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PubMed2003

Neural substrates of decision making in adults with attention deficit hyperactivity disorder.

OBJECTIVE: The characteristics of attention deficit hyperactivity disorder (ADHD) include abnormalities in reward responsivity that may interfere with decision making. The study examined reward responsivity in ADHD by comparing the neural correlates of decision making in adults with childhood-onset ADHD and in healthy adults. METHOD: The neural correlates of performance on a decision-making task and a control task were compared in 10 adults with ADHD and 12 age-matched healthy volunteers by using [(15)O]H(2)O positron emission tomography. The decision-making task tested the ability to weigh short-term rewards against long-term losses. The control task matched all components of the decision-making task except for the decision-making process and related contingency. RESULTS: The ventral and dorsolateral prefrontal cortex and the insula were activated during performance of the decision-making task in both the ADHD and healthy groups; however, activation in the ADHD group was less extended and did not involve other regions, such as anterior cingulate and hippocampus, that subserve emotion/memory processes. Direct comparison of data from the ADHD subjects and the healthy volunteers suggested that the healthy subjects engaged the hippocampal and insular regions more than did the ADHD subjects and that the ADHD subjects recruited the caudal part of the right anterior cingulate more than did the healthy subjects. CONCLUSIONS: The findings suggest that the neural circuits engaged during decision making differ in subjects with ADHD and healthy comparison subjects. This difference may explain observed deficits in motivated behaviors in ADHD. A better understanding of the nature of these deficits could ultimately be applied to refine treatment strategies for ADHD.

Adult↗
PubMed2006

Cellular basis of reduced cortical reelin expression in schizophrenia.

OBJECTIVE: The authors' goals were to establish the cellular origin of the reduced cortical reelin expression that occurs in schizophrenia and to relate it to markers of synaptic pathology. METHOD: In situ hybridization was used to quantify reelin mRNA in the hippocampal formation and dorsolateral prefrontal cortex of brains from 13 subjects with schizophrenia and 12 subjects without schizophrenia. Results were correlated with the expression of three synaptic protein genes in the dentate gyrus. RESULTS: Reelin mRNA was expressed by layer I neurons, interneurons, and interstitial white matter neurons. In subjects with schizophrenia, less reelin mRNA was expressed by interstitial white matter neurons in the hippocampal formation and by all three cell types in the prefrontal cortex. Reelin and synaptic protein expression correlated positively. CONCLUSIONS: Interstitial white matter neurons, presumed remnants of the cortical subplate, contribute to the reduction in reelin mRNA in schizophrenia. Down-regulation of reelin expression may in turn contribute to the synaptic pathology of the disorder.

Cell Adhesion Molecules, Neuronal↗
PubMed2001

Dissociative flashbacks after right frontal injury in a vietnam veteran with combat-related posttraumatic stress disorder.

A Vietnam veteran with a combat-related posttraumatic stress disorder developed recurrent dissociative flashbacks (related to the atrocities of a specific war incident) several months after suffering a traumatic brain injury. CT disclosed a small lesion in the right dorsolateral prefrontal cortex. SPECT demonstrated more extensive functional changes in prefrontal and anterior paralimbic brain regions, mainly in the right hemisphere. This case further implicates the provocative effect of physical stimuli (brain damage) in reawakening old dormant memories and the preferential role of the right hemisphere for the storage of traumatic memories.

Brain Mapping↗
PubMed2001

Psychiatric symptoms associated with cortical-subcortical dysfunction in Alzheimer's disease.

Positron emission tomography was used to evaluate 3 Alzheimer's disease (AD) patients: 1 with major depression, 1 with emotional lability, and 1 with apathy. Compared with 5 non-mood-disordered AD patients, the patient with depression had diminished relative regional cerebral blood flow (rel-CBF) in the anterior cingulate and superior temporal cortices, bilaterally. This patient also showed diminished rel-CBF in the left dorsolateral prefrontal and right medial temporal and parietal cortices. The patient with emotional lability had diminished rel-CBF in the anterior cingulate and dorsolateral prefrontal cortices, bilaterally, and left basal ganglia. The patient with apathy had diminished rel-CBF in the basal ganglia and dorsolateral prefrontal cortex, bilaterally. Results are consistent with the hypothesis of a common frontal-temporal-subcortical substrate (e.g., involving aminergic nuclei) in the etiology of depression in AD. Frontal-subcortical dysfunction may also be associated with emotional lability and apathy in AD, although these may be related to a greater involvement of frontal-basal ganglia circuits.

Affect↗
PubMed2003

No evidence of a homogeneous frontal neuropsychological profile in a sample of schizophrenic subjects.

The authors obtained a frontal functions profile for 81 schizophrenic patients using six neuropsychological tests that evaluate the dorsolateral prefrontal cortex functions, i.e., working memory, executive functions, and strategic performance. They then analyzed the test performances with a cluster analysis, which produced a four-cluster solution. The results support the hypothesis that neuropsychological dysfunctions in schizophrenia are heterogeneous. The performances on many of the neuropsychological tests were also strongly correlated with verbal and nonverbal IQ, as measured by the Wechsler Adult Intelligence Scale-Revised.

Adult↗
PubMed1992

Cerebral blood flow and mental processes in schizophrenia.

The patterns of cerebral blood flow associated with three syndromes of schizophrenic symptoms are compared with the loci of cerebral activation in normal subjects during the performance of mental processes implicated in the three syndromes. The psychomotor poverty syndrome, which has been shown to involve a diminished ability to generate words, is associated with decreased perfusion of the dorsolateral prefrontal cortex at a locus which is activated in normal subjects during the internal generation of words. The disorganization syndrome, which has been shown to involve impaired suppression of inappropriate responses (eg in the Stroop test), is associated with increased perfusion of the right anterior cingulate gyrus at a location activated in normal subjects performing the Stroop test. The reality distortion syndrome, which evidence suggests arises from disordered internal monitoring of activity, is associated with increased perfusion in the medial temporal lobe at a locus activated in normal subjects during the internal monitoring of eye movements.

Adult↗
PubMed2003

Electrophysiology of the frontal lobe.

The electrophysiology of the frontal lobe appears to be unimpressive when the view is limited to the routine EEG recording of a healthy waking adult. There is usually low voltage fast activity, which becomes more pronounced when recorded with depth leads. Three special EEG patterns of marginal to slightly abnormal character are discussed: a) rhythmical midfrontal 6-7/sec activity of juveniles, b) rhythmical midfrontal sharp 4-6/sec activity of infancy and early childhood with arousal from sleep, and c) frontal intermittent rhythmical delta activity (FIRDA) in waking adults with frontopolar maximum, possibly related to thought processes under abnormal conditions. With extension of the frequency range, ultraslow (DC-like) as well as fast beta (gamma, 40-80/sec) and ultrafast activity (80-1000/sec) are found particularly over the frontal lobes. Ultraslow baseline shifts are arousal-related and mixed with overlying ultrafast waves. Attention control and the "working memory" involve chiefly the dorsolateral prefrontal cortex, investigated with P300 responses and likely to show ultrafast spectra. Perception-related 40-80/sec gamma activity has been thought to be associated with the entrance into consciousness. Initiation and design of motor activity spreads from prefrontal to the frontomotor cortex, associated with powerful event-related potentials: contingent negative variation (CNV) and "Bereitschafts potential" ("readiness potential," RP). Neuroscientific research of the highest frontal lobe functions has become a very active domain of neuroimaging. With the use of the extended frequency range, EEG and also evoked potential studies could add further information with acquisition in real time. Ultrafast frequency ranges presented in computerized frequency analysis and mapping might show impressive correlates of highest frontal lobe functions.

Arousal↗
PubMed2006

Widespread sensorimotor and frontal cortical atrophy in Amyotrophic Lateral Sclerosis.

BACKGROUND: Widespread cortical atrophy in Amyotrophic Lateral Sclerosis (ALS) has been described in neuropathological studies. The presence of cortical atrophy in conventional and scientific neuroimaging has been a matter of debate. In studies using computertomography, positron emission tomography, proton magnetic resonance spectroscopy and conventional T2-weighted and proton-weighted images, results have been variable. Recent morphometric studies by magnetic resonance imaging have produced conflicting results regarding the extent of grey and white matter involvement in ALS patients. METHODS: The authors used optimized voxel-based morphometry as an unbiased whole brain approach to detect differences between regional grey and white matter volumes. Seventeen patients with a diagnosis of ALS according to El-Escorial criteria and seventeen age-matched controls received a high resolution anatomical T1 scan. RESULTS: In ALS patients regional grey matter volume (GMV) reductions were found in the pre- and postcentral gyrus bilaterally which extended to premotor, parietal and frontal regions bilaterally compared with controls (p < 0.05, corrected for the entire volume). The revised ALS functional rating scale showed a positive correlation with GMV reduction of the right medial frontal gyrus corresponding to the dorsolateral prefrontal cortex. No significant differences were found for white matter volumes or when grey and white matter density images were investigated. There were no further correlations with clinical variables found. CONCLUSION: In ALS patients, primary sensorimotor cortex atrophy can be regarded as a prominent feature of the disease. Supporting the concept of ALS being a multisystem disorder, our study provides further evidence for extramotor involvement which is widespread. The lack of correlation with common clinical variables probably reflects the fact that heterogeneous disease processes underlie ALS. The discrepancy within all published morphometric studies in ALS so far may be related to differences in patient cohorts and several methodological factors of the data analysis process. Longitudinal studies are required to further clarify the time course and distribution of grey and white matter pathology during the course of ALS.

Adult↗
PubMed1995

Regional brain activity in chronic schizophrenic patients during the performance of a verbal fluency task.

BACKGROUND: This study examined the pattern of cerebral blood flow observed in chronic schizophrenic patients while they performed a paced verbal fluency task. Such tasks engage a distributed brain system associated with willed action. Since willed action is impaired in many chronic schizophrenic patients we hypothesised that task performance would be associated with an abnormal pattern of blood flow. METHOD: Positron emission tomography (PET) was applied to 18 chronic schizophrenic patients stratified into three groups on the basis of verbal fluency performance and current symptoms. Regional cerebral blood flow (rCBF) was measured while the patients performed (a) verbal fluency, (b) word categorisation, and (c) word repetition. Results were compared with six normal controls matched for age, sex and premorbid IQ. Analysis was restricted to six brain regions previously identified in studies of normal volunteers. RESULTS: In five brain areas, including the left dorsolateral prefrontal cortex, the patients showed the same pattern of activation as control subjects. However, in the left superior temporal cortex, all patient groups failed to show the normal decrease in blood flow when verbal fluency was compared with word repetition. CONCLUSION: These observations suggest that (a) chronic schizophrenic patients can show a normal magnitude of frontal activation when matched for performance with controls, and (b) they fail to show the expected reductions of activity in the superior temporal cortex. This latter result may reflect abnormal functional connectivity between frontal and temporal cortex.

Adult↗
PubMed1997

Neuropsychological correlates of syndromes in schizophrenia.

BACKGROUND: On the basis of Liddle's three-syndrome model of schizophrenia, it was predicted that: (1) symptoms of psychomotor poverty would be particularly correlated with impaired performance on neuropsychological tests likely to reflect functioning of the dorsolateral prefrontal cortex; (2) disorganisation would be particularly correlated with impaired performance on tests sensitive to medio-basal prefrontal functioning; and (3) reality distortion would be particularly correlated with measures sensitive to temporal lobe functioning. METHOD: The above hypotheses were tested on 87 subjects with a confirmed diagnosis of schizophrenia. Patients' symptoms were scored for each of the three syndromes. Patients completed six neuropsychological tests designed to measure impairment in specific areas of the brain. RESULTS: There was no support for the first two hypotheses. There was, however, evidence of a specific relationship between reality distortion and neuropsychological performance usually considered to be related to left temporal lobe functioning. CONCLUSIONS: Although not directly supporting the first two hypotheses; the results are, in general, consistent with there being different cortical-subcortical circuits associated with each of psychomotor poverty and disorganisation. Temporal lobe functioning appears to have particular significance for the reality distortion syndrome.

Adult↗
PubMed2000

Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk. Focal dysfunction and distributed disconnectivity reappraised.

BACKGROUND: PET studies of verbal fluency in schizophrenia report a failure of 'deactivation' of left superior temporal gyrus (STG) in the presence of activation of left dorsolateral prefrontal cortex (DLPFC), which deficit has been attributed to underlying 'functional disconnectivity'. AIM: To test whether these findings provide trait-markers for schizophrenia. METHOD: We used H2(15)O PET to examine verbal fluency in 10 obligate carriers of the predisposition to schizophrenia, 10 stable patients and 10 normal controls. RESULTS: We found no evidence of a failure of left STG deactivation in carriers or patients. Instead, patients failed to deactivate the precuneus relative to other groups. We found no differences in functional connectivity between left DLPFC and left STG but patients exhibited significant disconnectivity between left DLPFC and anterior cingulate cortex. CONCLUSIONS: Failure of left STG 'deactivation' and left fronto-temporal disconnectivity are not consistent findings in schizophrenia; neither are they trait-markers for genetic risk. Prefrontal functional disconnectivity here may characterise the schizophrenic phenotype.

Heterozygote↗
PubMed2005

Cortical mechanisms of saccade generation from execution to decision.

Several cortical areas are involved in the control of ocular motor behavior, but little is known about the cognitive processes occurring prior to saccade triggering. The use of functional brain imaging allows a better understanding of the networks involved specifically in distinct processes of saccade generation. The use of sophisticated visual stimulation paradigms in functional imaging studies suggests that the decision process of where to look when faced with visual alternatives is subserved by a prefrontoparietal network, including the dorsolateral prefrontal cortex.

Animals↗
PubMed2000

Neural activation during performance of number-letter sequencing.

Recent advances in neuroimaging have enabled researchers to establish relatively specific areas of the brain that are involved in working memory. In this positron emission tomography study we examined the pattern of neural activation associated with performance on number-letter sequencing, a purported measure of working memory included in the new Wechsler scales for memory and intelligence. After controlling for basic audition, verbalization, and attention, areas of activation were observed in the orbital frontal lobe, dorsolateral prefrontal cortex, and posterior parietal cortex. This is highly consistent with reports from the literature on activation patterns associated with working memory. More activation peaks were observed in the right hemisphere, suggesting the participants utilized visualization of the verbal information. Consistent with task conceptualization, this study provides support for number-letter sequencing as a task involving working memory.

Adult↗
PubMed2003

Differential activation on fMRI of monozygotic twins discordant for AD.

This is the first report of fMRI in monozygotic twins discordant for AD. FMRI brain activation patterns were examined during visuospatial and verbal working memory tasks. The affected twin had greater parietal involvement bilaterally during both working memory tasks and reduced left dorsolateral prefrontal cortex activity on the visuospatial memory task. Thus, fMRI may identify additional brain regions recruited in patients with AD to perform a given cognitive task.

Aged↗
PubMed2003

[11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy.

Microglia, the brain's intrinsic macrophages, bind (R)-PK11195 when activated by neuronal injury. The authors used [11C](R)-PK11195 PET to localize in vivo microglial activation in patients with multiple system atrophy (MSA). Increased [11C](R)-PK11195 binding was primarily found in the dorsolateral prefrontal cortex, putamen, pallidum, pons, and substantia nigra, reflecting the known distribution of neuropathologic changes in MSA. Providing an indicator of disease activity, [11C](R)-PK11195 PET can thus be used to characterize the in vivo neuropathology of MSA.

Aged↗
PubMed2004

Neural substrate of antisaccades: role of subcortical structures.

BACKGROUND: Experimental and clinical studies suggest that the dorsolateral prefrontal cortex (DLPFC) and the superior colliculus (SC) are crucial for the cancellation of reflexive eye movements toward distracting stimuli. However, the contribution of subcortical structures remains unknown. The basal ganglia provide serial tonic inhibitory connections between the DLPFC and the SC, and could therefore be involved in preventing the triggering of unnecessary saccades. The DLPFC could also exert its inhibitory effect on the SC through direct prefronto-tectal pathways that travel in the internal capsule (IC). Since thalamic dysfunction may be responsible for reduced DLPFC activation, it may be hypothesized that the thalamus could also participate in saccadic inhibition. METHODS: The authors recorded reflexive saccade triggering (prosaccade task) and inhibition (antisaccade task) in 29 patients with a single lesion affecting the striatum, the thalamus, or the IC, and compared these results to control subjects. RESULTS: A normal error rate in the antisaccade task was found in patients with 1) a basal ganglia lesion, 2) a thalamic lesion, or 3) a lesion restricted to the posterior half of the posterior limb of the IC. An increased error rate in the antisaccade task was found in patients with a lesion affecting the anterior limb, the genu, or the anterior half of the posterior limb of the IC. CONCLUSION: These results suggest that neither the basal ganglia nor the thalamus plays a major role in reflexive saccade suppression, but support the hypothesis of a direct DLPFC inhibitory control of saccade triggering on the SC.

Adult↗
PubMed2004

High-frequency rTMS improves time perception in Parkinson disease.

Patients with Parkinson disease (PD) are impaired in time processing. The authors investigated the effects of high-frequency (5 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with PD performing a time reproduction task. The authors found significant improvement in time processing induced by rTMS when trains were applied over the right dorsolateral prefrontal cortex (DLPFC) but not over the supplementary motor area, suggesting that the circuit involving the basal ganglia and the DLPFC might constitute the neural network subserving time perception.

Aged↗