concordant to epileptic focus but reveals already spread seizure activities.     

CBF changes in drug naive juvenile myoclonic epilepsy patients

Abstract Purpose The role of thalamus and brainstem in generalized epilepsy has been suggested in previous studies. The aim of the present study was to assess regional cerebral blood flow (rCBF) abnormality in juvenile myoclonic epilepsy (JME) patients. Methods ^99mTc-ethylcysteinate dimer brain single photon emission computed tomography (SPECT) was performed in 19 drug naive JME patients and 25 normal controls with the similar age and gender distribution. Differences of rCBF between a JME group and a normal control group were examined by the statistical parametric mapping of brain SPECT images using independent t test. The regression analyses in SPM were also performed between rCBF and the age of seizure onset or the disease duration in JME group. Results Compared to normal controls, the JME group showed a significant rCBF reduction in bilateral thalami, red nucleus, midbrain, pons, left hippocampus, and in the cerebelli (FDR corrected p < 0.01) whereas rCBF increase in the left superior frontal gyrus (uncorrected p < 0.001 but FDR corrected p > 0.05). Disease duration was negatively correlated with rCBF in bilateral frontal cortices, caudate nuclei, brainstem and cerebellar tonsils. Conclusions Our results suggest that abnormal neural networks in the thalamus, hippocampus, brainstem and cerebellum are associated with JME.     

Regional cerebral blood flow in patients with orally localized somatoform pain disorder: a single photon emission computed tomography study

Aim: Somatoform pain disorder is characterized by persistent and chronic pain at one or more sites without an associated general medical condition and in which psychological factors are thought to play a role. This study aimed to investigate the pathological features of somatoform pain disorder localized to the oral region by single photon emission computed tomography (SPECT). Methods: Ten patients (nine females and one male; average age 55.0 ± 14.4 years) having somatoform pain disorder with oral symptoms participated. SPECT was performed using N‐isopropyl‐4‐[¹²³I] iodoamphetamine intravenous injections, and regional cerebral blood flow (rCBF) was assessed by three‐dimensional stereotactic surface projections. We also selected 12 healthy individuals (seven females and five males; average age 61.8 ± 13.2 years) to act as controls. Results: Both the patient and control groups showed no atrophy or infarction on CT or magnetic resonance imaging. The patient group showed higher rCBF in the subcortical area, especially in the thalamus and cingulate gyri, than the control group. In contrast, the patient group showed lower rCBF in the bilateral frontal and occipital lobes as well as in the left temporal lobe. Conclusions: These results suggest that the biological process involved in somatoform pain disorder of the oral region is characterized by changes in limbic and cortical functions. The finding that somatoform pain disorder with oral symptoms is associated with brain functional changes will help to develop treatment regimes for this disorder and clarify the underlying pathology.     

强迫症的局部脑血流动态显像研究

目的　探讨强迫症患者各脑叶的代谢状态及脑功能异常与其发病的关系。　　方法　采用单光子发射计算机扫描 (SPECT)技术 ,对未服药的 2 2例强迫症患者于静息及症状诱发状态下行局部脑血流 (rCBF)动态显像研究。　　结果　 1 8例有rCBF异常 ,表现为皮层内局限性放射性分布稀疏、缺损区 ,异常脑叶主要为顶叶、额叶、颞叶 ,并发现脑功能异常与强迫症状的严重程度及药物治疗反应有关。　　结论　大脑顶叶、额叶等脑叶的功能异常是部分强迫症发病的神经病理学基础     

Frontal hypoperfusion in depressed patients with dementia of Alzheimer type demonstrated on 3DSRT

Aims: Depressive symptoms are common in patients with dementia of Alzheimer type (DAT) and contribute to clinical morbidity. Previous studies have suggested that hypoperfusion in the prefrontal cortex and anterior cingulate gyrus are involved in the pathophysiology of depression in DAT. Using 3‐D stereotactic region of interest (ROI) template (3DSRT), fully automated ROI analysis software, the purpose of the present study was to investigate the relationship between depressive symptoms and regional cerebral blood flow (rCBF) in DAT. Methods: Technetium‐99m‐ethyl cysteinate dimer (^99mTc‐ECD) single‐photon emission computed tomography (SPECT) and Japanese version of the Neuropsychiatric Inventory (NPI) were carried out in 35 patients diagnosed as having mild–moderate DAT according to DSM‐IV. These patients were divided into the depressive group (D group: n = 17) and non‐depressive group (ND group: n = 18) using the NPI depression items. All data from SPECT images were analyzed using 3DSRT software. On 3DSRT the perfusion ratios (rCBF of bilateral callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, lenticular nucleus, thalamus and hippocampus/cerebellar hemisphere) of each segment were compared between the D group and the ND group. Results: The perfusion ratios of the left callosomarginal segment for the D group were significantly lower (P < 0.05) than those of the ND group. Conclusions: Hypoperfusion in the left frontal cortex contributes to the expression of depressive symptoms in patients with DAT.     

Effect of continuous positive airway pressure on regional cerebral blood flow in patients with severe obstructive sleep apnea syndrome

ObjectivesObstructive sleep apnea (OSA) is commonly associated with neural and cognitive deficits induced by recurrent hypoxemia and sleep fragment. The aims of this study were to use statistical parametric mapping (SPM) to analyze changes in regional cerebral blood flow (rCBF) in untreated patients with severe OSA before and after nasal continuous positive airway pressure (CPAP) treatment, examine the impact of OSA-related variables on rCBF, and assess the therapeutic effect of nasal CPAP treatment.MethodsThirty male patients with severe OSA underwent brain single photon emission computed tomography (SPECT) scans twice before and after nasal CPAP treatment for ≥6 months, whereas 26 healthy controls underwent a single SPECT scan. The rCBF differences were compared between two OSA sub-groups (untreated and treated) and the control group, and correlations between rCBF differences and clinical parameters were analyzed.ResultsCompared with the controls, the untreated OSA patients showed a significantly lower rCBF in multiple brain areas. After the treatment, partial reversal of the rCBF decreases was observed in the limbic and prefrontal areas. Moreover, complete reversal of the rCBF decreases was observed in the medial orbitofrontal, angular and cerebellar areas. Significant improvements in some clinical and polysomnographic variables (Epworth Sleepiness Scale, apnea–hypopnea index, CPAP duration, and arousal index) paralleled the rCBF changes after the treatment.ConclusionsDecreased rCBF in severe OSA was significantly reversible by CPAP treatment and correlated with the improvements in the apnea–hypopnea index, arousal index, CPAP duration and Epworth Sleepiness Scale. These results suggest that long-term CPAP treatment improves rCBF in areas responsible for executive, affective, and memory function.     

Effects of successive repetitive transcranial magnetic stimulation on motor performances and brain perfusion in idiopathic Parkinson's disease

We studied the effects of 0.2 Hz repetitive transcranial magnetic stimulation (rTMS) successively performed 6 times for 2 weeks in 12 patients with idiopathic Parkinson's disease (PD). Ten patients received rTMS to the bilateral frontal cortex (frontal rTMS) and six patients received rTMS to the bilateral occipital cortex (occipital rTMS). Before and after rTMS, we evaluated regional cerebral blood flow (rCBF) using 99m-Tc-ECD single photon emission computed tomography (SPECT) and clinical tests.In an analysis with statistic parametric mapping, both frontal and occipital rTMS reduced rCBF in the cortical areas around the stimulated site. The activities of daily living (ADL) and motor scores of Unified Parkinson's Disease Rating Scale (UPDRS), pronation-supination movements, and buttoning up significantly improved after frontal rTMS than before it, while occipital rTMS had no significant effects in clinical tests.The findings of the present study suggest that successive 0.2 Hz rTMS has outlasting inhibitory effects on neuronal activity around the stimulated cortical areas. Because there were no significant relations between improved clinical tests and reduced rCBF, we speculate that the indirect effects of 0.2 Hz rTMS on subcortical structures are related to improved parkinsonian symptoms. Further studies recruiting large numbers of subjects are required to confirm the efficacy of 0.2 Hz rTMS on PD.     

Bilateral thalamic damage,cortical hypometabolism and behavioural disturbances

Thalamic damage could be responsible for reduced metabolism in anterior cortical areas. In order to investigate an anatomical lesion and impairment of regional blood flow (rCBF) in distant cortical areas, we studied by magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) a patient with bilateral thalamic infarction, who presented with sudden consciousness impairment, drowsiness, gaze paralysis, dysphagia and bilateral Babinski sign. Three weeks later the neurological symptoms disappeared, but a severe mental deterioration was evident MRI showed thalamic bilateral damage of posterior and medial areas, involving part of the pulvinar, more evident for the right thalamus. A ^99mTc-HMPAO SPECT showed a decrease of rCBF over frontal and parietal regions, more evident for the right hemisphere. Six months later a severe memory impairment was still evident and MRI and SPECT picture were unchanged. The persistent memory defect could be related to a loss of cortical activation following the thalamic damage. The absence of primary lesions of cortical regions on CT scan and MRI and the neuroanatomical considerations on the diffuse projections running from medial nuclei and pulvinar to large parts of anterior neocortex supported this hypothesis.     

Single photon emission computerized tomography during and between seizures

Summary In three patients, patterns of brain activity were measured by ^99mTc-hexamethyl-propyleneamineoxime (^99mTc-HM-PAO) brain SPECT (single photon emission computerized tomography) in ictal and interictal states. Increased relative blood flow indicated the focus of partial seizures, its spreading to adjacent cortical regions and to distant brain structures via neuronal pathways. Ictal patterns of regional cerebral blood flow (rCBF) were in agreement with clinical symptomatology. Successive SPECT studies were performed after 3–7 days in the absence of electroencephalographic and clinical signs of seizures but still revealed increased relative blood flow in the focus of the seizures. SPECT studies, performed 2–6 weeks after the last clinically observable seizures, demonstrated the transition from increased to decreased relative blood flow in the focus of the seizures. In one patient, the EEG was complementary to and corresponded with the rCBF patterns in the ictal state. However, the dynamics of interictal changes could only be assessed by brain SPECT.     

Effects of behavior therapy on regional cerebral blood flow in obsessive-compulsive disorder

Very few functional neuroimaging studies have been performed on patients with obsessive-compulsive disorder (OCD) undergoing behavior therapy, even though it is recognized to be an effective treatment for this disorder. We measured the regional cerebral blood flow (rCBF) using the Xenon inhalation method in 31 treatment-refractory patients with OCD and the same number of age-matched normal controls. We also studied changes in rCBF in 22 OCD patients who had demonstrated a significant improvement after the behavior therapy. The OCD patients showed a significant bilateral elevation in the rCBF in the basal ganglia compared with the normal controls. After successful treatment, a significant decrease was found in the rCBF in the right head of the caudate nucleus that tended to correlate with clinical improvement.     

The effects of clozapine on cognitive function and regional cerebral blood flow in the negative symptom profile schizophrenia

OBJECTIVE: Cognitive function and regional cerebral blood flow (rCBF) were studied in negative symptom profile schizophrenic patients by using WCST and SPECT. METHODS: Twenty-one schizophrenic patients who matched the criteria of Andreason's negative symptom profile received SPECT and WCST, and then were treated with clozapine for 8 consecutive weeks. There were 28 and 12 normal subjects as the control groups of WCST and SPECT, respectively. RESULTS: Compared with controls, significantly poorer performance on total trials of category (TT), persevering errors (PE), and non-persevering errors (NPE) of WCST were found in schizophrenia (p < 0.05). The total score of the scale for assessment negative symptoms (SANS) was significantly related with poor TT (r = 0.45, p < 0.01) and PE performance (r = 0.45, p < 0.01). The poor TT, PE, and NPE tasks of WCST and SANS scores in the negative schizophrenic patients were significantly improved through clozapine treatment (p < 0.05). The schizophrenic patients had a significantly lower rCBF in bilateral frontal and temporal lobes and lower change rate of rCBF in bilateral frontal lobes during WCST compared to normal controls (p < 0.05). CONCLUSIONS: Negative symptom profile schizophrenia has cognitive deficits and lower rCBF in bilateral frontal and temporal lobes, which suggests that negative symptom profile schizophrenic patients have hypofrontality. Clozapine can improve negative symptoms and improve cognitive dysfunction, although it cannot improve reduced rCBF in the frontal lobes.     

Decreased thalamic blood flow in obsessive-compulsive disorder patients responding to fluvoxamine

Functional imaging studies have pointed to a role of the orbitofrontal cortex (OFC), striatum and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Effective treatment has been found to change brain activity within this circuitry. The aim of the present study was to explore possible differential effects of OCD responders and non-responders to drug treatment on the regional cerebral blood flow (rCBF). Measurements of rCBF were carried out in 15 out of 22 patients with OCD who completed an open-label trial with fluvoxamine. Patients were studied with 99mTc-HMPAO single photon emission computed tomography (SPECT) before and after 12 weeks of treatment. In addition, structural magnetic resonance imaging was obtained on all patients. Regions of interest comprised the OFC, caudate nucleus, putamen and thalamus. Seven patients responded to treatment. Levels of rCBF decreased significantly in the left caudate nucleus and the left and right putamen in both responders and non-responders to treatment. In responders, but not in non-responders, a significant decrease in rCBF was found in the right thalamus. Pre-treatment cerebellar and whole brain HMPAO uptake was significantly higher in responders to treatment compared with non-responders. We suggest that the thalamus plays a central role in the response to drug treatment.