Cortical Lobule Research Articles

Renal Lobulation—A Benign Macroanatomical Variation?

Introduction: Renal lobulation (also known as fetal or embryonic lobulation) is a rare variation during development in which renal lobules have a visible anatomical space between them, and this can be seen in 0.5–4% of adults. Material and methods: this study was conducted on 54 human kidneys from patients who died due to causes unrelated to renal pathology which were fixed in a 10% formaldehyde solution and then carefully dissected. Results: The group with fetal lobulation (n = 16) was associated with a length M = 9.89 (SD = 0.6, p = 0.15). By comparison, the kidneys without lobulation (n = 38) were associated with a numerically longer length M = 10.29 (SD = 0.607, p = 0.098). To test the hypothesis that lobulation is associated with a statistically significant different length a Mann–Whitney test was performed, which indicated that the length of the kidneys is smaller in scase of lobulation U = 198, Z = −2.04, p = 0.04. Cross-tabulation also demonstrated that kidney lobulation may be influenced by the presence of polar arteries with r = 0.41 (p < 0.02). The likelihood ratio was 7.28, df 1, p = 0.003, with an odds ratio of 6.857 (CI 95% = 1.84–25.61). Logistic regression analysis demonstrated that kidneys with lobulation were 6.85 times more likely to have polar arteries than kidneys without lobulation. Conclusions: the data from our research indicate that even though no pathological conditions have been linked with lobulated kidneys, the incidence of vascular variations (specifically polar arteries) is higher when there is persistent fetal lobulation.

Ultrasound Features to Differentiate COVID-19 Vaccine-Induced Benign Adenopathy from Breast Cancer Related Malignant Adenopathy

Rationale and ObjectiveTo identify nodal features used to distinguish coronavirus disease 2019 (COVID-19) vaccine-Induced benign reactive adenopathy from malignant adenopathy.Materials and MethodsThis IRB-approved, single-institution, retrospective study compared features of 77 consecutive patients with benign adenopathy secondary to a messenger RNA COVID-19 vaccine with 76 patients with biopsy-proven malignant adenopathy from breast cancer. Patient demographics and nodal features were compared between the two groups using univariate and multivariate logistic regression models. A receiver operating characteristic analysis with the maximum value of Youden's index was performed for the cutoff value of cortical thickness for predicting nodal status.ResultsThe mean cortical thickness was 5.1 mm ± 2.8 mm among benign nodes and 8.9 mm ± 4.5 mm among malignant nodes (p < 0.001). A cortical thickness ≥3.0 mm had a sensitivity of 100% and a specificity of 21% (area under the curve [AUC] = 0.60, 95% confidence interval [CI]: 0.52-0.68). When the cutoff for cortical thickness was increased to ≥5.4 mm, the sensitivity decreased to 74%, while the specificity increased to 69% (AUC = 0.77, 95% CI: 0.70-0.84).Cortical thickness correlated with nodal morphology type (r2 = 0.57). An axillary node with generalized lobulated cortical thickening had a 7.5 odds ratio and a node with focal cortical lobulation had a 123.0 odds ratio compared to one with diffuse, uniform cortical thickening only (p < 0.001).ConclusionCortical thickness and morphology are predictive of malignancy. Cortical thickness cutoff of ≥5.4 mm demonstrates higher specificity and improved accuracy for detecting malignant adenopathy than a cutoff of ≥3.0 mm.

Comparative histological studies on the renal medulla in broiler chicken and broiler duck

Kidneys of six each of adult broiler chicken and broiler ducks were used in the present study. In the histological studies, the kidneys of all studied birds showed two zones, the cortex and medulla. The medulla occupied only a small portion of the kidney. In chicken a greater number of distinct cone-shaped medullary lobules were seen among cortical lobules while in duck they were lesser in number, more rounded in outline and were not cone shaped as in chicken. In the case of chicken more than one cortical lobule drained into a medullary lobule. Mammalian type of nephrons that occupied the juxta medullary region presented loop of Henle that was located within the medullary cone. Collecting ducts from different medullary lobules united together to form several large collecting ducts within the medulla which in turn united to form ureteral branches.

Substantially thinner internal granular layer and reduced molecular layer surface in the cerebellar cortex of the Tc1 mouse model of down syndrome – a comprehensive morphometric analysis with active staining contrast-enhanced MRI

Down Syndrome is a chromosomal disorder that affects the development of cerebellar cortical lobules. Impaired neurogenesis in the cerebellum varies among different types of neuronal cells and neuronal layers. In this study, we developed an imaging analysis framework that utilizes gadolinium-enhanced ex vivo mouse brain MRI. We extracted the middle Purkinje layer of the mouse cerebellar cortex, enabling the estimation of the volume, thickness, and surface area of the entire cerebellar cortex, the internal granular layer, and the molecular layer in the Tc1 mouse model of Down Syndrome. The morphometric analysis of our method revealed that a larger proportion of the cerebellar thinning in this model of Down Syndrome resided in the inner granule cell layer, while a larger proportion of the surface area shrinkage was in the molecular layer.

Leptospirosis in Northern Sea Otters (Enhydra lutris kenyoni) from Washington, USA.

We diagnosed leptospirosis in six northern sea otters (Enhydra lutris kenyoni) that stranded on beaches in Washington State, US in 2002. Significant gross findings included cyanotic oral mucous membranes, renal swelling, congestion or pale streaks on the cut surface of renal lobules, hematuria, dehydration, lymphadenopathy, pulmonary congestion, and rarely adrenal hemorrhage and congestion. Histopathology showed lymphoplasmacytic tubulointerstitial nephritis with intraluminal spirochetes and immunoreactivity to leptospiral antigens in the renal tubules and interstitium. A quantitative polymerase chain reaction (qPCR) using kidney or urine for the leptospiral lipL32 gene was positive with cycle threshold values indicative of abundant or moderate amounts of nucleic acid. A microscopic agglutination test showed the highest serum antibody titer to serovar Pomona and positive titers to serovars Autumnalis, Bratislava, Hebdomadis, Grippotyphosa, Icterohaemorrhagiae, Pyrogenes, Ballum, Canicola, and Hardjo. Although antibodies to Leptospira interrogans have been previously detected in sea otters, this report describes the pathology of leptospirosis in diseased free-ranging sea otters.

Multilevel synchronization of tubuloglomerular feedback is modulated by nitric oxide (692.10)

Previously we showed that NO modulates synchronization of both mechanisms of renal autoregulation. We did not, however, provide a mechanism to explain TGF synchronization after L‐NAME. L‐NAME changed TGF synchronization in a way we did not understand. Here we show that TGF synchronization may become stronger within cortical lobules after L‐NAME, resulting in two mechanisms of synchronization within a synchronized cluster. Male Long‐Evans rats (N=8) were anaesthetized (isoflurane) and their left kidneys were exposed. Cortical perfusion during control and NOS inhibition (L‐NAME, 10mg/kg i.v.) was monitored by laser speckle perfusion imaging. The TGF frequency range (0.01‐0.06 Hz) was isolated with a band pass filter. Clusters of synchronized nephrons were identified based on phase coherence (PC) between all pairs of imaged pixels. During control, TGF was synchronized moderately over large areas (~5x7 mm). After L‐NAME, each cluster had areas with high PC (strong synchronization) in the center and lower, but significant, PC in the surround. When the PC reference pixel was moved systematically there was strong synchronization within smaller ~800 x 800 um areas. The position of the high PC areas was consistent with an anatomical basis for synchronization. We conclude that TGF synchronization becomes stronger within cortical lobules while remaining weakly synchronized among lobules within the larger clusters.Grant Funding Source: Supported by CIHR MOP‐102694

Potential Use of Contrast-Enhanced Ultrasound (CEUS) in the Detection of Metastatic Superficial Lymph Nodes in Melanoma Patients

Malignant melanoma represents a significant and growing public health burden worldwide. Ultrasonography is the most useful diagnostic modality for regional lymph nodal staging. Because any focal areas of cortical lobulation or thickening-swelling should also be considered as a sign of metastases, we are going to report the usefulness of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign or malignant lymph nodes in patients with malignant melanoma based on blood stream patterns and investigate the diagnostic capability. After the excision of cutaneous melanoma with positive excision margins but with negative sentinel lymph node, 540 patients underwent US of superficial lymph nodes. The inclusion criteria for CEUS consisted of both major signs (absence of the echogenic hilus, round shape, and peripheral capsular vascularity) and minor ones (the presence of focal cortical thickening). The diagnostic capability was evaluated by comparing the cytological findings with the enhancement pattern on CEUS. US in combination with CEUS correctly classified 534/540 patients. CEUS applied to lymph nodes with focal cortical thickening on grayscale US confirmed great sensitivity (0.98) and specificity (0.99) but above all, it showed a markedly improved accuracy of 0.99. The likelihood ratios confirmed the good performance of the methods used. CEUS increases the diagnostic accuracy of US in the differential diagnosis of benign and malignant LNs but it also allows us, when possible, to avoid unnecessary invasive operations such as LN FNAC. Moreover, CEUS may guide FNAC in the case of focal cortical thickening on the basis of hypoperfusion, with a reduction in the number of false negatives and much earlier detection of nodal metastatic foci.

DNA Methylation/Demethylation Network Expression in Psychotic Patients with a History of Alcohol Abuse

Recent studies suggest that protracted and excessive alcohol use induces an epigenetic dysregulation in human and rodent brains. We recently reported that DNA methylation dynamics are altered in brains of psychotic (PS) patients, including schizophrenia and bipolar disorder patients. Because PS patients are often comorbid with chronic alcohol abuse, we examined whether the altered expression of multiple members of the DNA methylation/demethylation network observed in postmortem brains of PS patients was modified in PS patients with a history of chronic alcohol abuse. DNA-methyltransferase-1 (DNMT1) mRNA-positive neurons were counted in situ in prefrontal cortex samples obtained from the Harvard Brain Tissue Resource Center, Belmont, MA. 10-11-translocation (TETs 1, 2, 3), apolipoprotein B editing complex enzyme (APOBEC-3C), growth and DNA-damage-inducible protein 45β (GADD45β), and methyl-binding domain protein-4 (MBD4) mRNAs were measured by quantitative real-time polymerase chain reaction in inferior parietal cortical lobule samples obtained from the Stanley Foundation Neuropathology Consortium, Bethesda, MD. We observed an increase in DNMT1 mRNA-positive neurons in PS patients compared with non-PS subjects. In addition, there was a pronounced decrease in APOBEC-3C and a pronounced increase in GADD45β and TET1 mRNAs in PS patients with no history of alcohol abuse. In PS patients with a history of chronic alcohol abuse, the numbers of DNMT1-positive neurons were not increased significantly. Furthermore, the decrease in APOBEC-3C mRNA was less pronounced, while the increase in TET1 mRNA had a tendency to be potentiated in those PS patients that were chronic alcohol abusers. GADD45β and MBD4 mRNAs were not influenced by alcohol abuse. The effect of chronic alcohol abuse on DNA methylation/demethylation network enzymes cannot be attributed to confounding demographic variables or to the type and dose of medication used. Based on these results, we hypothesize that PS patients may abuse alcohol as a potential attempt at self-medication to normalize altered DNA methylation/demethylation network pathways. However, before accepting this conclusion, we need to study alterations in the DNA methylation/demethylation pathways and the DNA methylation dynamics in a substantial number of alcoholic PS and non-PS patients. Additional investigation may also be necessary to determine whether the altered DNA methylation dynamics are direct or the consequence of an indirect interaction of alcohol with the neuropathogenetic mechanisms underlying psychosis.

Role of axillary ultrasound after neoadjuvant chemotherapy in women with node-positive breast cancer (T1-4, N1-2, M0) at initial diagnosis (ACOSOG Z1071).

1107 Background: The role of axillary ultrasound (AUS) after neoadjuvant chemotherapy (NAC) to assess for residual nodal disease in patients presenting with node positive breast cancer remains unclear. ACOSOG Z1071 is a prospective multi-institutional trial evaluating sentinel node biopsy in patients with biopsy proven node positive breast cancer (T0-4, N1-2, M0) receiving NAC. Herein we report on the secondary objective evaluating the correlation of lymph node (LN) features on AUS with residual nodal disease. Methods: AUS images from diagnosis and after NAC were centrally reviewed for cortex size, LN size and LN morphology. Morphologic features were defined as: type I, no visible cortex, type II, &lt; 3 mm hypoechoic cortex, type III, &gt; 3mm hypoechoic cortex, type IV, generalized lobulated hypoechoic cortex, type V, focal hypoechoic cortical lobulation, and type VI, totally hypoechoic node with no hilum. Type I and II are considered normal. Results: Surgical and imaging data are available on 294 patients. Median age was 50 years (range 23-93 years), mean initial tumor size 3cm (0 to 15cm) and clinical stage II in 64.5% and III in 35.5%. The maximum LN diameter decreased after NAC (mean 22mm pre-NAC to 14mm post-NAC)(p&lt;0.0001); however, there was no significant difference after NAC between the pathologically N+ (13mm, range 5-46mm) and N0 cases (12mm, range 3-32mm)(p=0.13). LN cortical thickness correlated with residual nodal disease after NAC (p-value = 0.04). Using a cutoff point of cortical thickness of 3 mm, the sensitivity was 33% (48/145) and specificity 80% (66/82). AUS morphological features after NAC was associated with false negative rate 62%, false positive rate 28%, sensitivity 38%, and specificity 72%. Conclusions: AUS after NAC is useful to assess nodal response. Cortical thickness was the best predictor of residual nodal metastasis. LN size and morphological features do not reliably exclude residual nodal metastasis in patients after NAC. [Table: see text]

Cerebellar plasticity and the automation of first-order rules.

Theories of corticocerebellar function propose roles for the cerebellum in automating motor control, a process thought to depend on plasticity in cerebellar circuits that exchange information with the motor cortex. Little is known, however, about automating behaviors beyond the motor domain. The present study tested the hypothesis that cerebellar plasticity also subserves the development of automaticity in behavior based on low-order rules. Human subjects were required to learn two sets of first-order rules in which visual stimuli of different shapes each arbitrarily instructed a particular finger movement. We used event-related functional magnetic resonance imaging to scan subjects while these response rules became increasingly automatic with practice, as assessed with a dual-task procedure. We found that the amplitude of the blood oxygenation level-dependent signal gradually decreased as a function of practice, as responses became increasingly automatic, and that this effect was greater for a set of rules that became automatic rapidly compared with a second set, which became automatic more slowly. These trial-by-trial activity changes occurred in Crus I of cerebellar cortical lobule HVIIA, in which neurons exchange information with the prefrontal cortex rather than the motor cortex. Activity in Crus I was time locked specifically to the processing of these rules, rather than to subsequent actions. The results support the hypothesis that decreases in cerebellar cortical activity underlie the automation of behavior, whether related to motor control and motor cortex or to response rules and prefrontal cortex.

Memory Consolidation in the Cerebellar Cortex

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABAA agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage.

Electrophysiological Localization of Eyeblink-Related Microzones in Rabbit Cerebellar Cortex

The classically conditioned eyeblink response in the rabbit is one of the best-characterized behavioral models of associative learning. It is cerebellum dependent, with many studies indicating that the hemispheral part of Larsell's cerebellar cortical lobule VI (HVI) is critical for the acquisition and performance of learned responses. However, there remain uncertainties about the distribution of the critical regions within and around HVI. In this learning, the unconditional stimulus is thought to be carried by periocular-activated climbing fibers. Here, we have used a microelectrode array to perform systematic, high-resolution, electrophysiological mapping of lobule HVI and surrounding folia in rabbits, to identify regions with periocular-evoked climbing fiber activity. Climbing fiber local field potentials and single-unit action potentials were recorded, and electrode locations were reconstructed from histological examination of brain sections. Much of the sampled cerebellar cortex, including large parts of lobule HVI, was unresponsive to periocular input. However, short-latency ipsilateral periocular-evoked climbing fiber responses were reliably found within a region in the ventral part of the medial wall of lobule HVI, extending to the base of the primary fissure. Small infusions of the AMPA/kainate receptor antagonist CNQX into this electrophysiologically defined region in awake rabbits diminished or abolished conditioned responses. The known parasagittal zonation of the cerebellum, supported by zebrin immunohistochemistry, indicates that these areas have connections consistent with an essential role in eyeblink conditioning. These small eyeblink-related areas provide cerebellar cortical targets for analysis of eyeblink conditioning at a neuronal level but need to be localized with electrophysiological identification in individual animals.

Evolution of the cerebellar cortex: The selective expansion of prefrontal-projecting cerebellar lobules

It has been suggested that interconnected brain areas evolve in tandem because evolutionary pressures act on complete functional systems rather than on individual brain areas. The cerebellar cortex has reciprocal connections with both the prefrontal cortex and motor cortex, forming independent loops with each. Specifically, in capuchin monkeys cerebellar cortical lobules Crus I and Crus II connect with prefrontal cortex, whereas the primary motor cortex connects with cerebellar lobules V, VI, VIIb, and VIIIa. Comparisons of extant primate species suggest that the prefrontal cortex has expanded more than cortical motor areas in human evolution. Given the enlargement of the prefrontal cortex relative to motor cortex in humans, our hypothesis would predict corresponding volumetric increases in the parts of the cerebellum connected to the prefrontal cortex, relative to cerebellar lobules connected to the motor cortex. We tested the hypothesis by comparing the volumes of cerebellar lobules in structural MRI scans in capuchins, chimpanzees and humans. The fractions of cerebellar volume occupied by Crus I and Crus II were significantly larger in humans compared to chimpanzees and capuchins. Our results therefore support the hypothesis that in the cortico-cerebellar system, functionally related structures evolve in concert with each other. The evolutionary expansion of these prefrontal-projecting cerebellar territories might contribute to the evolution of the higher cognitive functions of humans.

Cortical morphologic features of axillary lymph nodes as a predictor of metastasis in breast cancer: in vitro sonographic study.

The purpose of this study was in vitro sonographic-pathologic correlation of findings in dissected axillary lymph nodes from breast cancer patients undergoing axillary lymph node dissection and classification of the sonographic appearance of the nodes on the basis of cortical morphologic features to facilitate early recognition of metastatic disease. High-resolution sonography was used for in vitro examination of 171 lymph nodes from 19 axillae in 18 patients with unknown nodal status who underwent axillary lymph node dissection for early infiltrating breast cancer. The images were evaluated by two blinded observers, and discordant readings were referred to a third blinded observer. Each lymph node was classified as one of types 1-6 according to cortical morphologic features. Types 1-4 were considered benign, ranging from hyperechoic with no visible cortex to thickened generalized hypoechoic cortical lobulation. Type 5 (focal hypoechoic cortical lobulation) and type 6 (hypoechoic node with absent hilum) nodes were considered metastatic. The reference standard for metastatic disease was histopathologic evaluation of sectioned nodes by a single pathologist blinded to sonographic findings. Largest nodal diameter also was measured. Interobserver agreement was 77% for classification of nodal morphology (types 1-6) and 88% for characterization of a node as benign or malignant. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of cortical shape in prediction of metastatic involvement of axillary nodes were 77%, 80%, 36%, 96%, and 80%. Type 4 nodes had the most false-negative findings (four of 36). Node size ranged from 0.2 to 3.8 cm, and subcentimeter nodes of all types were detected. In breast cancer, axillary lymph nodes can be classified according to cortical morphologic features. Predominantly hyperechoic nodes (types 1-3) can be considered benign. Generalized cortical lobulation (type 4) is uncommonly a false-negative finding, but metastasis, if present, is invariably detected at sentinel node mapping. The presence of asymmetric focal hypoechoic cortical lobulation (type 5) or a completely hypoechoic node (type 6) should serve as a guideline for universal performance of fine-needle aspiration for preoperative staging of breast cancer. This classification, when verified with larger samples, may serve as a useful clinical guideline if proven with results of in vivo studies.

Symbolic representations of action in the human cerebellum

Cerebellar cortical areas connected to the neocortical motor system process information important for the sensory guidance of action. Converging evidence also supports the view that cerebellar cortical areas connected with the prefrontal cortex process information similarly in the cognitive domain. Here, we test the hypothesis that the prefrontal-projecting zones in the human cerebellum process the abstract content of information embedded within sensory cues. Specifically, we use event-related fMRI to determine whether symbolic visual instructions activate the prefrontal-projecting zones of the cerebellum. On the basis of connectional anatomy, we predicted that such activity would be found in lobule HVIIA and adjacent vermal territories in the same lobule. Our experimental design enabled us to investigate activity time-locked specifically to instructions foraction that were either purely symbolic, or specified actions directly. Such activity was independent of action. Activity specifically time-locked to symbolic cues (compared with non-symbolic control cues) activated cerebellar cortical lobule HVIIA (Crus I and Crus II). Our results provide support for the view that prefrontal-projecting areas of the cerebellar cortex process information that is of a purely abstract nature.

Microvascular growth and remodelling: the interplay between sprouting and intussusceptive angiogenic mechanisms

Embryonic development is associated with extensive vascular growth and remodeling. We studied the developing chick kidney and lung with special attention to the interplay between sprouting and intussusceptive vascular growth modes. During inauguration, the early meso-, metanephros and the lung were characterised by extensive microvascular sprouting. By E7, E13 and E15 respectively, the vascular growth mode switched to intussusception, which contributed to rapid organ vasculature growth. A phenomenal finding was that future renal lobules arose as large glomerular tufts, supplied by large vessels, which were split into smaller intralobular feeding and draining vessels with subsequent formation of solitary glomeruli. This glomerular duplication and kidney specific angioarchitecture was achieved by intussusception, i.e., by formation of pillars in rows and their successive merging to delineate the vascular entities. In the embryonic lung, intussusceptive angiogenesis contributes to a remarkably rapid expansion of the primordial vascular plexus, which successively surrounds and encloses the primitive parabronchi. As the vasculature develops increased blood flow stimulates formation of pillars in rows, their subsequent fusion and concomitant delineation of slender, solitary vascular entities from the disorganised meshwork, thus crafting the chicken lung-specific angioarchitecture. Morphometric investigations revealed that sprouting is preponderant in the early period of development, but is subsequently contemporaneous with intussusceptive angiogenesis and is supplanted by the latter by the time of hatching. Strong VEGF-A expression was associated with the sprouting phase of angiogenesis while bFGF and PDGF-B was upregulated during the phase of intussusceptive microvascular growth. We conclude that microvascular growth and remodelling in avian kidney and lung follows an adroitly crafted pattern, which entails a precise spatiotemporal interplay between sprouting and intussusceptive angiogenic growth modes supported partly by VEGF-A, bFGF and PDGF-B.

Cerebellar contributions to working memory

Anatomical studies show the existence of two well-characterized cortico-cerebellar ‘loops’ that connect prefrontal and cortical motor areas each with their own modules in the cerebellar cortex. The involvement of the cerebellar ‘motor’ modules in motor skills is well established, but little is understood about the way that cerebellar prefrontal modules process information from the prefrontal cortex. This question is particularly important for understanding the human cortico-cerebellar system because the prefrontal loop appears to have expanded significantly during the course of evolution. Here, we investigate whether cerebellar modules known to be connected with the prefrontal cortex (specifically within cerebellar cortical lobule VII) become engaged by the execution of skilled cognitive operations. We tested the anatomically specific hypothesis that this area would be activated by the skilled maintenance and manipulation of items within verbal working memory. We used the Paced Auditory Serial Addition Test (PASAT) in combination with a sparse sampling method to avoid artefact caused by speech-related head movement on the BOLD timecourse. Consistent with our hypothesis, we report that activity in the experimental condition was evoked in medial portions of cerebellar cortical lobule VII (relative to a closely matched control task). As would be anticipated, the motor demands common to experimental and control tasks activated face areas of the motor cortex as well as connected motor areas of the cerebellar cortex. We discuss this evidence in the context of theories of cortico-cerebellar information processing.

Spatial-Temporal Current Source Correlations and Cortical Connectivity

The purpose of this study was to explore spatial-temporal correlations between 3-dimensional current density estimates using Low Resolution Electromagnetic Tomography (LORETA). The electroencephalogram (EEG) was recorded from 19 scalp locations from 97 subjects. LORETA current density was computed for 2,394 gray matter pixels. The gray matter pixels were grouped into 33 left hemisphere and 33 right hemisphere regions of interest (ROIs) based on groupings of Brodmann areas. The average source current density in a given region of interest (ROI) was computed for each 2 second epoch of EEG and then a Pearson product correlation coefficient was computed over the time series of successive 2 second epochs of current density between all pairwise combinations of ROIs during the resting eyes-closed EEG session. Rhythmic changes in source correlation as a function of distance were present in all regions of interest. Also, maximum correlations at certain frequencies were present independent of distance. The occipital regions exhibited the highest short distance correlations and the frontal regions exhibited the highest long distance correlations. In general, the right hemisphere exhibited higher intra-hemispheric source correlations than the left hemisphere especially in the temporal, parietal and occipital cortex. The strongest left vs. right hemisphere differences were in the alpha frequency band (8-12 Hz) and in the gamma frequency band (37-40 Hz). The pattern of spatial frequencies in different cortical lobules is consistent with differences in neural packing density and the operation of 'U' shaped fiber systems. The general conclusions were: 1--the higher the packing density then the greater the intra-cortical connection contribution to LORETA source correlations, 2--spatial frequencies are primarily due to intra-cortical 'U' shaped fiber connections and long distance fiber connections, 3--posterior and temporal cortical intra-hemispheric coupling is generally stronger in the right hemisphere than in the left hemisphere.

Microvascular growth, development, and remodeling in the embryonic avian kidney: The interplay between sprouting and intussusceptive angiogenic mechanisms

Embryonic development is associated with extensive vascular growth and remodeling. We used immunohistochemical, light and electron microscopical techniques, as well as vascular casting methods to study the developing chick embryo kidney with special attention to the interplay between sprouting and intussusceptive vascular growth modes. During inauguration at embryonic day 5 (E5), the early mesonephros was characterised by extensive microvascular sprouting. By E7, the vascular growth mode switched to intussusception, which contributed to rapid kidney vasculature growth up to E11, when the first obvious signs of vascular degeneration were evident. The metanephros underwent similar phases of vascular development inaugurating at E8 with numerous capillary sprouts and changing at E13 to intussusceptive growth, which was responsible for vascular amplification and remodeling. A phenomenal finding was that future renal lobules arose as large glomerular tufts, supplied by large vessels, which were split into smaller intralobular feeding and draining vessels with subsequent formation of solitary glomeruli. This glomerular duplication was achieved by intussusception, i.e., by formation of pillars in rows and their successive merging to delineate the vascular entities. Ultimately, the maturation of the vasculature was achieved by intussusceptive pruning and branching remodeling. An interesting finding was that strong VEGF expression was associated with the sprouting phase of angiogenesis while bFGF was upregulated during the phase of intussusceptive microvascular growth. We conclude that microvascular growth and remodeling in avian kidney follows an adroitly crafted pattern, which entails a precise spaciotemporal interplay between sprouting and intussusceptive angiogenic growth modes supported partly by VEGF and bFGF.

Temporal properties of cerebellar-dependent memory consolidation.

Classical conditioning of the nictitating membrane response in rabbits is a well defined model of cerebellar-dependent motor memory. This memory undergoes a period of consolidation after the training session, when it is sensitive to reversible inactivations of the cerebellar cortex, but not of the cerebellar nuclei, with the GABA(A) receptor agonist muscimol. Here, the temporal properties of this cerebellar cortex-dependent consolidation were examined using delayed infusions of muscimol in cortical lobule HVI. Cortical infusions delayed by 5 or 45 min after a conditioning session produced significant and very similar impairments of consolidation, but infusions delayed by 90 min produced little or no impairment. Behavioral measures indicate that the muscimol infusions produced significant effects after approximately 30 min and they lasted for a few hours. So, over a time window beginning approximately 1 hr after the end of the training session and closing 1 hr after that, intracortical activity is critical for consolidation of this motor memory.