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Neuromodulation technologies are crucial for investigating neuronal connectivity and brain function. Magnetic neuromodulation offers wireless and remote deep brain stimulations that are lacking in optogenetic- and wired-electrode-based tools. However, due to the limited understanding of working principles and poorly designed magnetic operating systems, earlier magnetic approaches have yet to be utilized. Furthermore, despite its importance in neuroscience research, cell-type-specific magnetic neuromodulation has remained elusive. Here we present a nanomaterials-based magnetogenetic toolbox, in conjunction with Cre-loxP technology, to selectively activate genetically encoded Piezo1 ion channels in targeted neuronal populations via torque generated by the nanomagnetic actuators in vitro and in vivo. We demonstrate this cell-type-targeting magnetic approach for remote and spatiotemporal precise control of deep brain neural activity in multiple behavioural models, such as bidirectional feeding control, long-term neuromodulation for weight control in obese mice and wireless modulation of social behaviours in multiple mice in the same physical space. Our study demonstrates the potential of cell-type-specific magnetogenetics as an effective and reliable research tool for life sciences, especially in wireless, long-term and freely behaving animals., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

mTOR signaling, involving mTORC1 and mTORC2 complexes, critically regulates neural development and is implicated in various brain disorders. However, we do not fully understand all of the upstream signaling components that can regulate mTOR signaling, especially in neurons. Here, we show a direct, regulated inhibition of mTOR by Tanc2, an adaptor/scaffolding protein with strong neurodevelopmental and psychiatric implications. While Tanc2-null mice show embryonic lethality, Tanc2-haploinsufficient mice survive but display mTORC1/2 hyperactivity accompanying synaptic and behavioral deficits reversed by mTOR-inhibiting rapamycin. Tanc2 interacts with and inhibits mTOR, which is suppressed by mTOR-activating serum or ketamine, a fast-acting antidepressant. Tanc2 and Deptor, also known to inhibit mTORC1/2 minimally affecting neurodevelopment, distinctly inhibit mTOR in early- and late-stage neurons. Lastly, Tanc2 inhibits mTORC1/2 in human neural progenitor cells and neurons. In summary, our findings show that Tanc2 is a mTORC1/2 inhibitor affecting neurodevelopment.

Neuronal-related activity can be estimated from functional magnetic resonance imaging (fMRI) data with no knowledge of the timings of blood oxygenation level-dependent (BOLD) events by means of deconvolution with regularized least-squares. This work proposes two improvements on the deconvolution algorithm of sparse paradigm free mapping (SPFM): a new formulation that enables the estimation of neuronal events with long, sustained activity; and the implementation of a subsampling approach based on stability selection that avoids the choice of any regularization parameter. The proposed method is evaluated on real fMRI data and compared with both the original SPFM algorithm and conventional analysis with a general linear model (GLM) that is aware of the temporal model of the neuronal-related activity. We demonstrate that the novel stability-based SPFM algorithm yields activation maps with higher resemblance to the maps obtained with GLM analyses and offers improved detection of neuronal-related events over SPFM, particularly in scenarios with low contrast-to-noise ratio.

Netrin-G ligand-3 (NGL-3) is a postsynaptic adhesion molecule known to directly interact with the excitatory postsynaptic scaffolding protein postsynaptic density-95 (PSD-95) and trans-synaptically with leukocyte common antigen-related (LAR) family receptor tyrosine phosphatases to regulate presynaptic differentiation. Although NGL-3 has been implicated in the regulation of excitatory synapse development by in vitro studies, whether it regulates synapse development or function, or any other features of brain development and function, is not known. Here, we report that mice lacking NGL-3 (Ngl3-/- mice) show markedly suppressed normal brain development and postnatal survival and growth. A change of the genetic background of mice from pure to hybrid minimized these developmental effects but modestly suppressed N-methyl-D-aspartate (NMDA) receptor (NMDAR)-mediated synaptic transmission in the hippocampus without affecting synapse development, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR)-mediated basal transmission, and presynaptic release. Intriguingly, long-term depression (LTD) was near-completely abolished in Ngl3-/- mice, and the Akt/glycogen synthase kinase 3β (GSK3β) signaling pathway, known to suppress LTD, was abnormally enhanced. In addition, pharmacological inhibition of Akt, but not activation of NMDARs, normalized the suppressed LTD in Ngl3-/- mice, suggesting that Akt hyperactivity suppresses LTD. Ngl3-/- mice displayed several behavioral abnormalities, including hyperactivity, anxiolytic-like behavior, impaired spatial memory, and enhanced seizure susceptibility. Among them, the hyperactivity was rapidly improved by pharmacological NMDAR activation. These results suggest that NGL-3 regulates brain development, Akt/GSK3β signaling, LTD, and locomotive and cognitive behaviors., Competing Interests: The authors have declared that no competing interests exist.

As the use of ultra-high field (UHF; ≥7T) magnetic resonance (MR) imaging expands, there is an increasing need to establish high-resolution MR imaging protocols for patients with neurological disease. Magnetization transfer (MT) imaging has been used to provide information about changes in the magnitude of the restricted protons that are caused by tissue damages. Several studies have found that MTR has a good sensitivity to measure changes in myelin concentration within the brain. Because of the much higher specific absorption rate (SAR) of tissue and longer acquisition time required for UHF, however, in-vivo studies using conventional pulsed MT sequences at UHF have not been well utilized. In this study, we introduce a new MT data acquisition approach using a 7T MR system, variable density magnetization transfer (vdMT) imaging, which can be reasonably included in a routine patient scan protocol with a much shorter scan time and reduced discomfort to the patient. To reduce SAR and scan time while maintaining at least similar MTR image quality to that obtained with the conventional method, a higher density of MT RF pulses was applied in the center of k-space, and sparsely applied MT RF pulses were used in the outer part of k-space. The fraction of k-space receiving 100% MT RF density and TR were optimized based on in-vivo ROI analysis, and results were confirmed with high-resolution MTR map using a vdMT approach from healthy controls and patients with multiple sclerosis (MS). The experimental results confirmed that vdMT imaging can cover a whole brain volume in an acceptable scan time for routine patient scans while providing MTR image quality at least similar to that obtained with conventional MT imaging (correlation coefficient=0.95 in an agar-gel phantom [MT offset frequency=1kH], 0.90 in a postmortem MS brain, and 0.85 in the 4 healthy volunteers). MS lesions were associated with signal reductions in the postmortem MS brains and in the patients with MS. In this study, we have described a new approach for acquiring high-resolution MTR map of the whole brain volume using 7T MR imaging. This vdMT method provides similar image quality to that obtained with the conventional method, and shortens the scan time by reducing SAR. These results suggest that vdMT approach is a method that could be used for UHF scans of patients with neurological disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Motivation: In an effort to better understand the molecular drivers of synaptic and neurophysiologic dysfunction in Alzheimer's disease (AD), we analyzed neuronal gene expression data from human AD brain tissue to identify master regulators of synaptic gene expression., Results: Master regulator analysis identifies ZCCHC17 as normally supporting the expression of a network of synaptic genes, and predicts that ZCCHC17 dysfunction in AD leads to lower expression of these genes. We demonstrate that ZCCHC17 is normally expressed in neurons and is reduced early in the course of AD pathology. We show that ZCCHC17 loss in rat neurons leads to lower expression of the majority of the predicted synaptic targets and that ZCCHC17 drives the expression of a similar gene network in humans and rats. These findings support a conserved function for ZCCHC17 between species and identify ZCCHC17 loss as an important early driver of lower synaptic gene expression in AD., Availability and Implementation: Matlab and R scripts used in this paper are available at https://github.com/afteich/AD_ZCC., Contact: aft25@cumc.columbia.edu., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Purpose: While MP2RAGE shows the potential to generate B1 insensitive T1 contrast, the long TR of MP2RAGE (≥6s at 7T) is essential to provide the large dynamic range of apparent T1 relaxation for dual inversion time acquisitions. We present a 2 direction (2D) accelerated MP2RAGE, which provides an increased flip angle while maintaining similar dynamic recovery as 1D accelerated MP2RAGE., Method: Simulations were conducted to optimize 2D accelerated MP2RAGE parameters and healthy subjects were scanned with 1D and 2D accelerated MP2RAGE at 7T. Images were compared visually and contrast to noise (CNR) between brain tissues was measured., Result: Simulations showed that CNR is primarly determined by the TR, followed by the number of the first partition encoding steps in MP2RAGE. Keeping TR constant, a smaller number of partition encoding steps increases the achievable maximal CNR. In-vivo 2D MP2RAGE improves CNR between white and gray matters by 9% when compared to 1D accelerated MP2RAGE with identical voxel size., Conclusion: We presented 2D accelated MP2RAGE at 7T with the increased flip angle. We show that this leads to CNR improvement, and consequently a reduction of scan time to be compared to 1D accelerated MP2RAGE., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The metabolite response during a memory task in Alzheimer's disease (AD) patients is unknown., Objective: To investigate the metabolite changes in subjects with AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) elderly during a memory task using functional magnetic resonance spectroscopy (fMRS)., Methods: This study involved 23 young normal controls (YC), 24 CN elderly, 24 aMCI, and 24 mild and probable AD individuals. fMRS data were acquired at the precuneus and posterior cingulate brain regions during a face-name association task. Statistical analyses of quantified metabolites were performed to evaluate differences of the metabolite values between the stimulation conditions and among the four subject groups. Receiver operating curve analysis was performed to evaluate whether the metabolic changes after functional activations can differentiate the subject groups., Result: Glutamine and glutamate complex (Glx) was statistically significantly different between the fixation and repeat conditions in aMCI (p = 0.0492) as well as between the fixation and the novel conditions in the AD (p = 0.0412) group. The total N-acetylaspartate (tNAA) was statistically significantly different among the four subject groups in the fixation condition (DF = 3, F = 7.673, p <  0.001), the novel condition (DF = 3, F = 6.945, p <  0.001), and the repeat condition (DF = 3, F = 7.127, p <  0.001). tNAA, tCr, and mIns could be used to differentiate CN from aMCI. Furthermore, tNAA, tCr, Glx, and Glu could also differentiate CN from AD, and aMCI from AD., Conclusion: Glx was altered during a stimulation that may be used to evaluate neuronal dysfunction in a demented patient. tNAA and tCr were reduced in patients with AD.

Background: A systems biology approach based on the assembly and interrogation of gene regulatory networks, or interactomes, was used to study neuroadaptation processes associated with the transition to alcohol dependence at the molecular level., Results: Using a rat model of dependent and non-dependent alcohol self-administration, we reverse engineered a global transcriptional regulatory network during protracted abstinence, a period when relapse rates are highest. We then interrogated the network to identify master regulator genes that mechanistically regulate brain region-specific signatures associated with dependent and non-dependent alcohol self-administration. Among these, the gene coding for the glucocorticoid receptor was independently identified as a master regulator in multiple brain regions, including the medial prefrontal cortex, nucleus accumbens, central nucleus of the amygdala, and ventral tegmental area, consistent with the view that brain reward and stress systems are dysregulated during protracted abstinence. Administration of the glucocorticoid antagonist mifepristone in either the nucleus accumbens or ventral tegmental area selectively decreased dependent, excessive, alcohol self-administration in rats but had no effect on non-dependent, moderate, alcohol self-administration., Conclusions: Our study suggests that assembly and analysis of regulatory networks is an effective strategy for the identification of key regulators of long-term neuroplastic changes within specific brain regions that play a functional role in alcohol dependence. More specifically, our results support a key role for regulatory networks downstream of the glucocorticoid receptor in excessive alcohol drinking during protracted alcohol abstinence.

Purpose: Measurements of magnetization transfer (MT) metrics, such as the steady-state (SS) MT ratio and apparent longitudinal relaxation rate require multiple MT irradiation durations and a long experimental time. To overcome these problems, we propose a novel method using a short MT off-resonance pulse with and without on-resonance inversion preparation pulse., Theory and Methods: Computer simulations were performed to examine the accuracy of the proposed method and to find the optimal off-resonance irradiation pulse duration (Tirad) and power level (ω1). Our approach, with echo planar imaging data acquisition, was applied to animals at 9.4 T and humans at 3 T with ω1/2π = 100 Hz and 177 Hz, respectively. Steady-state MT ratio and relaxation rate were obtained from a pair of MT images at a Tirad, with and without inversion., Results: For Tirad ≥ 0.4 s, steady-state MT ratio, and relaxation rate measured at any single Tirad agreed well with those of the conventional fitting method that uses multiple Tirad. Our simulation indicates that a higher ω1 can use a shorter Tirad., Conclusion: Steady-state MT ratio and relaxation rate can be determined from MT data with only one, short Tirad by incorporation of an inversion prepulse. This MT imaging approach is simple, fast, and easily implementable., (Copyright © 2013 Wiley Periodicals, Inc.)

Background and Purpose: Traumatic brain injury is common in fighting athletes such as boxers, given the frequency of blows to the head. Because DTI is sensitive to microstructural changes in white matter, this technique is often used to investigate white matter integrity in patients with traumatic brain injury. We hypothesized that previous fight exposure would predict DTI abnormalities in fighting athletes after controlling for individual variation., Materials and Methods: A total of 74 boxers and 81 mixed martial arts fighters were included in the analysis and scanned by use of DTI. Individual information and data on fight exposures, including number of fights and knockouts, were collected. A multiple hierarchical linear regression model was used in region-of-interest analysis to test the hypothesis that fight-related exposure could predict DTI values separately in boxers and mixed martial arts fighters. Age, weight, and years of education were controlled to ensure that these factors would not account for the hypothesized effects., Results: We found that the number of knockouts among boxers predicted increased longitudinal diffusivity and transversal diffusivity in white matter and subcortical gray matter regions, including corpus callosum, isthmus cingulate, pericalcarine, precuneus, and amygdala, leading to increased mean diffusivity and decreased fractional anisotropy in the corresponding regions. The mixed martial arts fighters had increased transversal diffusivity in the posterior cingulate. The number of fights did not predict any DTI measures in either group., Conclusions: These findings suggest that the history of fight exposure in a fighter population can be used to predict microstructural brain damage.

We propose an unbiased implicit-reference group-wise (IRG) image registration method and demonstrate its applications in the construction of a brain white matter fiber tract atlas and the analysis of resting-state functional MRI (fMRI) connectivity. Most image registration techniques pair-wise align images to a selected reference image and group analyses are performed in the reference space, which may produce bias. The proposed method jointly estimates transformations, with an elastic deformation model, registering all images to an implicit reference corresponding to the group average. The unbiased registration is applied to build a fiber tract atlas by registering a group of diffusion tensor images. Compared to reference-based registration, the IRG registration improves the fiber track overlap within the group. After applying the method in the fMRI connectivity analysis, results suggest a general improvement in functional connectivity maps at a group level in terms of larger cluster size and higher average t-scores.

Nonrigid registration of diffusion magnetic resonance imaging (MRI) is crucial for group analyses and building white matter and fiber tract atlases. Most current diffusion MRI registration techniques are limited to the alignment of diffusion tensor imaging (DTI) data. We propose a novel diffeomorphic registration method for high angular resolution diffusion images by mapping their orientation distribution functions (ODFs). ODFs can be reconstructed using q-ball imaging (QBI) techniques and represented by spherical harmonics (SHs) to resolve intra-voxel fiber crossings. The registration is based on optimizing a diffeomorphic demons cost function. Unlike scalar images, deforming ODF maps requires ODF reorientation to maintain its consistency with the local fiber orientations. Our method simultaneously reorients the ODFs by computing a Wigner rotation matrix at each voxel, and applies it to the SH coefficients during registration. Rotation of the coefficients avoids the estimation of principal directions, which has no analytical solution and is time consuming. The proposed method was validated on both simulated and real data sets with various metrics, which include the distance between the estimated and simulated transformation fields, the standard deviation of the general fractional anisotropy and the directional consistency of the deformed and reference images. The registration performance using SHs with different maximum orders were compared using these metrics. Results show that the diffeomorphic registration improved the affine alignment, and registration using SHs with higher order SHs further improved the registration accuracy by reducing the shape difference and improving the directional consistency of the registered and reference ODF maps.

Most current automated segmentation methods are performed on T(1)- or T(2)-weighted MR images, relying on relative image intensity that is dependent on other MR parameters and sensitive to B(1) magnetic field inhomogeneity. Here, we propose an image segmentation method based on quantitative longitudinal magnetization relaxation time (T(1)) of brain tissues. Considering the partial volume effect, fractional volume maps of brain tissues (white matter, gray matter, and cerebrospinal fluid) were obtained by fitting the observed signal in an inversion recovery procedure to a linear combination of three exponential functions, which represents the relaxations of each of the tissue types. A Look-Locker acquisition was employed to accelerate the acquisition process. The feasibility and efficacy of this proposed method were evaluated using simulations and experiments. The potential applications of this method in the study of neurological disease as well as normal brain development and aging are discussed., (Published by Elsevier Inc.)

We propose an unbiased group-wise diffeomorphic registration technique to normalize a group of diffusion tensor (DT) images. Our method uses an implicit reference group-wise registration framework to avoid bias caused by reference selection. Log-Euclidean metrics on diffusion tensors are used for the tensor interpolation and computation of the similarity cost functions. The overall energy function is constructed by a diffeomorphic demons approach. The tensor reorientation is performed and implicitly optimized during the registration procedure. The performance of the proposed method is compared with reference-based diffusion tensor imaging (DTI) registration methods. The registered DTI images have smaller shape differences in terms of reduced variance of the fractional anisotropy maps and more consistent tensor orientations. We demonstrate that fiber tract atlas construction can benefit from the group-wise registration by producing fiber bundles with higher overlaps.

In this study, it is demonstrated that fat saturation (FS) preparation (prep) pulses generate incidental magnetization transfer contrast (MTC) in multislice Look-Locker (LL) imaging. It is shown that frequency-selective FS prep pulses can invoke MTC through the exchange between free and motion-restricted protons. Simulation reveals that the fractional signal loss by these MTC effects is more severe for smaller flip angles (FAs), shorter repetition times (TRs), and greater number of slices (SN). These incidental MTC effects result in a signal attenuation at a steady state (up to 30%) and a T(1) measurement bias (up to 20%) when using inversion recovery (IR) LL echo-planar imaging (EPI) sequences. Furthermore, it is shown that water-selective MRI using binomial pulses has the potential to minimize the signal attenuation and provide unbiased T(1) measurement without fat artifacts in MR images., ((c) 2009 Wiley-Liss, Inc.)

A fast T(1) measurement sequence using inversion recovery Look-Locker echo-planar imaging at steady state (IR LL-EPI SS) is presented. Delay time for a full magnetization recovery is not required in the sequence, saving acquisition time significantly for high-resolution T(1) mapping. Imaging parameters of the IR LL-EPI SS sequence were optimized to minimize the bias from the excitation pulses imperfection and to maximize the accuracy and reliability of T(1) measurements, which are critical for its applications. Compared with the conventional inversion recovery Look-Locker echo-planar imaging (IR LL-EPI) sequence, IR LL-EPI SS method preserves similar accuracy and reliability, while saving 20% in acquisition time. Optimized IR LL-EPI SS provided quantitative T(1) mapping with 1 x 1 x 4 mm(3) resolution and whole-brain coverage (28 slices) in approximately 4 min.

Purpose: To evaluate an algorithm based on algebraic estimation of T1 values (three-point estimation) in comparison with computational curve-fitting for the postprocessing of quantitative cerebral perfusion scans., Materials and Methods: Computer simulations were performed to quantify the magnitude of the expected error on T1 and consequently cerebral perfusion using the three-point estimation technique on a Look-Locker (LL) EPI scan. In 50 patients, quantitative cerebral perfusion was calculated using the bookend method with three-point estimation and curve-fitting. The bookend method, a novel approach for calculating quantitative cerebral perfusion based on changes in T1 values after a contrast injection, is currently being validated. The number of computations was used as a measure of computation speed for each method. Student's paired t-test, Bland-Altman, and correlation analyses were performed to evaluate the accuracy of estimation., Results: There was a 99.65% reduction in the number of computations with three-point estimation. Student's t-test showed no significant difference in cerebral perfusion (P=0.80, 0.49, paired t-test N=50, quantitative cerebral blood flow-white matter [qCBF-WM], qCBF-gray matter [qCBF-GM]) when compared to curve-fitting. The results of the two techniques were strongly correlated in patients (slope=0.99, intercept=1.58 mL/(100 g/minute), r=0.86) with a small systemic bias of -0.97 mL/(100 g/minute) in Bland-Altman analysis., Conclusion: The three-point estimation technique is adequate for rapid calculation of qCBF. The estimation scheme drastically reduces processing time, thus making the method feasible for clinical use., (Copyright (c) 2008 Wiley-Liss, Inc.)

The steady-state (SS) approach has been proposed to measure quantitative cerebral blood volume (CBV). However, it is known that the CBV value in SS (CBVSS) is subject to error resulting from the effects of water diffusion from the intra- to extravascular space. CBVSS measurements were simulated in both fast- and no-water-exchange limits, and compared with measured CBVSS values to determine which limiting case is appropriate. Twenty-eight patients were scanned with a segmented Look-Locker echo-planar imaging (LL-EPI) sequence before and after the injection of 0.1 mmol/kg of a T1-shortening contrast agent. Signal changes and T1 values of brain parenchyma and the blood pool were measured pre- and postcontrast. These signal changes and T1 values, in combination with the simulated results, were used to estimate water-exchange rates. We found that the intra- to extravascular water-exchange rates in white matter (WM) and gray matter (GM) were 0.9 and 1.6 s-1, respectively. With these water-exchange rates, the fast-water-exchange limit of the CBV values showed good agreement with the simulation (r=0.86 in WM, and 0.78 in GM). The CBV values with the correction for water-exchange effects were recalculated as 2.73+/-0.44 and 5.81+/-1.12 of quantitative cerebral blood water volume (%) in WM and GM, respectively., (Copyright (c) 2006 Wiley-Liss, Inc.)

Purpose: To improve the accuracy of dynamic susceptibility contrast (DSC) measurements of cerebral blood flow (CBF) and volume (CBV)., Materials and Methods: In eight volunteers, steady-state CBV (CBV(SS)) was measured using TrueFISP readout of inversion recovery (IR) before and after injection of a bolus of contrast. A standard DSC (STD) perfusion measurement was performed by echo-planar imaging (EPI) during passage of the bolus and subsequently used to calculate the CBF (CBF(DSC)) and CBV (CBV(DSC)). The ratio of CBV(SS) to CBV(DSC) was used to calibrate measurements of CBV and CBF on a subject-by-subject basis., Results: Agreement of values of CBV (1.77 +/- 0.27 mL/100 g in white matter (WM), 3.65 +/- 1.04 mL/100 g in gray matter (GM)), and CBF (23.6 +/- 2.4 mL/(100 g min) in WM, 57.3 +/- 18.2 mL/(100 g min) in GM) with published gold-standard values shows improvement after calibration. An F-test comparison of the coefficients of variation of the CBV and CBF showed a significant reduction, with calibration, of the variability of CBV in WM (P < 0.001) and GM (P < 0.03), and of CBF in WM (P < 0.0001)., Conclusion: The addition of a CBV(SS) measurement to an STD measurement of cerebral perfusion improves the accuracy of CBV and CBF measurements. The method may prove useful for assessing patients suffering from acute stroke.

Unlabelled: The ictal hyperperfusion (compared with the interictal state) of the cerebellum and basal ganglia has not been investigated systematically in patients with temporal lobe epilepsy (TLE). Their ictal perfusion patterns were analyzed in relation to temporal and frontal hyperperfusion during TLE seizures using SPECT subtraction., Methods: Thirty-three TLE patients had interictal and ictal SPECT, video-electroencephalographic (EEG) monitoring, and volumetric MRI. SPECT subtraction with MRI coregistration was performed using commercial software. The presence of ictal hyperperfusion was determined in the ipsilateral and contralateral temporal lobe, frontal lobe, cerebellum, and basal ganglia., Results: All patients showed ictal hyperperfusion in the temporal lobe of seizure origin. Vermian cerebellar hyperperfusion (CH) was observed in 26 patients (78.8%) and hemispheric CH was found in 25 (75.8%). Compared with the side of the epileptogenic temporal lobe, there were 7 patients with ipsilateral hemispheric CH (28.0%), 15 with contralateral hemispheric CH (60.0%), and 3 with bilateral hemispheric CH (12.0%). CH was observed more frequently in patients with additional frontal hyperperfusion (14/15, 93.3%; 2 ipsilateral to the seizure focus, 10 contralateral, and 2 bilateral) than in patients without frontal hyperperfusion (11/18, 61.1%). Among 18 patients with temporal hyperperfusion without frontal hyperperfusion, 11 patients showed hemispheric CH (5 ipsilateral to seizure focus, 5 contralateral, 1 bilateral). Hyperperfusion in the basal ganglia (BGH) was seen in 11 of the 15 patients with temporal and frontal hyperperfusion (73.3%) and in 11 of the 18 with only temporal hyperperfusion (61.1%). In 17 patients with unilateral BGH (13 ipsilateral to the seizure focus, 4 contralateral), CH contralateral to the BGH was observed in 14 (82.5%), CH ipsilateral to the BGH was found in 2 (11.8%), and CH bilateral to the BGH was found in 1 (5.9%)., Conclusion: During TLE seizures, hemispheric CH occurred not only in contralateral but also in ipsilateral or bilateral cerebellar hemispheres to the side of seizure origin. Although temporal lobe origin seizures associated with additional frontal hyperperfusion produced more frequent hemispheric CH, seizures showing only temporal hyperperfusion without frontal hyperperfusion could produce BGH and CH. To determine the side of hemispheric CH, the most important factor appears to be the side of BGH, not the side of seizure origin.

Studies with rat brain illustrate the usefulness of formol-calcium-fixed tissue for studying both enzymatic "chemoarchitectonics" and intracellular organelles. Unembedded frozen sections and polyvinyl alcohol-embedded sections may be used to demonstrate the activities of DPNH-tetrazolium reductase localized in mitochondria and ergastoplasm, TPNH-tetrazolium reductase localized in mitochondria, ATPase (and/or apyrase or ADPase) in cell membranes, and acid phosphatase in lysosomes.(1) Among the observations recorded are: (1) the presence of lysosomes in all cells of the brain; (2) the presence of numerous large lysosomes near the nuclei of capillary endothelial cells; (3) a polarized arrangement of large lysosomes in epithelial cells of the ependyma and choroid plexus; (4) the presence of ATPase activity in the cell membranes of some neurons; (5) the presence of either an apyrase or combination of ATPase and ADPase in the cell membranes of neuroglia and capillaries; (6) the presence of both DPNH- and TPNH-tetrazolium reductase activities in neuroglia; (7) the presence of DPNH- and TPNH-tetrazolium reductase activities in mitochondria and of DPNH-tetrazolium reductase activity in Nissl substance. The possible functional significance of these localizations is briefly discussed, as is their relation to "quantitative histochemistry" data available in the literature.