Parkinson’s disease (PD) and autism are prevalent diseases in two disparate age groups. The neuropathology underlying these diseases involves the major neurotransmitters, dopamine and GABA, and/ or their receptors. The current study investigated mRNA gene expressions of the GAD67 in autistic striatum and the DRD1 in the Parkinsonian dorsolateral prefrontal cortex. In situ hybridization histochemistry for GAD67 mRNA levels in postmortem striatal specimens from autistic individuals was compared to those of normal controls. Similarly, a nonradioactive in situ hybridization newly emerging method, RNAscope, was used to assess the D1 receptor mRNA gene expression in postmortem specimens of the dorsolateral prefrontal cortex of PD and control brains. The GAD67 mRNA labeling intensity that was measured on X-ray films and on emulsion radioautograph sections did not vary significantly between the autistic samples and the normal control samples. On the other hand, DRD1 mRNA levels showed a significant increase in the Parkinsonian dorsolateral prefrontal cortex specimens as compared to their normal counterparts. The GAD65 mRNA labeling results corresponded with the GAD67 mRNA levels. The similar GAD67 and GAD65 mRNA patterns in the autism group and the control group may suggest that the hyper-excitability hypothesis can be accounted for by an increase in the glutamatergic activity rather than a decrease in the GABAergic system. The increase in the DRD1 mRNA in the Parkinson’s disease dorsolateral prefrontal cortex may be interpreted in light of the expected upregulation of the D1 receptor in cases of dopamine depletion as the treatment-status was unknown. In conclusion, research investigating the neurotransmitters’ gene expression in Parkinson’s disease and in autism spectrum disorder needs more neurobiological studies in order to establish some knowledge regarding the temporality, and the genetic profile mapping of the diseases. Likewise, more research is encouraged to relate the symptoms and behaviors associated with disease to their anatomical origins.

No description available.

Previous research indicates that many important changes in executive functions, or higher cognitive capacities, occur between the ages of three and five years. Additionally, a distinction can be made between the cognitive functions associated with two different cortical regions. The functions of the dorsolateral prefrontal cortex (DL-PFC) are assessed using 'cool' tasks that are abstract and decontextualised. In contrast, the functions of the orbitofrontal cortex (OFC) are assessed using 'hot' tasks that require flexible appraisal of the affective significance of stimuli (Zelazo & Müller, 2002). Different clinical populations have been hypothesized to differ in terms of their impairment on tasks associated with each area of functioning. Current research conclusions regarding the primacy of hot versus cool executive function impairments are limited, however, as they have not taken complexity into account. That is, tasks currently used in investigations of hot and cool executive functions might differ in terms of the complexity of the cognitive processes that the tasks require. Therefore, comparisons across tasks may be misleading because these tasks vary in terms of the demands they place on participants as well as their hot versus cool status. While complexity theories have been applied to a number of cool tasks, only one hot task, those measuring theory-of-mind abilities, have been analysed in terms of complexity. One aim of the current research was to modify several tasks presumed to measure OFC performance to include a complexity manipulation. Tasks from three hot domains (conditional discrimination, the Children's Gambling Task, and future-oriented decision-making) were analysed in terms of their relational complexity, that is, the number of related entities or arguments inherent in a task or concept (Halford, 1993). Based on these complexity analyses, binary-relational and ternary-relational items of each of these tasks were developed or existing tasks were selected and/or modified. The binary-relational items were closely matched to the ternary-relational items in terms of stimuli and procedure, however, they were lower in complexity. After pilot testing, the three new measures of hot executive functioning were included in a larger test battery that was administered to a sample of 120 normally developing 3-, 4-, 5- and 6-year-old children. Existing binary- and ternary-relational items assessing theory-of-mind (a hot task) and three cool measures (transitivity, class inclusion and the Dimensional Change Card Sort test) were also included. The inclusion of measures of both hot and cool executive functions, each with complexity manipulated, allowed for the examination of a possible differential age of emergence of executive abilities associated with the DL-PFC versus the OFC. In support of the relational complexity approach, significant complexity effects were found across all seven tasks. Items at a higher level of complexity were experienced as relatively more difficult by children of all ages. Significant effects of age were also observed, with performance across all tasks increasing with age. The age effects were strongest on the ternary-relational items. The pass-fail data indicated that the majority of children in all age groups succeeded on the binary-relational items. However, it was not until a median of five years of age that children were able to process ternary relations. Consequently, the ternary-relational items produce the greatest differences in performance between the four age groups. The overall pattern of the results also suggested that a distinction can be made between the ages of emergence of abilities associated with the OFC versus the DL-PFC. The results of the pass-fail percentages, patterns of age-related change and age effects on domain factor scores all suggested that while hot executive functions may begin to develop around four years of age, similar levels of improvement are not seen in cool executive functions until five years of age. Thus, the ability to succeed on ternary-relational items of hot executive function tasks appeared to emerge slightly earlier than the cool executive function tasks. Complexity appears to be a critical factor underlying children's performance on executive function tasks, and future assessment regarding the development of executive abilities will benefit from keeping this in mind. While some refinement of new task items may be beneficial, the current test battery may have utility in further examinations of the executive profiles underlying clinical groups, such as children with autism and ADHD.

Normal aging is associated with a decline in different cognitive domains and local structural atrophy as well as decreases in dopamine concentration and receptor density. To date, it is largely unknown how these reductions in dopaminergic neurotransmission affect human brain regions responsible for reward-based decision making in older adults. Using a learning criterion in a probabilistic object reversal task, we found a learning stage by age interaction in the dorsolateral prefrontal cortex (dIPFC) during decision making. While young adults recruited the dlPFC in an early stage of learning reward associations, older adults recruited the dlPFC when reward associations had already been learned. Furthermore, we found a reduced change in ventral striatal BOLD signal in older as compared to younger adults in response to high probability rewards. Our data are in line with behavioral evidence that older adults show altered stimulus-reward learning and support the view of an altered fronto-striatal interaction during reward-based decision making in old age, which contributes to prolonged learning of reward associations.

Behavioral studies have documented impaired working memory in childhood brain tumor survivors; however, neural mechanisms have yet to be identified using fMRI. The current study investigated BOLD response differences between twenty survivors (Mean age=23.1(4.14), 55% female) and twenty age- and gender-matched controls from the start to the end of a twenty minute 3-back task. There were no differences in task performance between groups or over time. Effects of practice were present in left prefrontal regions, with both groups showing decreases in activation as the task progressed. There were qualitative and quantitative differences in the brain regions that survivors recruited relative to controls in bilateral prefrontal (including the dorsolateral prefrontal cortex) and parietal cortices. Findings suggest that areas under top-down control of the dorsolateral prefrontal cortex become less activated with practice, and that survivors may require more top-down processing and attentional control to perform at similar levels to healthy controls.

Research on the neural correlates of lucid dreaming has recently gained more underlying data. By exploring seven studies that investigated the neural basis of lucid dreaming, this essay sought to examine which neural correlates are associated with lucid dreaming and how proposed neural correlates relate to phenomenological aspects. Dorsolateral prefrontal cortex (DLPFC) was judged as the region most associated with lucid dreaming, in support of a DLPFC hypothesis. Support for reactivation of DLPFC in lucid dreaming consisted of data from electroencephalography, functional magnetic resonance imaging, and transcranial direct current stimulation. Phenomenological aspects associated with this region involved meta-awareness, working-memory, decision-making, and conscious perception. Other regions of interest were parietal areas, frontal areas, and precuneus. Data was not always compatible, implying need for further research. The possibility of further research was judged as promising, based on a recent study inducing lucid dreaming in a significant percent of its test subjects.

No description available.

Executive functioning is a multidimensional concept encompassing higher-order adaptive abilities, such as judgment, decision-making, self-monitoring, planning, and emotional regulation. Disruption in executive functioning often results in devastating impairments in vitally-important areas of life, such as one's ability to hold employment and maintain social relationships. Executive functions have been associated primarily with the prefrontal cortex. However, the nature and degree of the association between frontal lobe damage and performance on executive functioning tests remains controversial. Research suggests that the association may vary based on the specific location of damage within the prefrontal cortex, as well as the used measure of executive functioning. Few investigations have systematically addressed these variables. The current study employed the lesion method to investigate the relationship between performance on a battery of executive functioning tests and damage to specific regions of the prefrontal cortex. Three groups of participants with lesions in one of the locations of interest [ventromedial prefrontal (VMPC, n = 14), dorsolateral prefrontal (DLPC, n = 14), and non-frontal (n = 18)] were administered the Delis-Kaplan Executive Function System (D-KEFS, 2001), a comprehensive battery of executive functioning tests. Results revealed no statistically-significant differences between group performances on the D-KEFS primary measures. However, a qualitative analysis of the results revealed several meaningful group differences. It appears that some relationship exists between frontal lobe damage, particularly in the DLPC, and decreased performance on several executive functioning tests but further research overcoming the methodological limitations of most existing literature on this topic is needed to clearly resolve this issue.

The reticular-activating hypofrontality model of acute exercise (RAH) predicts exercise-induced hypoactivity in frontal cortex which mediates executive function. Connors Continuous Performance Test (CCPT) was used to investigate changes in executive function during- and post treadmill running in healthy volunteers (n=30, 15 male). In a randomized order, subjects performed the CCPT at rest, during low- (LI; 63% maximal heart rate; MHR) and moderate intensity (MI; 75% MHR). Separately, subjects then performed isocalorifically matched exercise bouts of LI, MI and high intensity interval training (HIT) consisting of 4x4 min with 90% MHR and 3 min recovery at 60-70% MHR. Repeated measures ANOVAs revealed main effects of exercise intensity for reaction time RT during- (p≤0.001) and post exercise (p≤0.0001). Subsequent analyses showed an overall increase of RT during exercise compared to rest (p≤0.005). RT decreased significantly from rest to post exercise levels in an exercise intensity dependent, linear fashion (p≤0.0001). Commission errors showed a non significant linear trend to increase both during (p=0.057), and post exercise (p=0.052) as a function of intensity. In a follow up study, we sought to relate observed exercise effects to frontal cortex activity through the use of transcranial direct current stimulation (tDCS) (n=4) and transcranial magnetic stimulation (TMS) over the dorsolateral prefrontal cortex (DLPFC). Prior to TMS stimulation cortical excitability was estimated post running through motor-evoked potentials (MEP) elicited from the primary motor cortex (M1) induced by single burst TMS and measured in the first dorsal interosseous (FDI) muscle using electromyography. At rest, inhibitory cathodal tDCS with left DLPFC cathode and right supraorbital anode led to improved reaction time and increased amount of commission errors, whereas anodal stimulatory tDCS in the immediate post exercise period was unable to recover the post exercise effect. Continuous theta burst stimulation over the left DLPFC post running further impaired inhibitory control and facilitated reaction time. Different findings during- and after- exercise suggests that potential contributing mechanisms such as computational and metabolic factors may be differentially active during these respective conditions. Furthermore, the fact that an inhibitory TMS protocol pronounced the post running effects even more and that we were able to mimic the reported RAH effects at rest with inhibitory frontal tDCS, but observed different patterns during exercise, suggests that the latter state cannot be fully explained by reducing activity in the left frontal cortex alone. Failure to modify the after exercise effect with stimulatory tDCS also supports an interplay of different factors and might emphasize the strong, robust effects of exercise that cannot simply be attenuated by current application. Increases in MEP post running for 35min paired with the observed performance decrements imply an excited state of M1 and might serve as an explanatory cross-link to central fatigue suggesting that a hypofrontal state might enhance the motor cortical drive to activate muscles.

Les hallucinations auditives (HA) sont présentes chez 70% à 80% des patients atteints de schizophrénie et sont résistantes aux traitements pharmacologiques dans environs 25% cas. Ces symptômes induisent une détresse importante chez les sujets et grèvent le pronostic. Dans ce travail, nous avons mis en avant des altérations cérébrales spécifiques aux HA chez des patients atteints de schizophrénie. Dans une première étude, en utilisant la méthode de DTI, nous avons montré que les patients atteints de schizophrénie avec HA ont une intégrité du faisceau arqué, supérieure à celle mesurée chez des patients atteints de schizophrénie sans HA. Dans une seconde étude, en utilisant la méthode de SRM, nous avons montré une augmentation de NAA, reflet du métabolisme neuronal, dans le cortex préfrontal dorsolatéral de l'hémisphère droit chez les patients atteints de schizophrénie avec HA comparé au CPFDL gauche et à des patients atteints de schizophrénie sans HA. Dans ces deux études, le taux de NAA du CPFDL droit et l'intégrité du faisceau arqué ont été associés à la sévérité des HA présentes chez les patients. Dans notre dernière étude, nous avons montré une association entre le taux de BDNF périphérique, marqueur de la plasticité neuronale, et le taux de NAA mesuré dans le CPFDL droit, chez les patients atteints de schizophrénie résistante. Ces résultats montrent qu'il existe une pathophysiologie spécifique des HA chez les patients atteints de schizophrénie et mettent en avant l'importance de stratifier les patients sur la base de leurs symptômes prédominants dans les futures études pathophysiologiques de la schizophrénie / Auditory hallucinations (AH) are present in 70% to 80% of patients with schizophrenia and are resistant to pharmacological treatments in 25% of cases. These symptoms induce significant distress in patients and predict a bad prognosis. In this work we have highlighted cerebral alterations specific to AH in patients suffer from schizophrenia. In a first study, using DTI method, we showed that patients with schizophrenia and AH have an arcuate fasciculus integrity, reflected by the measurement of fractional anisotropy (FA) greater than the one measured in patients with schizophrenia without AH. In a second study, using MRS method, we showed an increase of NAA level measured in the dorsolateral prefrontal cortex (DLPFC) in the right hemisphere in patients with schizophrenia and AH compared to the DLPFC in the left hemisphere and compared to patients with schizophrenia and without AH. Moreover, in these two studies we showed an association between AH severity and the arcuate fasciculus integrity in the left hemisphere and an association between AH severity and NAA levels in the right DLPFC. Finally, in our last study, we quantified BDNF levels using ELISA method and showed an association between peripheral BDNF level, a marker of neuronal plasticity, and NAA levels in the right DLPFC, marker of neuronal metabolism, in patients with treatment-resistant schizophrenia. These results show that there is a specific pathophysiology of AH in patients with schizophrenia and highlight the importance of stratifying patients on the basis of their predominant symptoms in future pathophysiological studies of schizophrenia