Modulation of a brain-behavior relationship in verbal working memory by rTMS

We investigated whether the brain-behavior relationship (BBR) between regional cerebral blood flow (rCBF) as measured by positron emission tomography (PET) and individual accuracy in verbal working memory (WM) can be modulated by repetitive transcranial magnetic stimulation (rTMS) of the left or right middle frontal gyrus (MFG). Fourteen right-handed male subjects received a 30-s rTMS train (4 Hz, 110% motor threshold) to the left or right MFG during a 2-back WM task using letters as stimuli. Simultaneously an rCBF PET tracer was injected and whole-brain functional images were acquired. A hypothesis-driven region-of-interest-analysis of the left and right MFG BBR as well as an explorative whole-brain analysis correlating the individual accuracy with rCBF was carried out. Without rTMS we found a negative BBR in the left but no significant BBR in the right MFG. This negative BBR is best explained by an increased effort of volunteers with an inferior task performance. Left-sided rTMS led to a shift of the BBR towards the superior frontal gyrus (SFG) and to a positive BBR in anterior parts of the left SFG. With rTMS of the right MFG the BBR was posterior and inferior in the left inferior frontal gyrus. Beyond the cognitive subtraction approach this correlation analysis provides information on how the prefrontal cortex is involved based on individual performance in working memory. The results are discussed along the idea of a short-term plasticity in an active neuronal network that reacts to an rTMS-induced temporary disruption of two different network modules.     

Visual exploration of form and position with identical stimuli: functional anatomy with PET

Visual form and position perception in primates is thought to engage two different sets of cortical visual areas. However, the original concept of two functionally different and anatomically segregated pathways has been challenged by recent investigations. Using identical stimuli in the centre of the visual field with no external cues, we examined whether discrimination of form aspects and position aspects would indeed activate occipito-temporal and occipito-parietal areas, respectively. We measured and localised regional cerebral blood flow (rCBF) changes in the brain with positron emission tomography (PET) and 15O-butanol while the subjects performed four visual tasks: position discrimination (PD), form discrimination (FD), joint form and position discrimination (FPD), and a control task. Discrimination of form contrasted with discrimination of position resulted in rCBF increases in the lateral occipital and fusiform gyri. Discrimination of position contrasted with discrimination of form yielded rCBF increases in the left frontal eye field and middle frontal gyrus. No extra activations were seen when the joint form and position discrimination task was contrasted with either the individual form and position discrimination tasks. When the individual form and position discrimination tasks were contrasted with the control task, form discrimination resulted in activations in both occipito-temporal and occipito-parietal visual cortical regions, as well as in the right middle-frontal gyrus. Position discrimination resulted in activation in occipito-parietal visual cortical regions, the left frontal eye field and the left middle frontal gyrus. These findings are consistent with the view that the processing of visual position information activates occipito-parietal visual regions. On the other hand, the processing of 2D visual form information, in addition to the activation of occipito-temporal neuronal populations, also involves the parietal cortex. Form and position discrimination activated different nonsymmetrical prefrontal fields. Although the visual stimuli were identical, the network of activated cortical fields depended on whether the task was a form discrimination task or a position discrimination task, indicating a strong task dependence of cortical networks underlying form and position discrimination in the human brain. In contrast to former studies, however, these task-dependent macronetworks are overlapping in the posterior parietal cortex, but differentially engage the occipito-temporal and the prefrontal cortex.     

Correlation between extraversion and regional cerebral blood flow in response to olfactory stimuli

OBJECTIVE: Extraversion, a trait associated with individual differences in approach motivation and the experience of positive emotional states, is negatively correlated with certain psychiatric disorders, including depression and social phobia. The authors examined the correlation between extraversion and regional cerebral blood flow (rCBF) while participants were exposed to olfactory stimuli in order to further characterize individual differences in hedonic processing associated with this trait. METHOD: Twelve healthy participants were exposed to pleasant and unpleasant odors while rCBF was measured using [(15)O] water PET. The NEO Five-Factor Inventory was used to assess extraversion. Associations between extraversion scores and rCBF in each olfactory stimulus condition were assessed by correlational analysis. RESULTS: During the pleasant smell condition, extraversion was correlated with rCBF in the amygdala and occipital cortex. During the unpleasant smell condition, extraversion was correlated with rCBF in the occipital cortex and inferior temporal gyrus. CONCLUSIONS: These results provide important evidence for the biological basis of extraversion and indicate that there are systematic individual differences in patterns of brain activation in response to affective stimuli.     

STN stimulation alters pallidal-frontal coupling during response selection under competition.

To investigate the effects of bilateral subthalamic nucleus (STN) stimulation on patterns of brain activation during random number generation (RNG), a task that requires suppression of habitual counting and response selection under competition. We used H(2)(15)O positron emission tomography to investigate the changes of regional cerebral blood flow (rCBF) induced by bilateral STN stimulation during a RNG task, in six patients with Parkinson's disease. Paced RNG at 1 Hz was compared with a control counting task. Both tasks were performed off medication with deep brain stimulation on and off. Subthalamic nucleus stimulation had a negative effect on performance of fast-paced RNG, leading to reduced randomness and increased habitual counting. Subthalamic nucleus stimulation also induced a reduction of rCBF in the left dorsal frontal gyrus, inferior frontal gyrus, dorsolateral prefrontal cortex, posterior and right anterior cingulate, and an increase of rCBF in the right internal globus pallidum (GPi) during RNG. Stimulation of the STN significantly altered pallidal coupling with frontal and temporal areas compared with when the stimulators were off. In conclusion, during RNG: (i) STN stimulation activates its output neurons to the GPi; (ii) STN stimulation induces increased inhibition of a prefrontal-cingulate network. This is the first direct evidence that STN stimulation significantly alters pallidal coupling with prefrontal, cingulate, and temporal cortices during performance of a task that requires response selection under competition.     

Taste-olfactory convergence, and the representation of the pleasantness of flavour, in the human brain

The functional architecture of the central taste and olfactory systems in primates provides evidence that the convergence of taste and smell information onto single neurons is realized in the caudal orbitofrontal cortex (and immediately adjacent agranular insula). These higher-order association cortical areas thus support flavour processing. Much less is known, however, about homologous regions in the human cortex, or how taste-odour interactions, and thus flavour perception, are implemented in the human brain. We performed an event-related fMRI study to investigate where in the human brain these interactions between taste and odour stimuli (administered retronasally) may be realized. The brain regions that were activated by both taste and smell included parts of the caudal orbitofrontal cortex, amygdala, insular cortex and adjoining areas, and anterior cingulate cortex. It was shown that a small part of the anterior (putatively agranular) insula responds to unimodal taste and to unimodal olfactory stimuli, and that a part of the anterior frontal operculum is a unimodal taste area (putatively primary taste cortex) not activated by olfactory stimuli. Activations to combined olfactory and taste stimuli where there was little or no activation to either alone (providing positive evidence for interactions between the olfactory and taste inputs) were found in a lateral anterior part of the orbitofrontal cortex. Correlations with consonance ratings for the smell and taste combinations, and for their pleasantness, were found in a medial anterior part of the orbitofrontal cortex. These results provide evidence on the neural substrate for the convergence of taste and olfactory stimuli to produce flavour in humans, and where the pleasantness of flavour is represented in the human brain.     

Changes of cognition and regional cerebral activity during acute hypoglycemia in normal subjects: A H215O positron emission tomographic study

Blurred vision and cognitive difficulties are prominent symptoms during acute insulin‐induced hypoglycemia. Our hypothesis was that changes in cerebral activity reflect these symptoms. Positron emission tomography (PET) with oxygen‐15‐labelled water was used to measure relative changes in regional cerebral blood flow (rCBF) as a marker of cerebral activity. Hypoglycemia was induced by intravenous insulin infusion in 19 healthy men performing two different cognitive tasks of varying complexity. The hypoglycemic stimulus [plasma glucose 2.2 mmol/liter (0.4)] produced a significant hormonal counterregulatory response. During the low cognitive load, rCBF decreased in response to hypoglycemia in a large bilateral area in the posterior part of the temporal lobe, and rCBF increased bilaterally in the anterior cingulate gyrus, the right frontal gyrus, the fusiform gyrus, thalamus, and the left inferior part of the frontal gyrus. During the high cognitive load, rCBF decreased bilaterally in a large region in the posterior part of the temporal gyrus and increased in the left and right anterior cingulate gyrus, left and right frontal gyrus, right parahippocampal and lingual gyrus, and left superior temporal gyrus. Visual impairment during hypoglycemia was associated with deactivation in the ventral visual stream. The anterior cingulate gyrus was activated during hypoglycemia in a load‐dependent manner. Areas on the frontal convexity were differentially activated in response to the cognitive load during hypoglycemia. Our findings suggest that hypoglycemia induces changes in sensory processing in a cognition‐independent manner, whereas activation of areas of higher order functions is influenced by cognitive load as well as hypoglycemia. © 2009 Wiley‐Liss, Inc.     

Naming of newly learned objects: a PET activation study

The present study tracked the naming-related brain activity by positron emission tomography (PET) when successfully learned unfamiliar objects were named. Ten Finnish-speaking subjects participated in the study. Prior to the PET scan, each subject underwent a 4-day long training period in which 40 names of rare unfamiliar objects were taught. The stimulus categories were as follows: unfamiliar but real objects for which both the name and the definition were given during training, only the name was given, no information was given. In addition, familiar objects and visual noise patterns were used. The unfamiliar items mainly represented ancient domestic tools unknown to modern-day people. As semantic support did not affect the PET results, all trained items were pooled together. The trained objects vs. familiar objects contrast revealed rCBF increases in the left inferior frontal cortex (Broca's area), the left anterior temporal area, and the cerebellum. Likewise, the trained objects vs. unfamiliar objects (for which no information was given) contrast revealed more extensive left frontal (roughly Broca's area) and cerebellar rCBF increases, while anterior temporal activation was bilateral. Familiar objects, contrasted with both visual noise patterns and a rest condition, elicited activation increases in expected areas, i.e., bilateral occipital regions and the fusiform gyrus. Our results indicate that the naming of newly learned objects recruits more extensive brain areas than the naming of familiar items, namely a network that includes left-dominant frontotemporal areas and cerebellum. Its activity is tentatively related to enhanced lexical-semantic and lexical-phonological retrieval, as well as associative memory processes.     

The effects of presentation rate during word and pseudoword reading: a comparison of PET and fMRI

The effect of stimulus rate and its interaction with stimulus type on brain activity during reading was investigated using functional magnetic resonance imaging (fMRI). This (i) enabled the segregation of brain regions showing differential responses, (ii) identified the optimum experimental design parameters for maximizing sensitivity, and (iii) allowed us to evaluate further the sources of discrepancy between positron emission tomography (PET) and fMRI signals. The effect of visual word rate has already been investigated in a previous PET study. However, rate effects can be very different in PET and fMRI, as seen in previous studies of auditory word processing. In this work, we attempt to replicate rate-sensitive activations observed with PET using fMRI. Our objective was to characterize the discrepancies in regionally specific rate-sensitive effects between the two imaging modalities. Subjects were presented with words and pseudowords at varying rates while performing a silent reading task. The analysis specifically identified regions showing (i) an effect of stimulus rate on brain activity during reading; (ii) modulation of this effect by word type; and (iii) increased activity during reading relative to rest, but with no dependence on stimulus rate. The results identified similar effects of rate for words and pseudowords (no interactions between rate and word type reached significance). Irrespective of word type, strong positive linear effects of rate (i.e., activity increasing with rate) were detected in visual areas, right superior temporal gyrus, and bilateral precentral gyrus. These findings replicate the results of the previous PET study, confirming that activation in regions associated with visual processing and response generation increases with the number of stimuli. Likewise, we detected rate-independent effects reported in the previous PET study in bilateral anterior middle temporal, inferior frontal, and superior parietal regions. These results differentiate the functionally specific responses in rate-dependent and rate-independent areas. However, for negative effects of rate, fMRI did not replicate the effects seen in PET, suggesting some form of hemodynamic "rectification." The discussion focuses on differences between evoked rCBF and BOLD signals.     

Interconnected large-scale systems for three fundamental cognitive tasks revealed by functional MRI

The specific brain areas required to execute each of three fundamental cognitive tasks - object naming, same-different discrimination, and integer computation - are determined by whole-brain functional magnetic resonance imaging (fMRI) using a novel technique optimized for the isolation of neurocognitive systems. This technique (1) conjoins the activity associated with identical or nearly identical tasks performed in multiple sensory modalities (conjunction) and (2) isolates the activity conserved across multiple subjects (conservation). Cortical regions isolated by this technique are, thus, presumed associated with cognitive functions that are both distinguished from primary sensory processes and from individual differences. The object-naming system consisted of four brain areas: left inferior frontal gyrus, Brodmann's areas (BAs) 45 and 44; left superior temporal gyrus, BA 22; and left medial frontal gyrus, BA 6. The same-different discrimination system consisted of three brain areas: right inferior parietal lobule, BA 40; right precentral gyrus, BA 6; and left medial frontal gyrus, BA 6. The integer computation system consisted of five brain areas: right middle frontal gyrus, BA 6; right precentral gyrus, BA 6; left inferior parietal lobule, BA 40; left inferior frontal gyrus, BA 44; and left medial frontal gyrus, BA 6. All three neurocognitive systems shared one common cortical region, the left medial frontal gyrus, the object-naming and integer computation systems shared the left inferior frontal gyrus, and the integer computation and same-different discrimination systems shared the right precentral gyrus. These results are consistent with connectionist models of cognitive processes where specific sets of remote brain areas are assumed to be transiently bound together as functional units to enable these functions, and further suggest a superorganization of neurocognitive systems where single brain areas serve as elements of multiple functional systems.     

难治性癫痫患者脑网络介数及其异常脑区间功能连接变化研究

目的基于图论的分析方法了解难治性癫痫患者脑功能网络介数属性变化,探讨介数异常脑区间功能连接改变的意义。方法采集难治性癫痫患者及健康被试RS-f MRI数据后,通过Gretna中Network Analysis模块预处理并计算出各脑区的介数值,经统计检验找出介数值有差异脑区;运用REST软件将上述脑区作为ROI两两之间做功能连接,经统计检验后找出脑区间差异的连接。结果与对照组相比,癫痫组介数值升高的脑区有右侧额下回三角部、右侧嗅皮质;介数值下降的脑区有右侧额上回背外侧、左侧额上回眶部、左侧前扣带回、右侧颞上回、右侧颞下回;与健康被试相比,额下回三角部与颞上回之间的连接降低。结论难治性癫痫患者脑功能网络介数属性及异常脑区间的功能连接改变,引起脑区间信息交流的障碍,可能导致癫痫患者认知功能的损伤。     

老年抑郁症患者的脑正电子发射体层摄影术显像分析

目的 探讨老年抑郁症患者脑^18氟-脱氧葡萄糖（18^F-FDG）正电子发射体层摄影术（PET）显像的特点。方法 分别对6例老年抑郁症患者（GD组）及10名健康体检者（对照组）进行脑^18 F-FDGPET显像，按年龄、简易智力状态检查量表总分和性别构成配对，用统计参数图第2版软件比较两组间脑局部葡萄糖代谢的差别。结果 GD组较对照组在双侧尾状核、额下回、颞上回、额中回，右侧核外、额上回、舌回和左侧扣带回、中央前回等脑区局部葡萄糖代谢减低（均P〈0．005）。GD组无局部脑葡萄糖代谢增加的脑区。结论 老年抑郁症患者存在基底节区、前额叶、颞叶和边缘系统的局部葡萄糖代谢下降。     

Identification of human gustatory cortex by activation likelihood estimation

Over the last two decades, neuroimaging methods have identified a variety of taste-responsive brain regions. Their precise location, however, remains in dispute. For example, taste stimulation activates areas throughout the insula and overlying operculum, but identification of subregions has been inconsistent. Furthermore, literature reviews and summaries of gustatory brain activations tend to reiterate rather than resolve this ambiguity. Here, we used a new meta-analytic method [activation likelihood estimation (ALE)] to obtain a probability map of the location of gustatory brain activation across 15 studies. The map of activation likelihood values can also serve as a source of independent coordinates for future region-of-interest analyses. We observed significant cortical activation probabilities in: bilateral anterior insula and overlying frontal operculum, bilateral mid dorsal insula and overlying Rolandic operculum, and bilateral posterior insula/parietal operculum/postcentral gyrus, left lateral orbitofrontal cortex (OFC), right medial OFC, pregenual anterior cingulate cortex (prACC) and right mediodorsal thalamus. This analysis confirms the involvement of multiple cortical areas within insula and overlying operculum in gustatory processing and provides a functional "taste map" which can be used as an inclusive mask in the data analyses of future studies. In light of this new analysis, we discuss human central processing of gustatory stimuli and identify topics where increased research effort is warranted.     

Frontal cortex functional connectivity changes during sound categorization

Using functional connectivity analysis of functional magnetic resonance imaging data, we investigated the role of the inferior frontal gyrus in categorization of simple sounds. We found stronger functional connectivity between left inferior frontal gyrus and auditory processing areas in the temporal cortex during categorization of speech (vowels, syllables) and nonspeech (tones, combinations of tones and sweeps) sounds relative to an auditory discrimination task; the hemispheric lateralization varied depending on the speech-like properties of the sounds. Our results attest to the importance of interactions between temporal cortex and left inferior frontal gyrus in sound categorization. Further, we found different functional connectivity patterns between left inferior frontal gyrus and other brain regions implicated in categorization of syllables compared with other stimuli, reflecting the greater facility for categorization of syllables.     

Functional connections between activated and deactivated brain regions mediate emotional interference during externally directed cognition

Recent evidence shows that task‐deactivations are functionally relevant for cognitive performance. Indeed, higher cognitive engagement has been associated with higher suppression of activity in task‐deactivated brain regions ‐ usually ascribed to the Default Mode Network (DMN). Moreover, a negative correlation between these regions and areas actively engaged by the task is associated with better performance. DMN regions show positive modulation during autobiographical, social, and emotional tasks. However, it is not clear how processing of emotional stimuli affects the interplay between the DMN and executive brain regions. We studied this interplay in an fMRI experiment using emotional negative stimuli as distractors. Activity modulations induced by the emotional interference of negative stimuli were found in frontal, parietal, and visual areas, and were associated with modulations of functional connectivity between these task‐activated areas and DMN regions. A worse performance was predicted both by lower activity in the superior parietal cortex and higher connectivity between visual areas and frontal DMN regions. Connectivity between right inferior frontal gyrus and several DMN regions in the left hemisphere was related to the behavioral performance. This relation was weaker in the negative than in the neutral condition, likely suggesting less functional inhibitions of DMN regions during emotional processing. These results show that both executive and DMN regions are crucial for the emotional interference process and suggest that DMN connections are related to the interplay between externally‐directed and internally‐focused processes. Among DMN regions, superior frontal gyrus may be a key node in regulating the interference triggered by emotional stimuli.     

Enhanced salience and emotion recognition in Autism: a PET study

OBJECTIVE: This study examined neural activation of facial stimuli in autism when the salience of emotional cues was increased by prosodic information. METHOD: Regional cerebral blood flow (rCBF) was measured while eight high-functioning men with autism and eight men without autism performed an emotion-recognition task in which facial emotion stimuli were matched with prosodic voices and a baseline gender-recognition task. RESULTS: Emotion processing in autistic subjects, compared to that in comparison subjects, resulted in lower rCBF in the inferior frontal and fusiform areas and higher rCBF in the right anterior temporal pole, the anterior cingulate, and the thalamus. CONCLUSIONS: Even with the enhanced emotional salience of facial stimuli, adults with autism showed lower activity in the fusiform cortex and differed from the comparison subjects in activation of other brain regions. The authors suggested that the recognition of emotion by adults with autism is achieved through recruitment of brain regions concerned with allocation of attention, sensory gating, the referencing of perceptual knowledge, and categorization.     

Regional cerebral blood flow and abnormal eating behavior in Prader–Willi syndrome

Background: Prader–Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder and is generally regarded as a genetic model of obesity. Individuals with PWS exhibit behavioral symptoms including temper tantrums, rigid thinking, and compulsive behavior. The most striking feature of PWS is abnormal eating behavior, including hyperphagia, intense preoccupation with food, and incessant food seeking. To explore brain regions associated with the behavioral symptoms of PWS, we investigated differences in resting-state regional cerebral blood flow (rCBF) between individuals with PWS and healthy controls. Correlation analyses were also performed to examine the relationship between rCBF and altered eating behavior in PWS individuals. Methods: Twelve adults with PWS and 13 age- and gender-matched controls underwent resting-state single photon emission computerized tomography (SPECT) with N-isopropyl-p-[¹²³I] iodoamphetamine (IMP). The rCBF data were analyzed on a voxel-by-voxel basis using SPM5 software. Results: The results demonstrated that compared with controls, individuals with PWS had significantly lower rCBF in the right thalamus, left insular cortex, bilateral lingual gyrus, and bilateral cerebellum. They had significantly higher rCBF in the right inferior frontal gyrus, left middle/inferior frontal gyrus (anterior and posterior clusters), and bilateral angular gyrus. Additionally, rCBF in the left insula, which was significantly lower in PWS individuals, was negatively correlated with the eating behavior severity score. Conclusions: These results suggest that specific brain regions, particularly the left insula, may be partly responsible for the behavioral symptoms in PWS.     

Reappraising the voices of wrath

Cognitive reappraisal recruits prefrontal and parietal cortical areas. Because of the near exclusive usage in past research of visual stimuli to elicit emotions, it is unknown whether the same neural substrates underlie the reappraisal of emotions induced through other sensory modalities. Here, participants reappraised their emotions in order to increase or decrease their emotional response to angry prosody, or maintained their attention to it in a control condition. Neural activity was monitored with fMRI, and connectivity was investigated by using psychophysiological interaction analyses. A right-sided network encompassing the superior temporal gyrus, the superior temporal sulcus and the inferior frontal gyrus was found to underlie the processing of angry prosody. During reappraisal to increase emotional response, the left superior frontal gyrus showed increased activity and became functionally coupled to right auditory cortices. During reappraisal to decrease emotional response, a network that included the medial frontal gyrus and posterior parietal areas showed increased activation and greater functional connectivity with bilateral auditory regions. Activations pertaining to this network were more extended on the right side of the brain. Although directionality cannot be inferred from PPI analyses, the findings suggest a similar frontoparietal network for the reappraisal of visually and auditorily induced negative emotions.     

Cortical activation pattern during saccadic eye movements in humans: localization by focal cerebral blood flow increases.

Regional cerebral blood flow (rCBF) was measured in human subjects during saccadic eye movements by a 254-channel dynamic gamma camera. Focal rCBF increases were repeatedly observed in an area within the middle precentral and premotor regions which corresponds to the frontal eye field in humans. Our findings suggest that this region is localized between the "face" and "hand" areas in the precentral gyrus and extends anteriorly out of the primary motor strip into the adjacent premotor zone. In addition, saccades were associated with focal blood flow increases in regions corresponding to the frontal supplementary motor area and to the posterior temporooccipital visual association cortex. Similar changes in patterns of rCBF occurred during contralateral and ipsilateral horizontal saccades and also during vertical saccades, and did not differ between the right and left hemispheres. Focal rCBF increases were observed in the frontal eye field during several additional test procedures including ocular fixation and visual perception of a nonmoving target, auditory stimulation with closed eyes, and reading. It is presumed that these focal flow increases reflect increased localized neuronal activity and metabolic rate and therefore permit visualization of the cortical activation pattern associated with saccadic eye movements in humans.     

Cortical responses to self and others

The extrastriate body area (EBA) is one among the multiple, functionally specialized regions of the human visual cortex exhibiting modulation by body-related stimuli. Here we investigate whether activation patterns differ for the perception of one's own body and the bodies of others. We used functional magnetic resonance imaging to identify body-related brain areas and to see how these areas differentiate between images of one's own body and those of others in the absence of facial or motion cues. Whole brain explorative group-level analysis identified body-related blood oxygen level dependent (BOLD) signal enhancement in five regions of the right and in one region of the left hemisphere (right: in the extrastriate visual and parietal cortex and in the precentral gyrus, left: in the extrastriate visual cortex). General linear model group-level random effects analysis of the self-other contrast revealed self-related responses in the extrastriate and parietal regions in the right hemisphere but also in the right middle frontal gyrus. These results suggest the existence of a cortical network for the extraction of body-related information and another cortical network for the extraction of self-related body information. The two networks partially overlap in the right superior and inferior parietal cortices, but are clearly segregated in the extrastriate visual cortex and in the middle frontal gyrus. In addition, we report that the classical EBA is only involved in the analysis of body-related information but not in the assignment of body identity. The latter appears to be accomplished by a network in right hemisphere comprising the fusiform body area, regions of the superior parietal lobe, the inferior parietal cortex, and the middle frontal gyrus.     

Functional effects of antipsychotic drugs: comparing clozapine with haloperidol.

BACKGROUND: Using positron emission tomography (PET) with (15)O water, we compared regional cerebral blood flow (rCBF) patterns induced by clozapine or haloperidol in individuals with schizophrenia. Based on the known clinical characteristics of each drug, we hypothesized that brain regions where the drugs show similar rCBF patterns are among those mediating their antipsychotic actions; whereas, regions where the drugs produce different rCBF patterns are among those mediating their different drug actions, namely, haloperidol's motor side effects or clozapine's unique therapeutic action. METHODS: Persons with schizophrenia were scanned using PET with (15)O water, first after withdrawal of all psychotropic medication (n = 6), then again after treatment with therapeutic doses of haloperidol (n = 5) or clozapine (n = 5). RESULTS: Both drugs increased rCBF in the ventral striatum and decreased rCBF in hippocampus and ventrolateral frontal cortex. The rCBF increase associated with haloperidol was greater than that with clozapine in the dorsal and ventral striatum; the rCBF increase with clozapine was greater than that with haloperidol in cortical regions, including anterior cingulate and dorsolateral frontal cortex. CONCLUSIONS: These data suggest that the rCBF increase in ventral striatum and/or the decrease in hippocampus and/or ventrolateral frontal cortex mediate a common component of antipsychotic action of these drugs. The increased rCBF in dorsal striatum by haloperidol could well be associated with its prominent motor side effects, whereas the increased rCBF in the anterior cingulate or dorsolateral frontal cortex may mediate the superior antipsychotic action of clozapine. The proposals based on these preliminary observations require further study.