Differences In Prefrontal Cortex Research Articles

Evaluation of the learning state of online video courses based on functional near infrared spectroscopy.

Studying brain activity during online learning will help to improve research on brain function based on real online learning situations, and will also promote the scientific evaluation of online education. Existing research focuses on enhancing learning effects and evaluating the learning process associated with online learning from an attentional perspective. We aimed to comparatively analyze the differences in prefrontal cortex (PFC) activity during resting, studying, and question-answering states in online learning and to establish a classification model of the learning state that would be useful for the evaluation of online learning. Nineteen university students performed experiments using functional near-infrared spectroscopy (fNIRS) to monitor the prefrontal lobes. The resting time at the start of the experiment was the resting state, watching 13 videos was the learning state, and answering questions after the video was the answering state. Differences in student activity between these three states were analyzed using a general linear model, 1s fNIRS data clips, and features, including averages from the three states, were classified using machine learning classification models such as support vector machines and k-nearest neighbor. The results show that the resting state is more active than learning in the dorsolateral prefrontal cortex, while answering questions is the most active of the three states in the entire PFC, and k-nearest neighbor achieves 98.5% classification accuracy for 1s fNIRS data. The results clarify the differences in PFC activity between resting, learning, and question-answering states in online learning scenarios and support the feasibility of developing an online learning assessment system using fNIRS and machine learning techniques.

Distinct age-related brain activity patterns in the prefrontal cortex when increasing cognitive load: A functional near-infrared spectroscopy study

Researchers have long observed distinct brain activity patterns in older adults compared with younger adults that correlate with cognitive performance. Mainly, older adults tend to show over-recruitment of bilateral brain regions during lower task loads and improved performance interpreted as compensation, but not observed at higher loads. However, there are discrepancies about whether increases in activity are compensatory and whether older adults can show compensation at higher loads. Our aim was to examine age-related differences in prefrontal cortex (PFC) activity and cognitive performance using functional near-infrared spectroscopy (fNIRS) during single and dual N-back tasks. Twenty-seven young adults (18–27 years) and 31 older adults (64–84 yrs) took part in the study. We used a robust fNIRS data methodology consisting of channel and region of interest analyses. Results showed differences in performance between task load conditions and age-related differences in reaction times but no age-group effects for accuracy. Older adults exhibited more bilateral PFC activation compared with young adults across all tasks and showed increases in brain activity in high compared to low load conditions. Our findings further support previous reports showing that older adults use compensatory recruitment of additional brain regions in PFC to maintain cognitive performance but go against the notion that such compensation is not present at higher cognitive loads. Additionally, our results indicate that fNIRS is a sensitive tool that can characterize adaptive cortical changes in healthy aging.

EFFECT OF HYPERTENSION ON PREFRONTAL CORTEX ACTIVATION IN OLDER ADULTS DURING INSTRUMENTED TRAIL WALKING TASKS

Abstract Hypertension (HTN) can lead to non-amnestic cognitive impairment. However, it is unclear if this cognitive impairment affects dual task walking in older adults with HTN. The objective of this study was to evaluate the differences in prefrontal cortex (PFC) oxygenated hemoglobin (HbO2) levels during comfortable walking (CW) and an instrumented trail walking task (TWT) in older adults with HTN. We hypothesized that older adults with HTN would show decreased activation, or lower PFC HbO2 using functional near-infrared spectroscopy, during TWT in comparison to older adults without HTN. There were 15 adults in HOA group (11 females; 65±9 years old), and 9 adults in HTN group (3 females; 68±8 years old). The experimental paradigm consisted of three tasks (CW, TWT-A, TWT-B) in each of two blocks, with difficulty increasing from TWT-A to TWT-B through the inclusion of task-switching. A linear mixed effect model was conducted to investigate the effects of cohort, task, block and interaction between them on HbO2. We found that: 1) HTN adults exhibited lower HbO2 levels compared to HOA (p< 0.001), during TWTs but not CW; and 2) increased HbO2 levels were observed in TWTs relative to CW. During TWTs, HTN adults showed decreased activation compared to HOA, which shows that their ability to focus on dual task execution is limited. The hypertensive adults face difficulty in matching the attentional demands of the dual task, similar to cognitively impaired older adults, which may be partly explained by capacity sharing theory.

Examining sex differences in responses to footshock stress and the role of the metabotropic glutamate receptor 5: an [18F]FPEB and positron emission tomography study in rats.

Clinical investigations suggest involvement of the metabotropic glutamate receptor 5 (mGluR5) in the pathophysiology of fear learning that underlies trauma-related disorders. Here, we utilized a 4-day fear learning paradigm combined with positron emission tomography (PET) to examine the relationship between mGluR5 availability and differences in the response of rats to repeated footshock exposure (FE). Specifically, on day 1, male (n = 16) and female (n = 12) rats received 15 footshocks and were compared with control rats who did not receive footshocks (n = 7 male; n = 4 female). FE rats were classified as low responders (LR) or high responders (HR) based on freezing to the context the following day (day 2). PET with [18F]FPEB was used to calculate regional mGluR5 binding potential (BPND) at two timepoints: prior to FE (i.e., baseline), and post-behavioral testing. Additionally, we used an unbiased proteomics approach to assess group and sex differences in prefrontal cortex (PFC) protein expression. Post-behavioral testing we observed decreased BPND in LR females, but increased BPND in HR males relative to baseline. Further, individuals displaying the greatest freezing during the FE context memory test had the largest increases in PFC BPND. Males and females displayed unique post-test molecular profiles: in males, the greatest differences were between FE and CON, including upregulation of mGluR5 and related molecular networks in FE, whereas the greatest differences among females were between the LR and HR groups. These findings suggest greater mGluR5 availability increases following footshock exposure may be related to greater contextual fear memory. Results additionally reveal sex differences in the molecular response to footshock, including differential involvement of mGluR5-related molecular networks.

Sex-dependent prefrontal cortex activation in regular cocaine users: A working memory functional magnetic resonance imaging study.

Although two thirds of patients with a cocaine use disorder (CUD) are female, little is known about sex differences in the (neuro)pathology of CUD. The aim of this explorative study was to investigate sex‐dependent differences in prefrontal cortex (PFC) functioning during a working memory (WM) functional magnetic resonance imaging (fMRI) task in regular cocaine users (CUs), as PFC deficits are implicated in the shift from recreational cocaine use to CUD. Neural activation was measured using fMRI during a standard WM task (n‐back task) in 27 male and 28 female CUs and in 26 male and 28 female non‐cocaine users (non‐CUs). Although there were no main or interaction effects of sex and group on n‐back task performance, WM‐related (2‐back > 0‐back) PFC functioning was significantly moderated by sex and group: female compared with male CUs displayed higher WM‐related activation of the middle frontal gyrus (MFG), whereas female compared with male non‐CUs displayed lower WM‐related MFG activation. Additionally, WM‐related activation of the inferior frontal gyrus, insula, and putamen was negatively associated with cocaine use severity in female but not male CUs. These data support the hypothesis of sex‐dependent PFC differences in CUs and speculatively suggest that PFC deficits may be more strongly implicated in the development, continuation, and possibly treatment of CUD in females. Most importantly, the current data stress the importance of studying both males and females in psychiatry research as not doing so could greatly bias our knowledge of CUD and other psychiatric disorders.

Epigenome-wide meta-analysis of DNA methylation differences in prefrontal cortex implicates the immune processes in Alzheimer\u2019s disease

DNA methylation differences in Alzheimer’s disease (AD) have been reported. Here, we conducted a meta-analysis of more than 1000 prefrontal cortex brain samples to prioritize the most consistent methylation differences in multiple cohorts. Using a uniform analysis pipeline, we identified 3751 CpGs and 119 differentially methylated regions (DMRs) significantly associated with Braak stage. Our analysis identified differentially methylated genes such as MAMSTR, AGAP2, and AZU1. The most significant DMR identified is located on the MAMSTR gene, which encodes a cofactor that stimulates MEF2C. Notably, MEF2C cooperates with another transcription factor, PU.1, a central hub in the AD gene network. Our enrichment analysis highlighted the potential roles of the immune system and polycomb repressive complex 2 in pathological AD. These results may help facilitate future mechanistic and biomarker discovery studies in AD.

Structural brain abnormalities in children and adolescents with comorbid autism spectrum disorder and attention-deficit/hyperactivity disorder

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) share high rates of comorbidity, with the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition now acknowledging the comorbid diagnosis of ASD and ADHD. Although structural abnormalities in the prefrontal cortex, cerebellum, and basal ganglia occur in both ASD and ADHD, no structural studies have focused exclusively on patients with comorbid ASD and ADHD. We thus aimed to clarify the structural features and developmental changes in patients with comorbid ASD and ADHD in a relatively large sample from two sites. Ninety-two patients were age-matched to 141 typically developing (TD) controls (age range: 5–16 years) and assessed for volumetric characteristics using structural magnetic resonance imaging (i.e. surface-based morphometry). While there were no significant differences in prefrontal cortex, cerebellum, and basal ganglia volumes, patients with ASD and ADHD exhibited significantly lower left postcentral gyrus volumes than TD controls. We observed significantly lower postcentral gyrus volumes exclusively in children and preadolescents, and not in adolescents. Our findings suggest that abnormal somatosensory, attributed to delayed maturation of the left postcentral gyrus, leads to the core symptoms experienced by patients with comorbid ASD and ADHD.

Cerebral and Skeletal Muscle Tissue Oxygenation during Exercise in Children with Sickle Cell Anemia

Introduction: Sickle cell anemia (SCA) causes impaired tissue oxygenation. Children with SCA have lower peak fitness levels compared to controls. The contribution of alterations in skeletal muscle and cerebral tissue oxygenation to exercise limitation in SCA remains unclear. Near infrared spectroscopy (NIRS) is a validated, non-invasive method to measure tissue oxygen saturation. We hypothesize that compared to controls, children with SCA will exhibit greater reductions in regional tissue oxygen saturation (StO2) measured in the quadriceps (vastus lateralis) and pre frontal cortex (PFC) across all workloads during maximal cardiopulmonary exercise testing (CPET). Methods: We used the CASMED ELITE NIRS tissue oximeter to measure tissue oxygen saturation in the PFC and vastus lateralis (VL) muscle during all phases of maximal CPET, including warm up, active exercise and recovery, in 17 subjects with SCA (mean age 13.5 years) and 13 controls (mean age 15.2 years). Maximal CPET was conducted by cycle ergometry using a standard ramp protocol until volitional exhaustion was reached by all participants. Peak oxygen consumption (VO2) was measured from breath-by breath gas exchange data collected during CPET. Results: All subjects and controls completed maximal CPET without adverse events. Peak VO2 was not statistically different in subjects with SCA versus controls (25.3±4.7 vs 29.5±8.9 mL/kg/min, p=0.22). Compared to controls, subjects with SCA had significantly lower PFC StO2 at all time points during exercise, including warm up, 20%, 40%, 60%, 80% and 100% of peak work load (p<0.01) (Figure 1a). Subjects with SCA demonstrated a significant decrease in PFC StO2 from warm up to 80% peak work load (-3.0±2.9% , p=0.002) and from warm up to 100% peak work load (-5.4±3.4 %, p<0.001) (Figure 1b). In contrast, controls did not demonstrate significant decreases in PFC StO2 from warm up to any point during exercise testing. VL StO2 did not significantly differ between subjects and controls during exercise (p=0.149, Figure 1c). Subjects with SCA demonstrated a significant increase in VL StO2 from warm up to 0% (+3.2±2.8%, p<0.001) and 20% peak work load (+2.3±2.5%, p=0.002) and a significant decrease in StO2 from warm up to 60% (-4.8±4.6%, p<0.001), 80% (-8.6±5.9%, p<0.001) and 100% peak work load (-10.5±6.3%, p<0.001) (Figure 1d). Controls had significant increase in VL StO2 from warm up to 0% peak work load (+4.3±4.0%, p=0.02) and a significant decrease only at 80% (-6.5±6.3%, p=0.003). Differences in PFC and VL StO2 between subjects and controls were also examined at the highest VO2 achieved by all participants. At a VO2 of 17.6 mL/kg/min, PFC StO2 was significantly lower in subjects with SCA versus controls (69.2±6.6 vs 79.5±5.3%, p<0.001). There was a trend toward lower VL StO2 in subjects versus controls (67.7±9.0 vs 73.2±7.9%, p=0.09). Conclusion: Unlike VL tissue oxygenation, PFC tissue oxygenation is relatively well preserved in subjects with SCA and controls during maximal CPET. However, compared to controls, subjects with SCA have lower PFC tissue oxygenation at warm up and during exercise as well as demonstrate significantly greater decreases in PFC tissue oxygenation during later stages of exercise. In contrast, VL tissue oxygenation is similar at warm up and during exercise for subjects and controls. VL tissue oxygenation increases during initial stages of exercise in a similar fashion in subjects with SCA and controls but subsequent decreases from warm up are greater in subjects with SCA during later stages of exercise. Future studies may further elucidate how SCA contributes to these observed differences in regional tissue oxygenation during exercise and their potential impact on exercise safety and fitness in this population. Disclosures No relevant conflicts of interest to declare.

Effects of Aging on Working Memory Performance and Prefrontal Cortex Activity: A Time-Resolved Spectroscopy Study

Objective This study aimed to employ time-resolved spectroscopy (TRS) to explore age-related differences in prefrontal cortex (PFC) activity while subjects performed a working memory task. Methods We employed TRS to measure PFC activity in ten healthy younger and ten healthy older subjects while they performed a working memory (WM) task. All subjects performed the Sternberg test (ST) in which the memory-set size varied between one and six digits. Using TRS, we recorded changes in cerebral blood oxygenation as a measure of changes in PFC activity during the task. In order to identify left/right asymmetry of PFC activity during the working memory task, we calculated the laterality score, i.e., Δoxy-Hb (right Δoxy-Hb—left Δoxy-Hb); positive values indicate greater activity in the right PFC, while negative values indicate greater activity in the left PFC. Results During the ST, statistical analyses showed no significant differences between the younger and older groups in accuracy for low memory-load and high memory-load. In high memory-load tasks, however, older subjects were slower than younger subjects (P < 0.05). We found that the younger group showed right lateral responses with a stronger right than left activation in the frontal pole, whereas the older group showed bilateral responses (P < 0.05). Conclusions The present results are consistent with the hemispheric asymmetry reduction in older adults (HAROLD) model; working memory tasks cause asymmetrical PFC activation in younger adults, while older adults tend to show reduced hemispheric lateralization.

Prefrontal glucose metabolism in medication-resistant major depression.

Medication-resistant depression (MRD) is associated with poorer attentional performance and immense socioeconomic costs. We aimed to investigate the central pathophysiology of MRD, previously linked to impaired prefrontal cortex function. A total of 54 participants (22 with MRD, 16 with non-resistant depression, 16 healthy controls) were recruited. Non-MRD status was confirmed by a prospective 6-week antidepressant trial. All medication-free participants underwent a go/no-go task to study prefrontal cortical function (attention) and positron emission tomography scans to study regional cerebral glucose metabolism (rCMglu) at rest. The MRD group had worse attentional ratings and decreased rCMglu compared with the non-MRD and control groups. Attentional performance was positively associated with prefrontal cortex rCMglu. The prefrontal cortex differences between MRD and non-MRD groups remained after adjusting for past depressive episodes (F(1,35) = 4.154, P = 0.043). Pronounced hypofrontality, with the associated attentional deficits, has a key role in the neuropathology of medication-resistant depression.

Differences in prefrontal cortex GABA/glutamate ratio after acute restraint stress in rats are associated with specific behavioral and neurobiological patterns

In patients suffering from stress-related pathologies and depression, frontal cortex GABA and glutamate contents are reported to decrease and increase, respectively. This suggests that the GABA and/or glutamate content may participate in pathological phenotype expression. Whether differences in frontal cortex GABA and glutamate contents would be associated with specific behavioral and neurobiological patterns remains unclear, especially in the event of exposure to moderate stress. We hypothesized that an increase in prefrontal cortex GABA/glutamate ratio would be associated with a blunted prefrontal cortex activation, an enhanced hypothalamo-pituitary–adrenocortical (HPA) axis activation and changes in behavior. Rats being restrained for 1-h were then tested in an open-field test in order to assess their behavior while under stress, and were sacrificed immediately afterward. The GABA/glutamate ratio was assessed by 1H high-resolution magic angle spinning magnetic resonance spectroscopy (1H-HRMAS-MRS). The neurobiological response was evaluated through prefrontal cortex mRNA expression and plasma corticosterone levels. The stressed rats were distributed into two subgroups according to their high (H-G/g) or low (L-G/g) GABA/glutamate ratio. Compared to the L-G/g rats, the H-G/g rats exhibited a decrease in c-fos, Arc, Npas4, Nr4a2 mRNA expression suggesting blunted prefrontal cortex activation. They also showed a more pronounced stress with an enhanced rise in corticosterone, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), creatine kinase (CK) and lactate dehydrogenase (LDH) levels, as well as behavioral disturbances with decreased locomotion speed. These changes were independent from prefrontal cortex energetic status as mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) pathway activities were similar in both subpopulations. The differences in GABA/glutamate ratio in the frontal cortex observed in the stressed animals may participate in shaping individual differences in psychophysiological reactions.

BDNF Polymorphisms Are Linked to Poorer Working Memory Performance, Reduced Cerebellar and Hippocampal Volumes and Differences in Prefrontal Cortex in a Swedish Elderly Population

BackgroundBrain-derived neurotrophic factor (BDNF) links learning, memory and cognitive decline in elderly, but evidence linking BDNF allele variation, cognition and brain structural differences is lacking.Methods367 elderly Swedish men (n = 181) and women (n = 186) from Prospective Investigation of the Vasculature in Uppsala seniors (PIVUS) were genotyped and the BDNF functional rs6265 SNP was further examined in subjects who completed the Trail Making Task (TMT), verbal fluency task, and had a magnetic resonance imaging (MRI) scan. Voxel-based morphometry (VBM) examined brain structure, cognition and links with BDNF.ResultsThe functional BDNF SNP (rs6265,) predicted better working memory performance on the TMT with positive association of the Met rs6265, and was linked with greater cerebellar, precuneus, left superior frontal gyrus and bilateral hippocampal volume, and reduced brainstem and bilateral posterior cingulate volumes.ConclusionsThe functional BDNF polymorphism influences brain volume in regions associated with memory and regulation of sensorimotor control, with the Met rs6265 allele potentially being more beneficial to these functions in the elderly.

Brain-Derived Neurotrophic Factor Val66Met Polymorphism Affects Resting Regional Cerebral Blood Flow and Functional Connectivity Differentially in Women Versus Men

The human Val⁶⁶Met single nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene impacts BDNF signaling at the cellular level. At the neural-systems level, it is associated with differences in prefrontal cortex (PFC) and hippocampal function during performance of cognitive and affective tasks. Because the impact of this variant on basal prefrontal and hippocampal activity is not known but may be relevant to understanding the function of this gene in health and disease, we studied 94 healthy individuals with H₂ ¹⁵O PET to assess regional cerebral blood flow (rCBF) during rest and tested for between-genotype differences. Because BDNF and gonadal steroid hormones conjointly influence neuronal growth, survival, and plasticity in hippocampus and PFC, we also tested for sex × genotype interactions. Finally, in light of the known impact of BDNF on plasticity and dendritic arborization, we complimented direct rCBF comparisons with connectivity analyses to determine how activity in hippocampal and prefrontal regions showing between-genotype group differences covaries with rCBF in other nodes throughout the brain in a genotype- or sex-dependent manner. Compared with Val homozygotes, Met carriers had higher rCBF in prefrontal (BA25 extending into BA10) and hippocampal/parahippocampal regions. Moreover, there were significant sex × genotype interactions in regions (including frontal, parahippocampal, and lateral temporal cortex) in which Val homozygotes showed higher rCBF in females than males, but Met carriers showed the opposite relationship. Functional connectivity analysis demonstrated that correlations of BA25, hippocampus, and parahippocampus with frontal and temporal networks were positive for Val homozygotes and negative for Met carriers. In addition, sex × genotype analysis of functional connectivity revealed that genotype affected directionality of the inter-regional correlations differentially in men versus women. Our data indicate that BDNF allelic variation and sex interactively affect basal prefrontal and hippocampal function.

Brain activity underlying impaired continence control in older women with overactive bladder

To identify, in subjects with overactive bladder (OAB), differences in brain activity between those who maintained and those who lost bladder control during functional magnetic resonance imaging (fMRI) of the brain with simultaneous urodynamics. Secondary analysis of a cohort of older women (aged >60) with proven urgency urinary incontinence, who, in the scanner, either developed detrusor overactivity and incontinence (the "DO group") or did not (the "no DO" group). A priori hypothesis: during urgency provoked by bladder filling, without DO, activity in regions related to continence control is diminished in the DO group; specifically (1a) less activation in supplementary motor area (SMA) and (1b) less deactivation in prefrontal cortex (PFC) and parahippocampal complex (PH). We also explored phenotypic (clinical and urodynamic) differences between the groups. During urgency preceding DO, the DO group showed stronger activation in SMA and adjacent regions (hypothesis 1a rejected), and less deactivation in PH but no significant difference in PFC (hypothesis 1b partially accepted). These subjects were older, with more changes in brain's white matter, decreased tolerance of bladder filling and greater burden of incontinence. (1) In older women with OAB, brain activity in the SMA is greater among those with more easily elicitable DO, suggesting a compensatory response to failure of control elsewhere. (2) OAB is heterogeneous; one possible phenotype shows severe functional impairment attributable partly to age-related white matter changes. (3) Functional brain imaging coupled with urodynamics may provide CNS markers of impaired continence control in subjects with OAB.

Regulation of estrogen receptor alpha gene expression in the mouse prefrontal cortex during early postnatal development

Estrogens have many functions in the developing rodent brain, and most of these depend on the presence of estrogen receptors. Understanding how expression of these receptors are regulated is crucial for understanding the roles of estradiol in the male and female brain during development In rodents, the prefrontal cortex (PFC) has been shown to be involved in working memory, attention, and behavioral inhibition. Many studies have demonstrated an effect of estradiol on sex difference in these functions attributed to differences in the PFC. We have previously demonstrated that estrogen receptor alpha (ERα) expression decreases in the isocortex across early postnatal development. This decrease corresponds with an increase in methylation of many sites along the ERα promoter. Here we have examined both ERα and ERβ mRNA expression in the PFC to determine if methylation also plays a role in this important brain region. We investigated expression of alternate promoters for ERα and methylation of CpG sites along two of these promoters. We found that the pattern of ERα mRNA expression in PFC was similar to the pattern of ERα expression in the isocortex and that there were no sex differences in the level of expression across development. We did, however, find subtle differences in promoter expression and methylation that may indicate a sex-specific difference in PFC during development resulting in a difference in adult response.

The effects of age on the neural correlates of episodic encoding.

Young and old adults underwent positron emission tomographic scans while encoding pictures of objects and words using three encoding strategies: deep processing (a semantic living/nonliving judgement), shallow processing (size judgement) and intentional learning. Picture memory exceeded word memory in both young and old groups, and there was an age-related decrement only in word recognition. During the encoding tasks three brain activity patterns were found that differentiated stimulus type and the different encoding strategies. The stimulus-specific pattern was characterized by greater activity in extrastriate and medial temporal cortices during picture encoding, and greater activity in left prefrontal and temporal cortices during encoding of words. The older adults showed this pattern to a significantly lesser degree. A pattern distinguishing deep processing from intentional learning of words and pictures was identified, characterized mainly by differences in prefrontal cortex, and this pattern also was of significantly lesser magnitude in the old group. A final pattern identified areas with increased activity during deep processing and intentional learning of pictures, including left prefrontal and bilateral medial temporal regions. There was no group difference in this pattern. These results indicate age-related dysfunction in several encoding networks, with sparing of one specifically involved in more elaborate encoding of pictures. These age-related changes appear to affect verbal memory more than picture memory.

Parcellation of the human prefrontal cortex using MRI

A methodology was developed for dividing prefrontal cortical gray matter into insular, orbital, inferior, middle, superior, cingulate, and frontal pole regions using anatomical criteria. This methodology was developed as a follow-up to one that measured whole prefrontal gray and white matter volumes in schizophrenic and control subjects. This study showed no overall volume differences in prefrontal cortex between schizophrenic and control subjects. The parcellation of prefrontal cortex was done to increase the probability of detecting abnormalities that were circumscribed to a particular portion of the region. A 1.5 Tesla magnet was used to acquire contiguous 1.5-mm coronal slices of the entire brain. Volumes were then measured in a group of right-handed male ( n = 15) subjects. Gray matter was parcellated using criteria that were mainly based on gross anatomy, as visualized in 3-dimensional renderings of the brain. Reliability of the parcellation scheme was very high ( r i = 0.80 and above). This methodology should be useful in the study of cortical pathology in a number of neurological disorders, including schizophrenia.

Brain corticotropin-releasing factor immunoreactivity and receptors in five inbred rat strains: relationship to forced swimming behaviour

In the present work we studied the relationship between behaviour in the forced swimming test (FST), a test that presumably measures depressive-like behaviour in rodents, and central corticotropin-releasing factor (CRF) concentration and binding in five strains of rats. The strains were: Brown-Norway (BN), Fisher (FIS) 344, Lewis (LEW), spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The FST data corresponding to the pretest showed significant inter-strain differences in both struggling and immobility: BN and WKY rats displayed lower levels of struggling and longer periods of immobility, LEW and SHR rats showed intermediate levels, and FIS rats were the most active. The results of the pretest were roughly similar to those observed in the test, the activity of WKY being extremely low. The CRF binding revealed significant inter-strain differences in prefrontal cortex and hippocampus, but not in cerebellum, pons-medulla or hypothalamus: in the prefrontal cortex, BN and FIS rats showed greater CRF binding than LEW, SHR and WKY rats; in the hippocampus BN rats showed higher levels of CRF binding than the other strains. The study of CRF content in various brain areas revealed inter-strain differences in prefrontal cortex and pons-medulla, but not in parietal-temporal cortex or in hypothalamus (CRF concentrations in the hippocampus were not detectable): CRF content in the prefrontal cortex was higher in BN than in the other strains, although the differences with FIS were not statistically significant; in the pons-medulla, FIS and LEW showed significantly higher CRF content than the other strains. From the present results it appears that BN and WKY rats were more prone to adopt passive strategies in the FST, but they did not show higher brain CRF immunoreactivity or down-regulation of CRF receptors. Hence, although there were inter-strains differences in all variables studied, no evidence for a relationship between the FST behaviour and central CRF activity was found.