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Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging.

OBJECTIVES: Gray and white matter volume deficits have been reported in a number of studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural magnetic resonance imaging (MRI) studies of adults with ADHD. This structural MRI study used an a priori region of interest approach. METHODS: Twenty-four adults with DSM-IV ADHD and 18 healthy controls comparable on age, socioeconomic status, sex, handedness, education, IQ, and achievement test performance had an MRI on a 1.5T Siemens scanner. Cortical and sub-cortical gray and white matter were segmented. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere. Based on a priori hypotheses we focused on prefrontal, anterior cingulate cortex (ACC) and overall gray matter volumes. General linear analyses of the volumes of brain regions, adjusting for age, sex, and total cerebral volumes, were used to compare groups. RESULTS: Relative to controls, ADHD adults had significantly smaller overall cortical gray matter, prefrontal and ACC volumes. CONCLUSIONS: Adults with ADHD have volume differences in brain regions in areas involved in attention and executive control. These data, largely consistent with studies of children, support the idea that adults with ADHD have a valid disorder with persistent biological features.

Adult↗

Spatio-temporal working memory and frontal lesions in man.

The delayed-response paradigm is thought to be a marker of the activity of the dorsolateral convexity of primates' prefrontal cortex, as this procedure requires the activation of working memory processes. Although the role of the dorsolateral prefrontal cortex (DLPC) in working memory seems to be well established, much remains to be understood about the processes this structure actually controls: encoding domain-specific information, its retention in short-term memory, its monitoring in working memory, or its selection and retrieval when a specific response program is required. To clarify the role of the DLPC in delayed-response tasks in humans, a set of sequencing paradigms was designed which incorporates the dissociation of (1) spatial and temporal parameters, (2) recall and recognition processes, and (3) the presence or absence of a delay. Performance of a group of patients with DLPC lesions (n = 8) was compared to that of age-matched normal subjects (n = 8). To verify the specificity of the results obtained for the DLPC lesioned patients, the performance of patients with a temporal lobotomy was also studied (n = 10). A significant effect of the delay was observed only in patients with DLPC lesions, affecting both their spatial and spatio-temporal recall, whereas their spatio-temporal recognition was normal. These findings suggest that the DLPC plays a role in the retrieval of visuospatial information for guiding a response program.

Brain Injuries↗

Dopamine receptor signaling molecules are altered in elderly schizophrenic cortex.

Alterations of molecules that mediate dopaminergic signal transduction have been found in schizophrenia, supporting the hypothesis of altered dopaminergic neurotransmission in this illness. To further explore this hypothesis, the authors measured transcript expression of three proteins involved in dopamine (DA) signaling in postmortem dorsolateral prefrontal and anterior cingulate cortex of elderly schizophrenic subjects and a comparison group. The transcript encoding calcyon, a protein that potentiates crosstalk between D1 DA receptors and Gq/11-linked receptors, was increased in schizophrenic prefrontal and cingulate cortex by 25%. Transcript levels of spinophilin, a protein enriched in dendritic spines that modulates excitatory neurotransmission, were increased 22% in dorsolateral prefrontal cortex but were unchanged in anterior cingulate cortex in schizophrenia. Levels of DARPP-32 mRNA, a downstream effector of dopaminergic neurotransmission, were similar in both groups for both cortical groups. These alterations in spinophilin and calcyon mRNA levels in schizophrenic prefrontal and cingulate cortex provide further evidence of altered dopaminergic neurotransmission in this illness.

Aged↗

Intracerebral recording of cortical activity related to self-paced voluntary movements: a Bereitschaftspotential and event-related desynchronization/synchronization. SEEG study.

To analyze the distribution of the cortical electrical activity related to self-paced voluntary movements, i.e. the movement-related readiness potentials (Bereitschaftspotential, BP) and the event-related desynchronization (ERD) and synchronization (ERS) of cortical rhythms using intracerebral recordings. EEG was recorded in 14 epilepsy surgery candidates during preoperative video-stereo-EEG monitoring. Subjects performed self-paced hand movements, with their right and left fingers in succession. EEG signals were obtained from a total of 501 contacts using depth electrodes located in primary and nonprimary cortical regions. In accordance with previous studies, BP was found consistently in the primary motor (M1) and somatosensory (S1) cortex, the supplementary motor area (SMA), and in a few recordings also in the cingulate cortex and in the dorsolateral prefrontal and premotor cortex. ERD and ERS of alpha and beta rhythms were also observed in these cortical regions. The distribution of contacts showing ERD or ERS was larger than the distribution of those showing BP. In contrast to BP, ERD and ERS frequently occurred in the lateral and mesial temporal cortex and the inferior parietal lobule. The number of contacts and cortical regions showing ERD and ERS and not BP suggests that the two electrophysiological phenomena are differently involved in the preparation and execution of simple voluntary movements. Substantial differences between BP and ERD in spatial distribution and the widespread topography of ERD/ERS in temporal and higher-order motor regions suggest that oscillatory cortical changes are coupled with cognitive processes supporting movement tasks, such as memory, time interval estimation, and attention.

Adolescent↗

Gender-moderated dorsolateral prefrontal reductions in 22q11.2 Deletion Syndrome: implications for risk for schizophrenia.

To investigate the impact of the microdeletion on morphology of the prefrontal cortex in 22q11.2 Deletion Syndrome (22q11.2 DS), high-resolution, anatomic magnetic resonance imaging was performed on 19 children and adolescents with 22q11.2 DS (11 females, 8 males) and 18 unaffected controls (10 females, 8 males). Tissue volumes of the dorsolateral, dorsomedial, orbitolateral, and orbitomedial prefrontal cortex were measured. Tasks of executive function and working memory were administered to investigate the association between anatomy and function. Whole brain volume and frontal lobe tissue volume were preserved in girls but reduced in boys with 22q11.2 DS relative to age-matched controls. Dorsolateral prefrontal cortex (DLPFC) volumes were reduced in participants with 22q11.2 DS, although the gender-by-diagnosis effect found for frontal lobe was not as robust for DLPFC. DLPFC volumes were associated with performance on tasks of planning and emotional facial recognition. Longitudinal studies are needed to clarify whether gender differences in frontal lobe and DLPFC persist with development, and whether the volumes of the DLPFC are associated with eventual deterioration in adaptive/psychosocial function that may presage the onset of schizophrenia, for which individuals with 22q11.2 DS are at a disproportionately high risk.

Analysis of Variance↗

A frontal variant of Alzheimer's disease exhibits decreased calcium-independent phospholipase A2 activity in the prefrontal cortex.

A frontal variant of Alzheimer's disease (AD) has recently been identified on neuropathological and neuropsychological grounds (Johnson, J.K., Head, E., Kim, R., Starr, A., Cotman, C.W., 1999. Clinical and pathological evidence for a frontal variant of Alzheimer Disease. Arch. Neurol. 56, 1233-1239). Frontal AD differs strikingly from typical AD by the occurrence of neurofibrillary tangle densities in the frontal cortex as high or higher than in the entorhinal cortex. Since cerebrocortical membranes are commonly abnormal in Alzheimer's disease (AD), we assayed frontal AD cases for enzymes regulating membrane phospholipid composition. We specifically measured activity of phospholipase A2s (PLA2s) in dorsolateral prefrontal and lateral temporal cortices of frontal AD cases (n=12), which have respectively high and low densities of neurofibrillary tangles. In neither cortical area was Ca(2+)-dependent PLA2 activity abnormal compared to controls (n=12). In contrast, a significant 42% decrease in Ca(2+)-independent PLA2 activity was found in the dorsolateral prefrontal, but not the lateral temporal, cortex of the frontal AD cases. Similarly, the dorsolateral prefrontal cortex, but not the lateral temporal cortex of the frontal AD cases suffered a 42% decrease in total free fatty acid content, though neither that decrease nor those in any one species of free fatty acid was significant. The observed biochemical changes probably occurred in neurons given (a) our finding that PLA2 activity of cultured human NT2 neurons is virtually all Ca(2+)-independent and (b) the finding of others that nearly all Ca(2+)-independent PLA2 in brain gray matter is neuronal. The decrease in Ca(2+)-independent PLA2 activity is not readily attributable to Group VI or VIII iPLA2s since neither NT2N neurons nor our brain homogenates were greatly inhibited by drugs potently suppressing those iPLA2s. Decreased Ca(2+)-independent PLA2 activity in frontal AD may reflect a compensatory response to pathologically accelerated phospholipid metabolism early in the disorder. That could cause an early elevation of prefrontal free fatty acids, which can stimulate polymerization of tau and thus promote the prefrontal neurofibrillary tangle formation characteristic of frontal AD.

Aged↗

Functional and effective connectivity in an fMRI study of an auditory-related task.

This study investigates the sets of brain areas that are functionally connected during an auditory goal-directed task. We used a paradigm including a resting state condition and an active condition, which consisted in active listening to the footsteps of walking humans. The regional brain activity was measured using fMRI and the adjusted values of activity in brain regions involved in the task were analysed using both principal component analysis and structural equation modelling. A first set of connected areas includes regions located in Heschl's gyrus, planum temporale, posterior superior temporal sulcus (in the so-called 'social cognition' area), and parietal lobe. This network could be responsible for the perceptual integration of the auditory signal. A second set encompassing frontal regions is related to attentional control. Dorsolateral- and medial-prefrontal cortex have mutual negative influences which are similar to those described during a visual goal-directed task [T. Chaminade & P. Fonlupt (2003) Eur. J. Neurosci., 18, 675-679.]. Moreover, the dorsolateral prefrontal cortex (DLPFC) exerts a positive influence on the auditory areas during the task, as well as a strong negative influence on the visual areas. These results show that: (i) the negative influence between the medial and lateral parts of the frontal cortex during a goal-directed task is not dependent on the input modality (visual or auditory), and (ii) the DLPFC activates the pathway of the relevant sensory modality and inhibits the nonrelevant sensory modality pathway.

Acoustic Stimulation↗

Functional brain maps of Tower of London performance: a positron emission tomography and functional magnetic resonance imaging study.

Regional cerebral blood flow (rCBF) and blood oxygenation level-dependent (BOLD) contrasts represent different physiological measures of brain activation. The present study aimed to compare two functional brain imaging techniques (functional magnetic resonance imaging versus [(15)O] positron emission tomography) when using Tower of London (TOL) problems as the activation task. A categorical analysis (task versus baseline) revealed a significant BOLD increase bilaterally for the dorsolateral prefrontal and inferior parietal cortex and for the cerebellum. A parametric haemodynamic response model (or regression analysis) confirmed a task-difficulty-dependent increase of BOLD and rCBF for the cerebellum and the left dorsolateral prefrontal cortex. In line with previous studies, a task-difficulty-dependent increase of left-hemispheric rCBF was also detected for the premotor cortex, cingulate, precuneus, and globus pallidus. These results imply consistency across the two neuroimaging modalities, particularly for the assessment of prefrontal brain function when using a parametric TOL adaptation.

Adult↗

Differential activation of the prefrontal cortex in successful and unsuccessful memory retrieval.

Six subjects underwent PET scans while they performed three versions of a recognition memory test for words and three versions of a control task. In each memory condition, the subjects discriminated between words presented in a prescan study list and words new to the experiment. During the 30 s scanning interval, the ratio of old and new words was 0:20, 4:16 or 16:4, depending on the experimental condition. Outside this interval, the ratio was 50:50 in all three conditions. The requirement in the control task was to discriminate between two character strings, the ratios of which were also manipulated during the 30 s scanning interval. Employing the control task as a covariate, analysis with statistical parametric mapping revealed that regional cerebral blood flow (rCBF) covaried with increasing density of old items in three regions of prefrontal cortex: right dorsolateral [Brodmann area (BA) 9/46], right medial (BA 32/8) and bilateral frontopolar cortex (BA 10). It is concluded that the prefrontal cortex, especially in the right hemisphere, is more active when a retrieval attempt succeeds than when it fails. This finding is consistent with the idea that the prefrontal cortex supports processes that operate selectively on the products of memory retrieval.

Adult↗

Prefrontal blood flow dysregulation in drug naive ADHD children without structural abnormalities.

Recent studies suggest a role for prefrontal cortex abnormalities in the pathogenesis of attention deficit/hyperactivity disorder (ADHD). We evaluated young drug-naive ADHD outpatients without MRI structural abnormalities to detect prefrontal cortex regional cerebral blood flow (rCBF) functional dysregulation; correlation between age and rCBF; and correlation between symptoms profile and rCBF. Functional brain activities (i.e. rCBF), neuropsychological attention performance and symptom profile were evaluated respectively by single photon emission computerized tomography (SPECT) scan, Stroop Test and the Child Attention Problem Rating Scale. There was a decreased rCBF in the left dorso lateral prefrontal cortex (DLPFC) compared to the right DLPFC of the subjects. In addition, there were positive correlations between age and relative rCBFs of the dorsolateral and orbital prefrontal cortex, and negative correlations between age and absolute rCBFs of the dorsolateral and orbital prefrontal cortex. Finally, higher levels of right relative rCBF and lower levels of left relative rCBF were predictors of higher severity of clinical symptom expression and neuropsychological attention impairment. The results of this study highlight the role of the DLPFC blood flow impairment in the pathogenesis of ADHD even in young subjects without structural abnormalities.

Adolescent↗

Metabolic mapping of the effects of cocaine during the initial phases of self-administration in the nonhuman primate.

Because most human studies of the neurobiological substrates of the effects of cocaine have been performed with drug-dependent subjects, little information is available about the effects of cocaine in the initial phases of drug use before neuroadaptations to chronic exposure have developed. The purpose of the present study, therefore, was to define the substrates that mediate the initial effects of cocaine in a nonhuman primate model of cocaine self-administration using the 2-[14C]deoxyglucose method. Rhesus monkeys were trained to self-administer 0.03 mg/kg per injection (N = 4) or 0.3 mg/kg per injection (N = 4) cocaine and compared with monkeys trained to respond under an identical schedule of food reinforcement (N = 4). Monkeys received 30 reinforcers per session, and metabolic mapping was conducted at the end of the fifth self-administration session. Cocaine self-administration reduced glucose utilization in the mesolimbic system, including the ventral tegmental area, ventral striatum, and medial prefrontal cortex. In addition, metabolic activity was increased in the dorsolateral and dorsomedial prefrontal cortex, as well as in the mediodorsal nucleus of the thalamus. These latter effects are distinctly different from those seen after the noncontingent administration of cocaine, suggesting that self-administration engages circuits beyond those engaged merely by the pharmacological actions of cocaine. The involvement of cortical areas subserving working memory suggests that strong associations between cocaine and the internal and external environment are formed from the very outset of cocaine self-administration. The assessment of the effects of cocaine at a time not readily evaluated in humans provides a baseline from which the effects of chronic cocaine exposure can be investigated.

Animals↗

Concurrent performance of two working memory tasks: potential mechanisms of interference.

When two tasks are performed simultaneously, performance often deteriorates, with concomitant increases in reaction time and error rate. Three potential neurophysiological mechanisms behind this deterioration in performance have been considered here: (i) dual-task performance requires additional cognitive operations and activation of cortical areas in addition to those active during single-task performance; (ii) two tasks interfere if they require activation of the same part of cortex; and (iii) cross-modal inhibition causes interference between two tasks involving stimuli from different sensory modalities. Positron emission tomography was used to measure regional cerebral blood flow (rCBF) during performance of an auditory working memory (WM) task, a visual WM task, both WM tasks (dual task) and a control condition. Compared to the control condition, the auditory and visual WM tasks activated sensory-specific areas in the superior temporal gyrus and occipital pole respectively. Both WM tasks also activated overlapping parts of cortex in the dorsolateral prefrontal, inferior parietal and cingulate cortex. There was no separate cortical area which was activated only in the dual task, and thus no area which could be associated with any dual task specific cognitive process such as task-coordination or divided attention. Decrease in rCBF in one WM task did not overlap with the areas of rCBF increase in the other WM task. However, an inhibitory mechanism could not be ruled out, since the rCBF increase in sensory specific areas was smaller in the dual-task condition than in the single-task conditions. The cortical activity underlying WM was to a large extent organized in a non-sensory specific, or non-parallel, way, and the results are consistent with the hypothesis that concurrent tasks interfere with each other if they demand activation of the same part of cortex.

Adult↗

Prenatal development of neurons in the human prefrontal cortex. II. A quantitative Golgi study.

The quantitative development of neurons in the human dorsolateral and lateral prefrontal cortex was studied in Golgi-impregnated tissue from postmortem brains ranging from 13.5 weeks of gestation up to the second postnatal month. Pyramidal neurons in the future layers III and V of the cortical plate, as well as different types of neurons in the transient subplate zone, were studied. The basal dendrites of the future layer III and V pyramidal neurons show a slow increase during the first two-thirds of the period of gestation. From 27-32 weeks of gestation on, there is a rapid increase in the length of basal dendrites of layer III and V pyramidal neurons, while the number of basal dendrites per pyramidal neuron appears to stabilize at 26/27 weeks of gestation. The increase in total length of basal dendrites per pyramidal neuron is mainly due to an increase in the number of bifurcations and the growth of terminal segments. Throughout the whole period studied, the size of the layer III pyramidal basal dendritic tree was smaller than that of layer V pyramidal neurons. Thus, not until postnatal life do the layer III pyramidal basal dendrites become larger than those of layer V. No statistically significant differences were found for data of the pyramidal neurons between the superior and middle frontal gyri. The dendritic size of subplate neurons, except for the subplate inverted pyramidal neurons, significantly exceeds the size of the basal dendrites of the pyramidal neurons up to the seventh gestational month, which indicates an earlier maturation of these subplate neurons. During the period examined, no clear decrease in the size of the subplate neurons was observed. The present study shows that the dendritic parameters of either subplate or cortical plate pyramidal neurons rapidly increase during the periods of ingrowth of afferent fibers into the subplate zone and cortical plate, respectively. In the Golgi preparations of the prefrontal cortex, the size of the subplate neurons does not show any clearly regressive changes at the end of the prenatal period.

Aging↗

Cortical and subcortical distribution of middle and long latency auditory and visual evoked potentials in a cognitive (CNV) paradigm.

OBJECTIVE: This study concerned sensory processing (post-stimulus late evoked potential components) in different parts of the human brain as related to a motor task (hand movement) in a cognitive paradigm (Contingent Negative Variation). The focus of the study was on the time and space distribution of middle and late post-stimulus evoked potential (EP) components, and on the processing of sensory information in the subcortical-cortical networks. METHODS: Stereoelectroencephalography (SEEG) recordings of the contingent negative variation (CNV) in an audio-visual paradigm with a motor task were taken from 30 patients (27 patients with drug-resistant epilepsy; 3 patients with chronic thalamic pain). The intracerebral recordings were taken from 337 cortical sites (primary sensorimotor area (SM1); supplementary motor area (SMA); the cingulate gyrus; the orbitofrontal, premotor and dorsolateral prefrontal cortices; the temporal cortex, including the amygdalohippocampal complex; the parietooccipital lobes; and the insula) and from subcortical structures (the basal ganglia and the posterior thalamus). The concurrent scalp recordings were obtained from 3 patients in the thalamic group. In 4 patients in the epilepsy group, scalp recordings were taken separately from the SEEG procedure. The middle and long latency evoked potentials following an auditory warning (S1) and a visual imperative (S2) stimuli were analyzed. The occurrences of EPs were studied in two time windows (200-300 ms; and over 300 ms) following S1 and S2. RESULTS: Following S1, a high frequency of EP with latencies over 200 ms was observed in the primary sensorimotor area, the supplementary motor area, the premotor cortex, the orbitofrontal cortex, the cingulate gyrus, some parts of the temporal lobe, the basal ganglia, the insula, and the posterior thalamus. Following S2, a high frequency of EP in both of the time windows over 200 ms was observed in the SM1, the SMA, the premotor and dorsolateral prefrontal cortex, the orbitofrontal cortex, the cingulate gyrus, the basal ganglia, the posterior thalamus, and in some parts of the temporal cortex. The concurrent scalp recordings in the thalamic group of patients twice revealed potentials peaking approximately at 215 ms following S1. Following S2, EP occurred with latencies of 215 and 310 ms, respectively. Following S1, separate scalp recordings in 4 patients in the epilepsy group displayed EP 3 times in the 'over 300 ms' time window. Following S2, EP were presented once in the '200-300 ms' time window and 3 times in the 'over 300 ms' time window. CONCLUSIONS: The SM1, the SMA, multiple sites of the frontal lobe, some parts of the temporal lobe, the cingulate gyrus, the basal ganglia, the insula, and the posterior thalamus all participate in a cortico-subcortical network that is important for the parallel cognitive processing of sensory information in a movement related task.

Adolescent↗

Impaired intentional content learning but spared incidental retention of contextual information in non-demented patients with Parkinson's disease.

We investigated the incidental and intentional learning performance of 29 patients with idiopathic Parkinson's disease (PD) and 20 healthy volunteers. Measures of incidental and intentional memory were assessed with a spoken verbal recall task followed by a temporal word order task, a picture recall task followed by a spatial picture location task, and a written word recall task followed by a judgement of word frequency task. A multivariate analysis of variance and appropriate post hoc tests revealed significant differences for all intentional learning variables. In all cases, PD patients performed worse than normal controls. No group differences were found for the incidental retention of contextual information. The results indicate that PD patients have a selective problem of intentional learning, whereas incidental learning of contextual information remains intact. Elaborate processing, attentional and organizing strategies in the systematic encoding, and recollection of information have been attributed to dorsolateral prefrontal activation. Preferential dysfunction of dorsolateral prefrontal cortex-associated memory processes is consistent with the previously reported uneven patterns of dopamine loss in the striatum of patients with idiopathic PD showing most severe dopamine depletion in the portion of the caudate nucleus that is anatomically connected to the dorsolateral frontal cortex.

Aged↗

Neuron activities of monkey prefrontal cortex during the learning of visual discrimination tasks with GO/NO-GO performances.

Neuronal activity in the dorsolateral and ventral prefrontal cortex was studied during the learning by six monkeys of the performance of a two-color visual discrimination task. The GO/NO-GO task or its reversal consisted of five periods: the Start Lamp Period, Lamp-off Period, Cue Period, Response Period, and ITI Period (Reward and Control Periods). In sum, 271 task-related neurons were studied by means of 545 penetrations. Discharge rates increased or decreased from the rate of ITI or preceding periods of the task. Discharge rate changes were of either the phasic or tonic pattern. During motor learning extending from a poor performance level (50-63% correct), through intermediate (60-83%), to well-trained levels (above 85%), the number of task-related neurons increased in the Cue, Response and ITI Periods, and more task-related neurons showed changes in more than one period. During the learning process, not only do more prefrontal neurons respond phasically to visual stimuli in the Cue and Response Periods or to reward or trial end in ITI, and become activated before lever release, but also they become active tonically in the Cue, Response and ITI Periods.

Animals↗

Inactivation of parietal and prefrontal cortex reveals interdependence of neural activity during memory-guided saccades.

Dorsolateral prefrontal and posterior parietal cortex share reciprocal projections. They also share nearly identical patterns of neuronal activation during performance of memory-guided saccades. To test the hypothesis that the reciprocal projections between parietal and prefrontal neurons may entrain their parallel activation, the present experiments have combined cortical cooling in one cortical area with single-unit recording in the other to more precisely determine the physiological interactions between the two during working memory performance. The activity of 105 cortical neurons during the performance of an oculomotor delayed response (ODR) task (43 parietal neurons during prefrontal cooling, 62 prefrontal neurons during parietal cooling) was compared across two blocks of trials collected while the distant cortical area either was maintained at normal body temperature or cooled. The mean firing rates of 71% of the prefrontal neurons during ODR performance changed significantly when parietal cortex was cooled. Prefrontal neurons the activity of which was modulated during the cue, delay, or saccade periods of the task were equally vulnerable to parietal inactivation. Further, both lower and higher firing rates relative to the precool period were seen with comparable frequency. Similar results were obtained from the converse experiment, in which the mean firing rates of 76% of the parietal neurons were significantly different while prefrontal cortex was cooled, specifically in those task epochs when the activity of each neuron was modulated during ODR performance. These effects again were seen equally in all epochs of the ODR task in the form of augmented or suppressed activity. Significant effects on the latency of neuronal activation during cue and saccade periods of the task were absent irrespective of the area cooled. Cooling was associated in some cases with a shift in the best direction of Gaussian tuning functions fit to neuronal activity, and these shifts were on average larger during parietal than prefrontal cooling. In view of the parallel between the similarity in activity patterns previously reported and the largely symmetrical cooling effects presently obtained, the data suggest that prefrontal and parietal neurons achieve matched activation during ODR performance through a symmetrical exchange of neuronal signals between them; in both cortical areas, neurons activated during the cue, delay, and also saccade epochs of the ODR task participate in reciprocal neurotransmission; and the output of each cortical area produces a mixture of excitatory and inhibitory drives within its target.

Animals↗

Voxel-based distribution of metabolic impairment in corticobasal degeneration.

This report emphasizes the precise topographic distribution of cerebral metabolic impairment in corticobasal degeneration (CBD) and the pathophysiological differences between CBD and progressive supranuclear palsy (PSP). Statistical parametric mapping (SPM96) analysis of 18FDG positron emission tomography (PET) data was performed in 22 patients with CBD compared with 46 healthy subjects (HS) and 21 patients with PSP who were studied at rest. A statistical threshold of p <0.001 was fixed, further corrected for multiple or independent comparisons (p <0.05). In comparison with HS, the metabolic impairment in CBD was asymmetrically distributed in the putamen, thalamus, precentral (Brodmann's area, BA 4), lateral premotor (BA 6/44) and supplementary motor areas (SMA, BA 6), dorsolateral prefrontal (8/9/46) cortex, and the anterior part of the inferior parietal lobe (BA 40) including the intraparietal sulcus (BA 7/40). A similar hypometabolic pattern was observed for most individual analyses. When PSP was compared with CBD, metabolic impairment predominated in the midbrain, anterior cingulate (BA 24/32), and orbitofrontal regions (BA 10). The reverse contrast showed more posterior involvement in CBD (BA 6 and 5/7/40) including SMA. Our data suggest that multiple components of neural networks related to both movement execution and production of skilled movements are functionally disturbed in CBD compared with both HS and PSP.

Adult↗