Clinical correlations with hippocampal atrophy

There is now a consensus that magnetic resonance imaging (MRI) is a sensitive and specific indicator of mesial temporal sclerosis (MTS) in patients with partial epilepsy. MTS is the most common pathological finding underlying the epileptogenic zone in patients undergoing temporal lobe surgery for medically refractory partial seizures. MRI-based hippocampal volumetric studies (i.e., quantitative MRI), has been shown to provide objective evidence for hippocampal atrophy in patients with MTS. The hippocampal volume in the epileptic temporal lobe has correlated with the neuronal cell densities in selected hippocampal subfields. A history of febrile seizures in childhood and age of unprovoked seizure onset have been associated with MRI-based hippocampal volumetry. There is conflicting evidence regarding the relationship between the duration of the seizure disorder and volumetry. Quantitative MRI has compared favorably to other noninvasive techniques (e.g., scalp-recorded EEG), in indicating the diagnosis of medical temporal lobe epilepsy (MTLE). MRI-identified hippocampal atrophy has also been a favorable prognostic indicator of seizure outcome after temporal lobe surgery. The presence of hippocampal atrophy appears to serve an in vivo surrogate for the presence of MTS.     

Hippocampal MRI volumetrics and temporal lobe substrates in medial temporal lobe epilepsy

Forty-nine consecutive patients undergoing anteromedial temporal lobe resection for medically intractable temporal lobe seizures, and averaging 2 yr (range 6 mo to 4 yr) postoperative follow-up, were selected for a retrospective study. This study correlated magnetic resonance imaging (MRI) derived hippocampal volumetrics, preoperative demographics, postoperative seizure control, and tissue analysis, including hippocampal CA (cornu ammonis) field neuronal, and glial cell counts, and immunohistochemistry (IHC) evidence for dentate sprouting and reorganization. These measures were compared in hippocampi with or without an adjacent presumptive epileptogenic temporal lobe mass. Mesial temporal sclerosis (MTS) was defined as >50% neuronal cell loss averaged across all CA fields with NPY (neuropeptide-y) and somatostatin reorganization. These patients may or may not include granule cell sprouting as determined by dynorphin staining. Patients were divided into two groups based on CA field neuronal cell counts, one averaging >50% cell loss and one averaging <50% cell loss. For the MTS group (N = 38), 89% had significant volumetric atrophy of the ipsilateral hippocampus, 74% had dentate reorganization, and complete seizure control was seen in 76% of these patients. In one subgroup of the <50% cell loss group, patients with medial temporal lobe epilepsy caused by a mass in the medial temporal lobe (mass group) (N = 6), 33% demonstrated significant volumetric atrophy of the hippocampus ipsilateral to the mass, 0% had dentate sprouting, and seizures were completely controlled in 67%. For the second subgroup of the <50% cell loss group, patients without mass lesions (N = 5) who were classified as the paradoxical medial temporal lobe epilepsy group (paradoxical group), 20% had ipsilateral hippocampal atrophy, 0% had dentate reorganization, and complete seizure control was seen in 60% of these patients. In conclusion, for the MTS group, hippocampal atrophy proven by MRI volumetrics was highly predictive of significant neuronal cell loss and an excellent indicator of success. However, in patients who had a foreign mass, hippocampal atrophy was not necessarily indicative of significant neuronal cell loss and MRI volumetrics was not a factor in the determination of a successful outcome. Furthermore, patients without mass lesions who have normal volumetrics but demonstrate hippocampal disease through invasive electrode monitoring, are likely to have paradoxical medial temporal lobe epilepsy, seizures beginning at a later age, and a lower, but not insignificant, success rate than the classical mesial temporal sclerosis group.     

Automatic detection of hippocampal atrophy on magnetic resonance images.

An automatic method for identifying hippocampal atrophy on magnetic resonance (MR) images obtained from patients with clinical evidence of temporal lobe epilepsy (TLE) is described. The method is based on the analysis of image intensity differences between patients and controls within a volume of interest (VOI) centred on the hippocampus. The core of the method is a fully automatic signal intensity-based inter-subject image registration technique. In particular, a global affine registration to a reference image is performed, followed by a local affine registration within the VOI. A mask produced by manual segmentation of the mean hippocampus for 30 control subjects enabled investigations to be restricted to a specified region of the VOI approximately corresponding to the hippocampus. Normal variations of hippocampal signal intensity were computed from images obtained for the 30 control subjects. The manual method of hippocampal volumetry, currently an important component of the pre-surgical evaluation of patients with clinical evidence of medically intractable TLE, is used to determine the lower 1st percentile limits of normal hippocampal volume. Hippocampi with volumes below this limit are defined as atrophic. We investigated whether the automatic method can correctly distinguish between 15 patients with significant hippocampal atrophy according to absolute volumes and a further 14 controls. ROC curves enabled evaluation of sensitivity and specificity in respect of an intensity threshold. 100% specificity is required when determining suitability of patients for neurosurgery, resulting in levels of 50% and 70% sensitivity in detecting atrophy in the right and left hippocampus, respectively. We propose that the method can be developed as an automatic screening procedure.     

Clinical applications: MRI, SPECT, and PET

MRI, PET, and SPECT are all used to image abnormalities in the epileptic brain. Comparison of the techniques is difficult because they measure different aspects of the epileptic process—structure, metabolism, and perfusion. SPECT is the only one that can be systematically applied during seizures, while all three are used to image interictal abnormalities. Literature review suggests that of interictal techniques, PET has the highest diagnostic sensitivity in temporal lobe epilepsy (TLE) (84% vs. 66% for SPECT, 55% for qualitative MRI, 71% for quantitative MRI) while SPECT has the highest sensitivity in extratemporal epilepsy (ETE) (60% vs. 43% for MRI and 33% for PET). The highest diagnostic sensitivity and specificity were achieved by ictal imaging with SPECT (90% in TLE, 81% in ETE). The techniques, however, were not always redundant. One reason for the wide discrepancy of results in TLE and ETE might be the differing pathologic substrates. A literature review of imaging findings associated with mesial temporal sclerosis (MTS), developmental lesion or tumor as the underlying abnormality associated with epilepsy supports this explantion. PET and MRI are much more sensitive to MTS than SPECT (100%, 95% vs. 70%). On the other hand, in developmental lesions the three techniques are equally sensitive (88–92%) and in tumors, MRI was most sensitive (96%) and SPECT least (82%). A study at NIH explains the differing sensitivities: using PET to measure both blood flow and metabolism revealed discrepant findings in the same patients. Preliminary evidence also indicates that the distribution of hyperperfusion on ictal SPECT can differentiate subtypes of TLE. Combining the results of refined imaging techniques holds great promise in epilepsy localization and diagnosis.     

Clinical correlations: MRI and EEG

Main structural correlates of epileptogenesis include hippocampal sclerosis, cortical dysgenesis, foreign tissue lesions, gliosis, and dual pathology (a combination of any two). These structural abnormalities are now increasingly defined with MRI, enabling systematic EEG correlative analyses. Hippocampal atrophy (HA) and increased T₂ signal in medial temporal structures predict the presence of mesial temporal sclerosis with a high degree of sensitivity and specificity. In 50 patients with clinical evidence of temporal lobe epilepsy and isolated HA, ictal scalp EEG was concordant to the atrophic temporal lobe in 33, nonlateralizing in 12, obscured in 3, and bilateral in 2, but it was discordant in none. Earlier reports of higher levels of discordance may be ascribed to the presence of dual pathology or to differing MRI and EEG criteria for localization. In a more inclusive group of 101 patients with unilateral HA, ictal scalp EEG was obtained in 99. It was unlocalized in 53, localized elsewhere in 9, and localized to the atrophic temporal lobe in 38. Of those, 51 patients had intracranial EEG: 12 were unlocalized, 29 were localized to the atrophic hippocampus, and 9 were localized elsewhere. There is thus a rare but definite subgroup of patients with unilateral HA who have EEG localization elsewhere than the atrophy. The successful cure of seizures in half these patients after removal of the EEG focus confirms the importance of this observation and emphasizes the search for more dual pathology that has remained undetected on MRI. About 10% of the patients with HA have significant atrophy bilaterally, and several series have confirmed that surgical success is predicted by removal of the EEG identified seizure onset area, not the more or less atrophic hippocampus. In patients with other kinds of dual pathology, including HA and foreign tissue lesions or cortical dysgenesis, EEG is also paramount in predicting the site of epileptogenesis for surgical intervention. EEG correlates of cortical dysgenesis are heterogeneous, but EEG has potential to provide accurate localization of the site of epileptogenesis in foreign tissue lesions also. In a study of 59 lesional patients, a small number of patients with low grade astrocytomas and oligodendrogliomas consistently localized by EEG to an area elsewhere than the lesion, and failed seizure control when the lesion was removed. Although MRI can demonstrate the structural correlate of the epilepsy in many situations, rare patients, particularly with certain tumors, cortical dysgenesis, and dual pathology, require EEG for accurate localization.     

MRI hippocampal volume and neuropsychology in epilepsy surgery

A review is provided of recent findings on relationships between neurocognitive test data and magnetic resonance imaging (MRI)-determined hippocampal volumes in nonlesional temporal lobectomy patients. The difference between the right and left hippocampal volumes is correlated with postoperative verbal memory in left temporal lobectomy patients who do not have lesional pathology. MRI hippocampal volume data are not associated with measures of executive functioning or naming. Sex differences have been found for verbal memory outcome as women have better verbal memory following left temporal lobectomy. Sex differences have also been found in the relationships between verbal and visual memory, and hippocampal volume data. The systematic combination of MRI-acquired morphological data and neuropsychological test data may further our understanding of neurocognitive function, and provide clinically useful data for counseling epilepsy surgery patients. The current data are promising with regard to prediction of memory outcome following temporal lobectomy, but they do not yet allow for prediction of specific individual patient outcomes. Rather, the currently available data support counseling patients based on the memory outcome of others with similar characteristics.     

Proton magnetic resonance spectroscopic images and MRI volumetric studies for lateralization of temporal lobe epilepsy

We obtained 2D magnetic resonance (MR) spectroscopic images (MRSI) and MRI volumetric measurements (MRIV) of amygdala and hippocampus in 30 consecutive patients with temporal lobe epilepsy (TLE) being evaluated for surgical treatment. Both MRSI and MRIV lateralization showed good agreement with the current gold standard of clinical-EEG lateralization. Each exam separately correctly lateralized 25 out of 30 patients with no false lateralization. Combining both exams, lateralization could be achieved in 28 out of 30 patients. The two patients with no significant asymmetry had bitemporal EEG abnormalities, and bilateral damage on both MRIV and MRSI. There was a good correlation between the magnitude of the MRSI and MRIV asymmetry (Pearson COEFFICIENT = 0.83; p < .0001). Both MRSI and MRIV were normal in our patients with seizures originating outside the temporal lobes. Both MRIV and MRSI can lateralize TLE in 83% of patients. Combination of the two modalities allows lateralization in 93% of patients. Patients who cannot be lateralized generally have symmetrical bitemporal abnormalities; they are not incorrectly lateralized. The structural and chemical pathologic abnormalities seen in TLE seem to be associated with the seizure focus, and may be as, or even more, reliable than a few recorded seizures in predicting the side from which most seizures originate.     

Application of high field spectroscopic imaging in the evaluation of temporal lobe epilepsy

Previous spectroscopic imaging studies of temporal lobe epilepsy have used comparisons of metabolite content or ratios to lateralize the seizure focus. Although highly successful, these studies have shown significant variations within each of the groups of healthy subjects and patients. This variation may arise from the natural differences seen in metabolite concentration in gray and white matter, the complex anatomy seen about the hippocampus, and the large voxels typically employed at 1.5 T. Using a 4.1 T whole body system, we have acquired spectroscopic images with 0.5 cc nominal voxels (1 cc after filtering) to evaluate the regional variation in metabolite content of the hippocampus, temporal gray and white matter, midbrain, and cerebellar vermis. Using a threshold value of 0.90 for CR/NAA, a value 90% of all normal hippocampal voxels lay below, we have correctly identified the presence of epileptogenic tissue in patients with unilateral as well as bilateral seizures. By using comparisons to healthy values of the CR/NAA ratio, this method enables the visualization of bilateral disease and provides information on the extent of gray matter involvement.     

Rapid stereological quantitation of temporal neocortex in TLE

To determine the extent of neocortical atrophy in the temporal lobe using rapid stereological analysis of magnetic resonance slices in patients with temporal lobe epilepsy and to compare the findings to those obtained by visual analysis of high-resolution magnetic resonance images. 25 patients with temporal lobe epilepsy, along with 25 age-matched controls were scanned using a 1.5 Tesla magnetic resonance imaging machine (GE signa systems Paris). Visual analysis was performed on standard high-resolution images. Volumetric analysis of hippocampus and temporal neocortex was performed using computer-aided stereology (MEASURE program, Patrick Barta, Johns Hopkins, Baltimore, USA). Stereological volumetric analysis demonstrated isolated hippocampal atrophy in only nine (36%) cases including three (12%) with bilateral disease. However, eight (32%) cases had combined hippocampal and neocortical atrophy and three (12%) had isolated neocortical atrophy. All volumetric measurements took less than 10 min. On the other hand, visual analysis suggested that 17 (68%) had hippocampal atrophy alone with only two (8%) having combined neocortical atrophy and a further two (8%) having isolated neocortical atrophy. Nearly half of the patients had temporal neocortical atrophy with or without hippocampal atrophy. This rapid, accurate and non-biased quantitative technique has wide clinical utility and is significantly more valuable in detecting neocortical atrophy than visual analysis alone. The results support the notion that abnormalities may be overlooked by current standards of routine magnetic resonance imaging.     

Existence of contralateral abnormalities revealed by texture analysis in unilateral intractable hippocampal epilepsy

We selected 23 patients with unilateral temporal lobe epilepsy characterized by ipsilateral hippocampal sclerosis and an apparently normal contralateral hippocampus on MR imaging. Images were acquired on a 0.28 T MR scanner using a conventional Carr-Purcell Meiboom Gill sequence in all patients and in 9 healthy subjects. Texture analysis was applied to axial MR images of the first and tenth echoes. Texture analysis detects macroscopic lesions and microscopic abnormalities that can not be observed visually. The presence of texture differences in the between normal (controls) and sclerotic hippocampi was ascertained by statistical discriminant analysis. The apparently normal contralateral hippocampi can be classified into three categories in terms of texture: 4 apparently healthy, 8 similar to sclerosis, and 11 different from either healthy or sclerosis. These findings are related to a certain degree of hippocampal alteration, which further investigation might help better characterize.     

MRI of the temporal lobe: normal variations, with special reference toward epilepsy.

Recent investigations of epilepsy, Alzheimer's disease, amnesia, and schizophrenia have used magnetic resonance imaging (MRI) to evaluate changes in temporal lobe structures. Normal variations in these structures need to be defined before one can use these structures to describe abnormal conditions. Twenty-nine normal volunteers were studied by coronal MRI. Frequent findings include notching of the uncus by the tentorium or adjacent vessels (22/29) and asymmetry of the temporal horns (20/29). This finding of uncal notching strengthens the evidence against "incisural sclerosis" as the basis for hippocampal sclerosis. Temporal horn dilatation occurred in four. However, mild asymmetry of the temporal horn was seen frequently at its anterior tip (16/29) and may be related to head rotation. Asymmetry of the choroidal fissure was never marked. Mild asymmetry was common at the hippocampal head (pes). Mild enlargement of the right temporal lobe by visual inspection is not uncommon. Subtle asymmetry of the white matter between the hippocampus and the collateral sulcus occurred in six. The collateral sulcus does not always point to the temporal horn. The occipitotemporal sulcus may point to the temporal horn. Asymmetric uncal protrusion (0/29) and Sylvian fissure dilatation (4/29) occur rarely.     

Application of spectroscopic imaging in epilepsy

Functional and anatomical neuroimaging has had a dramatic effect on the evaluation of patients for seizure surgery. The demonstration by PET that the epileptogenic focus has interictal metabolic abnormalities has allowed a greater number of patients to come to seizure surgery, with fewer of these patients requiring intracranial electrode evaluations. Metabolic changes have also been demonstrated utilizing single voxel and whole brain ¹H and ³¹P MRS imaging techniques with the interictal focus characterized by increased Pi, pH, and decreased PME and NAA. These findings can be used to accurately lateralize temporal lobe as well as frontal lobe epilepsy. Furthermore, there is evidence that these findings can be used to localize the seizure focus with the changes specific for the epileptogenic region; although, more diffuse changes both ipsilaterally and contralaterally have been seen. In patients with anterior hippocampal seizure foci the pH is significantly alkaline only in the ipsilateral hippocampus, whereas the increased Pi and decreased PME can be seen throughout the ipsilateral temporal lobe. When compared to controls the contralateral hemisphere is acidotic. Decreased NAA concentrations as well as NAA/Cr ratios have been demonstrated in the epileptogenic region in temporal and frontal lobe epilepsy. The decreased NAA has been correlated with the severity of cell loss, and may be a more sensitive measure than qualitative or quantitative measures of the hippocampal atrophy; however, the NAA decrease is more widespread than just the epileptogenic focus but may be maximal at the site of seizure initiation. In preliminary work, NAA maps of deviation from normality have suggested the maximal change to coincide with the epileptogenic region. These results suggest that in focal epilepsy there is abnormal metabolic activity throughout the brain detectable by MRS, with patterns of metabolic asymmetry that are useful for seizure localization.     

Quantitation of normal canine hippocampus formation volume: Correlation of MRI with gross histology

The hippocampal formation possesses an important role in the development and maintenance of short-term memory. In this study, magnetic resonance imaging (MRI) and gross histology were used to quantify the volume of the hippocampal formation in canines. High resolution MRI, using 1 mm thick slices and an intraplanar resolution of 0.35 mm was performed at 2.0 T both in vivo and in vitro following in situ fixation. The volumes of the hippocampal formations were determined from MR images and compared to those obtained from one mm thick gross histologic sections. The average volume of the canine hippocampal formation, measured from in vivo and in vitro MR images was 476.0 ± 79.5 and 467.3 ± 53.7 mm³, respectively. Determined from gross histology, the volume of the hippocampal formation was 463.6 ± 24.1 mm³. Quantitation of the canine hippocampal formation using in vivo MRI showed good correlation with in vitro MRI and histology, verifying the reliability and reproducibility of in vivo MRI measurements. High resolution MRI using 1 mm thick slices through the whole canine hippocampal formation is necessary for accurate volume determination of a structure of this size.     

Altered hemispheric symmetry found in left-sided mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE/HS) but not found in right-sided MTLE/HS

Purpose

The purpose was to investigate the altered hemispheric asymmetry in patients with mesial temporal lobe epilepsy with unilateral hippocampus sclerosis (MTLE/HS).

Materials and methods

This study examined the hemispheric asymmetry of regional gray matter (GM) and white matter (WM) volume among a group of 13 patients with left-sided MTLE/HS, a group of 10 patients with right-sided MTLE/HS and a group of 21 age- and gender- matched healthy controls by optimized voxel-based morphometry (VBM) based on magnetic resonance imaging.

Results

Compared to healthy controls, abnormal asymmetries were detected in the left-sided MTLE/HS patients. The left-sided MTLE/HS patients had more GM asymmetries (L<R) in the temporal lobes, including the inferior temporal gyrus, middle temporal gyrus and parahippocampal gyrus. There was significant asymmetry (L<R) in subcortical WM of the mesial temporal lobe in left-sided MTLE/HS patients. However, no significant difference was detected in terms of GM and WM asymmetry between the group with right-sided MTLE/HS and normal controls.

Conclusion

We should approach hemispheric asymmetry in left- and right-sided MTLE/HS patients differently. The study also demonstrates potential future use of VBM in detecting hemispheric asymmetries and lateralization of brain functions.     

Hippocampal volume is related to cognitive decline and fornicial diffusion measures in multiple sclerosis

Purpose

To assess for associations between hippocampal atrophy and measures of cognitive function, hippocampal magnetization transfer ratio (MTR), and diffusion measures of the fornix, the largest efferent white matter tract from the hippocampus, in patients with multiple sclerosis (MS) and controls.

Materials and Methods

A total of 53 patients with MS and 20 age- and sex-matched healthy controls participated in cognitive testing and scanning including high spatial-resolution diffusion imaging and a T1-MPRAGE scan. Hippocampal volume and fornicial thickness measures were calculated and compared to mean values of fornicial transverse diffusivity, mean diffusivity, longitudinal diffusivity, fractional anisotropy, mean hippocampal MTR, and scores on measures of episodic memory, processing speed, and working memory tasks.

Results

In patients with MS, hippocampal volume was significantly related to fornicial diffusion measures (P < 7 × 10^− 4) and to measures of verbal (P = 0.030) and visual spatial (P = 0.004) episodic memory and a measure of information processing speed (P < 0.037).

Discussion

These results highlight the role of the hippocampus in cognitive dysfunction in patients with MS and suggest that measures of hippocampal atrophy could be used to capture aspects of disease progression.     

Aberrant default mode network in subjects with amnestic mild cognitive impairment using resting-state functional MRI

Amnestic mild cognitive impairment (aMCI) is a syndrome associated with faster memory decline than normal aging and frequently represents the prodromal phase of Alzheimer's disease. When a person is not actively engaged in a goal-directed task, spontaneous functional magnetic resonance imaging (fMRI) signals can reveal functionally connected brain networks, including the so-called default mode network (DMN). To date, only a few studies have investigated DMN functions in aMCI populations. In this study, group-independent component analysis was conducted for resting-state fMRI data, with slices acquired perpendicular to the long axis of the hippocampus, from eight subjects with aMCI and eight normal control subjects. Subjects with aMCI showed an increased DMN activity in middle cingulate cortex, medial prefrontal cortex and left inferior parietal cortex compared to the normal control group. Decreased DMN activity for the aMCI group compared to the normal control group was noted in lateral prefrontal cortex, left medial temporal lobe (MTL), left medial temporal gyrus, posterior cingulate cortex/retrosplenial cortex/precuneus and right angular gyrus. Although MTL volume difference between the two groups was not statistically significant, a decreased activity in left MTL was observed for the aMCI group. Positive correlations between the DMN activity and memory scores were noted for left lateral prefrontal cortex, left medial temporal gyrus and right angular gyrus. These findings support the premise that alterations of the DMN occur in aMCI and may indicate deficiencies in functional, intrinsic brain architecture that correlate with memory function, even before significant MTL atrophy is detectable by structural MRI.     

Positive memory increases cataplexy-like behaviors in narcolepsy mice as revealed using conditioned place preference test

To examine the pathological effect of a mesial temporal seizure onset zone (SOZ) on local and inter-regional response to faces in the amygdala and other structures of the temporal lobe. Intracranial EEG data was obtained from the amygdala, hippocampus, fusiform gyrus and parahippocampal gyrus of nine patients with drug-refractory epilepsy during visual stimulation with faces and mosaics. We analyzed event-related potentials (ERP), gamma frequency power, phase-amplitude coupling and phase-slope-index and compared the results between patients with versus without a mesial temporal SOZ. In the amygdala and fusiform gyrus, faces triggered higher ERP amplitudes compared to mosaics in both patient groups and higher gamma power in patients without a mesial temporal SOZ. In the hippocampus, famous faces triggered higher gamma power for both groups combined but did not affect ERPs in either group. The differentiated ERP response to famous faces in the parahippocampal gyrus was more pronounced in patients without a mesial temporal SOZ. Phase-amplitude coupling and phase-slope-index results yielded bidirectional modulation between amygdala and fusiform gyrus, and predominately unidirectional modulation between parahippocampal gyrus and hippocampus. A mesial temporal SOZ was associated with an impaired response to faces in the amygdala, fusiform gyrus and parahippocampal gyrus in our patients. Compared to this, the response to faces in the hippocampus was impaired in patients with, as well as without, a mesial temporal SOZ. Our results support existing evidence for face processing deficits in patients with a mesial temporal SOZ and suggest the pathological effect of a mesial temporal SOZ on the amygdala to play a pivotal role in this matter in particular.     

经颅超声刺激人脑海马的数值仿真研究

颞叶癫痫、阿尔兹海默症等神经系统疾病与大脑海马的异常放电相关。近年兴起的经颅超声刺激治疗脑疾病具有无创、能深入脑组织和可调控海马神经元放电的特点。该文基于128阵元相控阵换能器、人头颅CT数据、水体建立超声经颅刺激海马数值仿真模型,数值仿真优选适应于海马刺激的换能器结构参数,并结合电容模型,探究超声声学参数对海马神经元放电的影响。结果表明曲率半径90 mm、开口半径56 mm、阵元半径2.0 mm、频率0.9 MHz的128阵元相控超声换能器可形成适应于刺激人脑海马大小的焦域;且在超声频率为0.9 MHz时对海马神经元放电有较好的抑制作用;在较小的占空比和较低的空间峰值时间平均声强条件下对神经元放电有较好的抑制作用。     

Electric stimulation fMRI of the perforant pathway to the rat hippocampus

The hippocampal formation is a brain system that is implicated in learning and memory. The major input to the hippocampus arrives from the entorhinal cortex (EC) to the dentate gyrus (DG) through the perforant path. In the present work, we have investigated the functional properties of this connection by concomitantly applying electrophysiological techniques, deep-brain electric microstimulation and functional magnetic resonance imaging in anesthetized rats. We systematically delivered different current intensities at diverse stimulation frequencies to the perforant path while recording electrophysiological and blood-oxygenation-level-dependent (BOLD) signals. We observed a linear relationship between the current intensity used to stimulate the hippocampal formation and the amplitude and extension of the induced BOLD response. In addition, we found a frequency-dependent spatial pattern of activation. With stimulation protocols and train frequencies used for kindling, the activity strongly spreads ipsilaterally through the hippocampus, DG, subiculum and EC.     

The diagnosis of hippocampal sclerosis: Other techniques

Pathologically, hippocampal sclerosis (HS) is characterized by neuronal loss and gliosis affecting particularly the pyramidal neurons of CA1, CA3, and CA4 with relative sparing of the CA2 neurons. This can be identified in vivo with magnetic resonance (MR) imaging techniques that can reveal both morphological and signal abnormalities. The morphological changes are atrophy and loss of the normal internal architecture of the hippocampus as seen in coronal section. There is also T₁- and T₂-weighted signal abnormality in the hippocampus. Quantitative techniques are very good at measuring any single one of these features, but the spectrum of HS includes cases in which a single feature can occasionally be misleading. Also, quantitation focuses entirely on the hippocampus, and it is becoming clear that HS may exist in the presence of other brain pathology that may affect proper management of the patient. Therefore, quantitative measures should always be interpreted in the context of optimised imaging sequences and visual inspection. For routine clinical purposes, the relative reliance on quantitation (hippocampal volume or T₂ measurements) depends entirely on the yield of visual inspection in any institution. This, in turn, depends on whether optimised imaging is performed and on the familiarity of the reporting specialist with the MRI features of HS. A technique which approaches 95–100% compared with pathology is essential in any epilepsy centre, and optimised visual analysis can achieve this. There are some cases where quantitation of a single feature can be misleading, so visual analysis should always be performed, and complements any quantitative study.