Mid-dorsolateral Prefrontal Cortex Research Articles

Interaction of the dorsolateral prefrontal cortex with the precuneal medial parietal cortex for the monitoring of information in working memory in the macaque monkey.

The executive control process of monitoring information in working memory depends on the mid-dorsolateral prefrontal cortical region (cytoarchitectonic areas 46 and 9/46) in interaction with the hippocampal memory system. Anatomical studies demonstrated strong connectivity between the mid-dorsolateral prefrontal cortex and the medial parietal area PGm that lies on the precuneus. Area PGm is also strongly connected with the attentional system on the lateral inferior parietal lobule (area PG) and the limbic retrosplenial/posterior cingulate region that interacts with the hippocampal memory system. Thus, in terms of anatomical connectivity, area PGm appears to be a critical node for the integration of executive control processing from the prefrontal cortex with the online attentional and memory related processing. This hypothesis was tested in macaque monkeys with the crossed unilateral lesion methodology. A unilateral lesion in the mid-dorsolateral prefrontal cortex was combined with a unilateral lesion in area PGm in the opposite hemisphere. The results demonstrated an impairment on the externally ordered working memory task that assesses the monitoring of information in working memory. Thus, the medial parietal area PGm is a critical node in mediating the functional interaction between the prefrontal region for the executive control process of monitoring information and the memory system.

Mapping causal links between prefrontal cortical regions and intra-individual behavioral variability

Intra-individual behavioral variability is significantly heightened by aging or neuropsychological disorders, however it is unknown which brain regions are causally linked to such variabilities. We examine response time (RT) variability in 21 macaque monkeys performing a rule-guided decision-making task. In monkeys with selective-bilateral lesions in the anterior cingulate cortex (ACC) or in the dorsolateral prefrontal cortex, cognitive flexibility is impaired, but the RT variability is significantly diminished. Bilateral lesions within the frontopolar cortex or within the mid-dorsolateral prefrontal cortex, has no significant effect on cognitive flexibility or RT variability. In monkeys with lesions in the posterior cingulate cortex, the RT variability significantly increases without any deficit in cognitive flexibility. The effect of lesions in the orbitofrontal cortex (OFC) is unique in that it leads to deficits in cognitive flexibility and a significant increase in RT variability. Our findings indicate remarkable dissociations in contribution of frontal cortical regions to behavioral variability. They suggest that the altered variability in OFC-lesioned monkeys is related to deficits in assessing and accumulating evidence to inform a rule-guided decision, whereas in ACC-lesioned monkeys it results from a non-adaptive decrease in decision threshold and consequently immature impulsive responses.

Specific age-correlated activation of top hierarchical motor control areas during gait-like plantar stimulation: An fMRI study.

A better understanding of gait disorders that are associated with aging is crucial to prevent adverse outcomes. The functional study of gait remains a thorny issue due to technical constraints inherent to neuroimaging procedures, as most of them require to stay supine and motionless. Using an MRI‐compatible system of boots reproducing gait‐like plantar stimulation, we investigated the correlation between age and brain fMRI activation during simulated gait in healthy adults. Sixty‐seven right‐handed healthy volunteers aged between 20 and 77 years old (49.2 ± 18.0 years; 35 women) were recruited. Two paradigms were assessed consecutively: (a) gait‐like plantar stimulation and (b) chaotic and not gait‐related plantar stimulation. Resulting statistical parametric maps were analyzed with a multiple‐factor regression that included age and a threshold determined by Monte‐Carlo simulation to fulfill a family‐wise error rate correction of p < .05. In the first paradigm, there was an age‐correlated activation of the right pallidum, thalamus and putamen. The second paradigm showed an age‐correlated deactivation of both primary visual areas (V1). The subtraction between results of the first and second paradigms showed age‐correlated activation of the right presupplementary motor area (Brodmann Area [BA] 6) and right mid‐dorsolateral prefrontal cortex (BA9‐10). Our results show age‐correlated activity in areas that have been associated with the control of gait, highlighting the relevance of this simulation model for functional gait study. The specific progressive activation of top hierarchical control areas in simulated gait and advancing age corroborate a progressive loss of automation in healthy older adults.

Cortical gyrification in children with attention deficit-hyperactivity disorder and prenatal alcohol exposure

BackgroundAn improved understanding of the neurodevelopmental differences between attention deficit hyperactivity disorder with and without prenatal alcohol exposure (ADHD + PAE and ADHD-PAE, respectively) is needed. Herein, we evaluated gyrification (cortical folding) in children with ADHD + PAE compared to that in children with familial ADHD-PAE and typically developing (TD) children. MethodsADHD + PAE (n = 37), ADHD-PAE (n = 25), and TD children (n = 27), aged 8–13 years, were compared on facial morphological, neurobehavioral, and neuroimaging assessments. Local gyrification index (LGI) maps were compared between groups using general linear modelling. Relationships between LGI and clincobehavioral parameters in children with ADHD ± PAE were evaluated using multivariate partial least squares. ResultsADHD + PAE and ADHD-PAE groups showed significantly lower LGI (relative to TD) in numerous regions, overlapping in medial prefrontal, parietal, and temporo-occipital cortices (p < 0.001). However, LGI in left mid-dorsolateral prefrontal cortex was uniquely lower in the ADHD + PAE group (p < 0.001). Partial least squares analysis identified one significant latent variable (accounting for 59.3 % of the crossblock correlation, p < 0.001), reflecting a significant relationship between a profile of lower LGI in prefrontal (including left mid-dorsolateral), insular, cingulate, temporal, and parietal cortices and a clinicobehavioral profile of PAE, including a flat philtrum and upper vermillion border, lower IQ, poorer behavioral regulation scores, and greater hyperactivity/impulsivity. ConclusionsChildren with ADHD + PAE uniquely demonstrate lower mid-dorsolateral LGI, with widespread lower LGI related to more severe facial dysmorphia and neurobehavioral impairments. These findings add insight into the brain bases of PAE symptoms, potentially informing more targeted ADHD treatments based on an objective differential diagnosis of ADHD + PAE vs. ADHD-PAE.

Sense of coherence, spontaneous brain activity, and burnout severity

IntroductionBurnout has become a critical issue in health care systems during the COVID-19 pandemic. Several studies report on the importance of peoples’ sense of coherence (SOC) or control over work for dealing with burnout. SOC implicates a stress-coping capacity involving comprehensibility, manageability, and meaningfulness. However, little is known on how SOC cognitively modulates burnout experiences.ObjectivesTo investigate neurocognitive mechanisms of SOC and burnout in medical professionals.MethodsForty-one registered nurses were enrolled. We used functional magnetic resonance imaging and measured resting-state brain activity. We identified brain regions associated with SOC and burnout levels by correlating these trait scores to regional fractional amplitude of low frequency fluctuations (fALFF). Subsequently, we investigated whether participants’ levels of SOC impacted their fALFF-burnout association by mediation analysis.ResultsSOC and depersonalization dimension of burnout were negatively correlated (p &lt; 0.01). The fALFF in the mid-dorsolateral prefrontal cortex (DLPFC) correlated positively with SOC scores, and negatively with depersonalization dimension of burnout (p &lt; 0.05). Furthermore, SOC mediated the negative relationship between DLPFC activity and burnout severity (p &lt; 0.05).ConclusionsOur data suggested that SOC alleviates burnout experience and supports prefrontal activity to prompt cognitive control; they may facilitate flexible shifting of perspective and optimistic reappraisal of work-stress. In effect, workplace-stressors may be acknowledged as being more meaningful than distressing. Without sufficient SOC, frequent exposures to stressors can lead to maladaptive coping to exhibit emotional numbing or depersonalization.DisclosureNo significant relationships.

Functionally dissociating ventro-dorsal components within the rostro-caudal hierarchical organization of the human prefrontal cortex

Cognitive control is proposed to rely on a rostral-to-caudal hierarchy of neural processing within the prefrontal cortex (PFC), with more rostral parts exerting control over more caudal parts. Anatomical and functional data suggest that this hierarchical organization of the PFC may be separated into a ventral and a dorsal component. Furthermore, recent studies indicate that the apex of the hierarchy resides within the mid-lateral rather the rostral PFC. However, investigating the hierarchical aspect of rostro-to-caudal processing requires quantification of the directed interactions between PFC regions.Using functional near-infrared spectroscopy (fNIRS) in a sample of healthy young adults we analyzed directed interactions between rostral and caudal PFC during passive watching of nature documentaries. Directed coherence (DC) as a measure of directed interaction was computed pairwise between 38 channels evenly distributed over the lateral prefrontal convexity.Results revealed an overall predominance of rostral-to-caudal directed interactions in the PFC that further dissociated along a ventro-dorsal axis: Dorsal regions exerted stronger rostro-caudally directed interactions on dorsal than on ventral regions and vice versa. Interactions between ventral and dorsal PFC were stronger from ventral to dorsal areas than vice versa. Results further support the notion that the mid-dorsolateral PFC constitutes the apex of the prefrontal hierarchy.Taken together these data provide novel evidence for parallel dorsal and ventral streams within the rostro-caudal hierarchical organization of the PFC. FNIRS-based analyses of directed interactions put forward a new perspective on the functional architecture of the prefrontal hierarchy and complement previous insights from functional magnetic resonance imaging.

Insula and amygdala resting-state functional connectivity differentiate bipolar from unipolar depression.

Distinguishing depressive episodes due to bipolar disorder (BD) or major depressive disorder (MDD) solely on clinical grounds is challenging. We aimed at comparing resting-state functional connectivity (rsFC) of regions subserving emotional regulation in similarly depressed BD and MDD. We enrolled 76 in-patients (BD, n = 36; MDD, n = 40) and 40 healthy controls (HC). A seed-based approach was used to identify regions showing different rsFC with the insula and the amygdala. Insular and amygdalar parcellations were then performed along with diagnostic accuracy of the main findings. Lower rsFC between the left insula and the left mid-dorsolateral prefrontal cortex and between bilateral insula and right frontopolar prefrontal cortex (FPPFC) was observed in BD compared to MDD and HC. These results were driven by the dorsal anterior and posterior insula (PI). Lower rsFC between the right amygdala and the left anterior hippocampus was observed in MDD compared to BD and HC. These results were driven by the centromedial and laterobasal amygdala. Left PI/right FPPC rsFC showed 78% accuracy differentiating BD and MDD. rsFC of amygdala and insula distinguished between depressed BD and MDD. The observed differences suggest the possibility of differential pathophysiological mechanisms of emotional dysfunction in bipolar and unipolar depression.

The impact of symptomatic mild traumatic brain injury on complex everyday activities and the link with alterations in cerebral functioning: Exploratory case studies

ABSTRACTThe objective of the study was to explore the neurophysiological correlates of altered functional independence using functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) after a mild traumatic brain injury (mTBI). The participants consisted of three individuals with symptomatic mTBI (3.9 ± 3.6 months post-mTBI) and 12 healthy controls. The main measures used were the Instrumental Activities of Daily Living (IADL) Profile observation-based assessment; a visual externally ordered working memory task combined to event-related potentials (ERP) and fMRI recordings; neuropsychological tests; post-concussion symptoms questionnaires; and the Activities of Daily Living (ADL) Profile interview. Compared to normal controls, all three patients had difficulty with a real-world complex budgeting activity due to deficits in planning, ineffective strategy use and/or a prolonged time to detect and correct errors. Reduced activations in the right mid-dorsolateral prefrontal cortex on fMRI as well as abnormal frontal or parietal components of the ERP occurred alongside these deficits. Results of this exploratory study suggest that reduced independence in complex everyday activities in symptomatic mTBI may be at least partly explained by a decrease in brain activation in the prefrontal cortex, abnormal ERP, or slower reaction times on working memory tasks. The study presents an initial attempt at combining research in neuroscience with ecological real-world evaluation research to further our understanding of the difficulties in complex everyday activities experienced by individuals with mTBI.

Extraversion mediates the relationship between structural variations in the dorsolateral prefrontal cortex and social well-being

Social well-being reflects the appraisal of one's circumstance and functioning in society, which is crucial for individuals' mental and physical health. However, little is known about the neural processes associated with social well-being. In this study, we used voxel-based morphometry (VBM) to identify the brain regions underlying individual differences in social well-being, as measured by the Social Well-being Scale (SWBS), in a large sample of young healthy adults. We found that social well-being was negatively correlated with gray matter volume in left mid-dorsolateral prefrontal cortex (mid-DLPFC) that is implicated in executive functioning, emotional regulation and social reasoning. The results remained significant even after controlling for the effect of socioeconomic status. Furthermore, although basic personality factors such as neuroticism, extraversion, and conscientiousness (as measured by the NEO Personality Inventory) all contributed to social well-being, only extraversion acted as a mediational mechanism underlying the association between the left mid-DLPFC volume and social well-being. Together, our findings provide the first evidence for the structural basis of individual differences in social well-being, and suggest that the personality trait of extraversion might play an important role in the acquisition and process of social well-being.

Larger mid-dorsolateral prefrontal gray matter volume in young binge drinkers revealed by voxel-based morphometry.

Binge drinking or heavy episodic drinking is a high prevalent pattern of alcohol consumption among young people in several countries. Despite increasing evidence that binge drinking is associated with impairments in executive aspects of working memory (i.e. self-ordered working memory), processes known to depend on the mid-dorsolateral prefrontal cortex (Brodmann areas 46 and 9), less is known about the impact of binge drinking on prefrontal gray matter integrity. Here, we investigated the effects of binge drinking on gray matter volume of mid- dorsolateral prefrontal cortex in youths. We used voxel-based morphometry on the structural magnetic resonance images of subjects reporting a persistent (at least three years) binge drinking pattern of alcohol use (n = 11; age 22.43±1.03) and control subjects (n = 21; age 22.18±1.08) to measure differences in gray matter volume between both groups. In a region of interest analysis of the mid-dorsolateral prefrontal cortex, after co-varying for age and gender, we observed significantly larger gray matter volume in the left mid-dorsolateral prefrontal cortex (Brodmann areas 46 and 9) in binge drinkers in comparison with control subjects. Furthermore, there was a significant positive correlation between left mid-dorsolateral prefrontal cortex volume and Self-Ordered Pointing Test (SOPT) total errors score in binge drinkers. The left mid-dorsolateral prefrontal cortex volume also correlated with the quantity and speed of alcohol intake. These findings indicate that a repeated exposure to alcohol −that does not meet criteria for alcohol dependence− throughout post-adolescent years and young adulthood is linked with structural anomalies in mid-dorsolateral prefrontal regions critically involved in executive aspects of working memory.

Development of active control within working memory

This study aimed to compare children’s performance on two mnemonic functions that engage the lateral prefrontal cortex. Brain imaging studies in adults have shown that the mid-ventrolateral prefrontal cortex is specifically involved in active controlled retrieval, and the mid-dorsolateral prefrontal cortex is specifically involved in monitoring mnemonic information (Petrides, 2005). Eighty-two children aged from 6 years, 8 months to 8 years, 7 months were tested. They showed equivalent success rates in active retrieval and monitoring with color and shape information. However, children were slower in monitoring than in active retrieval in color trials. The results demonstrate that the specialized contributions of the lateral prefrontal cortex emerge conjointly during childhood giving children multiple tools to exert an active control within memory.

Predicting Planning Performance from Structural Connectivity Between Left and Right Mid-Dorsolateral Prefrontal Cortex: Moderating Effects of Age During Postadolescence and Midadulthood

Complex cognitive abilities such as planning are known to critically rely on activity of bilateral mid-dorsolateral prefrontal cortex (mid-dlPFC). However, the functional relevance of the structural connectivity between left and right mid-dlPFC is yet unknown. Here, we applied global tractography to derive streamline counts as estimates of the structural connectivity between mid-dlPFC homologs and related it to planning performance in the Tower of London task across early to midadulthood, assuming a moderating effect of age. Multiple regression analyses with interaction effects revealed that streamline counts between left and right mid-dlPFC were negatively associated with planning performance specifically in early postadolescence. From the fourth life decade on, there was a trend for a reversed, positive association. These differential findings were corroborated by converging results from fractional anisotropy and white-matter density estimates in the genu of the corpus callosum where fibers connecting mid-dlPFC homologs traversed. Moreover, the results for streamline counts were regionally specific, marking the strength of mid-dlPFC connectivity as critical in predicting interindividual differences in planning performance across different stages of adulthood. Taken together, present findings provide first evidence for nonadditive effects of age on the relation between complex cognitive abilities and the structural connectivity of mid-dlPFC homologs.

Complementary roles of medial temporal lobes and mid‐dorsolateral prefrontal cortex for working memory for novel and familiar trial‐unique visual stimuli

It has been suggested that working memory (WM) for novel information requires the medial temporal lobes (MTL), but is not necessary for WM for familiar stimuli. In previous studies that directly compared WM for novel and familiar stimuli, only the novel stimuli were trial-unique. Here, 16 young human subjects performed a Sternberg WM task with visual scenes while in a functional magnetic resonance imaging scanner. All task stimuli were trial-unique, but were either new (Novel condition) or previously learned (Familiar condition). This design allowed investigation of whether MTL and prefrontal cortex (PFC) activity is related specifically to the novelty/familiarity of the stimuli or to their trial-unique status during WM. We observed greater hippocampal and parahippocampal activity during encoding and maintenance for novel than for familiar stimuli. In contrast, right mid-dorsolateral PFC (dlPFC) activity was greater during encoding of familiar than novel stimuli. The mid-dlPFC was not recruited during maintenance or for retrieval when the Familiar condition was contrasted with the Novel condition. However, left mid-dlPFC activity was present at retrieval when correct Match trials (i.e. hits) were contrasted with correct Non-match trials (i.e. correct rejections) for the Novel condition. The results support the hypothesis that MTL regions are required for the encoding and maintenance of novel stimuli during WM, demonstrating that the observed MTL activity is not related to the trial-uniqueness of the stimuli per se. Furthermore, the observed activation pattern in mid-dlPFC suggests a role for the mid-dlPFC in executive control-associated processes related to monitoring of scene familiarity at encoding and retrieval during WM.

The Influence of Pain on Cerebral Functioning after Mild Traumatic Brain Injury

More than 75% of patients with mild traumatic brain injury (MTBI) report chronic pain whose potential detrimental effects on cognitive recovery need to be identified. The objective of this study was to investigate the relationship between pain, performance on a working memory task, gray matter density, and mid-dorsolateral prefrontal cortex (mid-DLPFC) activation in subjects with a MTBI. For comparison purposes, we performed identical correlation analyses with a group of subjects without MTBI who sustained sports injuries. Twenty-four subjects who experienced a MTBI in the past 12 months, 16 control subjects, and 29 subjects with sport injuries were included. One hour prior to entering the magnetic resonance scanner, the subjects were asked to fill out the pain Visual Analogue Scale. Subsequently, a high-resolution T1-weighted image was acquired followed by a functional magnetic resonance imaging session using the visual externally ordered working memory task. Results showed that MTBI subjects reporting severe pain in the hour preceding the testing had reduced mid-DLPFC activation during the working memory task and poorer performance on the task. Subjects with sport injuries and severe levels of pain showed the reverse pattern: pain was associated with higher activation in the mid-DLPFC and did not correlate with performance. Gray matter density measures were independent of pain level. This study showed that behavioral performance and cerebral functioning are affected by pain after a MTBI. Moreover, this study suggests that pain, cognition, and cerebral functioning interactions could not easily be generalized from one clinical population to another.

Rostral–caudal gradients of abstraction revealed by multi-variate pattern analysis of working memory

The lateral frontal cortex (LFC) is thought to represent contextual and rule-based information that allows adaptive behavior according to circumstance. Recent progress has suggested that the representations of the LFC vary along its rostral-caudal axis with more abstract, higher level representations associated with rostral areas of the LFC and more concrete, lower level representations associated with caudal areas of the LFC. Here, we investigated this proposal. Subjects responded to stimuli based upon a nested series of contextual cues stored in working memory (WM) while being scanned with fMRI. Higher level context cues denoted an abstract rule set while lower level context cues provided more concrete information. Using multi-variate pattern analysis (MVPA), we found varying forms of representation along the rostral-caudal axis of the LFC depending on the type of information stored in WM. Rostral areas of frontal cortex in the lateral orbitofrontal cortex (OFC) represented the higher level context, but not more concrete information, and only when more concrete information was unavailable. Mid-level areas in the mid-dorsolateral prefrontal cortex (DLPFC) and inferior frontal junction (IFJ) represented more concrete rules, but only when the forthcoming response could not be anticipated. By contrast, the dorsal premotor cortex (PMd) and primary motor cortex (M1) represented contextual and response information when the forthcoming response could be anticipated on the basis of context. Collectively, these data indicate that representations dedicated to higher levels of abstraction become less discriminating when more concrete information becomes available. These patterns are consistent with rostral-caudal abstraction proposals of the LFC.

Linking planning performance and gray matter density in mid-dorsolateral prefrontal cortex: Moderating effects of age and sex

Planning of behavior relies on the integrity of the mid-dorsolateral prefrontal cortex (mid-dlPFC). Yet, only indirect evidence exists on the association of protracted maturation of dlPFC and continuing gains in planning performance post adolescence. Here, gray matter density of mid-dlPFC in young, healthy adults (18-32 years) was regressed onto performance on the Tower of London planning task while accounting for moderating effects of age and sex on this interrelation. Multiple regression analysis revealed an association of planning performance and mid-dlPFC gray matter density that was especially strong in late adolescence and early twenties. As expected, for males better planning performance was linked to reduced gray matter density of mid-dlPFC, possibly due to maturational processes such as synaptic pruning. Most surprisingly, females showed an inverted, positive interrelation of planning performance and mid-dlPFC gray matter density, indicating that sexually dimorphic development of dlPFC continues during early adulthood. Age and sex are hence important moderators of the link between planning performance and gray matter density in mid-dlPFC. Consequently, the assessment of moderator effects in regression designs can significantly enhance understanding of brain-behavior relationships.

The Function and Organization of Lateral Prefrontal Cortex: A Test of Competing Hypotheses

The present experiment tested three hypotheses regarding the function and organization of lateral prefrontal cortex (PFC). The first account (the information cascade hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the timing with which cue stimuli reduce uncertainty in the action selection process. The second account (the levels-of-abstraction hypothesis) suggests that the anterior-posterior organization of lateral PFC is based on the degree of abstraction of the task goals. The current study began by investigating these two hypotheses, and identified several areas of lateral PFC that were predicted to be active by both the information cascade and levels-of-abstraction accounts. However, the pattern of activation across experimental conditions was inconsistent with both theoretical accounts. Specifically, an anterior area of mid-dorsolateral PFC exhibited sensitivity to experimental conditions that, according to both accounts, should have selectively engaged only posterior areas of PFC. We therefore investigated a third possible account (the adaptive context maintenance hypothesis) that postulates that both posterior and anterior regions of PFC are reliably engaged in task conditions requiring active maintenance of contextual information, with the temporal dynamics of activity in these regions flexibly tracking the duration of maintenance demands. Activity patterns in lateral PFC were consistent with this third hypothesis: regions across lateral PFC exhibited transient activation when contextual information had to be updated and maintained in a trial-by-trial manner, but sustained activation when contextual information had to be maintained over a series of trials. These findings prompt a reconceptualization of current views regarding the anterior-posterior organization of lateral PFC, but do support other findings regarding the active maintenance role of lateral PFC in sequential working memory paradigms.

Mechanisms of Rule Acquisition and Rule Following in Inductive Reasoning

Despite the recent interest in the neuroanatomy of inductive reasoning processes, the regional specificity within prefrontal cortex (PFC) for the different mechanisms involved in induction tasks remains to be determined. In this study, we used fMRI to investigate the contribution of PFC regions to rule acquisition (rule search and rule discovery) and rule following. Twenty-six healthy young adult participants were presented with a series of images of cards, each consisting of a set of circles numbered in sequence with one colored blue. Participants had to predict the position of the blue circle on the next card. The rules that had to be acquired pertained to the relationship among succeeding stimuli. Responses given by subjects were categorized in a series of phases either tapping rule acquisition (responses given up to and including rule discovery) or rule following (correct responses after rule acquisition). Mid-dorsolateral PFC (mid-DLPFC) was active during rule search and remained active until successful rule acquisition. By contrast, rule following was associated with activation in temporal, motor, and medial/anterior prefrontal cortex. Moreover, frontopolar cortex (FPC) was active throughout the rule acquisition and rule following phases before a rule became familiar. We attributed activation in mid-DLPFC to hypothesis generation and in FPC to integration of multiple separate inferences. The present study provides evidence that brain activation during inductive reasoning involves a complex network of frontal processes and that different subregions respond during rule acquisition and rule following phases.

Electrophysiology and Functional MRI in Post-Acute Mild Traumatic Brain Injury

Symptoms persisting beyond the acute phase (>2 months) after a mild traumatic brain injury (MTBI) are often reported, but their origin remains controversial. Some investigators evoke dysfunctional cerebral mechanisms, while others ascribe them to the psychological consequences of the injury. We address this controversy by exploring possible cerebral dysfunction with functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) in a group of patients during the post-acute phase. Fourteen MTBI symptomatic patients (5.7±2.9 months post-injury) were tested with fMRI and ERP using a visual externally ordered working memory task, and were compared with 23 control subjects. Attenuated blood oxygen level dependent (BOLD) signal changes in the left and right mid-dorsolateral prefrontal cortex (mid-DLPFC), the putamen, the body of the caudate nucleus, and the right thalamus were found in the MTBI group compared with the control group. Moreover, symptom severity and BOLD signal changes were correlated: patients with more severe symptoms had lower BOLD signal changes in the right mid-DLPFC. For ERP, a group×task interaction was observed for N350 amplitude. A larger amplitude for the working memory task than for the control task was found in control subjects, but not in MTBI subjects, who had weak amplitudes for both tasks. This study confirms that persistent symptoms after MTBI cannot be uniquely explained by psychological factors, such as depression and/or malingering, and indicates that they can be associated with cerebral dysfunction. ERP reveals decreased amplitude of the N350 component, while fMRI demonstrates that the more severe the symptoms, the lower the BOLD signal changes in the mid-DLPFC.

Dissociable Contributions of Left and Right Dorsolateral Prefrontal Cortex in Planning

It is well established that the mid-dorsolateral prefrontal cortex (dlPFC) plays a critical role in planning. Neuroimaging studies have yielded predominantly bilateral dlPFC activations, but the existence and nature of functionally specific contributions of left and right dlPFC have remained elusive. In recent experiments, 2 independent parameters have been identified which substantially determine planning: 1) the degree of interdependence between consecutive steps (search depth) and 2) the degree to which the configuration of the goal state renders the order of single steps either clearly evident or ambiguous (goal hierarchy). Thus, search depth affects the actual mental generation and evaluation of action sequences, whereas goal hierarchy reflects the extraction of goal information from an encountered problem. Here, both parameters were independently manipulated in an event-related functional magnetic resonance imaging study using the Tower of London task. Results revealed a double dissociation as indicated by a significant crossover interaction of hemisphere and task parameter: in left dlPFC, activations were stronger for higher demands on goal hierarchy than on search depth, whereas the reversed result emerged in right dlPFC. In conclusion, often observed bilateral patterns of dlPFC activation in complex tasks may reflect the concomitant operation of specific cognitive processes that show opposing lateralizations.