Neocortical Surface Research Articles

Higher surface folding of the human premotor cortex is associated with better long-term learning capability

The capacity to learn enabled the human species to adapt to various challenging environmental conditions and pass important achievements on to the next generation. A growing body of research suggests links between neocortical folding properties and numerous aspects of human behavior, but their impact on enhanced human learning capacity remains unexplored. Here we leverage three training cohorts to demonstrate that higher levels of premotor cortical folding reliably predict individual long-term learning gains in a challenging new motor task, above and beyond initial performance differences. Individual folding-related predisposition to motor learning was found to be independent of cortical thickness and intracortical microstructure, but dependent on larger cortical surface area in premotor regions. We further show that learning-relevant features of cortical folding occurred in close spatial proximity to practice-induced structural brain plasticity. Our results suggest a link between neocortical surface folding and human behavioral adaptability.

Modification of gene expression and soluble factor secretion in the lateral ventricle choroid plexus: Analysis of the impacts on the neocortical development

The choroid plexus (ChP) is the center of soluble factor secretion into the cerebrospinal fluid in the central nervous system. It is known that various signaling factors secreted from the ChP are involved in the regulation of brain development and homeostasis. Intriguingly, the size of the ChP was prominently expanded in the brains of primates, including humans, suggesting that the expansion of the ChP contributed to mammalian brain evolution, leading to the acquisition of higher intelligence and cognitive functions. To address this hypothesis, we established transgenic (Tg) systems using regulatory elements that direct expression of candidate genes in the ChP. Overexpression of sonic hedgehog (Shh) in the developing ChP led to the expansion of the ChP with greater arborization. Shh produced in the ChP caused an increase in neural stem cells (NSCs) in the neocortical region, leading to the expansion of ventricles, ventricular zone and neocortical surface area, and neocortical surface folding. These findings suggest that the activation of Shh signaling via its enhanced secretion from the developing ChP contributed to the evolution of the neocortex. Furthermore, we found that Shh produced in the ChP enhanced NSC proliferation in the postnatal Tg brain, demonstrating that our Tg system can be used to estimate the effects of candidate factors secreted from the ChP on various aspects of brain morphogenesis and functions.

Dual activation of Shh and Notch signaling induces dramatic enlargement of neocortical surface area

The expansion of the neocortex represents a characteristic event over the course of mammalian evolution. Gyrencephalic mammals that have the larger brains with many folds (gyri and sulci) seem to have acquired higher intelligence, reflective of the enlargement of the neocortical surface area. In this process, germinal layers containing neural stem cells (NSCs) and neural progenitors expanded in number, leading to an increase in the total number of cortical neurons. In this study, we sought to expand neural stem/progenitor cells and enlarge the neocortical surface area by the dual activation of Shh and Notch signaling in transgenic (Tg) mice, promoting the proliferation of neural stem/progenitor cells by the Shh signaling effector while maintaining the undifferentiated state of NSCs by the Notch signaling effector. In the neocortical region of the Tg embryos, NSCs increased in number, and the ventricles, ventricular zone, and neocortical surface area were dramatically expanded. Furthermore, we observed that folds/wrinkles on the neocortical surface were progressively formed, accompanied by the vascular formation. These findings suggest that Shh and Notch signaling may be key regulators of mammalian brain evolution.

Brain-wide functional diffuse optical tomography of resting state networks

Objective. Diffuse optical tomography (DOT) has the potential in reconstructing resting state networks (RSNs) in human brains with high spatio-temporal resolutions and multiple contrasts. While several RSNs have been reported and successfully reconstructed using DOT, its full potential in recovering a collective set of distributed brain-wide networks with the number of RSNs close to those reported using functional magnetic resonance imaging (fMRI) has not been demonstrated. Approach. The present study developed a novel brain-wide DOT (BW-DOT) framework that integrates a cap-based whole-head optode placement system with multiple computational approaches, i.e. finite-element modeling, inverse source reconstruction, data-driven pattern recognition, and statistical correlation tomography, to reconstruct RSNs in dual contrasts of oxygenated (HbO) and deoxygenated hemoglobins (HbR). Main results. Our results from the proposed framework revealed a comprehensive set of RSNs and their subnetworks, which collectively cover almost the entire neocortical surface of the human brain, both at the group level and individual participants. The spatial patterns of these DOT RSNs suggest statistically significant similarities to fMRI RSN templates. Our results also reported the networks involving the medial prefrontal cortex and precuneus that had been missed in previous DOT studies. Furthermore, RSNs obtained from HbO and HbR suggest similarity in terms of both the number of RSN types reconstructed and their corresponding spatial patterns, while HbR RSNs show statistically more similarity to fMRI RSN templates and HbO RSNs indicate more bilateral patterns over two hemispheres. In addition, the BW-DOT framework allowed consistent reconstructions of RSNs across individuals and across recording sessions, indicating its high robustness and reproducibility, respectively. Significance. Our present results suggest the feasibility of using the BW-DOT, as a neuroimaging tool, in simultaneously mapping multiple RSNs and its potential values in studying RSNs, particularly in patient populations under diverse conditions and needs, due to its advantages in accessibility over fMRI.

Sonic hedgehog expands neural stem cells in the neocortical region leading to an expanded and wrinkled neocortical surface.

An expanded and folded neocortex is characteristic of higher mammals, including humans and other primates. The neocortical surface area was dramatically enlarged during the course of mammalian brain evolution from lissencephalic to gyrencephalic mammals, and this bestowed higher cognitive functions especially to primates, including humans. In this study, we generated transgenic (Tg) mice in which the expression of Sonic hedgehog (Shh) could be controlled in neural stem cells (NSCs) and neural progenitors by using the Tet-on system. Shh overexpression during embryogenesis promoted the symmetric proliferative division of NSCs in the neocortical region, leading to the expansion of lateral ventricles and tangential extension of the ventricular zone. Moreover, Shh-overexpressing Tg mice showed dramatic expansion of the neocortical surface area and exhibited a wrinkled brain when overexpression was commenced at early stages of neural development. These results indicate that Shh is able to increase the neocortical NSCs and contribute to expansion of the neocortex.

Immune-Induced Fever Is Dependent on Local But Not Generalized Prostaglandin E2 Synthesis in the Brain.

Fever occurs upon binding of prostaglandin E2 (PGE2) to EP3 receptors in the median preoptic nucleus of the hypothalamus, but the origin of the pyrogenic PGE2 has not been clearly determined. Here, using mice of both sexes, we examined the role of local versus generalized PGE2 production in the brain for the febrile response. In wild-type mice and in mice with genetic deletion of the prostaglandin synthesizing enzyme cyclooxygenase-2 in the brain endothelium, generated with an inducible CreERT2 under the Slco1c1 promoter, PGE2 levels in the CSF were only weakly related to the magnitude of the febrile response, whereas the PGE2 synthesizing capacity in the hypothalamus, as reflected in the levels of cyclooxygenase-2 mRNA, showed strong correlation with the immune-induced fever. Histological analysis showed that the deletion of cyclooxygenase-2 in brain endothelial cells occurred preferentially in small- and medium-sized vessels deep in the brain parenchyma, such as in the hypothalamus, whereas larger vessels, and particularly those close to the neocortical surface and in the meninges, were left unaffected, hence leaving PGE2 synthesis largely intact in major parts of the brain while significantly reducing it in the region critical for the febrile response. Furthermore, injection of a virus vector expressing microsomal prostaglandin E synthase-1 (mPGES-1) into the median preoptic nucleus of fever-refractive mPGES-1 knock-out mice, resulted in a temperature elevation in response to LPS. We conclude that the febrile response is dependent on local release of PGE2 onto its target neurons and not on the overall PGE2 production in the brain.SIGNIFICANCE STATEMENT By using mice with selective deletion of prostaglandin synthesis in brain endothelial cells, we demonstrate that local prostaglandin E2 (PGE2) production in deep brain areas, such as the hypothalamus, which is the site of thermoregulatory neurons, is critical for the febrile response to peripheral inflammation. In contrast, PGE2 production in other brain areas and the overall PGE2 level in the brain do not influence the febrile response. Furthermore, partly restoring the PGE2 synthesizing capacity in the anterior hypothalamus of mice lacking such capacity with a lentiviral vector resulted in a temperature elevation in response to LPS. These data imply that the febrile response is dependent on the local release of PGE2 onto its target neurons, possibly by a paracrine mechanism.

Virtual endocast of the early Oligocene Cedromus wilsoni (Cedromurinae) and brain evolution in squirrels.

Extant squirrels exhibit extensive variation in brain size and shape, but published endocranial data for living squirrels are limited, and no study has ever examined brain evolution in Sciuridae from the perspective of the fossil record to understand how this diversity emerged. We describe the first virtual endocast for a fossil sciurid, Cedromus wilsoni, which is known from a complete cranium from Wyoming (Orellan, Oligocene), and make comparisons to a diverse sample of virtual endocasts for living sciurids (N = 20). The virtual endocasts were obtained from high-resolution X-ray micro-computed tomography data. Comparisons were also made with endocasts of extinct ischyromyid rodents, the most primitive rodents known from an endocranial record, which provide the opportunity to study the neuroanatomical changes occurring near the base of Sciuridae. The encephalization quotient of C. wilsoni is higher than that of Ischyromys typus from the same epoch, and falls within the range of modern terrestrial squirrel variation, but below the range of extant scansorial, arboreal and gliding sciurids when using cheek-tooth area for the estimation of body mass. In a principal components analysis, the shape of the endocast of C.wilsoni is found to be intermediate between that of primitive fossil taxa and the modern sample. Cedromus wilsoni has a more expanded neocortical surface area, especially the caudal region of the cerebrum, compared with ischyromyid rodents. Furthermore, C. wilsoni had proportionally larger paraflocculi and a more complex cerebellar morphology compared with ischyromyid rodents. These neurological differences may be associated with improvements in vision, although it is worth noting that the size of the parts of the brain most directly involved with vision [the rostral (superior) colliculi and the primary visual cortex] cannot be directly assessed on endocasts. The changes observed could also relate to balance and limb coordination. Ultimately, the available evidence suggests that early squirrels were more agile and visually oriented animals compared with more primitive rodents, which may relate to the process of becoming arboreal. Extant sciurids have an even more expanded neocortical surface area, while exhibiting proportionally smaller paraflocculi, compared with C.wilsoni. This suggests that the neocortex may continue increasing in size in more recent sciurid rodents in relation to other factors than arboreality. Despite the fact that both Primates and Rodentia exhibit neocortical expansion through time, since the adoption of arboreality preceded major increases in the neocortex in Primates, those neurological changes may be related to different ecological factors, underlining the complexity of the inter-relationship between time and ecology in shaping the brain in even closely related clades.

Virtual endocasts of Eocene Paramys (Paramyinae): oldest endocranial record for Rodentia and early brain evolution in Euarchontoglires.

Understanding the pattern of brain evolution in early rodents is central to reconstructing the ancestral condition for Glires, and for other members of Euarchontoglires including Primates. We describe the oldest virtual endocasts known for fossil rodents, which pertain to Paramys copei (Early Eocene) and Paramys delicatus (Middle Eocene). Both specimens of Paramys have larger olfactory bulbs and smaller paraflocculi relative to total endocranial volume than later occurring rodents, which may be primitive traits for Rodentia. The encephalization quotients (EQs) of Pa. copei and Pa. delicatus are higher than that of later occurring (Oligocene) Ischyromys typus, which contradicts the hypothesis that EQ increases through time in all mammalian orders. However, both species of Paramys have a lower relative neocortical surface area than later rodents, suggesting neocorticalization occurred through time in this Order, although to a lesser degree than in Primates. Paramys has a higher EQ but a lower neocortical ratio than any stem primate. This result contrasts with the idea that primates were always exceptional in their degree of overall encephalization and shows that relative brain size and neocortical surface area do not necessarily covary through time. As such, these data contradict assumptions made about the pattern of brain evolution in Euarchontoglires.

First Digital Cranial Endocasts of late Oligocene Notohippidae (Notoungulata): Implications for Endemic South American Ungulates Brain Evolution

Notohippidae were middle-sized toxodonts recorded from the Eocene to the early Miocene. We provide the first description of the cranial endocasts of Rhynchippus equinus and Eurygenium latirostris based on three-dimensional reconstructions extracted from high-resolution X-ray computed tomography imagery. The endocasts of R. equinus and E. latirostris indicate that they were similar in size, proportions of the encephalic components, and neocortical design. The endocranial morphology of these notohippids is very close to that of toxodontids Adinotherium and Nesodon and differs markedly from both other Toxodontia and Typotheria. Notohippids, together with toxodontids, show the most complex neocortical surface among notoungulates. On the other hand, the neuromorphology of notohippids is in contrast to the neocortical morphological pattern described for Tertiary euungulates (Perissodactyla and Artiodactyla) from the Northern Hemisphere and litoptern Protetotheriidae, South American native euungulates. The relative brain size of R. equinus and E. latirostris compared with coeval holarctic euungulates from the late Oligocene are significantly below Perissodactyla and near the values obtained for Artiodactyla. Regarding the location of some functional neocortical areas, the expansion of the frontal lobe in Notohippidae may reflect the acquisition of heightened tactile sensitivity in the front of the snout, as recorded in the somatic sensory cortex of living euungulates. The bulging temporal lobe may reflect expansion of the auditory cortex, likely related to the marked enlargement of the middle ear chamber. Both neuromorphological and quantitative data suggest that during the late Paleogene, notohippids developed as complex and encephalized brains as those of the coeval Artiodactyla of northern continents.

532 nm Low-Power Laser Irradiation Facilitates the Migration of GABAergic Neural Stem/Progenitor Cells in Mouse Neocortex.

Background and ObjectiveAccumulating evidence has shown that low-power laser irradiation (LLI) affects cell proliferation and survival, but little is known about LLI effects on neural stem/progenitor cells (NSPCs). Here we investigate whether transcranial 532 nm LLI affects NSPCs in adult murine neocortex and in neurospheres from embryonic mice.Study Design/Materials and MethodsWe applied 532 nm LLI (Nd:YVO4, CW, 60 mW) on neocortical surface via cranium in adult mice and on cultured cells from embryonic mouse brains in vitro to investigate the proliferation and migration of NSPCs and Akt expression using immunohistochemical assays and Western blotting techniques.ResultsIn vivo experiments demonstrated that 532 nm LLI significantly facilitated the migration of GABAergic NSPCs that were induced to proliferate in layer 1 by mild ischemia. In vitro experiments using GABAergic NSPCs derived from embryonic day 14 ganglionic eminence demonstrated that 532 nm LLI for 60 min promoted the migration of GAD67-immunopositive NSPCs with a significant increase of Akt expression. Meanwhile, the LLI induced proliferation, but not migration, of NSPCs that give rise to excitatory neurons.ConclusionIt is concluded that 532 nm LLI promoted the migration of GABAergic NSPCs into deeper layers of the neocortex in vivo by elevating Akt expression.

The Genetic Association Between Neocortical Volume and General Cognitive Ability Is Driven by Global Surface Area Rather Than Thickness

Total gray matter volume is associated with general cognitive ability (GCA), an association mediated by genetic factors. It is expectable that total neocortical volume should be similarly associated with GCA. Neocortical volume is the product of thickness and surface area, but global thickness and surface area are unrelated phenotypically and genetically in humans. The nature of the genetic association between GCA and either of these 2 cortical dimensions has not been examined. Humans possess greater cognitive capacity than other species, and surface area increases appear to be the primary driver of the increased size of the human cortex. Thus, we expected neocortical surface area to be more strongly associated with cognition than thickness. Using multivariate genetic analysis in 515 middle-aged twins, we demonstrated that both the phenotypic and genetic associations between neocortical volume and GCA are driven primarily by surface area rather than thickness. Results were generally similar for each of 4 specific cognitive abilities that comprised the GCA measure. Our results suggest that emphasis on neocortical surface area, rather than thickness, could be more fruitful for elucidating neocortical-GCA associations and identifying specific genes underlying those associations.

Mapping arealisation of the visual cortex of non-primate species: lessons for development and evolution.

The integration of the visual stimulus takes place at the level of the neocortex, organized in anatomically distinct and functionally unique areas. Primates, including humans, are heavily dependent on vision, with approximately 50% of their neocortical surface dedicated to visual processing and possess many more visual areas than any other mammal, making them the model of choice to study visual cortical arealisation. However, in order to identify the mechanisms responsible for patterning the developing neocortex, specifying area identity as well as elucidate events that have enabled the evolution of the complex primate visual cortex, it is essential to gain access to the cortical maps of alternative species. To this end, species including the mouse have driven the identification of cellular markers, which possess an area-specific expression profile, the development of new tools to label connections and technological advance in imaging techniques enabling monitoring of cortical activity in a behaving animal. In this review we present non-primate species that have contributed to elucidating the evolution and development of the visual cortex. We describe the current understanding of the mechanisms supporting the establishment of areal borders during development, mainly gained in the mouse thanks to the availability of genetically modified lines but also the limitations of the mouse model and the need for alternate species.

Genetics of brain structure: Contributions from the vietnam era twin study of aging

Understanding the genetics of neuropsychiatric disorders requires an understanding of the genetics of brain structure and function. The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study focused on cognitive and brain aging. Here, we describe basic science work carried out within the VETSA MRI study that provides meaningful contributions toward the study of neuropsychiatric disorders. VETSA produced the first comprehensive assessment of the heritability of cortical and subcortical brain structure sizes, all within the same individuals. We showed that neocortical thickness and surface area are largely genetically distinct. With continuous neocortical thickness maps, we demonstrated regional specificity of genetic influences, and that genetic factors did not conform to traditional regions of interest (ROIs). However, there was some evidence for different genetic factors accounting for different types of cortex, and for genetic relationships across cortical regions corresponding to anatomical and functional connectivity and brain maturation patterns. With continuous neocortical surface area maps, we confirmed the anterior-posterior gradient of genetic influences on cortical area patterning demonstrated in animal models. Finally, we used twin methods to create the first map of cortical ROIs based entirely on genetically informative data. We conclude that these genetically based cortical phenotypes may be more appropriate for genetic studies than traditional ROIs based on structure or function. Our results also suggest that cortical volume-the product of thickness and surface area-is a problematic phenotype for genetic studies because two independent sets of genes may be obscured. Examples supporting the validity of these conclusions are provided.

PET-Based Confirmation of Orientation Sensitivity of TMS-Induced Cortical Activation in Humans

BackgroundCurrently, it is difficult to predict precise regions of cortical activation in response to transcranial magnetic stimulation (TMS). Most analytical approaches focus on applied magnetic field strength in the target region as the primary factor, placing activation on the gyral crowns. However, imaging studies support M1 targets being typically located in the sulcal banks. Objective/hypothesisTo more thoroughly investigate this inconsistency, we sought to determine whether neocortical surface orientation was a critical determinant of regional activation. MethodsMR images were used to construct cortical and scalp surfaces for 18 subjects. The angle (θ) between the cortical surface normal and its nearest scalp normal for ∼50,000 cortical points per subject was used to quantify cortical location (i.e., gyral vs. sulcal). TMS-induced activations of primary motor cortex (M1) were compared to brain activations recorded during a finger-tapping task using concurrent positron emission tomographic (PET) imaging. ResultsBrain activations were primarily sulcal for both the TMS and task activations (P < 0.001 for both) compared to the overall cortical surface orientation. Also, the location of maximal blood flow in response to either TMS or finger-tapping correlated well using the cortical surface orientation angle or distance to scalp (P < 0.001 for both) as criteria for comparison between different neocortical activation modalities. ConclusionThis study provides further evidence that a major factor in cortical activation using TMS is the orientation of the cortical surface with respect to the induced electric field. The results show that, despite the gyral crown of the cortex being subjected to a larger magnetic field magnitude, the sulcal bank of M1 had larger cerebral blood flow (CBF) responses during TMS.

The Guidance Molecule Semaphorin3A is Differentially Involved in the Arealization of the Mouse and Primate Neocortex

The visual cortex is organized into discrete domains characterized by their specific function, connectivity, chemoarchitecture, and cytoarchitecture. Gradients of transcription factors across the anteroposterior and mediolateral axes of the neocortex have previously been demonstrated to specify the main sensory regions. However, they do not account for the establishment of multiple areas in the primate visual cortex, which occupies approximately 50% of the neocortical surface. We demonstrate that the guidance molecule Semaphorin3A (Sema3A) is initially secreted in the cortical plate of the embryonic marmoset monkey and acts as an intrinsic cue to control the migration of subpopulations of neuronal progenitors and projection neurons expressing the receptor Neuropilin 1 (Npn1). During the first 2 postnatal weeks, Sema3A expression becomes primarily associated with ventral visual cortical areas, leading to the specific migration of Npn1+ neurons in the late maturing visual areas. In the mouse, Sema3A distribution is not arealized, but Npn1 expression becomes restricted to the posterior neocortex at embryonic day 16.5. The selective reduction in the striate cortex we observe in Sema3A-/- animals potentially results from the differential distribution of Npn1+ cells. Therefore, the Sema3A/Npn1 pathway participates to the parcellation of the visual neocortex in both the mouse and the marmoset, however, through different regulatory processes.

Cerebroprotective Effects of Emoxipin, Reamberin, and Mexidol in Alloxan Diabetes

The effects of original Russian preparations, derivatives of 3-hydroxypyridine and succinic acid (emoxipin, reamberin, mexidol), on the cellular composition of the cerebrocortical and diencephalic structures were studied and correlations of shifts in the cellular composition with changes in the severity of hyperglycemia in rats with alloxan diabetes were analyzed. The efficiency of 3-hydroxypyridine and succinic acid derivatives was evaluated in comparison with α-lipoic acid. Seven injections of the optimal doses of all the studied drugs prevented the neuron loss in layers I-III of the primary somatosensory cortex. In addition, emoxipin, reamberin, and α-lipoic acid prevented astrocyte loss in the neocortical surface layers and of neurons in the hypothalamic paraventricular nucleus. Reamberin limited microglial infiltration of the hippocampal field CA1. Injection of α-lipoic acid augmented the increase in astrocyte count in the paraventricular nucleus and potentiated the reduction of tigroid granularity of CA1 field neurons. Emoxipin and mexidol caused an increase in the counts of neurons and oligodendrocytes in CA1 field. By contrast, reamberin and α-lipoic acid reduced the counts of neurons and oligodendrocytes, respectively, in this hippocampal zone. More favorable effects of emoxipin and mexidol vs. reamberin and α-lipoic acid on the cellular composition of the hippocampus of rats with alloxan diabetes were explained by more effective correction of hyperglycemia under the effect of 3-hydroxypyridine derivatives.

Data mining neocortical high-frequency oscillations in epilepsy and controls

Transient high-frequency (100-500 Hz) oscillations of the local field potential have been studied extensively in human mesial temporal lobe. Previous studies report that both ripple (100-250 Hz) and fast ripple (250-500 Hz) oscillations are increased in the seizure-onset zone of patients with mesial temporal lobe epilepsy. Comparatively little is known, however, about their spatial distribution with respect to seizure-onset zone in neocortical epilepsy, or their prevalence in normal brain. We present a quantitative analysis of high-frequency oscillations and their rates of occurrence in a group of nine patients with neocortical epilepsy and two control patients with no history of seizures. Oscillations were automatically detected and classified using an unsupervised approach in a data set of unprecedented volume in epilepsy research, over 12 terabytes of continuous long-term micro- and macro-electrode intracranial recordings, without human preprocessing, enabling selection-bias-free estimates of oscillation rates. There are three main results: (i) a cluster of ripple frequency oscillations with median spectral centroid = 137 Hz is increased in the seizure-onset zone more frequently than a cluster of fast ripple frequency oscillations (median spectral centroid = 305 Hz); (ii) we found no difference in the rates of high frequency oscillations in control neocortex and the non-seizure-onset zone neocortex of patients with epilepsy, despite the possibility of different underlying mechanisms of generation; and (iii) while previous studies have demonstrated that oscillations recorded by parenchyma-penetrating micro-electrodes have higher peak 100-500 Hz frequencies than penetrating macro-electrodes, this was not found for the epipial electrodes used here to record from the neocortical surface. We conclude that the relative rate of ripple frequency oscillations is a potential biomarker for epileptic neocortex, but that larger prospective studies correlating high-frequency oscillations rates with seizure-onset zone, resected tissue and surgical outcome are required to determine the true predictive value.

Cortical Inactivation by Cooling in Small Animals

Reversible inactivation of the cortex by surface cooling is a powerful method for studying the function of a particular area. Implanted cooling cryoloops have been used to study the role of individual cortical areas in auditory processing of awake-behaving cats. Cryoloops have also been used in rodents for reversible inactivation of the cortex, but recently there has been a concern that the cryoloop may also cool non-cortical structures either directly or via the perfusion of blood, cooled as it passed close to the cooling loop. In this study we have confirmed that the loop can inactivate most of the auditory cortex without causing a significant reduction in temperature of the auditory thalamus or other subcortical structures. We placed a cryoloop on the surface of the guinea pig cortex, cooled it to 2°C and measured thermal gradients across the neocortical surface. We found that the temperature dropped to 20–24°C among cells within a radius of about 2.5 mm away from the loop. This temperature drop was sufficient to reduce activity of most cortical cells and led to the inactivation of almost the entire auditory region. When the temperature of thalamus, midbrain, and middle ear were measured directly during cortical cooling, there was a small drop in temperature (about 4°C) but this was not sufficient to directly reduce neural activity. In an effort to visualize the extent of neural inactivation we measured the uptake of thallium ions following an intravenous injection. This confirmed that there was a large reduction of activity across much of the ipsilateral cortex and only a small reduction in subcortical structures.

Neocortical reorganization in spina bifida

Normal brain development throughout childhood and adolescence is usually characterized by decreased cortical thickness in the frontal regions as well as region-specific patterns of increased white matter myelination and volume. We investigated total cerebral volumes, neocortical surface area, and neocortical thickness in 16 children with a neural tube defect, spina bifida myelomeningocele (SB), and 16 age-matched typically developing controls using a semi-automated, quantitative approach to MRI-based brain morphometry. The results revealed no significant group differences in total cerebral volume. However, group differences were observed in the global distribution of distinct tissue classes within the cerebrum: the SB group demonstrated a significant 15% reduction in total white matter and a 69% increase in cerebrospinal fluid, with no differences in total gray matter. Group comparisons of neocortical surface area assessments were significantly smaller in the occipital regions for SB, with no significant group differences in the frontal regions. Group comparisons of cortical thickness measurements demonstrated reduced cortical thickness in all regions except the frontal regions, where the SB group exhibited an increase relative to the PC group. Although regional patterns of thinning may be associated with the mechanical effects of hydrocephalus, the overall reduction in white matter and increased neocortical thickness in the frontal regions suggest that SB reflects a long-term disruption of brain development that extends far beyond the neural tube defect in the first weeks of gestation.

Automatic segmentation of human brain sulci

The neocortical surface has a rich and complex structure comprised of folds (gyri) and fissures (sulci). Sulci are important macroscopic landmarks for orientation on the cortex. A precise segmentation and labeling of sulci is helpful in human brain mapping studies relating brain anatomy and function. Due to their structural complexity and inter-subject variability, this is considered as a non-trivial task. An automatic algorithm is proposed to accurately segment neocortical sulci: vertices of a white/gray matter interface mesh are classified under a Bayesian framework as belonging to gyral and sulcal compartments using information about their geodesic depth and local curvature. Then, vertices are collected into sulcal regions by a watershed-like growing method. Experimental results demonstrate that the method is accurate and robust.