fMRI assessment of thalamocortical connectivity during attentional performance

Functional magnetic resonance imaging (fMRI) studies have shown dysfunction in key areas associated with the thalamocortical circuit in patients with schizophrenia. This study examined the functional connectivity involving the frontal-thalamic circuitry during a spatial focusing-of-attention task in 18 unmedicated patients with schizophrenia and 38 healthy controls. Functional connectivity was analyzed by assigning seed regions (in the thalamic nuclei (mediodorsal nucleus (MDN), pulvinar, anterior nucleus (AN)), the dorsolateral prefrontal cortex (Brodmann areas 9 and 46), and the caudate), and correlating their respective activity with that in the non-seed regions voxel-wise. Functional connectivity analysis demonstrated that functional connectivity was significantly impaired in patients, e.g., between the right pulvinar and regions such as the prefrontal and temporal cortices and the cerebellum. On the other hand, enhanced functional connectivity was found in patients e.g., between the AN and regions such as the prefrontal and temporal cortices. In addition, the patients had significantly lower task performance and less (but non-significant) brain activation than those of controls. These results revealed disturbed functional integration in schizophrenia, and suggested that the functional connectivity abnormalities in the thalamocortical circuitry, especially the frontal-thalamic circuitry, may underlie the attention deficits in schizophrenia patients. Further, this study suggested that functional connectivity analysis might be more sensitive than brain activation analysis in detecting the functional abnormalities in schizophrenia.     

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders

ABSTRACT: BACKGROUND: Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD. We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Result Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex-MTG-IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. CONCLUSIONS: These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.     

Correlations between microstructural alterations and severity of cognitive deficiency in Alzheimer's disease and mild cognitive impairment: a diffusional kurtosis imaging study

Object

Diffusional kurtosis imaging (DKI), a natural extension of diffusion tensor imaging (DTI), can characterize non-Gaussian diffusion in the brain. We investigated the capability of DKI parameters for detecting microstructural changes in both gray matter (GM) and white matter (WM) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) and sought to determine whether these DKI parameters could serve as imaging biomarkers to indicate the severity of cognitive deficiency.

Materials and Methods

DKI was performed on 18 AD patients and 12 MCI patients. Fractional anisotropy, kurtosis and diffusivity parameters in the temporal, parietal, frontal and occipital lobes were compared between the two groups using Mann–Whitney U test. The correlations between regional DKI parameters and mini-mental state examination (MMSE) score were tested using Pearson's correlation.

Results

In ADs, significantly increased diffusivity and decreased kurtosis parameters were observed in both the GM and WM of the parietal and occipital lobes as compared to MCIs. Significantly decreased fractional anisotropy was also observed in the WM of these lobes in ADs. With the exception of fractional anisotropy and radial kurtosis, all the five other DKI parameters exhibited significant correlations with MMSE score in both GM and WM.

Conclusion

Bearing additional information, the DKI model can provide sensitive imaging biomarkers for assessing the severity of cognitive deficiency in reference to MMSE score and potentially improve early detection and progression monitoring of AD based on characterizing microstructures in both the WM and especially the GM.     

Characterization of BOLD-fMRI signal during a verbal fluency paradigm in patients with intracerebral tumors affecting the frontal lobe

Previous studies have indicated that the BOLD-fMRI signal can be modified by tumor processes in close vicinity to functional brain areas. This effect has been investigated primarily for the perirolandic area but there is only a limited number of studies concerning frontal cortical regions. Therefore, the aim of the current study was to characterize BOLD-fMRI signal and activation patterns in patients with frontal brain tumors while performing a verbal fluency task. Six patients (ages 31-56 years) suffering from frontal (5 left sided and 1 right sided) intracerebral tumors were examined with fMRI while performing a verbal fluency task in a blocked paradigm design. Eight healthy volunteers served as the control group. The patients (5 right and 1 left handed) demonstrated left frontal activation which could be clearly located outside the tumor area and adjacent edema with varying degrees of additional right frontal activation. In the predominant left frontal activation cluster, the mean voxel based z-score and cluster size were not statistically different between patients and controls. The present fMRI study is indicating that language related BOLD signal changes in the frontal cortex of patients with tumors close to functional areas were comparable to the signal in normal controls. Additionally, the temporal hemodynamic response characteristic was comparable in both groups. This is an important finding consistent with PET results and corroborates the feasibility of functional mapping approaches in patients with tumors affecting the frontal lobe. Additional studies investigating alterations of the hemodynamic response depending on tumor location and histology are required in order to further elucidate the association between pathophysiology and BOLD fMRI signal.     

Aberrant resting-state cerebral blood flow and its connectivity in primary dysmenorrhea on arterial spin labeling MRI

PurposeThis study aimed to clarify the resting-state cerebral blood flow alteration patterns induced by primary dysmenorrhea, investigate the relationships between cerebral blood flow alterations and clinical parameters of patients with primary dysmenorrhea, and explore whether brain regions with abnormal cerebral blood flow also feature functional connectivity changes.MethodsArterial spin labeling imaging and clinical parameters were acquired in 42 patients with primary dysmenorrhea and 41 healthy controls during their menstrual phases. Differences in cerebral blood flow were compared between the two groups, and the clusters with significant group differences were selected as the regions of interest for further statistical analyses.ResultsCompared to healthy controls, patients with primary dysmenorrhea exhibited increased cerebral blood flow in the bilateral precuneus, left posterior cingulate cortex, and right rolandic operculum. Among patients with primary dysmenorrhea, we identified a negative correlation between the cerebral blood flow in the right rolandic operculum and the visual analogue score for anxiety, and greater correlation between the functional connectivity in the precuneus/posterior cingulate cortex and the right middle cingulate cortex, and between the right rolandic operculum and the left inferior parietal lobule and the bilateral postcentral gyrus.DiscussionCerebral blood flow abnormalities associated with primary dysmenorrhea were mainly concentrated in the areas comprising the default mode network in primary dysmenorrhea patients, which could be involved in the central mechanism of primary dysmenorrhea. Cerebral blood flow alteration in the rolandic operculum may underlie an anxiety-induced compulsive tendency in patients with primary dysmenorrhea. Investigating the enhanced connectivity among various pain-related brain regions could improve understanding of the onset and development of primary dysmenorrhea.     

A conditional Granger causality model approach for group analysis in functional magnetic resonance imaging

Granger causality model (GCM) derived from multivariate vector autoregressive models of data has been employed to identify effective connectivity in the human brain with functional magnetic resonance imaging (fMRI) and to reveal complex temporal and spatial dynamics underlying a variety of cognitive processes. In the most recent fMRI effective connectivity measures, pair-wise GCM has commonly been applied based on single-voxel values or average values from special brain areas at the group level. Although a few novel conditional GCM methods have been proposed to quantify the connections between brain areas, our study is the first to propose a viable standardized approach for group analysis of fMRI data with GCM. To compare the effectiveness of our approach with traditional pair-wise GCM models, we applied a well-established conditional GCM to preselected time series of brain regions resulting from general linear model (GLM) and group spatial kernel independent component analysis of an fMRI data set in the temporal domain. Data sets consisting of one task-related and one resting-state fMRI were used to investigate connections among brain areas with the conditional GCM method. With the GLM-detected brain activation regions in the emotion-related cortex during the block design paradigm, the conditional GCM method was proposed to study the causality of the habituation between the left amygdala and pregenual cingulate cortex during emotion processing. For the resting-state data set, it is possible to calculate not only the effective connectivity between networks but also the heterogeneity within a single network. Our results have further shown a particular interacting pattern of default mode network that can be characterized as both afferent and efferent influences on the medial prefrontal cortex and posterior cingulate cortex. These results suggest that the conditional GCM approach based on a linear multivariate vector autoregressive model can achieve greater accuracy in detecting network connectivity than the widely used pair-wise GCM, and this group analysis methodology can be quite useful to extend the information obtainable in fMRI.     

Hierarchical features of large-scale cortical connectivity

The analysis of complex networks has revealed patterns of organization in a variety of natural and artificial systems, including neuronal networks of the brain at multiple scales. In this paper, we describe a novel analysis of the large-scale connectivity between regions of the mammalian cerebral cortex, utilizing a set of hierarchical measurements proposed recently. We examine previously identified functional clusters of brain regions in macaque visual cortex and cat cortex and find significant differences between such clusters in terms of several hierarchical measures, revealing differences in how these clusters are embedded in the overall cortical architecture. For example, the ventral cluster of visual cortex maintains structurally more segregated, less divergent connections than the dorsal cluster, which may point to functionally different roles of their constituent brain regions.     

Tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus reflect secondary compensatory mechanisms

Background

Despite strong evidence that the pathophysiology of Tourette syndrome (TS) involves structural and functional disturbances of the basal ganglia and cortical frontal areas, findings from in vivo imaging studies have provided conflicting results. In this study we used whole brain diffusion tensor imaging (DTI) to investigate the microstructural integrity of white matter pathways and brain tissue in 19 unmedicated, adult, male patients with TS “only” (without comorbid psychiatric disorders) and 20 age- and sex-matched control subjects.

Results

Compared to normal controls, TS patients showed a decrease in the fractional anisotropy index (FA) bilaterally in the medial frontal gyrus, the pars opercularis of the left inferior frontal gyrus, the middle occipital gyrus, the right cingulate gyrus, and the medial premotor cortex. Increased apparent diffusion coefficient (ADC) maps were detected in the left cingulate gyrus, prefrontal areas, left precentral gyrus, and left putamen. There was a negative correlation between tic severity and FA values in the left superior frontal gyrus, medial frontal gyrus bilaterally, cingulate gyrus bilaterally, and ventral posterior lateral nucleus of the right thalamus, and a positive correlation in the body of the corpus callosum, left thalamus, right superior temporal gyrus, and left parahippocampal gyrus. There was also a positive correlation between regional ADC values and tic severity in the left cingulate gyrus, putamen bilaterally, medial frontal gyrus bilaterally, left precentral gyrus, and ventral anterior nucleus of the left thalamus.

Conclusions

Our results confirm prior studies suggesting that tics are caused by alterations in prefrontal areas, thalamus and putamen, while changes in the cingulate gyrus seem to reflect secondary compensatory mechanisms. Due to the study design, influences from comorbidities, gender, medication and age can be excluded.     

Occipital-parietal interactions during shifts of exogenous visuospatial attention: trial-dependent changes of effective connectivity

We studied neural interactions between brain areas involved in exogenous (stimulus-driven) control of visuospatial attention. With event-related functional magnetic resonance imaging (fMRI), we investigated changes of connectivity during shifts of spatial attention from an attended location to a previously unattended target location. Using a 3-T scanner, fMRI data were acquired from three healthy volunteers. According to a central visual cue, participants directed endogenous spatial attention to the left or the right visual hemifield for blocks of 56 s. Peripheral visual targets were presented unpredictably in either the attended hemifield (valid trials, 80%) or in the unattended hemifield (invalid trials, 20%) and participants performed a two-alternative forced-choice discrimination task with the target, irrespective of cue validity. In accordance with previous results, we found that the temporal–parietal junction (TPJ) mediates the shift of spatial attention toward stimuli presented at the unattended side (i.e., invalid trials). We critically studied the interaction between occipital areas responding to the visual stimuli and other brain regions in order to find regions functionally coupled with the occipital cortex during invalid trials. We found that the coupling between occipital areas processing visual stimuli and the TPJ selectively increased during invalid trials. Our results highlight how changes of connectivity between brain areas can describe attentional processes such as stimulus-driven shifts of spatial attention.     

The neural correlates of calculation ability in children: an fMRI study

Most studies investigating mental numerical processing involve adult participants and little is known about the functioning of these systems in children. The current study used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of numeracy and the influence of age on these correlates with a group of adults and a group of third graders who had average to above average mathematical ability. Participants performed simple and complex versions of exact and approximate calculation tasks while in the magnet. Like adults, children activated a network of brain regions in the frontal and parietal lobes during the calculation tasks, and they recruited additional brain regions for the more complex versions of the tasks. However, direct comparisons between adults and children revealed significant differences in level of activation across all tasks. In particular, patterns of activation in the parietal lobe were significantly different as a function of age. Findings support previous claims that the parietal lobe becomes more specialized for arithmetic tasks with age.     

Biophysical and neural basis of resting state functional connectivity: Evidence from non-human primates

Functional MRI (fMRI) has evolved from simple observations of regional changes in MRI signals caused by cortical activity induced by a task or stimulus, to task-free acquisitions of images in a resting state. Such resting state signals contain low frequency fluctuations which may be correlated between voxels, and strongly correlated regions are deemed to reflect functional connectivity within synchronized circuits. Resting state functional connectivity (rsFC) measures have been widely adopted by the neuroscience community, and are being used and interpreted as indicators of intrinsic neural circuits and their functional states in a broad range of applications, both basic and clinical. However, there has been relatively little work reported that validates whether inter-regional correlations in resting state fluctuations of fMRI (rsfMRI) signals actually measure functional connectivity between brain regions, or to establish how MRI data correlate with other metrics of functional connectivity. In this mini-review, we summarize recent studies of rsFC within mesoscopic scale cortical networks (100 μm–10 mm) within a well defined functional region of primary somatosensory cortex (S1), as well as spinal cord and brain white matter in non-human primates, in which we have measured spatial patterns of resting state correlations and validated their interpretation with electrophysiological signals and anatomic connections. Moreover, we emphasize that low frequency correlations are a general feature of neural systems, as evidenced by their presence in the spinal cord as well as white matter. These studies demonstrate the valuable role of high field MRI and invasive measurements in an animal model to inform the interpretation of human imaging studies.     

Assessment of the metabolic profile in Type 2 diabetes mellitus and hypothyroidism through proton MR spectroscopy

The metabolic changes in the brain of patients affected with Type 2 diabetes mellitus (DM) alone, both Type 2 DM and hypothyroidism and hypothyroidism only were investigated using proton magnetic resonance spectroscopy ((1)H MRS). Single-voxel spectroscopy was carried out in right and left frontal lobe white matter, left parietal white matter and left occipital gray matter. Choline (Cho)/creatine (Cr) value was found to be increased in the left occipital gray matter of the subjects affected with Type 2 DM and both Type 2 DM and hypothyroidism as compared to controls. No significant change in the Cho/Cr value in the occipital gray matter was observed in hypothyroid subjects as compared to controls. However, they showed an increased level of Cho/Cr in the frontal white matter. High Cho is associated with altered membrane phospholipid metabolism. The high Cho in frontal white matter in hypothyroids and occipital gray matter in diabetic patients suggests that, though both the diseases are endocrine disorders, they differ from each other in terms of regional brain metabolite changes.     

Long-duration transcutaneous electric acupoint stimulation alters small-world brain functional networks

Acupuncture, which is recognized as an alternative and complementary treatment in Western medicine, has long shown efficiencies in chronic pain relief, drug addiction treatment, stroke rehabilitation and other clinical practices. The neural mechanism underlying acupuncture, however, is still unclear. Many studies have focused on the sustained effects of acupuncture on healthy subjects, yet there are very few on the topological organization of functional networks in the whole brain in response to long-duration acupuncture (longer than 20 min). This paper presents a novel study on the effects of long-duration transcutaneous electric acupoint stimulation (TEAS) on the small-world properties of brain functional networks. Functional magnetic resonance imaging was used to construct brain functional networks of 18 healthy subjects (9 males and 9 females) during the resting state. All subjects received both TEAS and minimal TEAS (MTEAS) and were scanned before and after each stimulation. An altered functional network was found with lower local efficiency and no significant change in global efficiency for healthy subjects after TEAS, while no significant difference was observed after MTEAS. The experiments also showed that the nodal efficiencies in several paralimbic/limbic regions were altered by TEAS, and those in middle frontal gyrus and other regions by MTEAS. To remove the psychological effects and the baseline, we compared the difference between diffTEAS (difference between after and before TEAS) and diffMTEAS (difference between after and before MTEAS). The results showed that the local efficiency was decreased and that the nodal efficiencies in frontal gyrus, orbitofrontal cortex, anterior cingulate gyrus and hippocampus gyrus were changed. Based on those observations, we conclude that long-duration TEAS may modulate the short-range connections of brain functional networks and also the limbic system.     

时变动态贝叶斯网络模型及其在皮层脑电网络连接中的应用

大脑执行语言的发音需要顶叶、颞叶、额叶等多个脑区协同完成.皮层脑电具有高时间分辨率、较高空间分辨率和高信噪比等优势,为研究大脑的电生理特性提供了重要的技术手段.为了探索大脑对语言的动态处理过程,利用多尺度皮层脑电(标准电极与微电极)分析了被试在执行音节朗读任务时的皮层脑电信号的高频gamma段特征,提出采用时变动态贝叶斯网络构建单次实验任务的有向网络.结果显示该方法能够快速有效地构建语言任务过程中标准电极、微电极以及二者之间的有向网络连接,且反映了大规模网络(标准电极之间的连接)、局部网络(微电极之间的连接)以及大规模网络与局部网络之间的连接(标准电极与微电极之间的连接)随语言任务发生的动态改变.研究还发现,发音时刻之前与之后的网络连接存在显著性差异,且发音方式不同的音节网络间也存在明显差异.该研究将有助于癫痫等神经疾病的术前临床评估以及理解大脑对语言加工的实时处理过程.     

Automated human frontal lobe identification in MR images based on fuzzy-logic encoded expert anatomic knowledge

Identification of human brain structures in MR images comprises an area of increasing interest, which also presents numerous methodological challenges. Here we describe a new knowledge-based automated method designed to identify several major brain sulci and then to define the frontal lobes by using the identified sulci as landmarks. To identify brain sulci, sulcal images were generated by morphologic operations and then separated into different components based on connectivity analysis. Subsequently, the individual anatomic features were evaluated by using fuzzy membership functions. The crisp decisions, i.e., the identification of sulci, were made by taking the maximum of the summation of all the membership functions. The identification was designed in a hierarchical order. The longitudinal fissure was extracted first. The left and right central sulci were then identified based on the left and right hemispheres. Next, the lateral sulci were identified based on the central sulci and hemispheres. Finally, the left and right frontal lobes were defined from the two hemispheres. The method was evaluated by visual inspection, comparison with manual segmentation, and comparison with manually volumetric results in references. The average Jaccard similarities of left and right frontal lobes between the automated and manual segmentation were 0.89 and 0.91, respectively. The average Kappa indices of left and right frontal lobes between the automated and manual segmentation were 0.94 and 0.95, respectively. These results show relatively high accuracy of using this novel method for human frontal lobe identification and segmentation.     

Fractional amplitude of low-frequency fluctuation changes in functional dyspepsia: A resting-state fMRI study

Recently, there is an increasing interest in the study of the role of brain dysfunction in the pathogenesis of symptoms of functional dyspepsia (FD). More specifically, abnormal brain activities in patients with FD during the resting state have been proven by several positron emission tomography (PET) studies. Resting-state functional magnetic resonance imaging (fMRI) is also a valuable tool in investigating spontaneous brain activity abnormalities in pathological conditions. In the present study, we examined the amplitude of low-frequency fluctuations (ALFF) and fractional (f)ALFF changes in patients with FD by using fMRI. Twenty-nine patients with FD and sixteen healthy controls participated in this study. Between-group differences in ALFF/fALFF were examined using a permutation-based nonparametric test after accounting for the gender and age effects. The results revealed a significant between-group difference in fALFF but not in ALFF in multiple brain regions including the right insula, brainstem and cerebellum. Seed-based resting-state functional connectivity analysis revealed that FD patients have increased correlations between the right cerebellum and multiple brain regions including the bilateral brainstem, bilateral cerebellum, bilateral thalamus, left para-/hippocampus, left pallidum and left putamen. Furthermore, fLAFF values in the right insula were positively correlated with the severity of the disease. These findings have provided further evidence of spontaneous brain activity abnormalities in FD patients which might contribute to our understanding of the pathophysiology of the disease.     

Hierarchical clustering to measure connectivity in fMRI resting-state data

Low frequency oscillations, which are temporally correlated in functionally related brain regions, characterize the mammalian brain, even when no explicit cognitive tasks are performed. Functional connectivity MR imaging is used to map regions of the resting brain showing synchronous, regional and slow fluctuations in cerebral blood flow and oxygenation. In this study, we use a hierarchical clustering method to detect similarities of low-frequency fluctuations. We describe one measure of correlations in the low frequency range for classification of resting-state fMRI data. Furthermore, we investigate the contribution of motion and hardware instabilities to resting-state correlations and provide a method to reduce artifacts. For all cortical regions studied and clusters obtained, we quantify the degree of contamination of functional connectivity maps by the respiratory and cardiac cycle. Results indicate that patterns of functional connectivity can be obtained with hierarchical clustering that resemble known neuronal connections. The corresponding voxel time series do not show significant correlations in the respiratory or cardiac frequency band.     

Regional Absolute Quantification of the Neurochemical Profile of the Canine Brain: Investigation by Proton Nuclear Magnetic Resonance Spectroscopy and Tissue Extraction

The purpose of this study was to characterize the neurochemical profiles of various parts of the canine brain using proton nuclear magnetic resonance spectroscopy, tissue extraction, and external simulated phantom concentration quantification. The occipital, frontal, and temporal lobes, thalami, cerebellar cortices, and spinal cords of five pure bred adult beagles were collected, and heavy water solutions for the nuclear magnetic resonance sample were prepared using the methanol–chloroform–water extraction method. The metabolite concentrations in canine brain tissues were measured and compared with those found in human and rat brain tissues. In addition, the cross peaks of Lac, Glu/Gln, and mIns were identified using two-dimensional correlation spectroscopy in the canine frontal cortex. The present study demonstrated the absolute quantification of canine neuronal parts using in vitro high-resolution magnetic resonance spectroscopy, with tissue extraction used to accurately measure metabolite concentrations, thus providing valuable metabolic information regarding the various canine neuronal regions.     

脑功能激活光诱发机理小世界网络分析研究

研究光诱发和静息两种状态下的脑功能网络的信息传输枢纽、网络聚合能力和信息传输的最小路径的差异性。采用小世界网络理论对脑功能网络进行建模,通过对脑功能网络连接度、簇系数和最小路径进行分析,得出光诱发状态下的信息传输重要枢纽为岛叶、后扣带回功能区;丘脑、海马两处功能网络有较大聚合能力。光诱发过程从额上回经颞中回传输到枕中回。静息状态下的信息传输重要枢纽为楔叶、舌回;中央旁小叶、颞上回脑功能网络有较大聚合能力。静息状态下的左半区最佳信息传输路径为左额上回、左颞中回、右楔叶最后到左枕中回;右脑半区的为右额上回、右前扣带回、左枕下回最后到右枕中回。光诱发状态与静息状态的最佳传输路径有明显的区别。     

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.