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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2002

Alterations in trkB mRNA in the human prefrontal cortex throughout the lifespan.

Signalling through tyrosine kinase receptor B (trkB) influences neuronal survival, differentiation and synaptogenesis. trkB exists in a full-length form (trkB(TK+)), which contains a catalytic tyrosine kinase (TK) domain, and a truncated form (trkB(TK-)), which lacks this domain. In the rodent brain, expression of trkB(TK+) decreases and trkBTK- increases during postnatal life. We hypothesized that both forms of trkB receptor mRNA would be present in the human neocortex and that the developmental profile of trkB gene expression in human may be distinct from that in rodent. We detected both trkB(TK+) and trkB(TK-) mRNA in RNA extracted from multiple human brain regions by Northern blot. Using in situ hybridization, we found trkB(TK+) mRNA in all cortical layers, with highest expression in layer IV and intermediate-to-high expression in layers III and V of the human dorsolateral prefrontal cortex. trkB(TK+) mRNA was present in neurons with both pyramidal and nonpyramidal shapes in the dorsolateral prefrontal cortex. trkB(TK+) mRNA levels were significantly increased in layer III in young adults as compared with infants and the elderly. In the elderly, trkB(TK+) mRNA levels were reduced markedly in all cortical layers. Unlike the mRNA encoding the full-length form of trkB, trkB(TK-) mRNA was distributed homogeneously across the grey matter, and trkB(TK-) mRNA levels increased only slightly during postnatal life. The results suggest that neurons in the human dorsolateral prefrontal cortex are responsive to neurotrophins throughout postnatal life and that this responsiveness may be modulated during the human lifespan.

Adolescent↗

PubMed2000

The relationship between dorsolateral prefrontal neuronal N-acetylaspartate and evoked release of striatal dopamine in schizophrenia.

Schizophrenia has been linked to abnormal dopamine function, recently to excessive amphetamine-induced release of striatal dopamine, and also to pathology of prefrontal cortical neurons. It has been hypothesized that prefrontal pathology is a primary condition that leads to dopamine dysregulation. We evaluated in vivo the relationship between neuronal integrity in dorsolateral prefrontal cortex, assessed as N-acetylaspartate (NAA) relative concentrations measured with proton magnetic resonance spectroscopic imaging, and amphetamine-induced release of striatal dopamine, assessed with 11C-raclopride Positron Emission Tomography (PET) in patients with schizophrenia and in healthy subjects. In the patients, NAA measures in dorsolateral prefrontal cortex selectively predicted striatal displacement of 11C-raclopride after amphetamine infusions (rho = -0.76, p < .02). In contrast, NAA measures in other cortical regions and in healthy subjects did not show any correlation. These results support the hypothesis that in schizophrenia neuronal pathology of dorsolateral prefrontal cortex is directly related to abnormal subcortical dopamine function.

Adult↗

PubMed2003

Decreased N-acetylaspartate in children with familial bipolar disorder.

BACKGROUND: Relatively low levels of brain N-acetylaspartate, as measured by magnetic resonance spectroscopy, may indicate decreased neuronal density or viability. Dorsolateral prefrontal levels of N-acetylaspartate have been reported to be decreased in adults with bipolar disorder. We used proton magnetic resonance spectroscopy to investigate dorsolateral prefrontal N-acetylaspartate levels in children with familial bipolar disorder. METHODS: Subjects were 15 children and adolescents with bipolar disorder, who each had at least one parent with bipolar disorder, and 11 healthy controls. Mean age was 12.6 years for subjects and controls. Subjects were allowed to continue current medications. Proton magnetic resonance spectroscopy at 3-Tesla was used to study 8 cm(3) voxels placed in left and right dorsolateral prefrontal cortex. RESULTS: Bipolar subjects had lower N-acetylaspartate/Creatine ratios only in the right dorsolateral prefrontal cortex (p <.02). No differences in myoinositol or choline levels were found. CONCLUSIONS: Children and adolescents with bipolar disorder may have decreased dorsolateral prefrontal N-acetylaspartate, similar to adults with BD, indicating a common neuropathophysiology. Longitudinal studies of at-risk children before the onset and during the early course of bipolar disorder are needed to determine the role of prefrontal N-acetylaspartate as a possible risk marker and/or indication of early bipolar illness progression.

Adolescent↗

PubMed2001

Language switching and language representation in Spanish-English bilinguals: an fMRI study.

The current experiment was designed to investigate the nature of cognitive control in within- and between-language switching in bilingual participants. To examine the neural substrate of language switching we used functional magnetic resonance imaging (fMRI) as subjects named pictures in one language only or switched between languages. Participants were also asked to name (only in English) a separate set of pictures as either the actions or the objects depicted or to switch between these two types of responses on each subsequent picture. Picture naming compared to rest revealed activation in the dorsolateral prefrontal cortex, which extended down into Broca's area in the left hemisphere. There were no differences in the activation pattern for each language. English and Spanish both activated overlapping areas of the brain. Similarly, there was no difference in activation for naming actions or objects in English. However, there was increased intensity of activation in the dorsolateral prefrontal cortex for switching between languages relative to no-switching, an effect which was not observed for naming of actions or objects in English. We suggest that the dorsolateral prefrontal cortex serves to attenuate interference that results from having to actively enhance and suppress two languages in alternation. These results are consistent with the view that switching between languages involves increased general executive processing. Finally, our results are consistent with the view that different languages are represented in overlapping areas of the brain in early bilinguals.

Adult↗

PubMed2001

Increased frontal [(18)F]fluorodopa uptake in early Parkinson's disease: sex differences in the prefrontal cortex.

Previous imaging studies in Parkinson's disease have focused mainly on the striatum, a region with very high dopaminergic activity. Using modern high-sensitivity 3D [(18)F]fluorodopa (Fdopa)-PET, mesocortical monoamine projections can be studied. To study the frontal monoaminergic system in unmedicated early Parkinson's disease in vivo, we examined 20 early Parkinson's disease patients (10 women, 10 men) and 16 healthy subjects (nine women, seven men) with 3D Fdopa-PET, using standard region-of-interest-based analysis with MRI co-registration. Women with Parkinson's disease had 87% higher Fdopa uptake in the right dorsolateral prefrontal cortex (area 46) compared with men with Parkinson's disease, whereas there was no sex difference in the control group (sex x disease interaction, P = 0.03). The uptake in the right dorsolateral prefrontal cortex was 82% higher in men with Parkinson's disease and 219% higher in women with Parkinson's disease compared with control groups (effect of disease, P < 0.0001). Also in the left dorsolateral prefrontal cortex and in the medial frontal cortex, early Parkinson's disease patients had significantly (18-94%) higher Fdopa uptake compared with healthy controls. In the putamen, both men and women with Parkinson's disease had a significantly lower (27-46%) uptake compared with healthy controls. These results indicate that frontal monoaminergic activity is increased and that there is a sex difference in the prefrontal monoaminergic system in early Parkinson's disease. The reported sex difference may be linked to clinical sex differences in the symptoms and treatment response in Parkinson's disease.

Aged↗

PubMed2003

"Change the mind and you change the brain": effects of cognitive-behavioral therapy on the neural correlates of spider phobia.

Questions pertaining to the neurobiological effects of psychotherapy are now considered among the most topical in psychiatry. With respect to this issue, positron emission tomography (PET) findings indicate that cognitive and behavioral modifications, occurring in a psychotherapeutic context, can lead to regional brain metabolic changes in patients with major depression or obsessive-compulsive disorder. The goal of the present functional magnetic resonance imaging (fMRI) study, which constitutes the first neuroimaging investigation of the effects of cognitive-behavioral therapy (CBT) using an emotional activation paradigm, was to probe the effects of CBT on the neural correlates of spider phobia. In order to do so, fMRI was used in subjects suffering from spider phobia (n = 12) to measure, before and after effective CBT, regional brain activity during the viewing of film excerpts depicting spiders. Normal control subjects were also scanned (once) while they were exposed to the same film excerpts. Results showed that, in phobic subjects before CBT, the transient state of fear triggered, during the viewing of the phobogenic stimuli, was correlated with significant activation of the right dorsolateral prefrontal cortex (Brodmann area-BA 10), the parahippocampal gyrus, and the visual associative cortical areas, bilaterally. For normal control subjects (n = 13), only the left middle occipital gyrus and the right inferior temporal gyrus were significantly activated. In phobic subjects before CBT, the activation of the dorsolateral prefrontal cortex (BA 10) may reflect the use of metacognitive strategies aimed at self-regulating the fear triggered by the spider film excerpts, whereas the parahippocampal activation might be related to an automatic reactivation of the contextual fear memory that led to the development of avoidance behavior and the maintenance of spider phobia. After successful completion of CBT, no significant activation was found in the dorsolateral prefrontal cortex (BA 10) or the parahippocampal gyrus. These findings suggest that a psychotherapeutic approach, such as CBT, has the potential to modify the dysfunctional neural circuitry associated with anxiety disorders. They further indicate that the changes made at the mind level, within a psychotherapeutic context, are able to functionally "rewire" the brain.

Adaptation, Psychological↗

PubMed2005

Altered prefrontal dopaminergic function in chronic recreational ketamine users.

OBJECTIVE: Ketamine is a noncompetitive antagonist at the glutamatergic N-methyl-D-aspartate (NMDA) receptor that is used in human and animal medicine as an injectable anesthetic. The illegal use of ketamine as a recreational drug is rapidly growing. Very little is currently known about the consequences of repeated ketamine exposure in the human brain. Animal studies indicate that the prefrontal dopaminergic system is particularly vulnerable to the toxic effects of repeated administration of NMDA antagonists. In this study, dopamine D1 receptor availability was assessed by using positron emission tomography and the selective D1 receptor radioligand [11C]NNC 112 in a group of 14 recreational chronic ketamine users and matched healthy subjects. METHOD: History of ketamine abuse was confirmed in subjects by hair analysis. [11C]NNC 112 binding potential was measured with kinetic analysis using the arterial input function. RESULTS: Dorsolateral prefrontal cortex D1 receptor availability was significantly up-regulated in chronic ketamine users ([11C]NNC 112 binding potential: mean=1.68 ml/g, SD=0.40) relative to comparison subjects (mean=1.35 ml/g, SD=0.35). No significant differences were noted in other cortical, limbic, or striatal regions. In the chronic ketamine user group, dorsolateral prefrontal cortex [11C]NNC 112 binding potential up-regulation was significantly correlated with the number of vials of ketamine (with a vial representing approximately 200-300 mg of ketamine) used per week. CONCLUSIONS: Chronic ketamine users exhibited a regionally selective up-regulation of D1 receptor availability in the dorsolateral prefrontal cortex, a phenomenon observed following chronic dopamine depletion in animal studies. These data suggest that the repeated use of ketamine for recreational purposes affects prefrontal dopaminergic transmission, a system critically involved in working memory and executive function.

Adult↗

PubMed2001

Studies on [3H]CP-55940 binding in the human central nervous system: regional specific changes in density of cannabinoid-1 receptors associated with schizophrenia and cannabis use.

A number of studies suggested that cannabis use can cause or exacerbate psychoses and may increase the risk of developing schizophrenia. These findings suggest that changes in the cannabinoid system of the brain may be involved in the pathology of schizophrenia. To determine whether changes in the cannabinoid system were present in the brains of subjects with schizophrenia, we used in situ radioligand binding and autoradiography to measure the binding of [3H]CP-55940 to the cannabinoid-1 receptor in the dorsolateral prefrontal cortex (Brodmann's area 9), caudate-putamen and areas of the temporal lobe from schizophrenic and control subjects, some of whom had ingested cannabis close to death. There was an increase in the density of [3H]CP-55940 binding to cannabinoid-1 receptors in the dorsolateral prefrontal cortex from subjects with schizophrenia (mean+/-S.E.M.: 142+/-9.9 vs 119+/-6.6fmol/mg estimated tissue equivalents; P<0.05) that was independent of recent cannabis ingestion. There was an increase in the density of cannabinoid-1 receptors in the caudate-putamen from subjects who had recently ingested cannabis (151+/-9.0 vs 123+/-7.2fmol/mg estimated tissue equivalents; P<0.05) that was independent of diagnoses. These data indicate that there are changes in cannabinoid-1 receptors in the dorsolateral prefrontal cortex that may prove to be associated with the pathology of schizophrenia. By contrast, changes in the density of cannabinoid-1 receptors may occur in the caudate-putamen in response to cannabis ingestion.

Brain↗

PubMed2002

Dissociation of working memory processing associated with native and second languages: PET investigation.

Verbal working memory plays a significant role in language comprehension and problem-solving. The prefrontal cortex has been suggested as a critical area in working memory. Given that domain-specific dissociations of working memory may exist within the prefrontal cortex, it is possible that there may also be further functional divisions within the verbal working memory processing. While differences in the areas of the brain engaged in native and second languages have been demonstrated, little is known about the dissociation of verbal working memory associated with native and second languages. We have used H2(15)O positron emission tomography in 14 normal subjects in order to identify the neural correlates selectively involved in working memory of native (Korean) and second (English) languages. All subjects were highly proficient in the native language but poorly proficient in the second language. Cognitive tasks were a two-back task for three kinds of visually presented objects: simple pictures, English words, and Korean words. The anterior portion of the right dorsolateral prefrontal cortex and the left superior temporal gyrus were activated in working memory for the native language, whereas the posterior portion of the right dorsolateral prefrontal cortex and the left inferior temporal gyrus were activated in working memory for the second language. The results suggest that the right dorsolateral prefrontal cortex and left temporal lobe may be organized into two discrete, language-related functional systems. Internal phonological processing seems to play a predominant role in working memory processing for the native language with a high proficiency, whereas visual higher order control does so for the second language with a low proficiency.

Adult↗

PubMed1999

Expression of the myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP) in the prefrontal cortex and hippocampus of suicide victims.

BACKGROUND: Although suicide is a leading cause of death in the United States and represents a significant public health threat, little is known about the neurobiological or molecular factors that contribute to its pathophysiology. A number of studies now indicate that lithium has considerable efficacy in the prevention of suicide in patients with affective disorders, and accumulating evidence indicates that protein kinase C (PKC) and its substrates, in particular the myristoylated alanine-rich C kinase substrate (MARCKS), are primary targets of chronic lithium treatment. We therefore hypothesized that a dysregulation in MARCKS expression in key brain regions could contribute to the pathophysiology associated with suicide. To address this, we examined MARCKS, as well as the closely related MARCKS-related protein (MRP), mRNA expression in the hippocampus and dorsolateral prefrontal cortex of suicide victims and normal controls. METHOD: MARCKS and MRP mRNA expression was assessed by quantitative in situ hybridization histochemistry performed on postmortem hippocampal and dorsolateral prefrontal cortex sections from suicide (N = 9) and normal control (N = 10) brains. RESULTS: In the normal hippocampus, both MARCKS and MRP mRNA expression were highest in the granule cell layer and low-moderate in CA1, CA3, and hilus. A high level of MRP mRNA expression was also observed in the white matter of the fimbria/fornix. Neither MARCKS nor MRP mRNA expression levels differed significantly in the granule cell layer, CA3, hilus, or CA1 in suicide victims relative to normal controls (1-way ANOVA, p > .05). In the normal prefrontal cortex, MARCKS was expressed exclusively in gray matter (layers I-VI), whereas MRP was expressed in both gray and white matter. Neither MARCKS nor MRP mRNA expression levels in the gray and white matter regions of the dorsal prefrontal cortex differed between suicides and normal controls (1-way ANOVA, p > .05). CONCLUSION: The present findings are the first to demonstrate the expression and distribution of MARCKS and MRP in the human hippocampus and dorsolateral prefrontal cortex, and their expression pattern within these regions bears strong resemblance to those observed in the adult rat brain. Comparison of MARCKS and MRP mRNA expression in the hippocampus and prefrontal cortex of suicide victims and normal controls indicates that these 2 mRNAs are not differentially regulated in these regions. However, differences in MARCKS and MRP protein expression and function cannot be ruled out by the present findings.

Adult↗

PubMed2006

Preliminary evidence of differential relations between prefrontal cortex metabolism and sustained attention in depressed adults with bipolar disorder and healthy controls.

OBJECTIVES: To assess the relations between sustained attention as assessed by the Continuous Performance Test (CPT) and subgenual and dorsolateral prefrontal cortex metabolism in depressed patients with bipolar disorders and healthy controls. DESIGN: Cross-sectional case-control design. METHODS: Cerebral metabolic rates were assessed with 18F-fluoro-deoxyglucose and positron emission tomography (PET) in the regions of interest defined on co-registered structural magnetic resonance images in eight medication-free, depressed bipolar disorder patients and 27 healthy control participants. PET scans were obtained in a resting state and the CPT was administered within 1 week of the PET scan. RESULTS: Although there were no statistically significant differences in performance on the CPT or in cerebral metabolism between the two groups, our analyses revealed differential relations between the CPT and metabolism across the groups. Decreased subgenual prefrontal metabolism was associated with slower hit rate reaction time and more omission errors in the bipolar group, but not the control group. Decreased dorsolateral prefrontal metabolism in the bipolar group, but not the control group, was associated with more commission errors. CONCLUSIONS: This study extends previous neuroimaging findings of structural and functional relevance of the prefrontal region with attention to include depressed states in bipolar disorder. The results are consistent with interpretations that decreased prefrontal activity may represent failure to activate some areas of inhibitory control. Decreasing subgenual prefrontal cortex metabolism appears to relate to decreased attention whereas the decreased dorsolateral prefrontal cortex metabolism relates more to decreased inhibitory control.

Adult↗

PubMed2002

Dopaminergic modulation of high-level cognition in Parkinson's disease: the role of the prefrontal cortex revealed by PET.

This study examined the effects of L-dopa medication in patients with Parkinson's disease on cortical and subcortical blood flow changes during two tasks known to involve frontostriatal circuitry. Eleven patients with Parkinson's disease were scanned on two occasions, one ON L-dopa medication and one OFF L-dopa medication, during performance of the Tower of London planning task and a related test that emphasized aspects of spatial working memory. L-dopa-induced decreases were observed in the right dorsolateral prefrontal cortex during performance of both the planning and the spatial working memory tasks compared with the visuomotor control task. Conversely, L-dopa-induced blood flow increases were observed in the right occipital lobe during the memory task relative to the control task. Data from age-matched healthy volunteers demonstrated that L-dopa effectively normalized blood flow in these regions in the patient group. Moreover, a significant correlation was found between L-dopa-induced, planning related blood flow decreases in the right dorsolateral prefrontal cortex and L-dopa-induced changes in performance on the planning task. These data suggest that L-dopa ameliorates high-level cognitive deficits in Parkinson's disease by inducing relative blood flow changes in the right dorsolateral prefrontal cortex.

Brain↗

PubMed2005

Cumulative blood oxygenation-level-dependent signal changes support the 'time accumulator' hypothesis.

We studied time-related changes in the blood oxygenation-level-dependent signal during a time reproduction task. Nine healthy study participants retained and reproduced stimuli of varying durations in the multi-second range. During the encoding phase of the task, activity in the left dorsolateral prefrontal cortex inversely correlated with the interval duration, while an adjacent region in the dorsolateral prefrontal cortex showed positive correlation with duration in the reproduction phase. Cumulative signal increase during the reproduction phase, as found in the primary motor and supplementary motor areas, may also reflect the time-sensitive behavior. Signal accumulation in the right caudate nucleus is in agreement with presumed role of basal ganglia in time perception. These results support the 'time accumulator' hypothesis.

Adult↗

PubMed2006

The emotional power of music: how music enhances the feeling of affective pictures.

Music is an intriguing stimulus widely used in movies to increase the emotional experience. However, no brain imaging study has to date examined this enhancement effect using emotional pictures (the modality mostly used in emotion research) and musical excerpts. Therefore, we designed this functional magnetic resonance imaging study to explore how musical stimuli enhance the feeling of affective pictures. In a classical block design carefully controlling for habituation and order effects, we presented fearful and sad pictures (mostly taken from the IAPS) either alone or combined with congruent emotional musical excerpts (classical pieces). Subjective ratings clearly indicated that the emotional experience was markedly increased in the combined relative to the picture condition. Furthermore, using a second-level analysis and regions of interest approach, we observed a clear functional and structural dissociation between the combined and the picture condition. Besides increased activation in brain areas known to be involved in auditory as well as in neutral and emotional visual-auditory integration processes, the combined condition showed increased activation in many structures known to be involved in emotion processing (including for example amygdala, hippocampus, parahippocampus, insula, striatum, medial ventral frontal cortex, cerebellum, fusiform gyrus). In contrast, the picture condition only showed an activation increase in the cognitive part of the prefrontal cortex, mainly in the right dorsolateral prefrontal cortex. Based on these findings, we suggest that emotional pictures evoke a more cognitive mode of emotion perception, whereas congruent presentations of emotional visual and musical stimuli rather automatically evoke strong emotional feelings and experiences.

Acoustic Stimulation↗

PubMed2005

A systematic investigation of the functional neuroanatomy of auditory and visual phonological processing.

Neuroimaging studies of auditory and visual phonological processing have revealed activation of the left inferior and middle frontal gyri. However, because of task differences in these studies (e.g., consonant discrimination versus rhyming), the extent to which this frontal activity is due to modality-specific linguistic processes or to more general task demands involved in the comparison and storage of stimuli remains unclear. An fMRI experiment investigated the functional neuroanatomical basis of phonological processing in discrimination and rhyming tasks across auditory and visual modalities. Participants made either "same/different" judgments on the final consonant or rhyme judgments on auditorily or visually presented pairs of words and pseudowords. Control tasks included "same/different" judgments on pairs of single tones or false fonts and on the final member in pairs of sequences of tones or false fonts. Although some regions produced expected modality-specific activation (i.e., left superior temporal gyrus in auditory tasks, and right lingual gyrus in visual tasks), several regions were active across modalities and tasks, including posterior inferior frontal gyrus (BA 44). Greater articulatory recoding demands for processing of pseudowords resulted in increased activation for pseudowords relative to other conditions in this frontal region. Task-specific frontal activation was observed for auditory pseudoword final consonant discrimination, likely due to increased working memory demands of selection (ventrolateral prefrontal cortex) and monitoring (mid-dorsolateral prefrontal cortex). Thus, the current study provides a systematic comparison of phonological tasks across modalities, with patterns of activation corresponding to the cognitive demands of performing phonological judgments on spoken and written stimuli.

Acoustic Stimulation↗

PubMed2000

Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia.

BACKGROUND: The pathophysiological characteristics of schizophrenia appear to involve altered synaptic connectivity in the dorsolateral prefrontal cortex. Given the central role that layer 3 pyramidal neurons play in corticocortical and thalamocortical connectivity, we hypothesized that the excitatory inputs to these neurons are altered in subjects with schizophrenia. METHODS: To test this hypothesis, we determined the density of dendritic spines, markers of excitatory inputs, on the basilar dendrites of Golgi-impregnated pyramidal neurons in the superficial and deep portions of layer 3 in the dorsolateral prefrontal cortex (area 46) and in layer 3 of the primary visual cortex (area 17) of 15 schizophrenic subjects, 15 normal control subjects, and 15 nonschizophrenic subjects with a psychiatric illness (referred to as psychiatric subjects). RESULTS: There was a significant effect of diagnosis on spine density only for deep layer 3 pyramidal neurons in area 46 (P = .006). In the schizophrenic subjects, spine density on these neurons was decreased by 23% and 16% compared with the normal control (P = .004) and psychiatric (P = .08) subjects, respectively. In contrast, spine density on neurons in superficial layer 3 in area 46 (P = .09) or in area 17 (P = .08) did not significantly differ across the 3 subject groups. Furthermore, spine density on deep layer 3 neurons in area 46 did not significantly (P = .81) differ between psychiatric subjects treated with antipsychotic agents and normal controls. CONCLUSION: This region- and disease-specific decrease in dendritic spine density on dorsolateral prefrontal cortex layer 3 pyramidal cells is consistent with the hypothesis that the number of cortical and/or thalamic excitatory inputs to these neurons is altered in subjects with schizophrenia.

Adolescent↗

PubMed1998

Hypofrontality and negative symptoms in major depressive disorder.

UNLABELLED: The purpose of the current study was to compare regional cerebral blood flow (rCBF) in patients with major depressive disorder (MDD) to that of healthy subjects and to examine the relationship between rCBF, depressive symptoms (DS) and negative symptoms (NS) in these patients. METHODS: Eleven psychiatric inpatients with diagnosed (MDD) and 15 normal control subjects were administered the scale for the assessment of negative symptoms (SANS) and the modified Hamilton rating scale for depression with items descriptive of NS excluded (HRSD-DS). Each patient underwent a SPECT scan using 99mTc-HMPAO at rest. Cortical and subcortical regions of interest (ROIs) were symmetrically defined in each hemisphere. Cortical-to-cerebellar perfusion ratios were established quantitatively using ADAC software. RESULTS: Subjects in the MDD group had significantly lower rCBF in the frontal cortex and cinglulate gyrus (MANOVA, p = 0.038) due to differences in dorsolateral prefrontal cortex bilaterally (right F = 7.69, p = 0.01; left F = 8.41, p = 0.01) in the right orbitofrontal cortex (F = 6.79, p = 0.02) and in the cingulate gyrus (F = 5.34, p = 0.03). The MDD group also had lower rCBF in the posterior cortical structures (MANOVA, p = 0.072), which was due to decreased perfusion in the right parietal cortex (F = 7.54, p = 0.01). There were negative correlations between the SANS total score and rCBF in both the left dorsolateral prefrontal cortex (Pearson's correlation coefficient r = .-67, p < 0.05) and the left anterior temporal cortex (r = -0.71, p < 0.01) in MDD patients. Additionally, there were positive correlations between HRSD scores and rCBF in the left anterior temporal (r = 0.71, p < 0.01), left dorsolateral prefrontal (r = 0.70, p < 0.01), right frontal (r = 0.82, p < 0.01) and right posterior temporal (r = 0.74, p < 0.01) cortices. Cerebral blood flow was not correlated with either mini-mental state examination scores or age. CONCLUSION: This preliminary study replicates the finding of hypofrontality in MDD and indicates that decreased perfusion is associated specifically with negative symptom severity. These results support the hypothesis that, in MDD, negative symptoms and symptoms of depression are distinct phenomena and underscore the importance of negative symptom evaluation in neuroimaging studies of MDD and other disorders.

Adult↗

PubMed2000

Adolescent neuropsychological development after early right prefrontal cortex damage.

Adolescent development and pattern of recovery are described for a 15-year-old boy who sustained extensive right dorsolateral prefrontal cortex damage at age 7 from rupture and surgical treatment of a deep arteriovenous malformation. Follow-up evaluations at 4 years and most recently 8 years after illness have shown clear improvement in social-behavioral and almost all cognitive areas initially assessed. He demonstrated resolution of left hemispatial neglect and other visuospatial impairments in working memory, design fluency, and planning and organization. However, at the 8-year follow-up interval, an acquired form of attention deficit disorder remains evident. We hypothesized that this is the likely cause of comparatively lower scores in general intelligence, verbal learning and memory, discourse, and processing speed, that at the 4-year follow-up interval. New measures of emotional face and voice recognition showed only minor difficulties, principally in identifying vocal disgust and fear. Social and psychological maturation has continued to improve, with no evidence of developmental arrest or pervasive social impairment, although the individual is confused at times by complexities and nuances of social interaction. The pattern of findings 8 years after early right dorsolateral prefrontal cortex damage suggests remarkable recovery of primary visuospatial and social impairments, but lingering and somewhat worsening performance deficits which may be due to attentional difficulties and impulsive responding. Treatment of the attentional difficulties is currently being investigated.

Adolescent↗