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Results for “Dorsolateral Prefrontal Cortex”

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PubMed2003

Dissociation of spatial-, object-, and sound-coding neurons in the mediodorsal nucleus of the primate thalamus.

The mediodorsal nucleus (MD) is the thalamic gateway to the prefrontal cortex, an area of the brain associated with spatial and object working memory functions. We have recorded single-neuron activities from the MD nucleus in monkeys trained to perform spatial tasks with peripheral visual stimuli and a nonspatial task with foveally presented pictures of objects and faces-tasks identical to those we have previously used to map regional specializations in the dorso- and ventro-lateral prefrontal cortex, respectively. We found that MD neurons exhibited categorical specificity-either responding selectively to locations in the spatial tasks or preferentially to specific representations of faces and objects in the nonspatial task. Spatially tuned neurons were located in parts of the MD connected with the dorsolateral prefrontal cortex while neurons responding to the identity of stimuli mainly occupied more ventral positions in the nucleus that has its connections with the inferior prefrontal convexity. Neuronal responses to auditory stimuli were also examined, and vocalization sensitive neurons were found in more posterior portions of the MD. We conclude that MD neurons are dissociable by their spatial and nonspatial coding properties in line with their cortical connections and that the principle of information segregation in cortico-cortical pathways extends to the "association" nuclei of the thalamus.

Acoustic Stimulation↗

PubMed1999

Role of the prefrontal cortex in the control of express saccades. A transcranial magnetic stimulation study.

Single pulse transcranial magnet stimulation (TMS) was applied in five subjects during a saccadic gap task, i.e. with a temporal gap of 200 ms between the extinguishing of the central fixation point and the appearance of the lateral target. In all subjects, a significant increase of contralateral express saccades was found when TMS was applied over the dorsolateral prefrontal cortex (DPFC) at the end of the gap of 200 ms. Earlier stimulation over the DPFC during the gap had no significant effect. Furthermore, stimulation over the posterior parietal cortex with the same time intervals, and stimulation during a no gap task had no significant influence on express saccades. These results suggest that TMS is capable of interfering specifically with the functioning of the DPFC, probably by inhibition of this region. Possibly such stimulation of the DPFC reduces the inhibition by this region onto the superior colliculus, which results in a facilitation of express saccades.

Adult↗

PubMed2004

Brain perfusion correlates of the apathy inventory dimensions of Alzheimer's disease.

BACKGROUND: Apathy is defined as a lack of motivation in behavior, cognition and affect. This syndrome is frequent in various neuropsychiatric diseases but little is known about its pathophysiology. OBJECTIVES: The aim of this study was to investigate the metabolic correlates of the behavioral, cognitive and emotional, aspects of apathy in Alzheimer's disease (AD). METHOD: Thirty AD patients were included. Lack of initiative, lack of interest and of emotional blunting were assessed with the Apathy Inventory (IA), a tool designed to provide a separate assessment of the behavioral, cognitive and emotional, aspects of apathy. Brain perfusion was measured by (99m)Tc-labeled bicisate (ECD) single photon emission tomography. RESULTS: The Statistical Parametric Mapping software provides negative correlation between IA total score and brain perfusion in left and right superior orbito-frontal gyrus, and to a lesser extent in left middle frontal gyrus (BA10). Lack of initiative score was negatively correlated with perfusion in right anterior cingulate cortex. Lack of interest score was negatively correlated with perfusion in right middle orbitofrontal gyrus). Emotional blunting score correlated negatively with in left superior dorsolateral prefrontal cortex activity. CONCLUSION: These results underline that the cognitive, behavioral and affective components of motivation are mediated by different fronto-sub-cortical circuits and are differently lateralized. In particular, left prefrontal hypoperfusion is involved in emotional blunting, as it was often demonstrated in depressive disorders. These distinct components of apathy may be targeted by different therapeutic means, in which dopaminergic enhancement might play a major role.

Aged↗

PubMed2004

Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology.

Neurons in a small number of brain structures detect rewards and reward-predicting stimuli and are active during the expectation of predictable food and liquid rewards. These neurons code the reward information according to basic terms of various behavioural theories that seek to explain reward-directed learning, approach behaviour and decision-making. The involved brain structures include groups of dopamine neurons, the striatum including the nucleus accumbens, the orbitofrontal cortex and the amygdala. The reward information is fed to brain structures involved in decision-making and organisation of behaviour, such as the dorsolateral prefrontal cortex and possibly the parietal cortex. The neural coding of basic reward terms derived from formal theories puts the neurophysiological investigation of reward mechanisms on firm conceptual grounds and provides neural correlates for the function of rewards in learning, approach behaviour and decision-making.

Animals↗

PubMed2003

The cerebral correlates of set-shifting: an fMRI study of the trail making test.

The trail making test (TMT) pertains to a family of tests that tap the ability to alternate between cognitive categories. However, the value of the TMT as a localizing instrument remains elusive. Here we report the results of a functional magnetic resonance imaging (fMRI) study of a verbal adaptation of the TMT (vTMT). The vTMT takes advantage of the set-shifting properties of the TMT and, at the same time, minimizes the visuospatial and visuomotor components of the written TMT. Whole brain BOLD fMRI was performed during the alternating execution of vTMTA and vTMTB in seven normal adults with more than 12 years of formal education. Brain activation related to the set-shifting component of vTMTB was investigated by comparing performance on vTMTB with vTMTA, a simple counting task. There was a marked asymmetry of activation in favor of the left hemisphere, most notably in dorsolateral prefrontal cortex (BA 6 lateral, 44 and 46) and supplementary motor area/cingulate sulcus (BA 6 medial and 32). The intraparietal sulcus (BA 7 and 39) was bilaterally activated. These findings are in line with clinico-anatomic and functional neuroimaging data that point to a critical role of the dorsolateral and medial prefrontal cortices as well as the intraparietal sulci in the regulation of cognitive flexibility, intention, and the covert execution of saccades/anti-saccades. Many commonly used neuropsychological paradigms, such as the Stroop, Wisconsin Card Sorting, and go - no go tasks, share some patterns of cerebral activation with the TMT.

Adult↗

PubMed2005

Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits.

The clinical signs grouped under the concept of apathy are a common feature of prefrontal and basal ganglia lesions or dysfunctions and can therefore help to improve our understanding of the functional anatomy of the prefrontal-basal ganglia system. Apathy is here defined as a quantitative reduction of voluntary, goal-directed behaviors. The underlying mechanisms responsible for apathy can be divided into three subtypes of disrupted processing: 'emotional-affective', 'cognitive' and 'auto-activation'. Apathy due to the disruption of 'emotional-affective' processing refers to the inability to establish the necessary linkage between emotional-affective signals and the ongoing or forthcoming behavior. It may be related to lesions of the orbital-medial prefrontal cortex or to the related subregions (limbic territory) within the basal ganglia (e.g. ventral striatum, ventral pallidum). Apathy due to the disruption of 'cognitive' processing refers to difficulties in elaborating the plan of actions necessary for the ongoing or forthcoming behavior. It may be related to lesions of the dorsolateral prefrontal cortex and the related subregions (associative territory) within the basal ganglia (e.g. dorsal caudate nucleus). The disruption of 'auto-activation' processing refers to the inability to self-activate thoughts or self-initiate actions contrasting with a relatively spared ability to generate externally driven behavior. It is responsible for the most severe form of apathy and in most cases the lesions affect bilaterally the associative and limbic territories of the internal portion of the globus pallidus. It characterizes the syndrome of 'auto-activation deficit' (also known as 'psychic akinesia' or 'athymormia'). This syndrome implies that direct lesions of the basal ganglia output result in a loss of amplification of the relevant signal, consequently leading to a diminished extraction of this signal within the frontal cortex. Likewise, apathy occurring in Parkinson's disease could be interpreted as secondary to the loss of spatial and temporal focalization of the signals transferred to the frontal cortex. In both situations (direct basal ganglia lesions and nigro-striatal dopaminergic loss), the capacity of the frontal cortex to select, initiate, maintain and shift programs of actions is impaired.

Animals↗

PubMed1996

Apomorphine produces an acute dose-dependent therapeutic effect on neglect produced by unilateral destruction of the posterior parietal cortex in rats.

The neglect syndrome is a complex and devastating neurological disorder typically induced by unilateral destruction of one of three regions of the neocortex: the inferior parietal lobule, the dorsolateral prefrontal cortex or the cingulate cortex. Previous studies of neglect using a rodent model have indicated that disruption of dopaminergic mechanisms may underlie neglect. However, the pharmacological results were obtained using a rodent prefrontal model of the syndrome (medial agranular cortex), whereas the majority of cases of neglect in humans are produced by unilateral destruction of the posterior parietal cortex (inferior parietal lobule). The present study examined the effects of administration of the dopamine receptor agonist apomorphine on neglect induced by unilateral destruction of the posterior parietal cortex (PPC) in rats. The results indicated that administration of apomorphine produced a significant dose-dependent decrease in the severity of neglect. The results support the contention that neglect induced by cortical damage may be produced by a disruption of dopaminergic mechanisms, and that the PPC may be one component of a cortical system for directed attention.

Acoustic Stimulation↗

PubMed1981

Direct and indirect pathways from the amygdala to the frontal lobe in rhesus monkeys.

To elucidate the anatomical relationships between the frontal association cortex and the limbic system in primates, projections from the amygdala to frontal cortex were studied in the rhesus monkey using retrograde and anterograde tracing methods. Following injections of horseradish peroxidase (HRP) into the orbital prefrontal cortex, the gyrus rectus, the superior frontal gyrus, and the anterior cingulate gyrus of the frontal lobe, labeled neurons were found in the basolateral, basomedial, or basal accessory nuclei of the amygdala. None of these nuclei contained labeled neurons following HRP injections into the principal sulcus or the lateral inferior convexity of the frontal lobe. This selective distribution of amygdala connections was confirmed by injection tritiated amino acids into the amygdala. Silver grains were present only over the orbital cortex and gyrus rectus on the ventral surface of the frontal lobe and over the superior prefrontal gyrus and anterior cingulate gyrus on the medial wall of the hemisphere, while the dorsolateral prefrontal cortex was free of radioactivity. The isotope injection of the amygdala also revealed a projection to the magnocellular moiety of the mediodorsal nucleus (MDmc) which is known to innervate the same ventromedial regions of the frontal lobe that receive direct connections from the amygdala. Although MDmc and amygdala project to the same cortical regions, their terminal fields are different. The direct amygdala input terminates in layer 1 in orbital cortex and gyrus rectus and layer 2 in the dorsomedial cortex and cingulate gyrus, while the thalamic input is primarily to layer 3 and, in some areas, also the superficial half of layer 1. These findings indicate that the frontal lobe of rhesus monkeys can be subdivided into two separable cortical regions: 1) A ventromedial region including the anterior cingulate gyrus which receives both direct (amygdalo-cortical) and indirect (amygdalo-thalamo-cortical) input from the amygdala; and 2) a dorsolateral frontal region which is essentially devoid of either direct or indirect amygdalofugal axons. On the basis of its selective relationship with the amygdala, the ventromedial region may be considered the "limbic" portion of the frontal association cortex.

Amygdala↗

PubMed2000

Interindividual variation of cerebral activation during encoding and retrieval of words.

The aim of the present study was to compare the cerebral activation associated with encoding and retrieval in individual subjects with the average activation in the same group of subjects. Twelve volunteers performed two paradigms: 1) intentional encoding of words, and 2) recognition of learned words intermixed with new distracters. Echo-planar magnetic resonance imaging (MRI) of BOLD signal changes was used to compare cerebral activation between active and resting conditions. During encoding, activation of the left precentral gyrus related to the motor response was observed in some subjects. Averaged data showed increased activation of the left precentral gyrus, the supplementary motor area (SMA), the left inferior frontal gyrus and in the left temporo-occipital junction. During recognition, motor response-related activity was found in the precentral cortex and SMA in most subjects. Activation in other brain areas showed considerable interindividual variation. In the entire group, recognition showed activation of the left dorsolateral prefrontal cortex, the precentral gyrus, the SMA, and the temporo-occipital junction. The total amount and the distribution of task-related cerebral activation varies considerably between individuals and might correspond to individual preferences of cognitive strategies. The investigation of these interindividual variations will be an exciting scientific challenge in the near future.

Adult↗

PubMed2006

Neocortical connectivity during episodic memory formation.

During the formation of new episodic memories, a rich array of perceptual information is bound together for long-term storage. However, the brain mechanisms by which sensory representations (such as colors, objects, or individuals) are selected for episodic encoding are currently unknown. We describe a functional magnetic resonance imaging experiment in which participants encoded the association between two classes of visual stimuli that elicit selective responses in the extrastriate visual cortex (faces and houses). Using connectivity analyses, we show that correlation in the hemodynamic signal between face- and place-sensitive voxels and the left dorsolateral prefrontal cortex is a reliable predictor of successful face-house binding. These data support the view that during episodic encoding, "top-down" control signals originating in the prefrontal cortex help determine which perceptual information is fated to be bound into the new episodic memory trace.

Adult↗

PubMed2001

Syntactic processing in left prefrontal cortex is independent of lexical meaning.

In language comprehension a syntactic representation is built up even when the input is semantically uninterpretable. We report data on brain activation during syntactic processing, from an experiment on the detection of grammatical errors in meaningless sentences. The experimental paradigm was such that the syntactic processing was distinguished from other cognitive and linguistic functions. The data reveal that in syntactic error detection an area of the left dorsolateral prefrontal cortex, adjacent to Broca's area, is specifically involved in the syntactic processing aspects, whereas other prefrontal areas subserve general error detection processes.

Adult↗

PubMed1990

Prefrontal cortex and the bridging of temporal gaps in the perception-action cycle.

Normal behavior is characterized by a constant circular flow of influences from sensory receptors to motor effectors, to the physical environment, back to sensory receptors, and so on. This cybernetic cycle of influences (the perception-action cycle) governs all sequences of behavior to make them adaptive and goal directed. In the primate (including the human primate), considerable evidence indicates that dorsolateral prefrontal cortex is essential for the bridging of temporal gaps in the perception-action cycle, in other words, for mediating cross-temporal contingencies of behavior. This chapter summarizes some neuropsychological and neurophysiological evidence in support of this conclusion. The evidence has been obtained from monkeys performing delay tasks, which epitomize the principle of cross-temporal contingency.

Animals↗

PubMed2005

Effect of left prefrontal repetitive transcranial magnetic stimulation on food craving.

BACKGROUND: Dysfunction of the prefrontal cortex is implicated in craving for drugs and food. This study explores the effect of prefrontal cortex stimulation on food craving. METHODS: In a randomized double-blind parallel group study, 28 women, who reported frequent cravings for food were exposed to foods that typically elicit strong cravings before and after a single session of real or sham 10-Hz repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex at an intensity of 110% individual motor threshold. RESULTS: Self-reported food craving during exposure to the experimental foods remained stable before and after real stimulation compared with sham stimulation in which cravings increased over the experimental session. Consumption of snack foods within a 5-min period after stimulation did not differ between groups. CONCLUSIONS: Prefrontal stimulation inhibits the development of craving. A longer period of observation is necessary to establish whether there is an effect on food consumption.

Adolescent↗

PubMed2002

A preliminary functional magnetic resonance imaging study in offspring of schizophrenic parents.

Studies of high-risk offspring (HR) of schizophrenic patients have found abnormalities in attention, working memory and executive functions, suggesting impaired integrity of the prefrontal cortex and related brain regions. The authors conducted a preliminary high-field (3 T) functional magnetic resonance imaging (fMRI) study to assess performance and activation during a memory-guided saccade (MGS) task, which measures spatial working memory. HR subjects showed significant decreases in fMRI-measured activation in the dorsolateral prefrontal cortex (Brodmann's areas 8 and 9/46) and the inferior parietal cortex (Brodmann's area 40) compared to age- and sex-matched healthy controls (HC). Abnormal functional integrity of prefrontal and parietal regions of the heteromodal association cortical (HAC) regions in subjects at genetic risk for schizophrenia is consistent with findings observed in adults with the illness [Callicott et al., Cereb. Cortex 10 (2000) 1078; Manoach et al., Biol. Psychiatry 48 (2000) 99.]. These abnormalities need to be prospectively investigated in nonpsychotic individuals at risk for schizophrenia in order to determine their predictive value for eventual emergence of schizophrenia or related disorders.

Adolescent↗

PubMed2004

Evidence for progression in frontal cortical pathology in late-stage Huntington's disease.

Atrophy of the cerebral cortex in Huntington's disease is regionally heterogeneous and progressive, involving the entire cerebral mantle in terminal stages. Here, two areas (9 and 46) of the dorsolateral prefrontal cortex were analyzed in 11 late-stage (grades 3 or 4) Huntington's diseased patients and 8 normal control subjects. We used a 3-dimensional cell counting method to assess laminar cell density, number, and width. Reductions in overall cortical thickness in areas 9 (26%) and 46 (23%) were comparable. Area 9 exhibited loss of projection neurons in layers III (16%), V (31%), and VI (37%); these same layers were also reduced in width (25%, 34%, and 46%, respectively). In area 46, reductions in cortical width in layers II (18%) and VI (35%) were not accompanied by neuronal loss. Glial density was increased in deeper layers, reaching significance in layer VI (68%) of area 9 and in layer V (75%) of area 46; glial number was not altered. Thus, area 46 exhibited marked cortical thinning without apparent neuronal degeneration, whereas in area 9 neuronal loss was pronounced, consistent with an advanced phase of cortical pathology. Prominent involvement of corticothalamic neurons is discussed in the context of striatal loop circuitry and a possible pathologic cascade of cortical degeneration.

Adult↗

PubMed2002

Sustained attention in a counting task: normal performance and functional neuroanatomy.

We examined changes in relative cerebral flood flow (relCBF) using PET during a sustained attention paradigm which included auditory stimulation and different tasks of mental counting. Ten normal volunteers underwent PET (15O water) during a baseline state and under experimental conditions which included listening to clicks, serial counting with auditory stimulation, counting with no auditory stimulation, and an additional component of working memory and time estimation. All subjects performed within normal limits in a battery of neurocognitive tests, which included measures of attention and working memory. Both counting with auditory stimulation and counting with no auditory stimulation engaged motor cortex, putamen, cerebellum, and anterior cingulate. Furthermore, counting with no auditory stimulation relative to counting while listening resulted in significantly increased relCBF in the inferior parietal, dorsolateral prefrontal, and anterior cingulate. The findings obtained in this study support the notion that the parietal and dorsolateral prefrontal cortex are involved when time estimation and working memory are taking part in a task requiring sustained attention.

Acoustic Stimulation↗

PubMedDate not supplied

Remembering and knowing in patients with frontal lobe injuries.

Two experiments compared the performance of patients with pathology restricted to the prefrontal cortex to healthy controls on recognition tests that were followed by the remember/know procedure. Across both experiments, patients recognized roughly as many target items as control participants. Injuries centered in the frontal poles resulted in deficits that were selective to episodic remembering while apparently sparing semantic knowing. Patients with lesions restricted to dorsolateral prefrontal cortex were not impaired at either remembering or knowing. Results demonstrate a dissociation of cognitive function within the prefrontal cortex, and suggest that episodic remembering may share a family resemblance with other neurocognitive functions dependent upon polar aspects of the frontal lobes, such as self-recognition, anticipation, and planning.

Adult↗

PubMed1993

Regional cerebral blood flow in depression measured by positron emission tomography: the relationship with clinical dimensions.

We have previously reported focal abnormalities of regional cerebral blood flow (rCBF) in a group of 33 patients with major depression. This report, on an extended sample of 40 patients who demonstrated identical regional deficits to those previously described, examines the relationships between depressive symptoms and patterns of rCBF. Patients' symptom ratings were subjected to factor analysis, producing a three-factor solution. The scores for these three factors, which corresponded to recognizable dimensions of depressive illness, were then correlated with rCBF. The first factor had high loadings for anxiety and correlated positively with rCBF in the posterior cingulate cortex and inferior parietal lobule bilaterally. The second factor had high loadings for psychomotor retardation and depressed mood and correlated negatively with rCBF in the left dorsolateral prefrontal cortex and left angular gyrus. The third factor had a high loading for cognitive performance and correlated positively with rCBF in the left medial prefrontal cortex. These data indicate that symptomatic specificity may be ascribed to regional functional deficits in major depressive illness.

Adult↗