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Background: Electroconvulsive therapy (ECT) is an important treatment option for patients with major depressive disorder (MDD). However, the mechanisms of ECT in MDD are still unclear., Methods: Twenty-four patients with severe MDD and 14 healthy controls were enrolled in this study. Eight ECT sessions were conducted for MDD patients using brief-pulse square-wave signal at bitemporal locations. To investigate the regional cerebral blood flow in MDD patients before and after ECT treatments by resting-state functional magnetic resonance imaging (rs-fMRI), the patients were scanned twice (before the first ECT and after the eighth ECT) for data acquisition. Afterward, we adopted fractional amplitude of low-frequency fluctuations (fALFF) to assess the alterations of regional brain activity., Results: Compared with healthy controls, the fALFF in the cerebellum lobe, parahippocampal gyrus, fusiform gyrus, anterior cingulate gyrus, and thalamus in MDD patients before ECT (pre-ECT) was significantly increased. In another comparison, the fALFF in the cerebellum anterior lobe, fusiform gyrus, insula, parahippocampal gyrus, middle frontal gyrus, and inferior frontal gyrus in pre-ECT patients was significantly greater than the post-ECT fALFF., Limitations: Only two rs-fMRI scans were conducted at predefined times: before the first and after the eighth ECT treatment. More scans during the ECT sessions would yield more information. In addition, the sample size in this study was limited. The number of control subjects was relatively small. A larger number of subjects would produce more robust findings., Conclusions: The fALFF of both healthy controls and post-ECT patients in cerebellum anterior lobe, fusiform gyrus, and parahippocampal gyrus is significantly lower than the fALFF of pre-ECT patients. This finding demonstrates that ECT treatment is effective on these brain areas in MDD patients., (Copyright © 2018. Published by Elsevier B.V.)

Using fMRI, cerebral activations were studied in 24 classically-trained keyboard performers and 12 musically unskilled control subjects. Two groups of musicians were recruited: improvising (n=12) and score-dependent (non-improvising) musicians (n=12). While listening to both familiar and unfamiliar music, subjects either (covertly) appraised the presented music performance or imagined they were playing the music themselves. We hypothesized that improvising musicians would exhibit enhanced efficiency of audiomotor transformation reflected by stronger ventral premotor activation. Statistical Parametric Mapping revealed that, while virtually 'playing along׳ with the music, improvising musicians exhibited activation of a right-hemisphere distribution of cerebral areas including posterior-superior parietal and dorsal premotor cortex. Involvement of these right-hemisphere dorsal stream areas suggests that improvising musicians recruited an amodal spatial processing system subserving pitch-to-space transformations to facilitate their virtual motor performance. Score-dependent musicians recruited a primarily left-hemisphere pattern of motor areas together with the posterior part of the right superior temporal sulcus, suggesting a relationship between aural discrimination and symbolic representation. Activations in bilateral auditory cortex were significantly larger for improvising musicians than for score-dependent musicians, suggesting enhanced top-down effects on aural perception. Our results suggest that learning to play a music instrument primarily from notation predisposes musicians toward aural identification and discrimination, while learning by improvisation involves audio-spatial-motor transformations, not only during performance, but also perception., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Not all memory processes are equally affected by aging. A widely accepted hypothesis is that older adults rely more on familiarity-based processing, typically linked with the perirhinal cortex (PRC), in the context of impaired recollection, linked with the hippocampus (HC). However, according to the dedifferentiation hypothesis, healthy aging reduces the specialization of MTL memory subregions so that they may mediate different memory processes than in young adults. Using fMRI, we tested this possibility using a conceptual fluency manipulation known to induce familiarity-related PRC activity. The study yielded two main findings. First, although fluency equivalently affected PRC in both young (18-28; N=14) and older (62-80; N=15) adults, it also uniquely affected HC activity in older adults. Second, the fluency manipulation reduced functional connectivity between HC and PRC in young adults, but it increased it in older adults. Taken together, the results suggest that aging may result in reduced specialization of the HC for recollection, such that the HC may be recruited when fluency increases familiarity-based responding. This article is part of a Special Issue entitled SI: Memory & Aging., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Patients with affective disorders exhibit changes in regional brain function and show abnormal social adaptation. However, to our knowledge, no near-infrared spectroscopy (NIRS) study has examined the relationship between these two phenomena longitudinally. This study examined the region-specific functional abnormality associated with bipolar disorder (BD) and major depressive disorder (MDD), and the association between particular longitudinal changes in regional activation and social adaptation., Methods: We evaluated frontotemporal functioning during a verbal fluency test (VFT) for patients with BD (N=18), those with MDD (N=10), and healthy controls (HCs; N=14) using NIRS. NIRS measurements and the Social Adaptation Self-evaluation Scale (SASS) were administered twice with an interval of approximately 6 months., Results: The BD and MDD groups showed lesser activation than the HCs in the bilateral ventro-lateral prefrontal cortex and the anterior part of the temporal cortex (VLPFC/aTC). Longitudinal changes in SASS scores were positively associated with the extent of change in left VLPFC/aTC activation in the BD group and with right VLPFC/aTC activation in the MDD group., Limitations: Our small sample size limited statistical power, and the effect of medication and multiple comparisons cannot be excluded, although these effects were considered in the interpretation of the present results., Conclusion: Longitudinal increases of VLPFC/aTC activation were associated with improvement in social adaptation in patients with BD and those with MDD. NIRS measurement could be a useful tool for objective evaluation of changes in social adaptation in BD and MDD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). Large expansions of the CGG repeat (>200 repeats) consequently result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55-200 of CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA. Recent studies have shown that infants with FXS exhibit severely reduced resolution of temporal attention, whereas spatial resolution of attention is not impaired. Following from these findings in the full mutation, the current study used fMRI to examine whether premutation carriers would exhibit atypical temporal processing at behavioral and/or neural levels. Using spatial and temporal working memory (SWM and TWM) tasks, separately tagging spatial and temporal processing, we demonstrated that neurotypical adults showed greater activation in the 'when pathway' (i.e., the right temporoparietal junction: TPJ) during TWM retrieval than SWM retrieval. However, premutation carriers failed to show this increased involvement of the right TPJ during retrieval of temporal information. Further, multiple regression analyses on right TPJ activation and FMR1 gene expression (i.e., CGG repeat size and FMR1 mRNA) suggests that elevated FMR1 mRNA level is a powerful predictor accounting for reduced right TPJ activation associated with temporal processing in premutation carriers. In conclusion, the current study provides the first evidence on altered neural correlates of temporal processing in adults with the premutation, explained by their FMR1 gene expression., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Memory processes are mainly studied with subjective rating procedures. We used a morphing procedure to objectively manipulate the similarity of target stimuli. While undergoing functional magnetic resonance imaging, nineteen subjects performed a encoding and recognition task on face and scene stimuli, varying the degree of manipulation of previously studied targets at 0%, 20%, 40% or 60%. Analyses were performed with parametric modulations for objective stimulus status (morphing level), subjective memory (confidence rating), and reaction times (RTs). Results showed that medial temporal lobe (MTL) activity can be best explained by a combination of subjective and objective factors. Memory success is associated with activity modulation in the hippocampus both for faces and for scenes. Memory failures correlated with lower hippocampal activity for scenes, but not for faces. Activity changed during retrieval on similar areas activated during encoding. There was a considerable impact of RTs on memory-related areas. Objective perceptual identity correlated with activity in the left MTL, while subjective memory experience correlated with activity in the right MTL for both types of material. Overall, the results indicate that MTL activity is heterogeneous, showing both linear and non-linear activity, depending on the factor analyzed., (Copyright © 2011 Elsevier B.V. All rights reserved.)

It has been suggested that several regions of the brain, including subregions of the medial temporal lobe (MTL) and the posterior parietal cortex, contribute to source memory success in a material-general manner, with most models highlighting the importance of memory process rather than material type. For the MTL in particular, however, increasing evidence suggests that MTL subregions may be specialized for processing different materials, raising the possibility that source memory-related activity may be material-sensitive. Previous fMRI studies have not directly compared source memory activity for different categories of stimuli, and it remains unclear whether source memory effects, in the MTL or elsewhere, are influenced by material. To investigate this issue, young participants were scanned during study while they made semantic judgments about words, pictures of objects and scenes, and during test when they retrieved the context (source) in which these items were studied. Several regions, including the hippocampi, medial and lateral parietal cortex, exhibited source memory effects common to words, objects and scenes, at both study and test. Material-dependent source memory effects were also identified in the left posterior inferior frontal and left perirhinal cortex for words and objects, respectively, at study but not test. These results offer direct support for the hypothesis that the MTL and posterior parietal cortex make material-general contributions to recollection. These results also point to a dissociation between encoding and retrieval with regard to the influence of material on the neural correlates of source memory accuracy, supporting the idea that a relatively small proportion of the activity elicited by a stimulus during encoding is incorporated into an episodic memory representation of the stimulus., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Attention deficit/hyperactivity disorder (ADHD) is characterized by widespread structural and functional abnormalities in the brain. We applied different structural imaging techniques such as voxel-based morphometry (VBM), diffusion tensor imaging (DTI), and magnetization transfer imaging (MTI) to study anatomical differences between boys with ADHD and healthy controls, as well as functional magnetic resonance imaging (fMRI) together with independent component analysis (ICA) to detect functional alterations. 14 boys with ADHD and 12 controls were included in our study. Results of DTI showed the expected differences in frontal and cerebellar white matter. VBM and MTI indicated group differences in the temporal lobe. Applying ICA to fMRI data, we extracted four components; two positively correlated to our working memory paradigm and two negatively correlated. Positive components included activation in frontal and parietal regions. Negative components showed activation in anterior and posterior cingulate cortex/precuneus and temporal regions, and were interpreted as forming part of the default mode network. Group differences in the inferior temporal lobe were detected. Applying different techniques, we found differences between boys with ADHD and controls mainly located in the temporal lobe. Therefore, we postulate that research on ADHD should broaden its scope by including the temporal lobe as a potentially important locus of abnormalities in ADHD., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Unique and unusual responses to inkblot stimuli evoked by emotionally vulnerable psychiatric patients have been considered as examples of interference of emotion with perceptual processes. However, few studies have investigated the interaction between emotion-related and perception-related neural circuits during performance of the inkblot test. In our recent studies using the inkblot stimuli, enlargement of the amygdala was revealed in association with frequent production of unique responses to the inkblot stimuli. Additionally, our studies demonstrated right temporopolar activation associated with the production of unique responses, as well as left anterior prefrontal and bilateral occipitotemporal activation associated with the production of typical responses. On the basis of these results, we hypothesized that the amygdala is involved in modulation of the connectivity among the frontotemporal regions identified in the activation analysis. To address this issue, we performed a functional connectivity analysis of functional magnetic resonance imaging data, using physiophysiological interaction implemented in Statistical Parametric Mapping 2 (SPM2). This analysis revealed that the amygdala imposed a positive modulation on the connection from the anterior prefrontal region to the temporopolar region, and a negative modulation on the connection from the temporopolar region to the occipitotemporal regions. These results suggest that interference of emotion affects perception during the inkblot test., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Principal component analysis (PCA) provides a method to explore functional brain connectivity. The aim of this study was to identify regional cerebral blood flow (rCBF) distribution differences between Alzheimer's disease (AD) patients and controls (CTR) by means of volume of interest (VOI) analysis and PCA. Thirty-seven CTR, 30 mild AD (mildAD) and 27 moderate AD (modAD) subjects were investigated using single photon emission computed tomography with (99m)Tc-hexamethylpropylene amine oxime. Analysis of covariance (ANCOVA), PCA, and discriminant analysis (DA) were performed on 54 VOIs. VOI analysis identified in both mildAD and modAD subjects a decreased rCBF in six regions. PCA in mildAD subjects identified four principal components (PCs) in which the correlated VOIs showed a decreased level of rCBF, including regions that are typically affected early in the disease. In five PCs, including parietal-temporal-limbic cortex, and hippocampus, a significantly lower rCBF in correlated VOIs was found in modAD subjects. DA significantly discriminated the groups. The percentage of subjects correctly classified was 95, 70, and 81 for CTR, mildAD and modAD groups, respectively. PCA highlighted, in mildAD and modAD, relationships not evident when brain regions are considered as independent of each other, and it was effective in discriminating groups. These findings may allow neurophysiological inferences to be drawn regarding brain functional connectivity in AD that might not be possible with univariate analysis.

Participants read sentences presented one word at a time, half of which ended with a semantically incongruent ending. 1.5T functional magnetic resonance imaging data were collected from 11 participants, showing that the left posterior inferior temporal region, which has previously been termed the Language Formulation Area (LFA), responded to cloze probability. It is suggested, based on anatomical positioning and a literature review, that the responsiveness of the LFA to cloze probabilities may reflect a role in coordinating the lexical and non-lexical reading pathways. Finally, it is noted that previous studies have implicated this region in dyslexia and some speculations are made in this regard.

Objectives: Previous imaging reports showed over-activation of fronto-limbic structures in bipolar patients, particularly in response to emotional stimuli. In this study, for the first time, we used perfusion weighted imaging (PWI) to analyze lobar cerebral blood volume (CBV) in bipolar disorder to further explore the vascular component to its pathophysiology., Methods: Fourteen patients with DSM-IV bipolar disorder (mean age+/-SD=49.00+/-12.30 years; 6 males, 8 females) and 29 normal controls (mean age+/-SD=45.07+/-10.30 years; 13 males, 16 females) were studied. PWI images were obtained following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), with a 1.5 T Siemens magnet using an echo-planar sequence. The contrast of enhancement (CE), was calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE=Sm/So*100) for frontal, temporal, parietal, and occipital lobes, bilaterally, on two axial images. Higher CE values correspond to lower CBV and viceversa., Results: Bipolar patients had significantly lower CE values in left frontal and temporal lobes (p=0.01 and p=0.03, respectively) and significantly inverse laterality index for frontal lobe (p=0.017) compared to normal controls. No significant correlations between CE measure and age or clinical variables were found (p>0.05)., Conclusion: This study found increased left frontal and temporal CBV in bipolar disorder. Fronto-temporal hyper-perfusion may sustain over-activation of these structures during emotion modulation, which have been observed in patients with bipolar illness.

We report the first known case of anorexia nervosa (AN) with Marchiafava-Bignami Disease (MBD) that responded to high-dose intravenous corticosteroid administration. A 16-year-old Japanese female with AN was diagnosed with MBD after rapid weight loss. During the acute stage, she suffered from a sudden onset of coma. After regaining consciousness, she presented with lack of movement, apathy, labile affect, and poverty of speech. On admission, magnetic resonance imaging showed an area of demyelination in the splenium of the corpus callosum. Positron emission tomography obtained 7 days after admission showed areas of hypoperfusion in the medial temporal lobe and in regions anterior and posterior to the central sulcus.

Near-infrared spectroscopy (NIRS) is an optical imaging method that allows non-invasive in-vivo measurements of changes in the concentration of oxygenated (O(2)Hb) and deoxygenated (HHb) hemoglobin in brain tissue. For the present study, we examined 12 schizophrenic patients and 12 age- and gender-matched healthy controls by means of multi-channel NIRS (Optical Topography; ETG-100, Hitachi Medical Co., Japan) during performance of two versions of the Verbal Fluency Test (VFT; letter and category version). The results indicate that the verbal fluency tasks generally led to clear frontal activation in healthy controls, which was significantly reduced in schizophrenic patients. The letter version of the VFT induced overall stronger activation than the category version, the group difference being particularly pronounced for phonological fluency. Moreover, significant positive correlations between task-related activation effects in prefrontal and temporal NIRS channels were found in both schizophrenic patients and healthy controls. The results confirm functional deficits within the frontal lobe in patients suffering from schizophrenic illnesses, but do not confirm previous findings on abnormal fronto-temporal correlations or increased temporal activation in this group of patients. The data furthermore underline the usefulness of functional NIRS in monitoring hemodynamic responses associated with cognitive processes in healthy controls and patients with neuro-psychiatric disorders.

Since cross-sectional brain-imaging studies demonstrating frontotemporal cerebral hypoactivity in violent offenders have generally been carried out around the time of trial and sentencing, the findings might be influenced by the stressful situation of the subjects. It seems that no group of offenders with this finding has yet been followed longitudinally. We have re-examined nine offenders convicted of lethal or near-lethal violence in whom single photon emission tomography (SPECT) previously had demonstrated frontotemporal hypoperfusion. The mean interval between the initial and the follow-up examination was 4 years. The initially observed hypoactivity was found to have remained virtually unchanged at follow-up: no mean change in the group exceeded 5% in 12 assessed regions of interest. Although preliminary due to the small sample size, this study suggests that frontotemporal brain hypoactivity is a trait rather than a state in perpetrators of severe violent crimes.

The study of medial-temporal amnesics has established that much of the brain's store of general knowledge can be retrieved without the hippocampus. Several brain imaging studies, however, have reported that the hippocampus is active during the performance of semantic memory tasks. Although this activity may reflect memory encoding, it is also possible that it is due to the process of retrieving the semantic representations of the stimuli. Here we show in two H(2)(15)O positron emission tomography studies that cerebral blood flow (CBF) to the hippocampus covaries with superior performance during the retrieval of general knowledge. Left hippocampal CBF was associated with faster word meaning retrieval and right hippocampal CBF with better picture naming. A follow-up experiment failed to show that faster responding in the word meaning task was associated with better episodic memory for the stimuli and so weakens the proposal that the hippocampal activity was strictly related to memory encoding. In both experiments CBF to the lateral temporal cortex covaried with hippocampal CBF in a way that suggests that the hippocampus provides complementary support to activation within the association cortex.

Previous positron emission tomography (PET) studies have shown greater medial temporal lobe activation (MTL) for associative memory encoding relative to deep item-oriented encoding. Greater MTL activation has also been reported for associative novelty detection. Although it has been suggested that these patterns of MTL activation could reflect the creation of novel associations into memory, it is unclear whether associative encoding and associative novelty detection rely on the same MTL substructures. In this study, we used event-related functional magnetic resonance imaging (er-fMRI) to reproduce previous reports of greater hippocampal activation for associative encoding using both arbitrary and semantically related object pairs. This paradigm allowed us to assess whether the requirement for associative processing at encoding interacts with associative novelty. Contrasting the pattern of activation for associative versus item-oriented encoding revealed greater right hippocampal activation as well as parahippocampal activation bilaterally, reproducing the findings from previous PET experiments. The orthogonal contrast between arbitrary and related pairs revealed greater activation in the left parahippocampal region, but no significant interaction between the type of encoding (associative or item oriented) and the type of pairs (arbitrary or semantically related) was observed in the medial temporal lobe (MTL). These results suggest that both associative processing and associative novelty detection can activate the MTL. Most importantly, this study suggests that associative processing can activate the MTL regardless of the pre-existence of an association between the items of a pair.

The medial temporal lobe (MTL) is crucial for declarative memory formation, but the function of its subcomponents in associative memory formation remains controversial. Most functional imaging studies on this topic are based on a stepwise approach comparing a condition with and one without associative encoding. Extending this approach we applied additionally a parametric analysis by varying the amount of associative memory formation. We found a hippocampal subsequent memory effect of almost similar magnitude regardless of the amount of associations formed. By contrast, subsequent memory effects in rhinal and parahippocampal cortices were parametrically and positively modulated by the amount of associations formed. Our results indicate that the parahippocampal region supports associative memory formation as tested here and the hippocampus adds a general mnemonic operation. This pattern of results might suggest a new interpretation. Instead of having either a fixed division of labor between the hippocampus (associative memory formation) and the rhinal cortex (non-associative memory formation) or a functionally unitary MTL system, in which all substructures are contributing to memory formation in a similar way, we propose that the location where associations are formed within the MTL depends on the kind of associations bound: If visual single-dimension associations, as used here, can already be integrated within the parahippocampal region, the hippocampus might add a general purpose mnemonic operation only. In contrast, if associations have to be formed across widely distributed neocortical representations, the hippocampus may provide a binding operation in order to establish a coherent memory.

We evaluated the relationship between regional cerebral blood flow (rCBF) and clinical symptoms in patients with schizophrenia. Single photon emission computed tomography with N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) was used to study 29 patients with schizophrenia. Clinical symptoms were assessed using the Brief Psychiatric Rating Scale (BPRS). We examined the correlation between rCBF and each BPRS item score using Statistical Parametric Mapping software. Corrected P-values < 0.05 were considered as statistically significant. The suspiciousness score on the BPRS was positively correlated with rCBF in the left inferior temporal gyrus. There was no significant correlation between rCBF and any other items of the BPRS. There was no significant correlation between rCBF and chlorpromazine-equivalent dosage. This analysis permits the quantitative assessment of the severity of persecutory delusions in relation to left temporal perfusion in patients with schizophrenia.

Using continuous EEG-correlated fMRI, we investigated the Blood Oxygen Level Dependent (BOLD) signal correlates of interictal epileptic discharges (IEDs) in 63 consecutively recruited patients with focal epilepsy. Semi-automated spike detection and advanced modeling strategies are introduced to account for different EEG event types, and to minimize false activations from uncontrolled motion. We show that: (1) significant hemodynamic correlates were detectable in over 68% of patients in whom discharges were captured and were highly, but not entirely, concordant with site(s) of presumed seizure generation where known; (2) deactivations were less concordant and may non-specifically reflect the consequential or downstream effects of IEDs on brain activity; (3) a striking pattern of retrosplenial deactivation was observed in 7 cases mainly with focal discharges; (4) the basic hemodynamic response to IEDs is physiological; (5) incorporating information about different types of IEDs, their durations and saturation effects resulted in more powerful models for the detection of fMRI correlates; (6) focal activations were more likely when there was good electroclinical localization, frequent stereotyped spikes, less head motion and less background EEG abnormality, but were also seen in patients in whom the electroclinical focus localization was uncertain. These findings provide important new information on the optimal use and interpretation of EEG-fMRI in focal epilepsy and suggest a possible role for EEG-fMRI in providing new targets for invasive EEG monitoring.

Positron emission tomography (PET oxygen-15 labeled water or PET [15O]H2O) was used to identify changes in regional cerebral blood flow (rCBF) in response to acute vagus nerve stimulation (VNS) in four subjects with treatment-resistant major depression (TRMD). Four 90-s PET [15O]H2O scans were performed on each subject in an off-on sequence (2 VNS de-activated; 2 VNS activated). PET images were aligned, normalized for global uptake, and resampled to standard atlas space. Statistical t-images were used to evaluate change. VNS-induced increases in rCBF were found in the bilateral orbitofrontal cortex, bilateral anterior cingulate cortex, and right superior and medial frontal cortex. Decreases were found in the bilateral temporal cortex and right parietal area. Regions of change were consistent with brain structures associated with depression and the afferent pathways of the vagus nerve.

This study used event-related potentials (ERPs) to investigate the timing and scalp topography of working memory in post-traumatic stress disorder (PTSD). This study was designed to investigate ERPs associated with a specific working memory updating process. ERPs were recorded from 10 patients and 10 controls during two visual tasks where (a) targets were a specific word or (b) targets were consecutive matching words. In the first task, nontarget words are not retained in working memory. In the second task, as in delay-match-to-sample tasks, a non-target word defines a new target identity, so these words are retained in working memory. This working memory updating process was related to large positive ERPs over frontal and parietal areas at 400-800 ms, which were smaller in PTSD. Estimation of cortical source activity indicated abnormal patterns of frontal and parietal activity in PTSD, which were also observed in regional cerebral blood flow [Clark, C.R., McFarlane, A.C., Morris, P., Weber, D.L., Sonkkilla, C., Shaw, M., Marcina, J., Tochon-Danguy, H., Egan, G., 2003. Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Biological Psychiatry 53, 474-481]. Frontal and parietal cortex are known to be involved in distributed networks for working memory processes, interacting with medial temporal areas during episodic memory processes. Abnormal function in these brain networks helps to explain everyday concentration and memory difficulties in PTSD.

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.

Psychosis is commonly observed in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS). Interictal single photon emission computed tomography (SPECT) was performed to compare regional cerebral blood flow (rCBF) pattern of MTLE-HS patients with psychosis of epilepsy (POE) comorbidity and MTLE-HS patients without any psychiatric disorders (Control group). For this, 21 patients with POE and 23 Control patients were matched by educational level, clinical, demographic, electrophysiological, and MRI data. SPECT scans were acquired using (99m)Tc and interpreted with a semiquantitative method. We analyzed brain regions of interest (ROI) of frontal, temporal, and parietal cortex, in addition to subcortical structures. There were no significant statistical differences of ROI between the POE group and the Control group after Bonferroni adjustment. However, we observed a trend for rCBF increase of right posterior cingulate in the POE Group. This increase would be in accordance with recent findings of cingulate abnormalities in schizophrenia, suggesting that abnormal function in this region might be associated with the psychotic phenomena.

There is strong evidence for the importance of the serotonin (5-HT) system in the neurobiology of panic disorder (PD); however, the exact role of this system remains unclear. The 5-HT transporter (5-HTT) is a key element in 5-HT neurotransmission. The current study aimed to investigate the binding of 5-HTT in the brain of patients with PD. We used single-photon emission computed tomography with a radioligand that specifically labels the 5-HTT, [(123)I]nor-beta-CIT. Subjects comprised eight patients with current PD, eight patients with PD in remission, and eight healthy control subjects. The patients with current PD showed a significant decrease in 5-HTT binding in the midbrain, in the temporal lobes and in the thalamus in comparison to the controls. The binding of 5-HTT in patients with PD in remission was similar to findings in the control group in the midbrain and in the temporal lobes, but lower in the thalamus. Regional 5-HTT binding significantly and negatively correlated with the severity of panic symptoms. These findings point to a dysregulation of the 5-HT system in PD patients. Altered function of 5-HTT appears to be related to the clinical status of patients. Clinical improvement in the patients in remission is associated with normalization of 5-HTT binding.

Background: Posttraumatic stress disorder (PTSD) is recognized as a disorder mediated by specific neurobiological circuits. Functional imaging studies using script-driven trauma imagery and pharmacological challenges have documented altered cerebral function (activation and deactivation) in several brain regions, including the amygdala, hippocampus, prefrontal cortex and anterior cingulate. However, the neural substrates of PTSD remain poorly understood and the effect of selective serotonin reuptake inhibition on regional cerebral activity is deserving of further investigation., Methods: Eleven adult patients (seven men, four women) (mean age+S.D.=33.6+/-9.2 years) with a DSM-IV diagnosis of PTSD, as determined by the Structured Clinical Interview for DSM-IV (SCID-I) and the Clinician-Administered PTSD Scale (CAPS), underwent single photon emission computed tomography (SPECT) with Tc-99m HMPAO pre- and post-8 weeks of treatment with the selective serotonin reuptake inhibitor, citalopram. Symptoms were assessed at baseline and at 2-week intervals with the Clinician-Administered PTSD Scale (CAPS), Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impression Scale (CGI). Image analysis of baseline and post-treatment scans was performed using Statistical Parametric Mapping (SPM)., Results: Treatment with citalopram resulted in significant deactivation in the left medial temporal cortex irrespective of clinical response. On covariate analysis, a significant correlation between CAPS score reduction and activation in the left paracingulate region (medial prefrontal cortex) was observed post-treatment. No significant pre-treatment differences were observed between responders and non-responders in anterior cingulate perfusion., Conclusions: These preliminary findings are consistent with clinical data indicating temporal and prefrontal cortical dysfunction in PTSD and preclinical data demonstrating serotonergic innervation of these regions. However, further studies, in particular in vivo receptor imaging studies, are needed to confirm whether these regional abnormalities correlate with clinical features and treatment response.

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.

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.

The verbal fluency (VF) test is associated with prefrontal and cingulate functioning. We used positron emission tomography (PET) to test the hypothesis that inactivity in these regions can explain why patients with depression often perform poorly on this test. Forty-one patients with major depression and 46 controls were scanned during rest and during activation with the VF test. The differences between the two conditions were mapped for each of the two groups, and between-group differences in the activation pattern were calculated on a voxel-by-voxel basis. As predicted, the patients performed significantly more poorly on the test. In both groups activations were seen in the left anterior cingulate region, the left dorsolateral prefrontal cortex, the left medial prefrontal cortex, and the right cerebellum. Performance was correlated to the cerebral perfusion in to the left occipitotemporal gyrus and the left cerebellum. However, no difference in activation between the two groups was significant. The present study had sufficient power to detect potential differences between the two groups, and the subtraction tasks were appropriate. Therefore, the result supports the notion that abnormalities in the prefrontal cortex in depression are qualitative in nature rather than quantitative; this suggests depression involves dys-coordination of neural activity in the frontal lobes rather than a simple reduction in activity.

Several brain-imaging studies have found associations between aberrant functioning in the frontal and temporal lobes and violent offending. We have previously reported decreased frontotemporal perfusion unrelated to psychosis, substance abuse, or current medication in 21 violent offenders. In the present study, we compared the regional cerebral blood flow (rCBF) in a new group of 32 violent offenders to scores on the Psychopathy Checklist-Revised (PCL-R), which rates two aspects of psychopathy: disturbed interpersonal attitudes (Factor 1) and impulsive antisocial behavior (Factor 2). A recently proposed model has split Factor 1 into a new Factor 1 (deceitful interpersonal style), a new Factor 2 (affective unresponsiveness), and a Factor 3, which approximately corresponds to the old Factor 2. The rCBF was assessed by single-photon emission computed tomography (SPECT) with technetium-99m-d,l-hexamethylpropyleneamine oxime (HMPAO) in regions of interest (ROIs) placed in accordance with fusioned magnetic resonance images (MRI) and SPECT scans. Significant negative correlations were found between interpersonal features of psychopathy (the old and especially the new Factor 1) and the frontal and temporal perfusion. The two most clearly associated ROIs were the head of the caudate nuclei and the hippocampi. These findings in a group of violent offenders living under the same conditions, which reduced the number of state-related confounders, add to the evidence indicating that aberrant frontotemporal activity may be a factor in violent behavior.

Background: Recently, there have been studies suggesting that depressive pseudodementia would include early-stage dementing disorder. Through the comparison of the 99mTc-HMPAO single photon emission computed tomography (SPECT) image of depressive pseudodementia subjects, healthy comparison subjects, depressed subjects free of cognitive impairment, and dementia of Alzheimer's type (DAT) subjects, we aimed to see part of pathophysiology of the depressive pseudodementia of elderly patients., Methods: Study subjects consisted of seven patients with depressive pseudodementia, seven healthy comparison subjects, seven patients with depression free of cognitive impairment, and eleven patients with DAT. Depression patients were diagnosed according to DSM-III-R. DAT patients were diagnosed by DSM III-R and NINCDS-ADRDA criteria of DAT. Other measures for assessment include Hamilton Rating Scale for Depression and Mini Mental State Exam. All underwent 99mTc-HMPAO SPECT scan. The images of each group were analyzed using statistical parametric mapping of Friston, which compares the images on voxel-by-voxel basis., Results: The results were as follows (1) The DAT group showed significant decreases of cerebral blood flow (CBF) in the right frontal, right temporal region, and both parietal regions as compared with control group (P < 0.05). (2) The depression group showed a significant decrease of CBF in the left frontal region as compared with control group (P < 0.05). (3) The depressive pseudodementia group showed significant decreases of CBF in both parietal regions as compared with control group (P < 0.05). (4) The depressive pseudodementia group showed significant decreases of CBF in the right temporal region and both parietal regions as compared with depression group (P < 0.05). (5) The DAT group showed significant decreases of CBF in the right temporal region, both frontal regions, and both parietal regions as compared with depressive pseudodementia group (P < 0.05)., Limitations: The small number of subjects may make it difficult to generalize from our results. Because decreased CBF in depressive pseudodementia is found while the subjects were depressed, we cannot tell whether it is a state marker or a trait marker., Conclusions: The depressive pseudodementia group showed decreased CBF in the temporo-parietal region, similar to that of the DAT group and different from that of the depression group.

Background: In severe depression, studies of regional cerebral blood flow (rCBF) by SPECT have not produced uniform results. The association between changes in SPECT and electroconvulsive therapy (ECT) has shown somewhat conflicting data. No data are available on benzodiazepine receptor function SPECT studies in ECT., Methods: Twenty drug-resistant adult inpatients fulfilling the DSM-IIIR criteria for major depression were studied by SPECT (rCBF by relative ECD uptake in all, and benzodiazepine receptor function by iomazenil uptake in five subjects) before and 1 week after clinically successful bitemporal ECT. Clinical and neuropsychological test scores were used as references for the possible changes in SPECT., Results: An increased perfusion after ECT was observed in right temporal and bilateral parietal cortices, whereas no reductions in relative ECD uptake were seen after ECT. Iomazenil-SPECT revealed a highly significant increase in the benzodiazepine receptor uptake in all studied cortical regions except temporal cortices., Conclusions: Clinically successful ECT was associated with changes in vascular perfusion and GABAergic neurotransmission, providing new evidence for the mechanism of action of ECT and for the neurobiology of severe drug-resistant depression.

Single photon emission computed tomography was used to study 14 female patients with anorexia nervosa and 8 female normal comparison subjects. Automatic voxel-based analysis of the images was carried out using statistical parametric mapping (SPM) software. Statistics across the entire brain were displayed as Z scores (threshold: P<0.05). Compared with the normal comparison subjects, the anorectic patients were characterized by hypoperfusion in the medial prefrontal cortex and the anterior cingulate gyrus, and hyperperfusion in the thalamus and the amygdala-hippocampus complex. These results suggest that a dysfunction in neuronal circuitry may be related to anorexia nervosa.

Perfusion and metabolic studies in patients with Alzheimer's disease (AD) have so far yielded conflicting results on the functional status of the hippocampal region, whose deep location in the brain makes it critical to optimize the image-reconstruction technique employed in emission tomography. We used a brain-dedicated device (CERASPECT) to perform single photon emission computed tomography (SPECT) studies with 99mTc-hexamethylpropylene-amine-oxime in 22 consecutive patients (mean age: 74+/-6.5 years) with mild [mini-mental status examination (MMSE) score > or =15, mean 20.8+/-3.2], probable AD. The control subjects were 11 healthy elderly people (mean age: 70.5+/-6.5 years). In patients, the total score on the selective reminding test (SRT) was used as an index of memory function. Counts from a hippocampal and a temporoparietal region of interest in each hemisphere were referred to the average thalamic counts. To optimize SPECT images, we used conventional filtered back-projection (FBP) reconstruction and a new iterative method of conjugate gradients (CG), which takes into account the geometrical and physical characteristics of the gamma-camera. Hippocampal perfusion in the two hemispheres was significantly lower in patients than in control subjects, regardless of which reconstruction method was used, and correlated with the MMSE score. The correlation between hippocampal perfusion and the SRT score was significantly (bootstrap procedure) higher with the CG method than with the FBP method (CG: r=0.52 and 0.54; FBP: r=0.39 and 0.47, for the right and left hemisphere, respectively). These results show hippocampal hypoperfusion in patients with mild AD, a correlation between hippocampal perfusion and the severity of cognitive impairment, and enhanced identification of these subtle perfusional changes with the use of an alternative image-reconstruction method that improves the spatial resolution of SPECT images.

It is unclear whether the functional changes found in panic disorder reflect disturbed physiology of particular neurotransmitters. One method of investigating altered neurotransmission is to assess regional brain activations in response to agonist challenges. D-Fenfluramine is a medication that induces neuronal release of serotonin. Using ¿15OH(2)O and positron emission tomography (PET), measurements of regional cerebral blood flow (rCBF) were done at t=-20, -5, +20 and +35 relative to the IV D-fenfluramine injection (t=0) in nine panic-disordered and 18 healthy subjects. Subjects were otherwise healthy, right-handed, non-smoking and not taking psychotropic medication. ¿15OH(2)O PET scans were assessed with Statistical Parametric Mapping using individual global cerebral blood flow as a covariate. Comparisons of the (baseline) first two scans between healthy and panic-disordered subjects showed a decreased rCBF in the left posterior parietal-superior temporal cortex in the patient group. Fenfluramine-induced increases as defined by the last two scans minus the first two scans were compared between groups and a significantly greater increase in the same left posterior parietal-superior temporal region was found in panic-disordered subjects. Consistent with this finding, differences between the last two scans (post-fenfluramine) of the healthy and panic-disordered subjects showed an increased rCBF in the left superior temporal cortex in panic-disordered subjects. Functional pathology in the left parietal-superior temporal cortex in panic disorder may be related to abnormal modulation by serotonin.

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.

We evaluated regional cerebral blood flow in five patients with conversion disorder (three females, two males, mean age+/-S.D.: 29.8+/-9.5 years) with astasia-abasia. The patients underwent single photon emission computed tomography after the injection of 555 MBq of [99mTc]hexamethylpropyleneamine oxime. Uptake ratios between areas of decreased perfusion and normal brain regions were considered significantly decreased when there was a change > or = 10%. Four of the five patients had left temporal and one patient had left parietal perfusion decreases. Uptake ratios ranged from 0.72 to 0.88 (mean+/-S.D.: 0.81+/-0.08). Our findings suggest that alterations in regional brain perfusion may accompany conversion symptoms. Functional imaging may therefore offer a means of elucidating the neural correlates of conversion disorder.

Studies using single photon emission computed tomography (SPECT) have found low cerebral blood flow (CBF) in frontal and parietal cortices in patients with chronic opiate dependence. In the present study, SPECT with 99mTc-HMPAO as tracer was used to compare 27 detoxified opiate addicts with nine healthy control subjects. All the subjects were evaluated with clinical psychiatric (DSM-IV), psychometric and neuropsychological measures. Compared with normal control subjects, the addicts showed a non-significant reduction of whole brain perfusion values. Significant hypoperfusion in the right frontal and left temporal lobes was found in addicts with comorbid depression, and a significant decrease in CBF in the right frontal lobe was observed in those with antisocial tendencies. A significant negative correlation emerged between Depression subscale scores on the Minnesota Multiphasic Personality Inventory and left temporal CBF in the patients. No significant correlations were found, however, between measures of cognition and CBF in opiate addicts. The asymmetrical findings in CBF that characterized the addicts relative to normal control subjects may be more closely related to mood and behavioral traits than to substance abuse, per se.

Studies of regional cerebral blood flow in both schizophrenic and depressed patients have yielded contradictory findings. Single photon emission computed tomography (SPECT) was used to compare brain-perfusion patterns in 17 patients with schizophrenia and 12 patients with major depression and to evaluate the relationship of the findings to psychopathology. The images were analyzed both visually and quantitatively. Twelve of the 17 schizophrenic patients and 8 of the 12 depressed patients showed a pathological blood flow pattern. Hypoperfusion of the left temporal lobe was observed in seven of the schizophrenic and five of the depressed patients. Five of the schizophrenic patients also had a hypoperfusion of the left frontal lobe. Separation of both diagnostic cohorts in two subgroups with pathological and normal cerebral blood flow patterns revealed significantly higher levels of symptomatology in the group with hypoperfusion in the SPECT image. The analysis of different cerebral regions revealed statistically significant temporal hypoperfusion was significantly related to positive symptoms in schizophrenia. Our data suggest that left-sided temporal lobe dysfunction is related both to schizophrenia and major depression. The localization of hypoperfusion seems to be associated with the type of psychopathology (positive vs. negative symptoms in schizophrenia). Thus, the results support the model of paralimbic and prefrontal dysfunction in both diseases.

Regional cerebral blood flow (rCBF) was measured with technetium-99m hexamethylpropyleneamine oxime single photon emission computed tomography in 38 neuroleptic-treated schizophrenic patients. To improve the validity of the evaluation of symptomatology, we applied findings previously derived in a principal component analysis (PCA) of the Positive and Negative Syndrome Scale. The PCA had disclosed five orthogonal independent symptom structures (i.e., negative, hostile/excited, thought disordered, delusional/hallucinatory, and depressive components), and obtained factor scores for 70 schizophrenic subjects, including the present sample. Stepwise regression analysis elucidated some of the cortical regions in which relative rCBF predicted the severity of symptoms--namely, lateral and orbital prefrontal, lateral temporal, inferior parietal, and medial temporal regions. Findings suggested that symptom structures derived from PCA could prove helpful in elucidating the pathophysiology of neural mechanisms.

High resolution single photon emission computed tomography (SPECT) was used to evaluate regional cerebral blood flow (rCBF) in 14 acutely depressed elderly patients and 29 normal subjects. SPECT images of the two groups were randomized and blindly read. Foci of decreased radionuclide uptake were assessed by number and location. The total number of rCBF defects per whole brain study was significantly greater in the depressed patients than in the normal subjects. A significantly greater number of rCBF defects was found most strikingly in the lateral frontal and less prominently in the lateral and medial temporal brain regions of the depressed patients.

Positron emission tomography was used to study the effects of experimentally controlled mood states on cerebral blood flow (CBF), measured with the quantitative equilibrium infusion method and 15O-labeled water. Twenty-seven brain regions in each hemisphere were assessed in 16 normal subjects. CBF and heart rate were measured during happy and sad mood induction, and during two nonemotional control conditions: sex differentiation and resting baseline. Valence-specific effects of mood on CBF were obtained for subcortical, but not for frontal-temporal or control regions. CBF increased in left amygdala and decreased in right amygdala during sad mood relative to the averaged control conditions. These changes correlated with shifts toward negative affect. Correlations were opposite for subcortical (negative affect associated with lower left hemispheric CBF) compared with frontal-temporal cortical regions. Results support limbic involvement in regulating emotional states and suggest some reciprocity between subcortical and frontal-temporal regulation of emotional experience.

Single photon emission computed tomography (SPECT) examined changes in regional cerebral blood flow (rCBF) induced by passive auditory single-word stimulation. A split-dose SPECT technique was used between resting and activated states, in which a smaller amount of ligand (99m technetium hexamethyl propyleneamine oxide, HMPAO) was given with the first scan, accompanied by a prolonged scan time. A larger amount of ligand was given with the second scan, accompanied by a shorter scan time. This split-dose SPECT technique has met with previous success for other activation tasks. The brain regions of interest (ROIs) in this study were selected from ROIs previously found to be activated by passive auditory single-word stimulation and not by non-word stimuli in positron emission tomography (PET) rCBF studies. This study thus tested the sensitivity of SPECT with HMPAO to detect brain activation with a stimulus previously demonstrated to elicit changes in rCBF with PET. However, no significant difference was detected between resting and activated states in this study. Thus, SPECT was not as sensitive as PET in this activation task. Since SPECT is a less costly and more widely available modality to study brain activation than PET, it is important to delineate its potential capacities to maximize the efficiency of future research in this field.

We compared global and regional cerebral blood flow in 11 schizophrenic patients and 11 normal comparison subjects, all over the age of 45 years. The schizophrenic patients had lower global cortical uptake than the control subjects. Among the individual regions of interest, the schizophrenic patients had significant decrements in the left posterior frontal region and in the bilateral inferior temporal regions. The uptake did not correlate with age of onset or duration of schizophrenia, current daily neuroleptic dose, severity of psychopathology, or global cognitive impairment.

Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry was used to study the morphology of labeled axonal plexuses in the human lateral temporal cortex. Strongly stained non-pyramidal neurons and a dense NADPH diaphorase-positive network of fibers were observed in all cortical layers. Certain stained fibers are found to give rise to basket-like formations. Notably other fibers seem to innervate small blood vessels. In addition, numerous blood vessels show a punctate labeling over their surfaces. These findings provide new morphological and chemical details of the axonal innervation of the human neocortex.

Ten patients suffering from DSM-III-R simple phobia were studied under two conditions: (a) while listening to a 4 min relaxation tape, and (b) while listening to a 4 min audio tape describing exposure to the phobic stimulus. During each condition, subjects were injected with 99mTc-Exametazime, a marker of regional cerebral blood flow. Subjective and psychophysiological measures indicated a marked effect of the anxiety induction procedure. Ratio analysis of the SPET data revealed reductions in tracer uptake largely confined to posterior cerebral regions bilaterally. Analysis of brain regions of interest normalised to the whole brain slice showed reductions confined to right temporal/occipital regions. In general there was no clear association between subjective and physiological variables and changes in regional uptake of tracer as a consequence of the anxiety induction procedure. The changes in tracer uptake were dissimilar to those previously reported for other cognitive activation paradigms, providing some reassurance that those functional brain changes were not artefacts of non-specific changes in state anxiety. These posterior brain changes may reflect alterations in activation of the GABA/benzodiazepine complex.

Recent studies have reported that patients with unipolar major depression may show a lower whole brain cerebral blood flow (CBF) and reduced regional CBF in frontal, temporal, and parietal lobes. The present study used single photon emission computed tomography (SPECT) with the CBF marker Tc-99m-hexamethylpropyleneamineoxine (HMPAO) to measure the cortical CBF of six individual regions of interest (ROIs), total ROI, and left or right hemispheric total ROI in 43 unipolar depressed subjects and 12 normal control subjects. There were no significant differences in the distribution of Tc-99m-HMPAO uptake into total ROI, right or left global ROI, prefrontal, motor frontal, parietal, temporal, visual cortex, or associative visual cortex between patients with melancholic depression, simple major depression, or minor depression and healthy control subjects. There were also no significant differences in the right-left distribution of uptake between the patients and the control subjects. Hypoperfusion was observed in motor frontal and parietal cortex of patients who had been taking benzodiazepines during the study period. It is concluded that cortical CBF, as assessed with Tc-99m-HMPAO SPECT, is relatively intact in the present sample of patients with severe depression.