Mid-dorsolateral Frontal Cortex Research Articles

23-Prenatal stress, mood, and gray matter volume in young adulthood

This study aimed to determine whether prenatal stress, measured by the number of stressful life events during the first 20 weeks of pregnancy, might relate to mood dysregulation and altered brain structure in young adulthood. Participants included 93 mother – offspring pairs from a community-based birth cohort from the Czech Republic (European Longitudinal Study of Pregnancy and Childhood; ELSPAC-CZ). MRI analyses focused on overall cortical gray matter (GM) volume and GM volume of cortical regions previously associated with major depression. Higher prenatal stress predicted more mood dysregulation, particularly higher anxiety, fatigue and anger, lower overall cortical GM volume (corrected for brain size) and lower GM volume in mid-dorsolateral frontal cortex, anterior cingulate cortex and precuneus in young adulthood. We observed no Prenatal Stress by Sex interactions for any of the above relationships. We conclude that prenatal stress is an important risk factor that relates to worse mood states and altered brain structure in young adulthood irrespective of sex. Our results point to the importance and long lasting effects of prenatal programming and suggest that offspring of mothers who went through substantial stress during pregnancy might benefit from early intervention that would reduce the odds of mental illness in later life.

Prenatal Stress, Mood, and Gray Matter Volume in Young Adulthood.

This study aimed to determine whether prenatal stress, measured by the number of stressful life events during the first 20 weeks of pregnancy, might relate to mood dysregulation and altered brain structure in young adulthood. Participants included 93 young adults from a community-based birth cohort from the Czech Republic. Information on prenatal stress exposure was collected from their mothers in 1990-1992. Magnetic resonance imaging (MRI) and mood-related data were collected from the young adults in 2015. MRI analyses focused on overall gray matter (GM) volume and GM volume of cortical regions previously associated with major depression. Higher prenatal stress predicted more mood dysregulation, lower overall GM volume, and lower GM volume in mid-dorsolateral frontal cortex, anterior cingulate cortex, and precuneus in young adulthood. We observed no prenatal stress by sex interactions for any of the relations. We conclude that prenatal stress is an important risk factor that relates to worse mood states and altered brain structure in young adulthood irrespective of sex. Our results point to the importance and long-lasting effects of prenatal programming and suggest that offspring of mothers who went through substantial stress during pregnancy might benefit from early intervention that would reduce the odds of mental illness in later life.

Top-Down Control-Signal Dynamics in Anterior Cingulate and Prefrontal Cortex Neurons following Task Switching

The prefrontal cortex (PFC) and anterior cingulate cortex (ACC) have both been implicated in cognitive control, but their relative roles remain unclear. Here we recorded the activity of single neurons in both areas while monkeys performed a task that required them to switch between trials in which they had to look toward a flashed stimulus (prosaccades) and trials in which they had to look away from the stimulus (antisaccades). We found that ACC neurons had a higher level of task selectivity than PFC neurons during the preparatory period on trials immediately following a task switch. In ACC neurons, task selectivity was strongest after the task switch and declined throughout the task block, whereas task selectivity remained constant in the PFC. These results demonstrate that the ACC is recruited when cognitive demands increase and suggest a role for both areas in task maintenance and the implementation of top-down control.

Brain regions involved in the recognition of happiness and sadness in music

Here, we used functional magnetic resonance imaging to test for the lateralization of the brain regions specifically involved in the recognition of negatively and positively valenced musical emotions. The manipulation of two major musical features (mode and tempo), resulting in the variation of emotional perception along the happiness-sadness axis, was shown to principally involve subcortical and neocortical brain structures, which are known to intervene in emotion processing in other modalities. In particular, the minor mode (sad excerpts) involved the left orbito and mid-dorsolateral frontal cortex, which does not confirm the valence lateralization model. We also show that the recognition of emotions elicited by variations of the two perceptual determinants rely on both common (BA 9) and distinct neural mechanisms.

Honig's model of working memory and brain activation: an fMRI study.

The present study investigated changes in neuronal activation with fMRI related to Honig's model of working memory, which is much less studied compared with other working memory models. In contrast to other studies which have applied recognition procedures, the primary aim with the present study was to examine brain activation when subjects had to continuously recall and forget items held in working memory. The results showed that the mid-ventrolateral frontal cortex was particularly activated in the left hemisphere, whereas the mid-dorsolateral frontal cortex was particularly activated in the right hemisphere during execution of the working memory task. The findings are discussed in relation to process- and domain-specific accounts of working memory.

Cortico‐cortical connectivity of the human mid‐dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulation

Modulation of cortico-cortical connectivity in specific neural circuits might underlie some of the behavioural effects observed following repetitive transcranial magnetic stimulation (rTMS) of the human frontal cortex. This possibility was tested by applying rTMS to the left mid-dorsolateral frontal cortex (MDL-FC) and subsequently measuring functional connectivity of this region with positron emission tomography (PET) and TMS. The results showed a strong rTMS-related modulation of brain activity in the fronto-cingulate circuit. These results were confirmed in a parallel experiment in the rat using electrical stimulation and field-potential recordings. Future studies are needed to provide a direct link between the rTMS-induced modulation of cortical connectivity and its effects on specific behaviours.

Repetitive transcranial magnetic stimulation of mid-dorsolateral frontal cortex induces release of dopamine in the striatum

Repetitive transcranial magnetic stimulation of mid-dorsolateral frontal cortex induces release of dopamine in the striatum

Increased activation of the mid-dorsolateral frontal cortex during the monitoring of abstract visual and verbal stimuli

Increased activation of the mid-dorsolateral frontal cortex during the monitoring of abstract visual and verbal stimuli

Dissociating aspects of verbal working memory within the human frontal lobe: Further evidence for a “process-specific” model of lateral frontal organization

There is now converging evidence that suggests that working memory processes within the dorsolateral and ventrolateral frontal cortices are organized according to the type of processing required, rather than according to the nature (i.e., domain) of the information being processed, as has been widely assumed. For example, recent positron emission tomography (PET) studies have demonstrated that either, or both, of these two lateral frontal areas can be activated in spatial working memory tasks, depending on the precise executive processes that are called upon by the task being performed. Moreover, in a recent study using functional magnetic resonance imaging, performances of visual spatial and visual nonspatial working memory tasks were shown to involve identical regions of the lateral prefrontal cortex when all the factors unrelated to the type of stimulus domain were appropriately controlled. These results concur fully with recent reviews of the imaging literature, which have demonstrated that spatial and nonspatial working memory studies, in general, have produced a widely distributed pattern of overlapping activation foci within these lateral frontal regions. In this study, the effects of varying the executive requirements of a simple verbal working memory task (forward vs. backward digit span) were explored in 8 subjects, using PET, in order to establish whether this model generalizes to the verbal domain. As was expected, during forward digit span, significant activation was observed within the midventrolateral frontal cortex, but not within the middorsolateral frontal cortex. In contrast, during backward digit span, significant activation was observed in both regions. The results provide further evidence that the middorsolateral and midventrolateral frontal cortical areas make distinct functional contributions to memory and that this corresponds, in psychological terms, to a fractionation of working memory processes.

Activity in Ventrolateral and Mid-Dorsolateral Prefrontal Cortex during Nonspatial Visual Working Memory Processing: Evidence from Functional Magnetic Resonance Imaging

Whole-brain functional magnetic resonance imaging was used to study five healthy human subjects while they performed two nonspatial visual working memory tasks and one control task. In the first memory task, the subjects were required to view a sequence of three pattern stimuli, randomly selected from a familiar set of four stimuli, and then identify which one of three simultaneously presented stimuli was the one that had not been presented in the previous array. In the other task, the subjects were required to observe an identical sequence of three randomly selected pattern stimuli and then to respond by selecting those same stimuli in the order presented. In comparison to a baseline control task, increases in signal intensity were observed, bilaterally, in the mid-dorsolateral frontal cortex and in the right ventrolateral frontal cortex in both memory tasks. When the two tasks were compared directly, however, the first memory task, which had the higher monitoring requirement, yielded significantly greater signal intensity changes in area 9/46 of the right mid-dorsolateral frontal cortex. These results provide further evidence for the precise functional contribution made by the mid-dorsolateral frontal cortex in visual working memory tasks and concur closely with findings in nonhuman primates.

Cortico-cortical connectivity of the human mid-dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulation: a combined TMS/PET study

Cortico-cortical connectivity of the human mid-dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulation: a combined TMS/PET study

Architecture and connections of retrosplenial area 30 in the rhesus monkey (Macaca mulatta).

Because of the sharp curvature of the retrosplenial region around the splenium of the corpus callosum, standard coronal sections are not appropriate for architectonic analysis of its posteroventral part. In the present study, examination of the posteroventral retrosplenial region of the rhesus monkey in sections that were orthogonal to its axis of curvature (and therefore appropriate for architectonic analysis) has permitted definition of its architecture and precise extent. This analysis demonstrated that areas 29 and 30 of the retrosplenial cortex, as well as adjacent area 23 of the posterior cingulate cortex, extend together as an arch around the splenium of the corpus callosum and maintain their topographical relationship with one another throughout their entire course. Injections of anterograde and retrograde tracers confined to retrosplenial area 30 revealed that this area has reciprocal connections with adjacent areas 23, 19 and PGm, with the mid-dorsolateral part of the prefrontal cortex (areas 9, 9/46 and 46), with multimodal area TPO in the superior temporal sulcus, as well as the posterior parahippocampal cortex, the presubiculum and the entorhinal cortex. There are also bidirectional connections with the lateroposterior thalamic nucleus, as well as the laterodorsal and the anteroventral limbic thalamic nuclei. The connectivity of area 30 suggests that it may play a role in working memory processes subserved by the mid-dorsolateral frontal cortex in interaction with the hippocampal system.

Fiber system linking the mid-dorsolateral frontal cortex with the retrosplenial/presubicular region in the rhesus monkey

The present study investigated the origin, course, and terminations of the association fiber system linking the frontal cortex with the hippocampal system by means of the cingulum bundle. Injections of tritiated amino acids were placed within individual cytoarchitectonic areas of the frontal cortex in the rhesus monkey. It was demonstrated that the mid-dorsolateral frontal cortex (areas 46, 9/46, and 9) and its medial extension (medial areas 9 and 9/32) is the origin of a specific fiber pathway, running posteriorly as part of the cingulum bundle, and terminating mainly in the retrosplenial area 30 and the posterior presubiculum. This fiber bundle therefore provides the anatomical substrate of a functional interaction between the mid-dorsolateral frontal cortex and the hippocampal memory system for the monitoring of information within working memory.

Redefining the functional organization of working memory processes within human lateral prefrontal cortex.

It is widely held that the frontal cortex plays a critical part in certain aspects of spatial and non-spatial working memory. One unresolved issue is whether there are functionally distinct subdivisions of the lateral frontal cortex that subserve different aspects of working memory. The present study used positron emission tomography (PET) to demonstrate that working memory processes within the human mid-dorsolateral and mid-ventrolateral frontal regions are organized according to the type of processing required rather than according to the nature (i.e. spatial or non-spatial), of the information being processed, as has been widely assumed. Two spatial working memory tasks were used which varied in the extent to which they required different executive processes. During a 'spatial span' task that required the subject to hold a sequence of five previously remembered locations in working memory a significant change in blood-flow was observed in the right mid-ventrolateral frontal cortex, but not in the anatomically and cytoarchitectonically distinct mid-dorsolateral frontal-lobe region. By contrast, during a '2-back' task that required the subject to continually update and manipulate an ongoing sequence of locations within working memory, significant blood flow increases were observed in both mid-ventrolateral and mid-dorsolateral frontal regions. When the two working memory tasks were compared directly, the one that emphasized manipulation of information within working memory yielded significantly greater activity in the right mid-dorsolateral frontal cortex only. This dissociation provides unambiguous evidence that the mid-dorsolateral and mid-ventrolateral frontal cortical areas make distinct functional contributions to spatial working memory and corresponds with a fractionation of working memory processes in psychological terms.

Working memory in dorsolateral frontal cortex

It is widely held that the frontal cortex plays a critical role in certain aspects of both spatial and non-spatial working memory. The prevailing view in recent years has been that there are domain-specific subdivisions within dorsal and ventral regions of the prefrontal cortex, which subserve working memory for spatial and non-spatial information, respectively. However, Owen et al. have now used functional magnetic resonance imaging to demonstrate that performance of such tasks involves identical regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled[1xFunctional organization of spatial and nonspatial memory processing within the human lateral frontal cortex. Owen, A.M. et al. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 7721–7726Crossref | PubMed | Scopus (263)See all References[1]. Two similar tasks, one involving the short-term retention and manipulation of spatial information and the other involving non-spatial visual patterns both activated the mid-dorsolateral frontal cortex in six subjects. These data provide evidence that spatial and non-spatial working memory might not be mediated by dorsal and ventral regions, respectively, of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral frontal cortex make identical executive functional contributions to working memory.

Monitoring Selections from a Visual Array Activates the Mid-dorsolateral Frontal Cortex: Evidence from Functional MRI

Monitoring Selections from a Visual Array Activates the Mid-dorsolateral Frontal Cortex: Evidence from Functional MRI

Prefrontal Cortex Involvement in Selective Letter Generation: A Functional Magnetic Resonance Imaging Study

Cerebral responses to alternating periods of a control task and a selective letter generation paradigm were investigated with functional Magnetic Resonance Imaging (fMRI). Subjects selectively generated letters from four designated sets of six letters from the English language alphabet, with the instruction that they were not to produce letters in alphabetical order either forward or backward, repeat or alternate letters. Performance during this condition was compared with that of a control condition in which subjects recited the same letters in alphabetical order. Analyses revealed significant and extensive foci of activation in a number of cerebral regions including mid-dorsolateral frontal cortex, inferior frontal gyrus, precuneus, supramarginal gyrus, and cerebellum during the selective letter generation condition. These findings are discussed with respect to recent positron emission tomography (PET) and fMRI studies of verbal working memory and encoding/retrieval in episodic memory.

Specialized systems for the processing of mnemonic information within the primate frontal cortex.

The lateral frontal cortex is involved in various aspects of executive processing within short- and long-term memory. It is argued that the different parts of the lateral frontal cortex make distinct contributions to memory that differ in terms of the level of executive processing that is carried out in interaction with posterior cortical systems. According to this hypothesis, the mid-dorsolateral frontal cortex (areas 46 and 9) is a specialized system for the monitoring and manipulation of information within working memory, whereas the mid-ventrolateral frontal cortex (areas 47/12 and 45) is involved in the active retrieval of information from the posterior cortical association areas. Data are presented which support this two-level hypothesis that posits two distinct levels of interaction of the lateral frontal cortex with posterior cortical association areas. Functional activation studies with normal human subjects have demonstrated specific activity within the mid-dorsolateral region of the frontal cortex during the performance of tasks requiring monitoring of self-generated and externally generated sequences of responses. In the monkey, lesions restricted to this region of the frontal cortex yield a severe impairment in performance of the above tasks, this impairment appearing against a background of normal performance on several basic mnemonic tasks. By contrast, a more severe impairment follows damage to the mid-ventrolateral frontal region and functional activation studies have demonstrated specific changes in activity in this region in relation to the active retrieval of information from memory.

Planning and Spatial Working Memory: a Positron Emission Tomography Study in Humans

Previous work with both neurosurgical and neurodegenerative patient groups has suggested that high level planning is mediated by neural circuitry which includes both the prefrontal cortex and the striatum. In this study, the functional anatomy of cognitive planning was investigated further, using positron emission tomography (PET). Regional cerebral blood flow (rCBF) was measured in 12 normal volunteers while performing easy and difficult versions of (i) a modified Tower of London planning task; (ii) a mnemonic variant of this task that required short-term retention and reproduction of problem solutions; and (iii) a control condition that involved identical visual stimuli and motor responses. Significant increases in rCBF were observed in the left hemisphere, in both the mid-dorsolateral frontal cortex and in the head of the caudate nucleus, when the difficult planning task was compared with the control condition. Moreover, subtraction of a simple planning condition from the more difficult one revealed focal increases in rCBF in the caudate nucleus and the thalamus only. During both mnemonic variants of the planning task, changes were also observed in the mid-dorsolateral frontal cortex and in more ventral frontopolar regions, bilaterally. When compared directly, the planning and memory conditions differed in terms of these ventral activation foci, but not in the pattern of activation observed in mid-dorsolateral frontal cortex. These findings further implicate frontostriatal circuitry in high-level planning and provide evidence for functionally distinct contributions from ventral and dorsolateral frontal regions to spatial working memory.

Evidence for a two-stage model of spatial working memory processing within the lateral frontal cortex: a positron emission tomography study.

Previous work in nonhuman primates and in patients with frontal lobe damage has suggested that the frontal cortex plays a critical role in the performance of both spatial and nonspatial working memory tasks. The present study used positron emission tomography with magnetic resonance imaging to demonstrate the existence, within the human brain, of two functionally distinct subdivisions of the lateral frontal cortex, which may subserve different aspects of spatial working memory. Five spatial memory tasks were used, which varied in terms of the extent to which they required different executive processes. When the task required the organization and execution of a sequence of spatial moves retained in working memory, significant changes in blood flow were observed in ventrolateral frontal cortex (area 47) bi-laterally. By contrast, when the task required active monitoring and manipulation of spatial information within working memory, additional activation foci were observed in mid-dorsolateral frontal cortex (areas 46 and 9). These findings support a two-stage model of spatial working memory processing within the lateral frontal cortex.