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PubMed1986

Efferent projections of the basolateral amygdala in the opossum, Didelphis virginiana.

The autoradiographic anterograde axonal transport technique was used to study efferent projections of the opossum basolateral amygdala. All nuclei of the basolateral amygdala send topographically organized fibers to the bed nucleus of the stria terminalis (BST) via the stria terminalis (ST). Injections into rostrolateral portions of the basal nuclei label fibers that surround the commissural bundle of the ST, cross the midline by passing along the outer aspect of the anterior commissure, and terminate primarily in the contralateral BST, anterior subdivision of the basolateral nucleus (BLa), ventral putamen, and olfactory cortex. Each of the basal nuclei project ipsilaterally to the anterior amygdaloid area, substantia innominata and topographically to the ventral part of the striatum and adjacent olfactory tubercle. The posterior subdivision of the basolateral nucleus (BLp), but not the basomedial nucleus (BM), projects to the ventromedial hypothalamic nucleus. BLa and BLp have projections to the nucleus of the lateral olfactory tract and also send fibers to the central nucleus, as does the lateral nucleus (L). The lateral nucleus also has a strong projection to BM and both nuclei project to the amygdalo-hippocampal area. BLa and BLp send axons to the ventral subiculum and ventral lateral entorhinal area whereas L projects only to the latter area. The lateral nucleus and BLp project to the perirhinal cortex and the posterior agranular insular area. The BLa sends efferents to the anterior agranular insular area. Rostrally this projection is continuous with a projection to the entire frontal cortex located rostral and medial to the orbital sulcus. All of the nuclei of the basolateral amygdala project to areas on the medial wall of the frontal lobe that appear to correspond to the prelimbic and infralimbic areas of other mammals. Despite the great phylogenetic distance separating the opossum from placental mammals, the projections of the opossum basolateral amygdala are very similar to those seen in other mammals. The unique frontal projections of the opossum BLa to the dorsolateral prefrontal cortex appear to be related to the distinctive organization of the mediodorsal thalamic nucleus and prefrontal cortex in this species.

Amygdala↗

PubMed2004

Category-specific modulation of inferior temporal activity during working memory encoding and maintenance.

Findings from neurophysiology have supported the view that visual working memory (WM) relies on modulation of activity in object-selective populations of neurons in inferior temporal cortex. Here, using event-related functional magnetic resonance imaging, we investigated whether similar mechanisms support human visual working memory encoding and maintenance processes. We identified regions in inferior temporal cortex that exhibited category-specific responses during perception of faces (fusiform face area [FFA]) or scenes (parahippocampal place area [PPA]) and investigated whether activity in these regions would be modulated by demands to actively encode and maintain faces and scenes. Results showed that independent of perceptual stimulation, the FFA and PPA exhibited greater encoding- and maintenance-related activity when their favored stimulus was relevant to the recognition task. In contrast, maintenance-related activity in the dorsolateral prefrontal cortex (PFC) was modulated by memory load, regardless of the type of information that was task relevant. These results are consistent with the view that visual working memory encoding and maintenance processes are implemented through modulation of inferior temporal activity by prefrontal cortex.

Adult↗

PubMed2003

Effects of repetitive transcranial magnetic stimulation on memory subtypes: a controlled study.

Repetitive transcranial magnetic stimulation (rTMS) of human cortex may disrupt or facilitate cortical activity. The aim of the present study was to investigate the consequences of rTMS applied over different cortical areas during various memory tasks, measuring immediate, working and episodic verbal memory. The study was performed in 16 right-handed healthy men. A double-blind, cross-over, within-subject repeated measures design was used. There were five rTMS conditions: baseline without stimulation, high frequency (HF) rTMS over right and left dorsolateral prefrontal cortex (DLPFC) and over right cerebellum, and low frequency (LF) parameters over left DLPFC. Digits forwards and backwards and letter-number sequencing of the Wechsler Adults Intelligence Scale (WAIS) were used to assess immediate and working verbal memory, and logical memory of the Rivermead Behavioural Memory Test was used to assess episodic memory encoding. An analysis of variance (ANOVA) for repeated measures in the scores of each memory task according to rTMS conditions was used. Significantly lower scores in the number of memory units of the episodic memory task were observed when rTMS high frequency parameters were applied over left DLPFC (P=0.009). No significant differences were found in the other memory subtype tasks analysed during the different rTMS conditions. These findings provide evidence for the significant role of the left DLPFC in episodic verbal memory processes.

Adult↗

PubMed2005

Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: a double-blind placebo-controlled study.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive method to stimulate the cortex, and the treatment of depression is one of its potential therapeutic applications. Three recent meta analyses strongly suggest its benefits in the treatment of depression. The present study investigates whether repetitive TMS (rTMS) accelerates the onset of action and increases the therapeutic effects of amitriptyline. METHODS: Forty-six outpatients meeting DSM-IV criteria for nonpsychotic depressive episode were randomly assigned to receive rTMS (n = 22) or sham repetitive TMS (sham) (n = 24) during 4 weeks over dorsolateral prefrontal cortex (DLPFC) in this double-blind controlled trial. All patients were concomitantly taking amitriptyline (mean dose 110 mg/d). The rTMS group received 20 sessions (5 sections per week) of 5 Hz rTMS (120% of motor threshold and 1250 pulses per session). Sham stimulation followed the same schedule, however, using a sham coil. The efficacy variables were the Hamilton Depression Rating Scale-17 items (HAM-D/17), the Montgomery-Asberg Depression Rating Scale (MADRS), a Visual Analogue Scale (VAS), and the Clinical Global Impression (CGI). Tolerability was assessed by clinical examination and a safety screening of TMS side effects. RESULTS: Repetitive TMS had a significantly faster response to amitriptyline. There was a significant decrease in HAM-D/17 scores, already after the first week of treatment (p < .001 compared with baseline and p < .001 compared with sham). The decrease in HAM-D/17 scores in the rTMS group was significantly superior compared with the sham group throughout the study (p < .001 at fourth week). CONCLUSIONS: Repetitive TMS at 5 Hz accelerated the onset of action and augmented the response to amitriptyline.

Adult↗

PubMed1995

Structural differences in the cerebral cortex of healthy female and male subjects: a magnetic resonance imaging study.

There are both reproductive and nonreproductive behavioral differences between men and women. Brain regions involved in determining sexual behavior have been reported to differ between the sexes. Nonreproductive, cognitive functional differences between sexes might be reflected in higher-order cortical structural dimorphisms, which have not previously been studied. We hypothesized that cortical regions involved in verbal behavior (which is sexually dimorphic) would differ between sexes. Using magnetic resonance imaging, we assessed gray matter volumes in several cortical regions in 17 women and 43 men. Women had 23.2% (dorsolateral prefrontal cortex) and 12.8% (superior temporal gyrus) greater gray matter percentages (corrected for overall brain size and age) than men in a language-related cortical region, but not in a more visuospatially related cortical region. These data seem to establish sexually dimorphic structural differences in the cerebral cortex, consistent with prior cerebral blood flow reports.

Adult↗

PubMed2003

Competition for priority in processing increases prefrontal cortex's involvement in top-down control: an event-related fMRI study of the stroop task.

Prior work indicates that various aspects of task-irrelevant information (e.g. its salience, task-relatedness, emotionality) can increase the involvement of prefrontal cortex (PFC) in top-down attentional control. In light of these findings, we hypothesize that PFC's involvement increases when task-irrelevant information competes for priority in processing. In an event-related fMRI study using an oddball variant of the Stroop task, we examine the generality of this hypothesis using three manipulations designed to increase the ability of task-irrelevant information to compete for priority in processing. First, we investigated how the frequency of occurrence of task-irrelevant information affects PFC activity. Second, we examined whether conflicting color information (i.e. incongruent trials) increases activity in regions of PFC that are similar to or distinct from those sensitive to infrequently occurring task-irrelevant information. Finally, we examined the impact of the number of levels at which conflict could occur (e.g. non-response only, non-response and response). Activity in posterior-dorsolateral and posterior-inferior PFC increased for infrequently occurring task-irrelevant information, being largest when the task-irrelevant information contained conflicting color-information. In contrast, increases in mid-dorsolateral prefrontal cortex's activity were only noted when conflicting color information was present, being largest when conflict occurred at multiple levels. The anterior cingulate was primarily sensitive to the occurrence of conflict at the response level with only a small sub-region exhibiting sensitivity to non-response conflict as well. From these findings we suggest that posterior DLPFC and PIPFC are involved in biasing processing in posterior processing systems, mid-DLPFC is involved in biasing the processing of the contents of working memory, and ACC is primarily involved in response-related processes.

Attention↗

PubMed1999

Distinct prefrontal activations in processing sequence at the sentence and script level: an fMRI study.

Neuropsychological studies have shown that the prefrontal cortex is important in planning and monitoring everyday behaviour. In this study, using functional magnetic resonance imaging (fMRI), we investigated whether specific prefrontal regions are involved in processing a sequence of actions. Subjects were required to perform two different tasks: Script-event order and Sentence-word order. Script sequence and word sequence processing were found to activate partially overlapping areas which are known to be implicated in language processing. In addition, the Script-task activated a large area in the dorsolateral prefrontal cortex (Brodmann area 6 and 8, BA 6 and 8), in both the left and right hemispheres, as well as the left supplementary motor area and left angular gyrus (BA 39). Our results suggest that these prefrontal areas may be more specifically involved in the process of analysing sequential links in the action domain.

Adult↗

PubMed2000

Reward-dependent learning in neuronal networks for planning and decision making.

Neuronal network models have been proposed for the organization of evaluation and decision processes in prefrontal circuitry and their putative neuronal and molecular bases. The models all include an implementation and simulation of an elementary reward mechanism. Their central hypothesis is that tentative rules of behavior, which are coded by clusters of active neurons in prefrontal cortex, are selected or rejected based on an evaluation by this reward signal, which may be conveyed, for instance, by the mesencephalic dopaminergic neurons with which the prefrontal cortex is densely interconnected. At the molecular level, the reward signal is postulated to be a neurotransmitter such as dopamine, which exerts a global modulatory action on prefrontal synaptic efficacies, either via volume transmission or via targeted synaptic triads. Negative reinforcement has the effect of destabilizing the currently active rule-coding clusters; subsequently, spontaneous activity varies again from one cluster to another, giving the organism the chance to discover and learn a new rule. Thus, reward signals function as effective selection signals that either maintain or suppress currently active prefrontal representations as a function of their current adequacy. Simulations of this variation-selection have successfully accounted for the main features of several major tasks that depend on prefrontal cortex integrity, such as the delayed-response test, the Wisconsin card sorting test, the Tower of London test and the Stroop test. For the more complex tasks, we have found it necessary to supplement the external reward input with a second mechanism that supplies an internal reward; it consists of an auto-evaluation loop which short-circuits the reward input from the exterior. This allows for an internal evaluation of covert motor intentions without actualizing them as behaviors, by simply testing them covertly by comparison with memorized former experiences. This element of architecture gives access to enhanced rates of learning via an elementary process of internal or covert mental simulation. We have recently applied these ideas to a new model, developed with M. Kerszberg, which hypothesizes that prefrontal cortex and its reward-related connections contribute crucially to conscious effortful tasks. This model distinguishes two main computational spaces within the human brain: a unique global workspace composed of distributed and heavily interconnected neurons with long-range axons, and a set of specialized and modular perceptual, motor, memory, evaluative and attentional processors. We postulate that workspace neurons are mobilized in effortful tasks for which the specialized processors do not suffice; they selectively mobilize or suppress, through descending connections, the contribution of specific processor neurons. In the course of task performance, workspace neurons become spontaneously co-activated, forming discrete though variable spatio-temporal patterns subject to modulation by vigilance signals and to selection by reward signals. A computer simulation of the Stroop task shows workspace activation to increase during acquisition of a novel task, effortful execution, and after errors. This model makes predictions concerning the spatio-temporal activation patterns during brain imaging of cognitive tasks, particularly concerning the conditions of activation of dorsolateral prefrontal cortex and anterior cingulate, their relation to reward mechanisms, and their specific reaction during error processing.

Animals↗

PubMed1972

Movement organization and delayed alternation behavior of monkeys following selective ablation of frontal cortex.

The delayed alternation problem was tested in monkeys either according to the routine procedure (SS test), or when additional cues were added which were operating in the moment of executing the response. These additional cues involved different sensations in effort of the perfomed movement sliding heavy object vs. sliding light object (sS test), as well as different sensations in pattern of movement and joints - sliding vs. lifting of an object (SL test). In normal the training of SL task was the easiest one, whereas the sS task was in some animals much more difficult than the SS task, and in others equivalent to this task. Removals in dorsolateral prefrontal cortex were made: total, only principalis sulcus, and only the rest of the area. Total and principalis lesions produced a severe impairment of all three tasks, while the third lesion produced only a slight deficit. The character of the impairment in the first two groups largely depended on the order in which the animals learned the three tasks in the pre-operative training.

Animals↗

PubMed2004

Cortical selective vulnerability in motor neuron disease: a morphometric study.

Neuroimaging and neuropsychological studies have revealed that the primary motor cortex (PMC) and the extramotor cortical areas are functionally abnormal in motor neuron disease (MND, amyotrophic lateral sclerosis), but the nature of the cortical lesions that underlie these changes is poorly understood. In particular, there have been few attempts to quantify neuronal loss in the PMC and in other cortical areas in MND. We used SMI-32, an antibody against an epitope on non-phosphorylated neurofilament heavy chain, to analyse the size and density of SMI-32-positive cortical pyramidal neurons in layer V of the PMC, the dorsolateral prefrontal cortex (DLPFC) and the supragenual anterior cingulate cortex (ACC) in 13 MND and eight control subjects. There was a statistically significant reduction in the density of SMI-32-immunoreactive (IR) pyramidal neurons within cortical layer V in the PMC, the DLPFC and the ACC in MND subjects compared with controls [t (19) = 2.91, P = 0.009; estimated reduction 25%; 95% CI = 8%, 40%]. In addition, we studied the density and size of interneurons immunoreactive for the calcium-binding proteins calbindin-D(28K) (CB), parvalbumin (PV) and calretinin (CR) in the same areas (PMC, DLPFC and ACC). Statistically significant differences in the densities of CB-IR neurons were observed within cortical layers V (P = 0.003) and VI (P = 0.001) in MND cases compared with controls. The densities of CR- and PV-IR neurons were not significantly different between MND and control cases, although there were trends towards reductions of CR-IR neuronal density within the same layers and of PV-IR neuronal density within cortical layer VI. Loss of pyramidal neurons and of GABAergic interneurons is more widespread than has been appreciated and is present in areas associated with neuroimaging and cognitive abnormalities in MND. These findings support the notion that MND should be considered a multisystem disorder.

Aged↗

PubMed2001

Prefrontal regions involved in keeping information in and out of mind.

Goal-directed behaviour depends on keeping relevant information in mind (working memory) and irrelevant information out of mind (behavioural inhibition or interference resolution). Prefrontal cortex is essential for working memory and for interference resolution, but it is unknown whether these two mental abilities are mediated by common or distinct prefrontal regions. To address this question, functional MRI was used to identify brain regions activated by separate manipulations of working memory load and interference within a single task (the Sternberg item recognition paradigm). Both load and interference manipulations were associated with performance decrements. Subjects were unaware of the interference manipulation. There was a high degree of overlap between the regions activated by load and interference, which included bilateral ventrolateral and dorsolateral prefrontal cortex, anterior insula, anterior cingulate and parietal cortex. Critically, no region was activated exclusively by interference. Several regions within this common network exhibited a brain-behaviour correlation across subjects for the load or interference manipulation. Activation within the right middle frontal gyrus and left inferior frontal gyrus was correlated with the ability to resolve interference efficiently, but not the ability to manage an increased working memory load efficiently. Conversely, activation of the anterior cingulate was correlated with load susceptibility, but was not correlated with interference susceptibility. These findings suggest that, within the circuitry engaged by this task, some regions are more critically involved in the resolution of interference whereas others are more involved in the resolution of an increase in load. The anterior cingulate was engaged to a greater extent by the load than interference manipulation, suggesting that this region, which is thought to be involved in detecting the need for greater allocation of attentional resources, may be particularly implicated during awareness of the need for cognitive control. In the present study, interference resolution did not involve recruitment of additional inhibitory circuitry, but was instead mediated by a subset of the neural system supporting working memory.

Adolescent↗

PubMed2006

fMRI of parents of children with Asperger Syndrome: a pilot study.

BACKGROUND: People with autism or Asperger Syndrome (AS) show altered patterns of brain activity during visual search and emotion recognition tasks. Autism and AS are genetic conditions and parents may show the 'broader autism phenotype.' AIMS: (1) To test if parents of children with AS show atypical brain activity during a visual search and an empathy task; (2) to test for sex differences during these tasks at the neural level; (3) to test if parents of children with autism are hyper-masculinized, as might be predicted by the 'extreme male brain' theory. METHOD: We used fMRI during a visual search task (the Embedded Figures Test (EFT)) and an emotion recognition test (the 'Reading the Mind in the Eyes' (or Eyes) test). SAMPLE: Twelve parents of children with AS, vs. 12 sex-matched controls. DESIGN: Factorial analysis was used to map main effects of sex, group (parents vs. controls), and sexxgroup interaction on brain function. An ordinal ANOVA also tested for regions of brain activity where females>males>fathers=mothers, to test for parental hyper-masculinization. RESULTS ON EFT TASK: Female controls showed more activity in extrastriate cortex than male controls, and both mothers and fathers showed even less activity in this area than sex-matched controls. There were no differences in group activation between mothers and fathers of children with AS. The ordinal ANOVA identified two specific regions in visual cortex (right and left, respectively) that showed the pattern Females>Males>Fathers=Mothers, both in BA 19. RESULTS ON EYES TASK: Male controls showed more activity in the left inferior frontal gyrus than female controls, and both mothers and fathers showed even more activity in this area compared to sex-matched controls. Female controls showed greater bilateral inferior frontal activation than males. This was not seen when comparing mothers to males, or mothers to fathers. The ordinal ANOVA identified two specific regions that showed the pattern Females>Males>Mothers=Fathers: left medial temporal gyrus (BA 21) and left dorsolateral prefrontal cortex (BA 44). CONCLUSIONS: Parents of children with AS show atypical brain function during both visual search and emotion recognition, in the direction of hyper-masculinization of the brain. Because of the small sample size, and lack of age-matching between parents and controls, such results constitute a pilot study that needs replicating with larger samples.

Asperger Syndrome↗

PubMed2005

Neural correlates of a reversal learning task with an affectively neutral baseline: an event-related fMRI study.

Reversal learning may conceptually be dissected into acquiring stimulus-reinforcement associations and subsequently altering behavior by switching to new associations as stimulus-reinforcement contingencies reverse (i.e., affective switching). Previous imaging studies have found regions of the ventrolateral and orbitofrontal cortex (OFC) to be involved in both subprocesses. However, these studies did not contain an affectively neutral baseline, which precluded adequate assessment of main effects of reward, punishment, and affective switching. We aimed to determine the neural substrate of these main effects, and of common and dissociable regions for reward and punishment. Furthermore, we aimed to discriminate between stimulus-punishment association and affective switching, i.e., to assess affective switching proper. To this end, we implemented a reversal learning task with an affectively neutral baseline condition that matched the experimental task in visual complexity and motor demands. Interestingly, we found dorsolateral prefrontal cortex (DLPFC) and anterior PFC to be engaged in affective switching, a finding that has not been reported before to our knowledge. Enhanced responses in these areas may represent their involvement in cognitive set shifting per se unrelated to the affective context in a reversal learning design. In addition, OFC, insular and medial prefrontal cortex regions were involved in affective switching. Left medial and lateral OFC were shown to be common areas for feedback processing, whereas left ventral striatum and left lateral OFC were specifically activated by reward and punishment, respectively. These results extend our understanding of the neural substrate of reversal learning in humans.

Adult↗

PubMed2005

Lateral prefrontal cortex: architectonic and functional organization.

A comparison of the architecture of the human prefrontal cortex with that of the macaque monkey showed a very similar architectonic organization in these two primate species. There is no doubt that the prefrontal cortical areas of the human brain have undergone considerable development, but it is equally clear that the basic architectonic organization is the same in the two species. Thus, a comparative approach to the study of the functional organization of the primate prefrontal cortex is more likely to reveal the essential aspects of the various complex control processes that are the domain of frontal function. The lateral frontal cortex appears to be functionally organized along both a rostral-caudal axis and a dorsal-ventral axis. The most caudal frontal region, the motor region on the precentral gyrus, is involved in fine motor control and direct sensorimotor mappings, whereas the caudal lateral prefrontal region is involved in higher order control processes that regulate the selection among multiple competing responses and stimuli based on conditional operations. Further rostrally, the mid-lateral prefrontal region plays an even more abstract role in cognitive control. The mid-lateral prefrontal region is itself organized along a dorsal-ventral axis of organization, with the mid-dorsolateral prefrontal cortex being involved in the monitoring of information in working memory and the mid-ventrolateral prefrontal region being involved in active judgments on information held in posterior cortical association regions that are necessary for active retrieval and encoding of information.

Anatomy, Comparative↗

PubMed2006

Safety of rTMS to non-motor cortical areas in healthy participants and patients.

OBJECTIVE: rTMS is increasingly being used for stimulation to non-motor areas, but available safety guidelines are derived from experience with motor cortex rTMS. We reviewed the literature and our own data to assess the safety of rTMS to non-motor areas. METHODS: We reviewed for adverse effects all articles published from January 1998 to December 2003 that applied rTMS to non-motor areas, and analyzed data from our own studies from January 1997 to December 2003. RESULTS: Adverse effects were infrequent and generally mild. Headache was the most common, occurring in 23% of the subjects and more frequent with frontal rTMS. More serious adverse effects were rare and consisted of two seizures and four instances of psychotic symptoms induced by rTMS to the dorsolateral prefrontal cortex in patients with depression. CONCLUSIONS: Overall, as currently applied rTMS to non-motor areas appears to be safe with few, generally mild adverse effects. In future studies, we recommend systematic reporting of adverse effects and careful documentation of machine type, coils used, and actual intensity as a function of maximum stimulator output. Phosphene threshold might be used to index stimulation intensity when rTMS is applied to the visual cortex, and research should be directed to identifying other indexes of intensity for TMS to other non-motor areas. SIGNIFICANCE: rTMS under the present guidelines is safe, with minimal adverse effects, when applied to non-motor areas.

Adult↗

PubMed2004

When 'go' and 'nogo' are equally frequent: ERP components and cortical tomography.

In human electrophysiology, a considerable corpus of studies using event-related potentials have investigated inhibitory processes by employing the 'go-nogo' paradigm, which requires responding to one type of event while withholding the response to another type of event. Two event-related potential waveform features (N2 and P3) have been associated with larger amplitude in nogo trials than in go trials. Traditionally, these differences were thought to reflect response inhibition. Recently, the source localization of N2 to the anterior cingulate cortex, as well as the colocalization of N2 with error-related negativity, has been interpreted in terms of conflict monitoring. In order to isolate the contribution of inhibitory processes, we matched the frequency of the go and nogo events, thus minimizing differences in response conflict between event types. A data-driven analytical procedure contrasted go with nogo events across the entire event-related potential segment and found that N2 reliably differentiated between the two conditions while P3 did not. Tomographical analyses of the N2 difference observed in conditions of equal go and nogo trial frequency localized N2 to the right ventral and dorsolateral prefrontal cortex. Because a growing body of evidence implicates these brain regions in inhibitory processes, we conclude that N2 does, at least in part, reflect inhibition.

Adolescent↗

PubMed2003

Orbitofrontal cortex dysfunction in abstinent cocaine abusers performing a decision-making task.

Cocaine abusers demonstrate faulty decision-making as manifested by their inability to discontinue self-destructive drug-seeking behaviors. The orbitofrontal cortex (OFC) plays an important role in decision-making. In this preliminary study we tested whether 25-day-abstinent cocaine abusers show alterations in normalized cerebral blood flow (rCBF) in the OFC using PET with (15)O during the Iowa Gambling Task (a decision-making task). This task measures the ability to weigh short-term rewards against long-term losses. A control task matched the sensorimotor aspects of the task but did not require decision-making. Cocaine abusers (N = 13) showed greater activation during performance of the Iowa Gambling Task in the right OFC and less activation in the right dorsolateral prefrontal cortex (DLPFC) and left medial prefrontal cortex (MPFC) compared to a control group (N = 13). Better Iowa Gambling Task performance was associated with greater activation in the right OFC in both groups. Also, the amount of cocaine used (grams/week) prior to the 25 days of enforced abstinence was negatively correlated with activation in the left OFC. Greater activation in the OFC in cocaine abusers compared to a control group may reflect differences in the anticipation of reward while less activation in the DLPFC and MPFC may reflect differences in planning and working memory. These findings suggest that cocaine abusers show persistent functional abnormalities in prefrontal neural networks involved in decision-making and these effects are related to cocaine abuse. Compromised decision-making could contribute to the development of addiction and undermine attempts at abstinence.

Adult↗

PubMed2006

Three-month change in cerebral glucose metabolism in patients with nonarteritic ischemic optic neuropathy.

BACKGROUND: No specific therapy is available for non-arteritic ischemic optic neuropathy (NAION), a blinding disease, which is related to microvascular insufficiency of the optic disc and white matter lesions in brain MRI representing ischemia. We hypothesize that pentoxifylline, traditionally used for treatment of peripheral vascular disease due to its ability to decrease viscosity and increase erythrocyte flexibility, may be useful to improve blood flow in patients with NAION. Positron emission tomography (PET) to determine the change in glucose metabolic rate in the visual cortex of patients with NAION versus age-matched controls was performed after 3 months' administration of pentoxifylline. METHODS: Eight patients clinically diagnosed with NAION underwent clinical and laboratory evaluation, brain MRI and PET with fluoride-18 fluorodeoxyglucose (FDG). All patients were treated with oral pentoxifylline 400 mg three times a day for a period of at least 3 months. Three patients were included in the final PET data analysis. RESULTS: At baseline, PET revealed bilateral metabolic decreases especially in the ventral visual stream in all patients compared with 56 age- and gender-normalized controls. Metabolic changes were seen in the dorsal stream areas 17, 18, and 19, cerebellar region, dorsolateral prefrontal cortex, medial temporal lobe, and frontal eye fields 8 and 6. At 3 months following pentoxifylline, all three patients included in the final PET data analysis showed partial normalization from the baseline metabolism. CONCLUSIONS: Metabolic imaging with FDG-PET in NAION provides functional information not attainable with conventional brain MRI. The exact relevance of these results, and the role of pentoxifylline in these metabolic changes, should be determined by means of a larger randomized and controlled trial.

Administration, Oral↗