RESUMO
RATIONALE: After alcohol ingestion, the brain partly switches from consumption of glucose to consumption of the alcohol metabolite acetate. In heavy drinkers, the switch persists after abrupt abstinence, leading to the hypothesis that the resting brain may be "starved" when acetate levels suddenly drop during abstinence, despite normal blood glucose, contributing to withdrawal symptoms. We hypothesized that ketone bodies, like acetate, could act as alternative fuels in the brain and alleviate withdrawal symptoms. OBJECTIVES: We previously reported that a ketogenic diet during alcohol exposure reduced acute withdrawal symptoms in rats. Here, our goals were to test whether (1) we could reproduce our findings, in mice and with longer alcohol exposure; (2) ketone bodies alone are sufficient to reduce withdrawal symptoms (clarifying mechanism); (3) introduction of ketogenic diets at abstinence (a clinically more practical implementation) would also be effective. METHODS: Male C57BL/6NTac mice had intermittent alcohol exposure for 3 weeks using liquid diet. Somatic alcohol withdrawal symptoms were measured as handling-induced convulsions; anxiety-like behavior was measured using the light-dark transition test. We tested a ketogenic diet, and a ketone monoester supplement with a regular carbohydrate-containing diet. RESULTS: The regular diet with ketone monoester was sufficient to reduce handling-induced convulsions and anxiety-like behaviors in early withdrawal. Only the ketone monoester reduced handling-induced convulsions when given during abstinence, consistent with faster elevation of blood ketones, relative to ketogenic diet. CONCLUSIONS: These findings support the potential utility of therapeutic ketosis as an adjunctive treatment in early detoxification in alcohol-dependent patients seeking to become abstinent. TRIAL REGISTRATION: clinicaltrials.gov NCT03878225, NCT03255031.
Assuntos
Alcoolismo/metabolismo , Dieta Cetogênica , Corpos Cetônicos/metabolismo , Cetonas/uso terapêutico , Síndrome de Abstinência a Substâncias/prevenção & controle , Alcoolismo/sangue , Animais , Ansiedade/tratamento farmacológico , Encéfalo/metabolismo , Ensaios Clínicos como Assunto , Suplementos Nutricionais , Etanol/administração & dosagem , Etanol/efeitos adversos , Etanol/sangue , Glucose , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Síndrome de Abstinência a Substâncias/metabolismo , Síndrome de Abstinência a Substâncias/psicologiaRESUMO
Musical expertise is associated with structural and functional changes in the brain that underlie facilitated auditory perception. We investigated whether the phase locking (PL) and amplitude modulations (AM) of neuronal oscillations in response to musical chords are correlated with musical expertise and whether they reflect the prototypicality of chords in Western tonal music. To this aim, we recorded magnetoencephalography (MEG) while musicians and non-musicians were presented with common prototypical major and minor chords, and with uncommon, non-prototypical dissonant and mistuned chords, while watching a silenced movie. We then analyzed the PL and AM of ongoing oscillations in the theta (4-8 Hz) alpha (8-14 Hz), beta- (14-30 Hz) and gamma- (30-80 Hz) bands to these chords. We found that musical expertise was associated with strengthened PL of ongoing oscillations to chords over a wide frequency range during the first 300 ms from stimulus onset, as opposed to increased alpha-band AM to chords over temporal MEG channels. In musicians, the gamma-band PL was strongest to non-prototypical compared to other chords, while in non-musicians PL was strongest to minor chords. In both musicians and non-musicians the long-latency (> 200 ms) gamma-band PL was also sensitive to chord identity, and particularly to the amplitude modulations (beats) of the dissonant chord. These findings suggest that musical expertise modulates oscillation PL to musical chords and that the strength of these modulations is dependent on chord prototypicality.
Assuntos
Percepção Auditiva , Encéfalo/fisiologia , Música , Estimulação Acústica , Adolescente , Adulto , Potenciais Evocados Auditivos , Humanos , Magnetoencefalografia , Masculino , Adulto JovemRESUMO
Enkephalins are active in regulation of nociception in the body and are key in development of new synthetic peptide analogs that target centrally located opioid receptors. In this study, we investigated the in vivo blood-brain barrier (BBB) penetration behavior and antinociceptive activity of two cyclic enkephalin analogs with a thiourea (CycS) or a N-methyl-guanidine bridge (CycNMe), and their linear counterparts (LinS and LinNMe) in mice, as well as their in vitro metabolic stability. (125)I-LinS had the highest blood-brain clearance (K1=3.46µL/gmin), followed by (125)I-LinNMe, (125)I-CycNMe, and (125)I-CycS (K1=1.64, 0.31, and 0.11µL/gmin, respectively). Also, these peptides had a high metabolic stability (t1/2>1h) in mouse serum and brain homogenate, and half-inhibition constant (Ki) values in the nanomolar range with predominantly µ-opioid receptor selectivity. The positively charged NMe-enkephalins showed a higher antinociceptive activity (LinNMe: 298% and CycNMe: 205%), expressed as molar-dose normalized area under the curve (AUC) relative to morphine, than the neutral S-enkephalins (CycS: 122% and LinS: 130%).
Assuntos
Analgésicos/farmacocinética , Barreira Hematoencefálica/metabolismo , Encefalinas/farmacocinética , Metilguanidina/análogos & derivados , Metilguanidina/farmacocinética , Tioureia/análogos & derivados , Tioureia/farmacocinética , Analgésicos/administração & dosagem , Animais , Área Sob a Curva , Avaliação Pré-Clínica de Medicamentos , Encefalinas/administração & dosagem , Meia-Vida , Concentração Inibidora 50 , Injeções Intraventriculares , Masculino , Metilguanidina/administração & dosagem , Camundongos Endogâmicos ICR , Nociceptividade/efeitos dos fármacos , Dor Nociceptiva/tratamento farmacológico , Ratos Wistar , Tioureia/administração & dosagemRESUMO
OBJECTIVE: This study aimed to test the hypothesis that sacral nerve stimulation affects afferent vagal projections to the central nervous system associated with frontal cortex activation in patients with fecal incontinence. PATIENTS: Nine women and one man received temporary sacral nerve stimulation with permanent electrodes as a treatment for fecal incontinence. INTERVENTIONS: We used positron emission tomography to record indices of regional cerebral blood flow before and after 30 minutes of continuous stimulation. We repeated this procedure after 2 weeks of continued stimulation, before and 30 minutes after arrest of the stimulation. RESULTS: The initial stimulation activated a region of the contralateral frontal cortex that normally is active during focused attention. After 2 weeks of stimulation, this activation had been replaced by activity in parts of the ipsilateral caudate nucleus, a region of the brain thought to be specifically involved in learning and reward processing. CONCLUSIONS: Sacral nerve stimulation induces changes in cerebral activity consistent with an effect on afferent projections of the vagus. The initial activation of the frontal cortex may reflect focused attention, whereas the subsequent activation of the caudate nucleus may reflect recruitment of mechanisms involved in learning and reward processing. These changes may contribute to the improved continence, which is an acquired result of the stimulation.
Assuntos
Terapia por Estimulação Elétrica , Incontinência Fecal/terapia , Lobo Frontal/fisiopatologia , Plexo Lombossacral , Adulto , Idoso , Circulação Cerebrovascular/fisiologia , Estudos de Coortes , Eletrodos Implantados , Incontinência Fecal/diagnóstico por imagem , Incontinência Fecal/etiologia , Feminino , Lobo Frontal/irrigação sanguínea , Lobo Frontal/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Radiografia , Resultado do TratamentoRESUMO
Musical competence may confer cognitive advantages that extend beyond processing of familiar musical sounds. Behavioural evidence indicates a general enhancement of both working memory and attention in musicians. It is possible that musicians, due to their training, are better able to maintain focus on task-relevant stimuli, a skill which is crucial to working memory. We measured the blood oxygenation-level dependent (BOLD) activation signal in musicians and non-musicians during working memory of musical sounds to determine the relation among performance, musical competence and generally enhanced cognition. All participants easily distinguished the stimuli. We tested the hypothesis that musicians nonetheless would perform better, and that differential brain activity would mainly be present in cortical areas involved in cognitive control such as the lateral prefrontal cortex. The musicians performed better as reflected in reaction times and error rates. Musicians also had larger BOLD responses than non-musicians in neuronal networks that sustain attention and cognitive control, including regions of the lateral prefrontal cortex, lateral parietal cortex, insula, and putamen in the right hemisphere, and bilaterally in the posterior dorsal prefrontal cortex and anterior cingulate gyrus. The relationship between the task performance and the magnitude of the BOLD response was more positive in musicians than in non-musicians, particularly during the most difficult working memory task. The results confirm previous findings that neural activity increases during enhanced working memory performance. The results also suggest that superior working memory task performance in musicians rely on an enhanced ability to exert sustained cognitive control. This cognitive benefit in musicians may be a consequence of focused musical training.
Assuntos
Vias Auditivas , Cognição , Memória , Música , Estimulação Acústica , Adulto , Feminino , Humanos , Masculino , Rede Nervosa , Análise de RegressãoRESUMO
Cochlear implants (CIs) provide impressive speech perception for persons with severe hearing loss, but many CI recipients fail in perceiving speech prosody and music. Successful rehabilitation depends on cortical plasticity in the brain and postoperative measures. The present study evaluates the behavioral and neurologic effects of musical ear training on CI users' speech and music perception. The goal is to find and work out musical methods to improve CI users' auditory capabilities and, in a longer perspective, provide an efficient strategy for improving speech understanding for both adults and children with CIs.
Assuntos
Córtex Cerebral/fisiologia , Implante Coclear , Musicoterapia/métodos , Plasticidade Neuronal/fisiologia , Percepção da Fala/fisiologia , Ensaios Clínicos como Assunto , Estudos Cross-Over , Humanos , Percepção da Altura Sonora/fisiologia , Tomografia por Emissão de PósitronsRESUMO
To test the hypothesis that deep brain stimulation of the subthalamic nucleus (STN) restores the inhibitory output to the striatothalamocortical loop in Parkinson's disease, we obtained functional brain images of blood flow in 10 STN-stimulated patients with Parkinson's disease. Patients were immobile and off antiparkinsonian medication for 12 h. They were scanned with and without bilateral STN-stimulation with a 4-h interval between the two conditions. The order of DBS stimulation (ON or OFF) was randomized. Stimulation significantly raised regional cerebral blood flow (rCBF) bilaterally in the STN and in the left nucleus lentiformis. Conversely, flow declined in the left supplementary motor area (BA 6), ventrolateral nucleus of the left thalamus, and right cerebellum. Activation of the basal ganglia and deactivation of supplementary motor area and thalamus were both correlated with the improvement of motor function. The result is consistent with the explanation that stimulation in resting patients raises output from the STN with activation of the inhibitory basal ganglia output nuclei and subsequent deactivation of the thalamic anteroventral and ventrolateral nuclei and the supplementary motor area.
Assuntos
Corpo Estriado/fisiologia , Terapia por Estimulação Elétrica/métodos , Córtex Motor/fisiologia , Doença de Parkinson/terapia , Núcleo Subtalâmico/fisiologia , Núcleos Ventrais do Tálamo/fisiologia , Adulto , Idoso , Circulação Cerebrovascular/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Globo Pálido/anatomia & histologia , Globo Pálido/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/anatomia & histologia , Inibição Neural/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Doença de Parkinson/fisiopatologia , Resultado do Tratamento , Regulação para Cima/fisiologia , Núcleos Ventrais do Tálamo/anatomia & histologiaRESUMO
Goal-directed behavior lowers activity in brain areas that include the medial frontal cortex, the medial and lateral parietal cortex, and limbic and paralimbic brain regions, commonly referred to as the "default network." These activity decreases are believed to reflect the interruption of processes that are ongoing when the mind is in a restful state. Previously, the nature of these processes was probed by varying cognitive task parameters, but the presence of emotional processes, while often assumed, was little investigated. With fMRI, we studied the effect of systematic variations of both cognitive load and emotional stimulus connotation on task-related decreases in the default network by employing an auditory working memory (WM) task with musical sounds. The performance of the WM task, compared to passive listening, lowered the activity in medial and lateral, prefrontal, parietal, temporal, and limbic regions. In a subset of these regions, the magnitude of decrease depended on the memory load; the greater the cognitive load, the larger the magnitude of the observed decrease. Furthermore, in the right amygdala and the left precuneus, areas previously associated with processing of unpleasant dissonant musical sounds, there was an interaction between the experimental condition and the stimulus type. The current results are consistent with the previously reported effect of task difficulty on task-related brain activation decreases. The results also indicate that task-related decreases may be further modulated by the emotional stimulus connotation.
Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Cognição/fisiologia , Emoções/fisiologia , Estimulação Acústica/métodos , Adulto , Análise de Variância , Percepção Auditiva/fisiologia , Encéfalo/irrigação sanguínea , Feminino , Lateralidade Funcional/fisiologia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Memória de Curto Prazo/fisiologia , Música , Vias Neurais/irrigação sanguínea , Vias Neurais/fisiologia , Testes Neuropsicológicos , Oxigênio/sangue , Tempo de Reação/fisiologia , Inquéritos e Questionários , Adulto JovemRESUMO
Electrical stimulation with a transtympanic electrode on the promontory of the middle ear allows the tasks of gap detection and temporal difference limen (TDL) to be carried out by both normally hearing and deaf subjects. Previous neuroimaging of normally hearing subjects revealed a region in the right posterior temporal lobe that is crucial to duration discrimination. The present study tested the hypothesis that postlingually deaf subjects recruit this area when they make subtle temporal discriminations. Fourteen postlingually deaf adult cochlear implant candidates were stimulated in the ear chosen for implantation. Altered cerebral activity was recorded with positron emission tomography as incremental 15-O-labelled water uptake. On stimulation with tone bursts, we found bilateral activity close to the primary auditory cortex in all subjects. However, subjects performing well on the TDL task demonstrated right-lateralized fronto-temporal and left-lateralized temporal activity in the respective TDL and gap-detection tasks, while subjects who failed to detect duration differences of less than 200 ms in the TDL discrimination task only had frontal and occipital rather than temporal lobe activation. We conclude that the ability to involve the right posterior temporal region is important to duration discrimination. This ability can be evaluated pre-operatively.
Assuntos
Estimulação Acústica/métodos , Córtex Auditivo/fisiopatologia , Surdez/fisiopatologia , Percepção da Fala , Adulto , Idoso , Córtex Auditivo/diagnóstico por imagem , Cóclea/fisiopatologia , Cóclea/cirurgia , Surdez/diagnóstico , Surdez/diagnóstico por imagem , Orelha Média/fisiopatologia , Estimulação Elétrica/instrumentação , Estimulação Elétrica/métodos , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de EmissãoRESUMO
On the basis of anatomical and physiological data obtained on animal models, we recently proposed that neurons in the main visual extrageniculate nuclei complex, the pulvinar, are actively involved in higher-order visual processing. Pulvinar neurons have been shown to integrate the component signals of a plaid pattern into a coherent global percept (pattern-motion selectivity). Using positron emission tomography (PET), we have investigated the possibility that the human pulvinar is also involved in plaid-defined higher-order motion integration. Plaid patterns were presented to normal observers in two conditions (coherent vs. transparent) created by varying the relative spatial frequency of the two gratings comprising the plaid. Regions of interest analysis revealed a significant activation of the pulvinar in the coherent condition supporting the notion that the human pulvinar nucleus is involved in higher-order motion processing. Plaid pattern activation was also observed in the medial temporal gyrus (area MT/V5), a motion area with strong anatomical connections to the pulvinar. These data provide the first direct evidence that the human pulvinar is involved in complex motion integration, as previously shown in animal models, and further support the existence of cortico-thalamo-cortical computational networks involved in higher-order visual processing.
Assuntos
Percepção de Movimento/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Pulvinar/fisiologia , Adulto , Feminino , Humanos , Masculino , Estimulação Luminosa , Tomografia por Emissão de Pósitrons , Pulvinar/anatomia & histologia , Pulvinar/diagnóstico por imagem , Lobo Temporal/fisiologia , Tálamo/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologiaRESUMO
Musicians exchange non-verbal cues as messages when they play together. This is particularly true in music with a sketchy outline. Jazz musicians receive and interpret the cues when performance parts from a regular pattern of rhythm, suggesting that they enjoy a highly developed sensitivity to subtle deviations of rhythm. We demonstrate that pre-attentive brain responses recorded with magnetoencephalography to rhythmic incongruence are left-lateralized in expert jazz musicians and right-lateralized in musically inept non-musicians. The left-lateralization of the pre-attentive responses suggests functional adaptation of the brain to a task of communication, which is much like that of language.
Assuntos
Estimulação Acústica , Mapeamento Encefálico/métodos , Encéfalo/fisiologia , Música , Encéfalo/anatomia & histologia , Fenômenos Cronobiológicos , Comunicação , Humanos , Reprodutibilidade dos TestesRESUMO
Musicians and nonmusicians listened to major, minor, and dissonant musical chords while their BOLD brain responses were registered with functional magnetic resonance imaging. In both groups of listeners, minor and dissonant chords, compared with major chords, elicited enhanced responses in several brain areas, including the amygdala, retrosplenial cortex, brain stem, and cerebellum, during passive listening but not during memorization of the chords. The results indicate that (1) neural processing in emotion-related brain areas is activated even by single chords, (2) emotion processing is enhanced in the absence of cognitive requirements, and (3) musicians and nonmusicians do not differ in their neural responses to single musical chords during passive listening.
Assuntos
Emoções , Imageamento por Ressonância Magnética/métodos , Música , Estimulação Acústica , Adulto , Percepção Auditiva , Encéfalo/patologia , Mapeamento Encefálico , Cognição , Feminino , Humanos , Masculino , Modelos Neurológicos , Neurônios/patologia , Discriminação da Altura TonalRESUMO
3,4-Methylenedioxymethamphetamine (MDMA) acutely releases intraneuronal dopamine and serotonin and evokes hyperthermia which is linked to toxicity for serotonin fibers. The acute effects of MDMA on cerebral blood flow (CBF) in living brain have not been described in an animal model of MDMA intoxication. We predicted that MDMA-induced hyperthermia should correlate with increased CBF in the hypothalamus, a serotonin-rich brain region subserving thermoregulation. To test this prediction, we used positron emission tomography with statistical parametric mapping for exploratory analysis of the focal changes in the magnitude of CBF in the anesthetized female Landrace pig (n = 9) at 30 and 150 min after acute challenge with MDMA-HCl (1 mg/kg, i.v.). The MDMA treatment was followed by increased CBF in the occipital cortex and in the medial mesencephalon overlapping the dorsal raphé nucleus, and reduced CBF in the cerebellar vermis and in a cluster in the medulla encompassing the left locus coeruleus. The individual increase of body temperature correlated positively with increased CBF in the vicinity of the raphé nucleus, in the hypothalamus (regions linked to thermoregulation), and also in the medial frontal cortex, which together comprise the regions receiving the most dense serotonin innervations in pig brain. Thus, individual differences in the susceptibility to MDMA-induced hyperthermia in this population correlated with the magnitude of focal increases in CBF within specific brain regions endowed with a dense serotonin innervation, including regions linked to thermoregulation.
Assuntos
Encéfalo/efeitos dos fármacos , Artérias Cerebrais/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Febre/induzido quimicamente , N-Metil-3,4-Metilenodioxianfetamina/farmacologia , Sus scrofa/fisiologia , Animais , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Artérias Cerebrais/diagnóstico por imagem , Artérias Cerebrais/fisiologia , Circulação Cerebrovascular/fisiologia , Modelos Animais de Doenças , Feminino , Febre/fisiopatologia , Hipotálamo/irrigação sanguínea , Hipotálamo/diagnóstico por imagem , Hipotálamo/efeitos dos fármacos , Córtex Pré-Frontal/irrigação sanguínea , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/efeitos dos fármacos , Terminações Pré-Sinápticas/efeitos dos fármacos , Terminações Pré-Sinápticas/metabolismo , Núcleos da Rafe/irrigação sanguínea , Núcleos da Rafe/diagnóstico por imagem , Núcleos da Rafe/efeitos dos fármacos , Serotonina/metabolismo , Sus scrofa/anatomia & histologia , Tomografia Computadorizada de EmissãoRESUMO
The Stroop test (ST) assesses the integrity of prefrontal and cingulate functioning. Patients with major depression perform poorly on the ST, pointing to disturbed function in these areas. We therefore used positron emission tomography to study 41 in-patients with major depression and 46 age- and gender-matched controls during neuropsychological activation with the ST. Magnetic resonance imaging was used for coregistration and for description of the localization of white matter lesions (WML). The cerebral blood flow (CBF) changes during ST were mapped for each of the two study groups, and inter-group differences were calculated on a voxel-by-voxel basis. The patients were followed for 3 to 5 years to ensure diagnostic stability. The control group activated anterior cingulate regions, prefrontal cortices, insula, thalamus and cerebellum. Despite the patients' slower performance with more errors, no significant differences were found comparing the activations in the two groups. The performance was, however, correlated to the number of WML in frontal lobes, insula and adjacent to the basal ganglia, whereas WML in other locations was not related to performance. We thus partly explain the poorer performance by increased frequency of WML in frontostriatal pathways in the depressed patients, impairing neurotransmission.
Assuntos
Atenção/fisiologia , Encéfalo/fisiopatologia , Percepção de Cores , Doenças Desmielinizantes/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Aprendizagem por Discriminação/fisiologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Leitura , Semântica , Tomografia Computadorizada de Emissão , Adulto , Mapeamento Encefálico , Cerebelo/fisiopatologia , Córtex Cerebral/fisiopatologia , Corpo Estriado/fisiopatologia , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/psicologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Feminino , Lobo Frontal/fisiopatologia , Giro do Cíngulo/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Tempo de Reação/fisiologia , Valores de Referência , Fluxo Sanguíneo Regional/fisiologia , Transmissão Sináptica/fisiologia , Tálamo/fisiopatologiaRESUMO
The negative slow wave (NSW) is a late component of the event-related potential (ERP) in man modulated like the P300 by the stimulus, the task, and the response demand. Aiming at the development of a minipig model of schizophrenia, we investigated scalp ERPs in an auditory P300 paradigm in six Göttingen minipigs. Before training, we observed no difference between target and nontarget NSW. After training, target NSW amplitude was increased 50% compared to nontarget. A P350 was recognized, but the finding of a lack of target/nontarget difference is not conclusive.
Assuntos
Eletroencefalografia , Potenciais Evocados P300/fisiologia , Estimulação Acústica , Animais , Aprendizagem por Discriminação/fisiologia , Discriminação Psicológica/fisiologia , Potenciais Evocados Auditivos/fisiologia , Masculino , Suínos , Porco MiniaturaRESUMO
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.