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Diffusion tensor imaging (DTI) and volumetric magnetic resonance imaging (MRI) have shown white matter (WM) and deep grey matter (GM) abnormalities in the limbic system of multiple sclerosis (MS) participants. Structures like the fornix have been associated with cognitive impairment (CI) in MS, but the diffusion metrics are often biased by partial volume effects from cerebrospinal fluid (CSF) due to its small bundle size and intraventricular location. These errors in DTI parameter estimation worsen with atrophy in MS. The goal here was to evaluate DTI parameters and volumes of the fornix, as well as associated deep GM structures like the thalamus and hippocampus, with high-resolution fluid-attenuated inversion recovery (FLAIR)-DTI at 3T in 43 MS patients, with and without CI, versus 43 controls. The fornix, thalamus and hippocampus displayed atrophy and/or abnormal diffusion metrics, with the fornix showing the most extensive changes within the structures studied here, mainly in CI MS. The affected fornix volumes and diffusion metrics were associated with thalamic atrophy and atypical diffusion metrics in interconnected limbic GM, larger total lesion volume and global brain atrophy. Lower fractional anisotropy (FA) and higher mean and radial diffusivity in the fornix, lower hippocampus FA and lower thalamus volume were strongly correlated with CI in MS. Hippocampus FA and thalamus atrophy were negatively correlated with fatigue and longer time since MS symptoms onset, respectively. FLAIR-DTI and volumetric analyses provided methodologically superior evidence for microstructural abnormalities and extensive atrophy of the fornix and interconnected deep GM in MS that were associated with cognitive deficits.

Aim To treat upper third gastric cancer, proximal gastrectomy (PG), a function‐preserving procedure, is recommended for early lesions when at least half the distal stomach can be preserved, while total gastrectomy (TG) is standard for locally advanced lesions. Oncological feasibility, when applying PG for such lesions, remains unknown. Methods We reviewed patients undergoing TG for clinical (c) T2–T4 upper third gastric cancer between 2006 and 2015. Preoperative tumor locations were further classified into the cardia, fornix, and gastric body based on endoscopic findings. The metastatic rate and therapeutic value index for lymph node (LN) dissection were determined, and characteristics of patients with distal LN (No. 4d, 5, and 6) metastasis (DLNM) were reviewed. In addition, patients with pathological tumor invasion to the middle third (M) region were investigated. Results We studied 167 patients. There were 8 (4.8%) with DLNM and 41 (24.6%) with pathological tumor invasion to the M region. As to regional stations, therapeutic indices for LN dissection at stations No. 4d, 5, 6, and 12a were zero or extremely low. No DLNM was detected in cT2 lesions or cT3/T4 lesions located within the cardia and/or the fornix. In addition, none of the lesions located within the cardia and/or the fornix by preoperative endoscopy extended to the M region in the pathological specimen. Conclusions For upper third gastric cancer, PG without No. 12a dissection might be acceptable for cT2–T4 lesions located within the cardia and/or the fornix when considering the risk of DLNM and cancer‐positivity in the distal stump., The metastatic rate and therapeutic value index for distal lymph node (No. 4d, 5, and 6) were investigated in patients undergoing total gastrectomy for cT2–T4 upper third gastric cancer. In addition, pre‐ and postoperative tumor location was reviewed by preoperative endoscopy and the pathological specimen. For upper third gastric cancer, proximal gastrectomy might be acceptable for cT2–T4 lesions located within the cardia and/or the fornix when considering the risk of distal lymph node metastasis and cancer‐positivity in the distal stump.

Background Cognitive impairment frequently affects multiple sclerosis (MS) patients. However, its neuroanatomical correlates still need to be fully explored. We investigated the contribution of structural and functional magnetic resonance imaging (MRI) abnormalities in explaining cognitive impairment in MS. Methods Brain dual-echo, diffusion tensor, 3D T1-weighted and resting-state (RS) MRI sequences were acquired from 276 MS patients and 102 healthy controls. Using random forest analysis, the contribution of regional white matter (WM) lesions, WM fractional anisotropy (FA) abnormalities, gray matter (GM) atrophy and RS functional connectivity (FC) alterations to cognitive impairment in MS patients was investigated. Results Eighty-four MS patients (30.4%) were cognitively impaired. The best MRI predictors of cognitive impairment (relative importance [%]) (out-of-bag area under the curve [AUC]=0.795) were (a) WM lesions in the right superior longitudinal fasciculus (100%), left anterior thalamic radiation (93.4%), left posterior corona radiata (78.5%), left medial lemniscus (74.2%), left inferior longitudinal fasciculus (70.4%), left optic radiation (68.7%), right middle cerebellar peduncle (60.6%) and right optic radiation (53.5%); (b) decreased FA in the splenium of the corpus callosum (64.3%), left optic radiation (61.0%), body of the corpus callosum (51.9%), and fornix (50.9%); (c) atrophy of the left precuneus (91.4%), right cerebellum crus I (84.4%), right caudate nucleus (78.6%), left thalamus (76.2%) and left supplementary motor area (59.8%). The relevance of these MRI measures in explaining cognitive impairment was confirmed in a cross-validation analysis (AUC=0.765). Conclusions Structural damage in strategic WM and GM regions more than RS FC abnormalities explains cognitive impairment in MS patients.

Aims: To determine the underlying cellular changes and clinical correlates associated with pathology of the hypothalamus in amyotrophic lateral sclerosis (ALS), as hypothalamic atrophy occurs in the preclinical phase of the disease. Methods: The hypothalamus was pathologically examined in nine patients with amyotrophic lateral sclerosis in comparison to eight healthy control subjects. The severity of regional atrophy (paraventricular nucleus: PVN, fornix and total hypothalamus) and peptidergic neuronal loss (oxytocin, vasopressin, cocaine- and amphetamine-regulating transcript: CART, and orexin) was correlated with changes in eating behaviour, sleep function, cognition, behaviour and disease progression. Results: Tar DNA-binding protein 43 (TDP-43) inclusions were present in the hypothalamus of all patients with amyotrophic lateral sclerosis. When compared to controls, there was atrophy of the hypothalamus (average 21% atrophy, p = 0.004), PVN (average 30% atrophy p = 0.014) and a loss of paraventricular oxytocin-producing neurons (average 49% loss p = 0.02) and lateral hypothalamic orexin-producing neurons (average 37% loss, significance p = 0.02). Factor analysis identified strong relationships between abnormal eating behaviour, hypothalamic atrophy and loss of orexin-producing neurons. With increasing disease progression, abnormal sleep behaviour and cognition associated with atrophy of the fornix. Conclusions: Substantial loss of hypothalamic oxytocin-producing neurons occurs in ALS, with regional atrophy and the loss of orexin neurons relating to abnormal eating behaviour in ALS. Oxytocin- and orexin neurons display TDP43 inclusions. Our study points to significant pathology in the hypothalamus that may play a key role in metabolic and pathogenic changes in ALS. (Less)

Sensorineural hearing loss (SNHL) is the most common developmental sensory disorder due to a loss of function within the inner ear or its connections to the brain. While successful intervention for auditory deprivation with hearing amplification and cochlear implants during a sensitive early developmental period can improve spoken-language outcomes, SNHL patients can suffer several cognitive dysfunctions including executive function deficits, visual cognitive impairment, and abnormal visual dominance in speaking perception even after successful intervention. To evaluate whether long association fibers are involved in the pathogenesis of impairment on the extra-auditory cognitive process in SNHL participants, we quantitatively analyzed high-angular resolution diffusion imaging (HARDI) tractography-derived fibers in participants with SNHL. After excluding cases with congenital disorders, perinatal brain damage, or premature birth, we enrolled 17 participants with SNHL aged under 10 years old. Callosal pathways (CP) and six types of cortico-cortical association fibers (arcuate fasciculus [AF], inferior longitudinal fasciculus [ILF], inferior fronto-occipital fasciculus [IFOF], uncinate fasciculus [UF], cingulum fasciculus [CF], and fornix [Fx]) in both hemispheres were identified and visualized. The ILF and IFOF were partly undetected in three profound SNHL participants. Compared to age- and gender-matched neurotypical controls (NC), decreased volumes, increased lengths, and high apparent diffusion coefficient (ADC) values without difference in fractional anisotropy (FA) values were identified in multiple types of fibers in the SNHL group. The impairment of long association fibers in SNHL may partly be related to the association of cognitive dysfunction with SNHL.

Objective To further evaluate the relationship between the clinical profiles and limbic and motor brain regions and their connecting pathways in psychogenic nonepileptic seizures (PNES). Neurite Orientation Dispersion and Density Indices (NODDI) multicompartment modeling was used to test the relationships between tissue alterations in patients with traumatic brain injury (TBI) and multiple psychiatric symptoms. Methods The sample included participants with prior TBI (TBI; N = 37) but no PNES, and with TBI and PNES (TBI + PNES; N = 34). Participants completed 3T Siemens Prisma MRI high angular resolution imaging diffusion protocol. Statistical maps, including fractional anisotropy (FA), mean diffusivity (MD), neurite dispersion [orientation dispersion index (ODI)] and density [intracellular volume fraction (ICVF), and free water (i.e., isotropic) volume fraction (V‐ISO)] signal intensity, were generated for each participant. Linear mixed‐effects models identified clusters of between‐group differences in indices of white matter changes. Pearson’s r correlation tests assessed any relationship between signal intensity and psychiatric symptoms. Results Compared to TBI, TBI + PNES revealed decreases in FA, ICVF, and V‐ISO and increases in MD for clusters within cingulum bundle, uncinate fasciculus, fornix/stria terminalis, and corticospinal tract pathways (cluster threshold α = 0.05). Indices of white matter changes for these clusters correlated with depressive, anxiety, PTSD, psychoticism, and somatization symptom severity (FDR threshold α = 0.05). A follow‐up within‐group analysis revealed that these correlations failed to reach the criteria for significance in the TBI + PNES group alone. Interpretation The results expand support for the hypothesis that alterations in pathways comprising the specific PNES network correspond to patient profiles. These findings implicate myelin‐specific changes as possible contributors to PNES, thus introducing novel potential treatment targets.

Background and purpose Previous investigations show that bilinguals exhibit the first symptoms of dementia 4-5 years later than monolinguals. Therefore, bilingualism has been proposed as a cognitive reserve mechanism. Recent studies have advanced towards an understanding of the brain mechanisms underlying bilingualism's protection against dementia, but none of them deals with white matter (WM) diffusion. Methods In this study, the topic was investigated by measuring WM integrity in a sample of 35 bilinguals and 53 passive bilinguals with mild cognitive impairment. Results No significant differences were found between the groups in cognitive level, education, age or sex. However, bilinguals showed higher mean diffusivity in the fornix, but higher fractional anisotropy, lower mean diffusivity, axial diffusivity and radial diffusivity in the parahippocampal cingulum, and lower radial diffusivity in the right uncinate fasciculus. Significant correlations were also found between WM integrity in the left parahippocampal cingulum and the Boston Naming Test in passive bilinguals. Conclusions These results suggest that bilingualism contributes to a differential pattern of WM disintegration due to mild cognitive impairment in fibers related to bilingualism and memory.

Cortical atrophy and degraded axonal health have been shown to coincide during normal aging; however, few studies have examined these measures together. To lend insight into both the regional specificity and the relative timecourse of structural degradation of these tissue compartments across the lifespan, we analyzed grey matter (GM) morphometry (cortical thickness, surface area, volume) and estimates of white matter (WM) microstructure (fractional anisotropy, mean diffusivity) using traditional univariate and more robust multivariate techniques to examine age associations in 186 healthy adults aged 20-94 years old. Univariate analysis of each tissue type revealed that negative age associations were largest in frontal grey and white matter tissue and weaker in temporal, cingulate, and occipital regions, representative of not only an anterior-to-posterior gradient, but also a medial-to-lateral gradient. Multivariate partial least squares correlation (PLSC) found the greatest covariance between GM and WM was driven by the relationship between WM metrics in the anterior corpus callosum and projections of the genu, anterior cingulum, and fornix; and with GM thickness in parietal and frontal regions. Surface area was far less susceptible to age effects and displayed less covariance with WM metrics, while regional volume covariance patterns largely mirrored those of cortical thickness. Results support a retrogenesis-like model of aging, revealing a coupled relationship between frontal and parietal GM and the underlying WM, which evidence the most protracted development and the most vulnerability during healthy aging.

INTRODUCTIONWhite matter (WM) energy supply is crucial for axonal function and myelin maintenance. Providing ketones, the brain’s alternative fuel to glucose, is a therapeutic strategy to bypass the brain’s glucose-specific energy deficit in mild cognitive impairment (MCI). How an additional supply of ketones affects glucose or ketone uptake in specific WM fascicles in MCI has not previously been described.METHODSThis 6-month interventional study included MCI participants randomized to a placebo (n = 16) or ketogenic medium chain triglyceride (kMCT; n = 17) drink. A neurocognitive battery and brain imaging were performed pre- and post-intervention. WM fascicle uptake of ketone and glucose and structural properties were assessed using positron emission tomography and diffusion imaging, respectively.RESULTSKetone uptake was increased by 2.5 to 3.2-fold in nine fascicles of interest (P < 0.001) only in the kMCT group, an effect seen both in deep WM and in fascicle cortical endpoints. Improvement in processing speed was associated with WM ketone uptake globally and in individual fascicles, most importantly the fornix (r = +0.61; P = 0.014).DISCUSSIONA 6-month ketogenic supplementation in MCI improved WM energy supply globally. The significant positive association with processing speed suggests that ketones may have a role in myelin integrity in MCI.

PURPOSE To investigate the effect of Phenylephrine test on the upper eyelid crease position. MATERIAL AND METHODS This study follows a prospective and analytical design and included patients with unilateral acquired involutional ptosis recruited between January 2015 and January 2018. In the Phenylephrine test, 1 drop of Phenylephrine 10% was instilled on the inferior fornix of the ptotic eye and the eyelid crease position was evaluated 10 min after. RESULTS A total of 60 patients were included in the final sample. The mean Margin-to-reflex distance 1 (MRD1) of the ptotic eye was 2.1 ± 1.0 and 3.8 ± 0.6 mm before and 10 min after the instillation of Phenylephrine, respectively. The difference between the means was statistically significant (p

Background Cognitive deficits in Parkinson's disease (PD) may result from damage in the cortex as well as in the dopaminergic, noradrenergic, and cholinergic inputs to the cortex. Cholinergic inputs to the cortex mainly originate from the basal forebrain and are clustered in several regions, called Ch1 to Ch4, that project to the hippocampus (Ch1‐2), the olfactory bulb (Ch3), and the cortex and amygdala (Ch4). Objective We investigated changes in basal forebrain and their role in cognitive deficits in PD. Methods We studied 52 nondemented patients with PD (Hoehn & Yahr 1‐2) and 25 age‐matched healthy controls using diffusion and resting state functional MRI. Results PD patients had a loss of structural integrity within the Ch1‐2 and Ch3‐4 nuclei of the basal forebrain as well as in the fornix. Tractography showed that the probability of anatomical connection was decreased in PD between Ch3‐4 and the associative prefrontal cortex, occipital cortex, and peri‐insular regions. There was a reduction in functional connectivity between Ch1‐2 and the bilateral hippocampi and parahippocampal gyri, the left middle and superior temporal gyri, and the left fusiform gyrus and between Ch3‐4 and the right inferior frontal gyrus and the right and left thalamus. In Ch1‐2, loss of structural integrity and connectivity correlated with scores at the memory tests, whereas changes in Ch3‐4 correlated with scores of global cognition and executive functions. Conclusion This study highlights the association between deficits of different cholinergic nuclei of the basal forebrain and the extent of cognitive impairments in nondemented PD patients. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

The neurobiological underpinnings of anorexia nervosa (AN) are unclear. White matter deficits have been described in the illness, but findings are inconsistent between studies. The aim of this study was to investigate differences in white matter microstructure in AN using diffusion-weighted imaging (DWI). It was hypothesised that people with AN, relative to a healthy control (HC) group, would show decreased functional anisotropy (FA) and increased mean diffusivity (MD) in the fornix and superior longitudinal fasciculus, consistent with previous literature. Analyses were conducted on 23 females with AN and 26 age- and gender-matched HCs using tract-based spatial statistics (TBSS). The results revealed widespread FA decreases and MD increases in the AN group. Our hypothesis was largely supported, although FA differences were not specifically found in the fornix. The findings suggest extensive differences in white matter structure in AN, which may contribute to AN pathophysiology.

BACKGROUND The concept of prodromal Parkinson's disease (PD) involves variable combinations of nonmotor features and subtle motor abnormalities as a result of ongoing neurodegeneration in the brain stem including substantia nigra (SN) and abnormal findings upon transcranial sonography and nuclear imaging. Except for nuclear imaging, the predictive value of risk markers for the conversion to overt PD is low. OBJECTIVE The objective of this study was to determine whether PD risk markers are associated with changes in brain structure and to what extent cognitive changes are risk markers for PD. METHODS Diffusion-weighted imaging, voxel-based morphometry, and cortical thickness analysis was performed in 29 individuals with hyposmia and/or an increased SN hyperechogenicity (SN+) upon transcranial sonography and 28 controls without these 2 risk markers. Classical parkinsonian signs were an exclusion criterion. All of the participants underwent a neuropsychological test battery addressing executive functions, learning ability, and verbal fluency. RESULTS In the PD risk group, diffusion-weighted imaging mean diffusivity was increased in 4 left hemisphere clusters (posterior thalamus, inferior longitudinal fasciculus, fornix, corticospinal tract). A negative relationship of mean diffusivity and smell function was present for the posterior thalamus and the corticospinal tract. There was a significant correlation of mean diffusivity values and SN+ in all clusters. Neither voxel-based morphometry nor cortical thickness analysis revealed any group differences. No relevant group differences were observed for cognitive tests included. CONCLUSION PD-free individuals with PD risk markers show microstructural changes of the white matter, including areas relevant for motor and limbic processes. In addition, our study provides for the first time a neuroanatomical correlate for SN hyperechogenicity. © 2018 International Parkinson and Movement Disorder Society.

BACKGROUND Generalized q-sampling (GQI) and connectometry analysis provide new indices, i.e., quantitative anisotropy (QA) and spin distribution function (SDF) in comparison with diffusion tensor imaging (DTI). They may provide more age-related changes in white matter (WM) in aging. PURPOSE To investigate the feasibility of using GQI and connectometry analysis to determine WM properties changes in aging. STUDY TYPE Cross-cohort research. POPULATION Fifty normal adults (27 females) aged 21-71 years. FIELD STRENGTH/SEQUENCE T1 -weighted images (T1 WI) and high angular resolution diffusion imaging (HARDI) images were acquired at 1.5T. ASSESSMENT HARDI data were analyzed using DTI and GQI to obtain fractional anisotropy (FA), QA, fiber numbers, and fiber lengths for tract analysis and using q-space diffeomorphic reconstruction (QSDR) for the connectometry analysis. We compared differences of DTI, GQI, and connectometry analysis to reflect WM changes in aging. STATISTICAL TESTS Associations between FA, QA, and fiber numbers and lengths and age were analyzed using Pearson's correlation coefficients. The connectometry analysis was conducted using a multiple linear regression analysis, including age and gender as factors. Uncorrected P-value/false discovery rate (FDR) (corrected for multiple comparisons) 6 regions, P 7 regions, P < 0.05). However, DTI and GQI analyses revealed consistent results in some regions, including the genu of the corpus callosum (GCC), body of the corpus callosum (BCC), fornix (Fx), and anterior coronal radiation (ACR) (P < 0.05). The connectometry analysis showed more tract changes associated with age at an FDR of 0.05, which partially overlapped with the FA and QA. DATA CONCLUSION GQI and connectometry provide more information about age-related tracts and complement the DTI findings. LEVEL OF EVIDENCE 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2018;48:369-381.

Neuropathological and in vivo brain imaging studies agree that the cornu ammonis 1 and subiculum subfields of the hippocampus are most vulnerable to atrophy in the prodromal phases of Alzheimer's disease (AD). However, there has been limited investigation of the structural integrity of the components of the hippocampal circuit, including subfields and extra-hippocampal white matter structure, in relation to the progression of well-accepted cerebrospinal fluid (CSF) biomarkers of AD, amyloid-β 1-42 (Aβ) and total-tau (tau). We investigated these relationships in 88 aging asymptomatic individuals with a parental or multiple-sibling familial history of AD. Apolipoprotein (APOE) ɛ4 risk allele carriers were identified, and all participants underwent cognitive testing, structural magnetic resonance imaging, and lumbar puncture for CSF assays of tau, phosphorylated-tau (p-tau) and Aβ. Individuals with a reduction in CSF Aβ levels (an indicator of amyloid accretion into neuritic plaques) as well as evident tau pathology (believed to be linked to neurodegeneration) exhibited lower subiculum volume, lower fornix microstructural integrity, and a trend towards lower cognitive score than individuals who showed only reduction in CSF Aβ. In contrast, persons with normal levels of tau showed an increase in structural MR markers in relation to declining levels of CSF Aβ. These results suggest that hippocampal subfield volume and extra-hippocampal white matter microstructure demonstrate a complex pattern where an initial volume increase is followed by decline among asymptomatic individuals who, in some instances, may be a decade or more away from onset of cognitive or functional impairment.

Primary mucinous carcinomas of the periorbital region are very rare and often require differential diagnosis of metastatic disease. We describe a case of pure mucinous adenocarcinoma arising in the subconjunctival stroma of the ocular fornix in a female patient with a longstanding history of bilateral ocular cicatricial pemphigoid. Histologically, the tumor was composed of predominantly goblet-like cells floating in pools of mucin separated by delicate collagenous septa. The initial suspicion was of primary cutaneous mucinous carcinoma and less likely endocrine mucin-producing sweat gland carcinoma, however the CK7-/synaptophysin-/chromogranin-immunoprofile did not confirm either of the two. Focal areas of the tumor demonstrated peripheral staining for p63 and CK5/6 suggestive of an in situ component. Additional studies showed that the tumor cells were positive for CK20, CDX2, villin and MUC2. Given the final immunophenotype of the tumor, metastatic lesion from the lower gastrointestinal tract had to be ruled out. Thorough clinicoradiological work-up did not reveal any other primary tumors or evidence of metastatic disease elsewhere. Unique histomorphology, the presence of an in-situ component and negative clinical investigation suggest that this is a primary mucinous adenocarcinoma arising in the ocular fornix. This case may represent the first report of this entity in the literature.

Hundreds of wild California sea lions (Zalophus californianus) exposed to the algal neurotoxin domoic acid are treated in veterinary rehabilitation centers each year. Common chronic effects of toxic exposure in these animals are seizures and hippocampal damage, and they have been proposed as a natural animal model for human epilepsy. Humans with medial temporal lobe epilepsy present with white matter pathology in a number of tracts including the fornix and increased structural connectivity between the hippocampus and thalamus. However, there are no prior data on structural connectivity in sea lion brains, with or without neuropathology. In the present study, we used a novel diffusion tensor imaging technique to obtain high resolution (1mm isotropic) white matter maps in brains obtained opportunistically postmortem from wild sea lions with and without chronic clinical signs of toxic exposure to domoic acid. All animals had received a full veterinary workup and diagnosis prior to euthanasia. We measured hippocampal atrophy morphometrically, and all brains were examined histopathologically. In animals diagnosed with chronic domoic acid toxicosis, the fornix showed signs of altered diffusion properties indicative of pathology; these brains also had increased structural connectivity between hippocampus and thalamus in comparison to brains from animals with no neurological signs. These findings establish further parallels between human medial temporal lobe epilepsy and a naturally occurring condition in wild sea lions and simultaneously advance general knowledge of the deleterious effects of an increasingly common natural toxin.

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive decline in memory and other aspects of cognitive function. Diffusion-weighted imaging (DWI) offers a non-invasive approach to delineate the effects of AD on white matter (WM) integrity. Previous studies calculated either some summary statistics over regions of interest (ROI analysis) or some statistics along mean skeleton lines (Tract Based Spatial Statistic [TBSS]), so they cannot quantify subtle local WM alterations along major tracts. Here, a comprehensive WM analysis framework to map disease effects on 3D tracts both locally and globally, based on a study of 200 subjects: 49 healthy elderly normal controls, 110 with mild cognitive impairment, and 41 AD patients has been presented. 18 major WM tracts were extracted with our automated clustering algorithm-autoMATE (automated Multi-Atlas Tract Extraction); we then extracted multiple DWI-derived parameters of WM integrity along the WM tracts across all subjects. A novel statistical functional analysis method-FADTTS (Functional Analysis for Diffusion Tensor Tract Statistics) was applied to quantify degenerative patterns along WM tracts across different stages of AD. Gradually increasing WM alterations were found in all tracts in successive stages of AD. Among all 18 WM tracts, the fornix was most adversely affected. Among all the parameters, mean diffusivity (MD) was the most sensitive to WM alterations in AD. This study provides a systematic workflow to examine WM integrity across automatically computed 3D tracts in AD and may be useful in studying other neurological and psychiatric disorders. Hum Brain Mapp 38:1191-1207, 2017. © 2016 Wiley Periodicals, Inc.

Aim A complete and non-splice porcine small-intestine submucosa (SIS) patch was used for total pelvic anatomical repair of organ prolapse. Methods This study included a total of 17 patients with severe total pelvic organ prolapse, including five patients with combined stress urinary incontinence (SUI). Panhysterectomy was performed, and then a porcine SIS patch was placed on the anterior (posterior) vaginal wall. The top of the vaginal wall was moved to the corresponding side of the vaginal wall, and the patch was sutured to bilateral uterosacral ligaments, the sacrospinous ligament, and arcus tendineus fasciae pelvis. SUI was addressed at the same time. ‘Failure’ was defined as anterior or posterior wall prolapse beyond the hymen. Results The mean follow-up duration was 11.6 ± 7.45 months (2–24 months). No symptom recurrence was observed in the five patients with combined SUI. One patient who underwent porcine SIS patch placement on the posterior wall experienced stage II anterior vaginal wall prolapse after surgery. The vaginal wall and fornix of the remaining patients with patches were restored to stable anatomical positions (92.85%). No organ damage, infection, erosion, or rejection was observed, and no blood transfusion was necessary. Conclusion This study is the first to implement total pelvic anatomical repair using a complete and non-splice SIS. Our results suggest that this new surgical method is safe and can achieve satisfactory therapeutic effects, especially for patients with combined SUI.

Author(s): Loi, Richard Q; Leyden, Kelly M; Balachandra, Akshara; Uttarwar, Vedang; Hagler, Donald J; Paul, Brianna M; Dale, Anders M; White, Nathan S; McDonald, Carrie R | Abstract: ObjectiveDiffusion tensor imaging (DTI) has become a popular tool for delineating the location and extent of white matter injury in temporal lobe epilepsy (TLE). However, DTI yields nonspecific measures that are confounded by changes occurring within both the intracellular and extracellular environments. This study investigated whether an advanced diffusion method, restriction spectrum imaging (RSI) could provide a more robust measure of white matter injury in TLE relative to DTI due to RSI's ability to separate intraaxonal diffusion (i.e., neurite density; ND) from diffusion associated with extraaxonal factors (e.g., inflammation; crossing fibers).MethodsRSI and DTI scans were obtained on 21 patients with TLE and 11 age-matched controls. RSI-derived maps of ND, isotropic-hindered (IH) and isotropic-free (IF) water, and crossing fibers (CFs) were compared to DTI-derived fractional anisotropy (FA) maps. Voxelwise and tract-based analyses were performed comparing patients with TLE to controls on each diffusion metric.ResultsReductions in FA were seen primarily in frontotemporal white matter in TLE, and they were most pronounced proximal to the seizure focus. Reductions in ND corresponded to those seen in the FA maps; however, ND reductions were greater in magnitude, more lateralized to the epileptogenic hemisphere, and showed a broader pattern. Increases in IF/IH and effects from CFs also contributed to reduced FA in the ipsilateral parahippocampal cingulum and fornix, with decreases in IH extending into extratemporal regions. Reduced ND of the uncinate fasciculus was associated with longer disease duration, whereas FA was not associated with any clinical variables.SignificanceRSI may provide a more specific measure of white matter pathology in TLE, distinguishing regions primarily affected by axonal/myelin loss from those where CFs and increases in extracellular water also play a role. By providing a more specific measure of axonal/myelin loss, RSI-derived ND may better reflect overall white matter burden in epilepsy.

Objective The pathogenesis of borderline personality disorder (BPD) is not well understood. We examined the microstructure of white matter in patients with BPD. Method Treatment-naive young adult with BPD (N = 30) and young-adult healthy controls (HCs; N = 31) were subjected diffusion tensor imaging (DTI). Microstructural parameters were analyzed via tract-based spatial statistics (TBSS) and post hoc tractography. Results TBSS analysis revealed that, relative to the HC group, the BPD group had significantly lower fractional anisotropy (FA) values in the genu and body of the corpus callosum (CC), right superior corona radiate, right anterior corona radiate, as well as higher radial diffusivity (RD) in the left anterior thalamic radiation. Tractography showed that FA values of fiber bundles passing through the fornix were significantly reduced in BPD group relative to HCs. No significant correlations were observed between clinical symptom and DTI indices in BPD group (FDR corrected). Conclusion Focal microstructural alterations were found in BPD group, mainly in the limbic system and CC. The present findings support the fronto-limbic disconnectivity hypothesis and suggest that abnormal maturation of white matter structures may play an important role in mechanism of BPD.

Three-dimensional reconstruction of developing fiber pathways is essential to assessing the developmental course of fiber pathways in the whole brain. We applied diffusion spectrum imaging (DSI) tractography to five juvenile ex vivo cat brains at postnatal day (P) 35, when the degree of myelination varies across brain regions. We quantified diffusion properties (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) and other measurements (number, volume, and voxel count) on reconstructed pathways for projection (cortico-spinal and thalamo-cortical), corpus callosal, limbic (cingulum and fornix), and association (cortico-cortical) pathways, and characterized regional differences in maturation patterns by assessing diffusion properties. FA values were significantly higher in cortico-cortical pathways within the right hemisphere compared to those within the left hemisphere, while the other measurements for the cortico-cortical pathways within the hemisphere did not show asymmetry. ADC values were not asymmetric in both types of pathways. Interestingly, tract count and volume were significantly larger in the left thalamo-cortical pathways compared to the right thalamo-cortical pathways. The bilateral thalamo-cortical pathways showed high FA values compared to the other fiber pathways. On the other hand, ADC values did not show any differences across pathways studied. These results demonstrate that DSI tractography successfully depicted regional variations of white matter tracts during development when myelination is incomplete. Low FA and high ADC values in the cingulum bundle suggest that the cingulum bundle is less mature than the others at this developmental stage.

Focal lesions can affect connectivity between distal brain regions (connectional diaschisis) and impact the graph-theoretic properties of major brain networks (connectomic diaschisis). Given its unique anatomy and diverse range of functions, the hippocampus has been claimed to be a critical "hub" in brain networks. We investigated the effects of hippocampal lesions on structural and functional connectivity in six patients with amnesia, using a range of magnetic resonance imaging (MRI) analyses. Neuropsychological assessment revealed marked episodic memory impairment and generally intact performance across other cognitive domains. The hippocampus was the only brain structure exhibiting reduced grey-matter volume that was consistent across patients, and the fornix was the only major white-matter tract to show altered structural connectivity according to both diffusion metrics. Nonetheless, functional MRI revealed both increases and decreases in functional connectivity. Analysis at the level of regions within the default-mode network revealed reduced functional connectivity, including between nonhippocampal regions (connectional diaschisis). Analysis at the level of functional networks revealed reduced connectivity between thalamic and precuneus networks, but increased connectivity between the default-mode network and frontal executive network. The overall functional connectome showed evidence of increased functional segregation in patients (connectomic diaschisis). Together, these results point to dynamic reorganization following hippocampal lesions, with both decreased and increased functional connectivity involving limbic-diencephalic structures and larger-scale networks. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

BACKGROUND AND PURPOSE Distinct injuries to various limbic white matter pathways have been reported to be associated with different aspects of cognitive dysfunction in multiple sclerosis (MS). Diffusion tensor imaging (DTI) offers a noninvasive method to map tissue microstructural organization. We utilized quantitative magnetic resonance imaging methods to analyze the main limbic system—white matter structures in MS patients with cognitive impairment (CI). METHODS Ten cognitively nonimpaired MS (MSNI) patients and 36 patients with diagnosed CI (MSCI) underwent the minimal assessment of Cognitive Function in MS (MACFIMS) battery. DTI measures of fornix, cingulum, uncinate fasciculus (UF) included tract volume and corresponding fractional anisotropy (FA), mean (MD), axial (AD), and radial (AD) diffusivities. These were statistically analyzed for associations with CI after adjusting for the confounders. RESULTS Fornix FA and RD, left cingulum FA, MD, and RD, right cingulum FA, MD, and RD, and left UF FA showed significant differences between MSNI and MSCI (P < .001). Fornix FA (r = −.6) and RD (r = .52), and right cingulum FA (r = −.54) and RD (r = .5) correlated significantly with CI in regression analyses. CONCLUSIONS The extent of disruption of microstructural disorganization in the main limbic pathways using DTI impacts the extent of CI seen in subjects with MS.

Objective Several case reports of Wernicke's Encephalopathy in anorexia nervosa (AN) caused by thiamine deficiency have described mammillary body (MB) injury, but systematic studies are lacking. Here we evaluated whether underweight and weight-restored individuals with AN demonstrate evidence of abnormal MB morphology, via retrospective examination of a previously collected data set. Method Using standard-resolution T1-weighted magnetic resonance imaging at 3 Tesla, we measured MB volume and fornix area in a cross-sectional study of 12 underweight AN, 20 weight-restored AN, and 30 age- and sex-matched healthy comparisons. Because of the small size of these structures, a manual tracing approach was necessary to obtain accurate measurements. A blinded expert rater manually traced MB and fornix structures in each participant. Results We observed significantly smaller MB volumes in the underweight AN group. However, the weight-restored AN group exhibited significantly larger MB volumes. The right fornix was smaller in the weight-restored AN group only. Discussion These findings suggest the possibility that MB volume and fornix area could represent potential biomarkers of acute weight loss and restoration, respectively. Verification of this finding through prospective studies evaluating MB morphology, cognition, and thiamine levels longitudinally across individual illness trajectories might be warranted. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:920–929)

SummaryObjective Multiple hippocampal transection (MHT) is a surgical procedure developed to avoid postoperative memory decline. Its efficacy has been documented in only a few small series with relatively short observation periods. We prospectively evaluated the long-term seizure and cognitive outcomes of MHT combined with multiple subpial transection or lesionectomy (MHT + MST/L). Moreover, we quantitatively evaluated the structural and metabolic neuroradiologic changes after the procedure to elucidate the anatomofunctional correlates of memory preservation. Methods Twenty-four patients underwent MHT + MST/L for treatment of drug-resistant mesial temporal lobe epilepsy (mTLE) and were followed for more than 5 years. Indications for the procedure were the following: (1) verbally dominant-sided surgery in patients with a radiologically normal hippocampus or normal/near normal memory, and (2) surgery for patients with concomitant epileptic activity on the contralateral side, that is, when the surgery was considered a high risk for severe postoperative memory decline. Seizure outcome was evaluated using Engel's classification 1, 2, and 3 years after surgery, and at the last visit (LV). Three subgroups were evaluated as well: magnetic resonance imaging (MRI) negative (MN), hippocampal sclerosis (HS), and normal hippocampus with extrahippocampal lesion (NHEL). The long-term cognitive outcome was followed through to LV in patients who underwent verbally dominant-sided surgery. Hippocampal volume (HV), diffusion tensor parameters (DTP), and glucose utilization (GU) were determined from MRI and fluorodeoxyglucose–positron emission tomography (FDG-PET) studies performed before and >6 months after surgery. Results Whereas the rate of Engel class I as a whole was 71% at 1 year and 67% at LV, the rates in the MN, HS, and NHEL groups were 60%, 67%, and 100% at 1 year, respectively, and 70%, 56%, and 80% at LV, respectively. Memory indices after verbally dominant-sided surgery transiently declined at 1 month but recovered to and remained at the preoperative level through LV. The HV, DTP of the fornix, and GU of the temporal lobe on the treated side showed pathologic changes even when the transiently declined memory indices had recovered to the preoperative level. Significance The long-term outcome for complex partial seizures after MHT + MST/L was comparable to that seen after anterior temporal lobectomy. The long-term cognitive outcome was favorable, even for patients with a high risk of severe postoperative memory decline. MHT + MST/L may be a treatment option for mTLE in which resective surgery carries a risk of postoperative memory decline, particularly in patients without MRI lesion. A discrepancy between the preserved memory and the pathologic neuroradiologic changes indicates the necessity for further studies including functional MRI.

Major long-range white matter pathways (cingulum, fornix, uncinate fasciculus [UF], inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus [ILF], thalamocortical [TC], and corpus callosal [CC] pathways) were identified in eighty-three healthy humans ranging from newborn to adult ages. We tracked developmental changes using high-angular resolution diffusion MR tractography. Fractional anisotropy (FA), apparent diffusion coefficient, number, length, and volume were measured in pathways in each subject. Newborns had fewer, and more sparse, pathways than those of the older subjects. FA, number, length, and volume of pathways gradually increased with age and reached a plateau between 3 and 5 years of age. Data were further analyzed by normalizing with mean adult values as well as with each subject's whole brain values. Comparing subjects of 3 years old and under to those over 3 years old, the studied pathways showed differential growth patterns. The CC, bilateral cingulum, bilateral TC, and the left IFOF pathways showed significant growth both in volume and length, while the bilateral fornix, bilateral ILF and bilateral UF showed significant growth only in volume. The TC and CC took similar growth patterns with the whole brain. FA values of the cingulum and IFOF, and the length of ILF showed leftward asymmetry. The fornix, ILF and UF occupied decreased space compared to the whole brain during development with higher FA values, likely corresponding to extensive maturation of the pathways compared to the mean whole brain maturation. We believe that the outcome of this study will provide an important database for future reference.

Developmental dyslexia has been hypothesized to result from multiple causes and exhibit multiple manifestations, implying a distributed multidimensional effect on human brain. The disruption of specific white-matter (WM) tracts/regions has been observed in dyslexic children. However, it remains unknown if developmental dyslexia affects the human brain WM in a multidimensional manner. Being a natural tool for evaluating this hypothesis, the multivariate machine learning approach was applied in this study to compare 28 school-aged dyslexic children with 33 age-matched controls. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging were acquired to extract five multitype WM features at a regional level: white matter volume, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. A linear support vector machine (LSVM) classifier achieved an accuracy of 83.61% using these MRI features to distinguish dyslexic children from controls. Notably, the most discriminative features that contributed to the classification were primarily associated with WM regions within the putative reading network/system (e.g., the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamocortical projections, and corpus callosum), the limbic system (e.g., the cingulum and fornix), and the motor system (e.g., the cerebellar peduncle, corona radiata, and corticospinal tract). These results were well replicated using a logistic regression classifier. These findings provided direct evidence supporting a multidimensional effect of developmental dyslexia on WM connectivity of human brain, and highlighted the involvement of WM tracts/regions beyond the well-recognized reading system in dyslexia. Finally, the discriminating results demonstrated a potential of WM neuroimaging features as imaging markers for identifying dyslexic individuals.

Objective The aim of this research was to determine the prevalence and sonographic appearance of the hippocampal commissure in fetuses with isolated complete agenesis of the corpus callosum by three-dimensional neurosonography in the multiplanar mode. Methods This was a multicenter observational study. Stored volume datasets of fetuses with isolated complete agenesis of the corpus were retrospectively retrieved for analysis in three tertiary centers. The presence or absence of the hippocampal commissure was independently evaluated in the coronal and midsagittal planes by two operators. Postnatal follow-up was obtained in all cases. Results From November 2007 to February 2013, 41 cases between 19 and 30 weeks of gestation were retrieved for analysis. The hippocampal commissure was visible in the coronal and sagittal planes in 27/41 (65.8%), absent or not clearly recognizable in the remaining 14 cases. The qualitative analysis of the two operators was concordant in 100% of cases. Conclusions In more than half of fetuses with complete callosal agenesis, the hippocampal commissure may be visualized at prenatal ultrasound. This is a residual interhemispheric connection, which in normal cases is hidden by the corpus callosum itself. Further research is needed to establish if this has an impact on postnatal outcome. © 2015 John Wiley & Sons, Ltd.

Purpose White matter tractography reconstructions using conventional diffusion tensor imaging (DTI) near cerebrospinal fluid (CSF) spaces are often adversely affected by CSF partial volume effects (PVEs). This study evaluates the ability of free water elimination (FWE) DTI methods to minimize the PVE of CSF for deterministic tractography applications. Materials and Methods Ten healthy individuals were scanned with "traditional," FLAIR (fluid-attenuated inversion recovery), and FWE DTI scans. The fornix, corpus callosum, and cingulum bundles were reconstructed using deterministic tractography. The FWE DTI scan was performed twice to separately match total acquisition time (long FWE) and number of measurements (encoding directions, short FWE) to the FLAIR and "traditional" DTI scans. PVE resolution was determined based on reconstructed tract volume. All reconstructions underwent blinded review for anatomical correctness, symmetry, and completeness. Results Reconstructions of the fornix demonstrated that the FWE and FLAIR scans produce more complete, anatomically plausible reconstructions than "traditional" DTI. Additionally, the tract reconstructions using FWE-DTI were significantly larger than when FLAIR was used with DTI (P

Summary Obesity is associated with both structural and functional changes of the central nervous system. While gray matter alterations in obesity point to a consistent reduction with increasing body mass index (BMI), volumetric changes in white matter are more complex and less conclusive. Hence, more recently, diffusion tensor imaging (DTI) has been employed as a highly sensitive tool to investigate microstructural changes in white matter structure. Parameters of diffusivity and anisotropy are used to evaluate white matter and fibre integrity as well as axonal and myelin degeneration. Fractional anisotropy (FA) is the most commonly used parameter as it is the best estimate of fibre integrity. The focus of this review was on the relationship between obesity and brain alterations assessed by DTI. Altogether, these studies have shown a loss of white matter integrity with obesity-related factors, especially in tracts within the limbic system and those connecting the temporal and frontal lobe. More specifically, multiple studies found an inverse association between BMI and FA in the corpus callosum, fornix, cingulum and corona radiata in elderly and young adults as well as children. Furthermore, significant interactions were observed between BMI and age, pointing to accelerated ageing of white matter structure in obese.

Summary Objective To evaluate white matter (WM) integrity of distinct groups of patients with antiepileptic drug (AED)–resistant localization-related epilepsies. Methods We used diffusion tensor imaging (DTI) fiber-tractography and voxel-based morphometry (VBM) to investigate differences of WM micro- and macrostructural integrity in patients with different drug-resistant localization-related epilepsies: 17 with temporal lobe epilepsy with magnetic resonance imaging (MRI) signs of hippocampal sclerosis (TLE-HS), 17 with TLE and normal MRI (TLE-NL), 14 with frontal lobe epilepsy and subtle MRI signs of focal cortical dysplasia (FLE-FCD), and 112 healthy controls. We performed fiber-tractography using a semiautomatic deterministic method to yield average fractional anisotropy (FA), axial (AD), and radial (RD) diffusivity ipsilateral and contralateral to the epileptogenic zone of the following tracts based on their functional and anatomic relevance: body of fornix (BoF), body of cingulum (BoC), inferior frontal occipital (IFO), and uncinate fasciculi (UF). In addition, we performed VBM of the WM maps to assess macrostructural integrity differences among groups. Results TLE-HS had ipsilateral and contralateral decreased FA and increased RD for all tracts. VBM showed WM alterations mainly in the ipsilateral parahippocampal region and contralateral superior temporal gyrus. FLE-FCD showed bilateral FA decreases only in the BoC and ipsilateral RD increases also in the BoC. VBM showed WM reduction mainly in the ipsilateral precuneus and posterior and anterior cingulum. No significant WM alterations were found in the TLE-NL in DTI or VBM analysis. Significance WM abnormalities differ in distinct AED-resistant localization-related epilepsies. The diverse distribution of the WM damage in these patients suggests that the localization of the epileptic networks may play a role in the WM burden. However, the distinct degree of this damage, more accentuated in TLE-HS, also suggests that the underlying cause of the epilepsy is probably an additional factor to explain this WM damage.

Objective: Learning and memory deficits are a source of considerable morbidity after traumatic brain injury (TBI). We investigated the effect of different patterns of hippocampal stimulation via a fornix electrode on cognitively demanding tasks after TBI. Methods: Male Sprague-Dawley rats underwent fluid-percussion injury and were compared with sham-operated rats. Electrodes were implanted into the fornix and hippocampus, and stimulation of the fornix produced robust evoked potentials in the hippocampus. A 60-s delayed non-match-to-sample (DNMS) swim T-maze was serially performed using four stimulation patterns: no stimulation (No Stim), low-frequency stimulation (LFS, 5 Hz), high-frequency stimulation (HFS, 130 Hz), and theta-burst stimulation (TBS, 200 Hz in 50 ms trains, five trains per second; 60 µA biphasic pulses). In a separate cohort of sham and injured animals, Morris water maze (MWM) was performed with or without TBS. Results: In the DNMS swim T-maze, LFS and HFS did not significantly improve performance after TBI. However, there was a significant difference in performance between TBI + No Stim and TBI + TBS groups (P

Microstructural white matter tract correlations have been shown to reflect known patterns of phylogenetic development and functional specialization in healthy subjects. The aim of this study was to establish intertract correlations in a group of controls and to examine potential deviations from normality in temporal lobe epilepsy (TLE). We investigated intertract correlations in 28 healthy controls, 21 left TLE (LTLE) and 23 right TLE (RTLE). Nine tracts were investigated, comprising the parahippocampal fasciculi, the uncinate fasciculi, the arcuate fasciculi, the frontoparietal tracts, and the fornix. An abnormal increase in tract correlations was observed in LTLE, while RTLE showed intertract correlations similar to controls. In the control group, tract correlations increased with increasing fractional anisotropy (FA), while in the TLE groups tract correlations increased with decreasing FA. Cluster analyses revealed agglomeration of bilateral pairs of homologous tracts in healthy subjects, with such pairs separated in our LTLE and RTLE groups. Discriminant analyses aimed at distinguishing LTLE from RTLE, revealing that tract correlations produce higher rates of accurate group classification than FA values. Our results confirm and extend previous work by showing that LTLE compared to RTLE patients display not only more extensive losses in microstructural orientation but also more aberrant intertract correlations. Aberrant correlations may be related to pathologic processes (i.e., seizure spread) or to adaptive processes aimed at preserving key cognitive functions. Our data suggest that tract correlations may have predictive value in distinguishing LTLE from RTLE, potentially moving diffusion imaging to a place of greater prominence in clinical practice. Hum Brain Mapp, 36:85–98, 2015. © 2014 Wiley Periodicals, Inc.

Purpose An acquisition method that does not increase scan time or specific absorption rate is investigated for reducing the deleterious effects of cerebrospinal fluid (CSF) partial volume effects on diffusion tensor imaging (DTI) tractography. It is based on using a shorter repetition time (TR) by means of slice acquisition re-ordering to reduce the signal of long T1 CSF and a non-zero minimum diffusion weighting (b-value) to attenuate rapidly diffusing CSF signal with respect to brain tissue. Methods A target reduction of the CSF/brain signal ratio from 3.5 to 0.8 required a TR of 2.5 s and minimum b-value of 425 s/mm2. This was evaluated at 4.7 Tesla in eight healthy young adults for tractography of the fornix, which has considerable CSF contamination and is difficult to track from standard DTI. Results This method effectively reduced CSF signal relative to brain and yielded more robust tractography, increased tract volume, increased fractional anisotropy, and decreased mean diffusivity in the fornix relative to standard DTI. Conclusion CSF partial volume effects in DTI can be mitigated in acquisition through reduced TR and non-zero minimum diffusion weighting. The lack of RF absorption rate or scan time increases is attractive over other CSF suppression methods such as inversion recovery. Magn Reson Med 73:1075–1084, 2015. © 2014 Wiley Periodicals, Inc.

Purpose: To: 1) Present fornix tractography in its entirety for 20 healthy individuals to assess variability. 2) Provide individual and groupwise whole tract diffusion parameter symmetry assessments prior to clinical application. 3) Compare whole tract diffusion parameter assessments with tract-based spatial statistics (TBSS). Materials and Methods: Diffusion tensor imaging (DTI) data were acquired on a 3T Siemens magnetic resonance imaging (MRI) system using a single-shot spin echo planar imaging (EPI) sequence. Individual fornix tractography was conducted and whole tract diffusion parameter symmetries assessed. Whole tract results were compared with asymmetry contrasts conducted with voxelwise statistical analysis of diffusion parameters using TBSS. Results: The fornix tract could be visualized in its entirety including the columns, body, crura, and fimbria. Contrary to the crus and body, there were some tractography inconsistencies of the columns and fimbria across subjects. Although whole tract diffusion parameter asymmetries were nonsignificant, fractional anisotropy (FA) values bordered on statistical significance (P = 0.052). Using TBSS, significant FA asymmetries were identified (P less than or equal 0.01, corrected). Conclusion: The findings demonstrate consistency of fornix tractography as well as some variability in the columns and fimbria. While parametric assessment demonstrates diffusion parameter symmetry, permutation-based TBSS analysis reveals significant FA asymmetries in the crura and fimbriae. © 2013 Wiley Periodicals, Inc.

Background Chronic alcohol abuse is related to numerous deleterious neurobiological consequences, including loss of gray matter, damage to white matter (WM), and impairment of cognitive and motor functions. Aerobic exercise has been demonstrated to slow cognitive decline and decrease the negative neural changes resulting from normal aging and from several diseases. It is possible that exercise may also prevent or repair alcohol-related neurological damage. This study tested the hypothesis that aerobic exercise protects WM in anterior and dorsal areas of the brain from damage related to heavy alcohol use. Methods Sixty individuals underwent a diffusion tensor imaging session and completed measures of alcohol consumption, loss of control over drinking, and aerobic exercise participation. Analyses examined the relationship of exercise, alcohol, and their interaction to fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF), external capsule (EC), superior and anterior corona radiata, and fornix. The relationship of aerobic exercise and alcohol consumption to self-reported loss of control over drinking were also examined. Results A significant interaction was observed between alcohol consumption and aerobic exercise participation on FA in the SLF and EC. In the models examining loss of control over drinking, a significant interaction between aerobic exercise and alcohol consumption was observed, such that alcohol consumption was associated with loss of control more strongly for low exercisers than high exercisers. Conclusions These results indicate that the association between heavy alcohol consumption and WM damage in the EC and SLF and the association between alcohol consumption and loss of control over drinking are greater among individuals who do not exercise regularly. These results are consistent with the notion that exercise may protect WM integrity from alcohol-related damage.

The spectrum of cognitive symptoms in Parkinson's disease (PD) can span various domains, including executive function, language, attention, memory, and visuospatial skills. These symptoms may be attributable to the degradation of projection fibers associated with the underlying neurodegenerative process. The primary purpose of this study is to find microstructural correlates of impairments across these cognitive domains in PD using diffusion tensor imaging (DTI). Sixteen patients with PD with comprehensive neuropsychological evaluation and DTI data were retrospectively studied. Fractional anisotropy (FA) and mean diffusivity (MD) were assessed using regions-of-interest (ROI) analysis and confirmed with a voxel-based approach. Executive function directly correlated with FA and inversely correlated with MD in mostly frontal white matter tracts, especially the anterior limb of the internal capsule and genu of the corpus callosum. Likewise, language and attentional performance demonstrated correlations with DTI parameters in the frontal regions, but the attention domain additionally recruited regions widespread throughout the brain, with the most significant correlation identified in cingulate gyrus (cingulum). Lastly, memory impairment mainly involved MD alterations within the fornix. No significant correlations were found between visuospatial skills and DTI measures. Despite some overlap, unique patterns of white matter diffusivity underlie impairments in distinct cognitive domains in patients with PD. DTI combined with neurocognitive tests may be a valuable biomarker for identifying cognitive impairments in PD.

The eating disorder (ED) bulimia nervosa (BN) is most distinctively characterized by episodic binge eating, followed by purging behaviors (1), although individuals with BN also frequently restrict food intake in between binges. BN is associated with anxious traits (2) and comorbid anxiety disorders (3), as well as depression (1), but also altered taste perception (4; 5) and brain reward response (6–8). The neurobiologic underpinnings of increased anxiety in BN are still unknown, although brain serotonin 1A, 2A and dopamine D2/3 receptors have been associated with anxious traits in the past (9–12). Recently, we showed that brain white matter (WM) in AN was related to anxiety (13). In that study we used diffusion tensor imaging (DTI), and found that patients with AN had reduced WM integrity in the bilateral fimbria fornix, an outflux tract of the medial temporal cortex and hippocampus, as well as in the inferior and superior fronto-occipital fasciculus and cingulum. Importantly, fornix WM integrity, expressed as the so-called fractional anisotropy (FA), predicted inversely harm avoidance and trait anxiety in the AN individuals. That finding raised the question whether BN would have similar WM alterations that would predict high trait anxiety in the disorder. For a long time it has been known that WM lesions in the brain may lead to disconnection syndromes, and studies over the past ten years now have increasingly implicated more subtle WM tract functionality in neuropsychiatric disorders (14). WM functionality can be studied using DTI, a relatively new tool in psychiatric research that uses magnetic resonance imaging (MRI) to assess WM functionality. DTI maps WM pathways by measuring water diffusivity along axons expressed as FA (15). FA is therefore a measure of the integrity of axons, their myelination, and density. A second measure is the apparent diffusion coefficient (ADC), which measures water diffusivity at the voxel level and is thought to be an indicator of the health of the axonal cells. A higher ADC indicates dispersed water diffusion reflecting disruption of these cells (15). Studies have investigated WM functionality in, for instance, mood and psychotic disorders (16), most commonly reporting reduced FA values across many brain regions, but increased WM FA has also been reported (17). The functionality of WM has not been studied previously in BN. Psychiatric disorders including BN are characterized by a complex interplay of cognitive and emotional behavior and rely heavily on the connections between brain regions (18). Thus, functional WM alterations in BN could be an important aspect of the pathophysiology of this disorder. Only few brain-imaging studies have investigated brain structure such as gray matter (GM) or WM in BN. Early studies analyzed total GM or WM and cerebrospinal fluid volumes. The first structural studies have shown potential brain atrophy (19; 20) or widening of the sulci and enlargement of the ventricles despite normal body weight (21–23). With advancement in technology using ‘voxel based morphology’ (VBM), that is a whole brain analysis of structural brain images that are normalized to a standard space and compared across groups, studies now can in much more detail investigate localized volume alterations that could be related to a specific brain disorder. One recent study found normal GM volumes in BN but “drive for thinness” was positively related to parietal cortex GM volume (24). Another study found increased orbitofrontal cortex and ventral striatal GM volume compared to controls (25). In that study purging frequency and body mass index (BMI, weight in kg/height in m2) were directly related to the volume of those regions. One study in recovered BN indicated normal WM volume (26). Most studies did not take comorbid depression or medication use into account, factors that have been shown to affect brain volumes. This and the differing analysis techniques most likely account for the conflicting results and more definite studies are still needed. Various neurotransmitter alterations were also found in BN, such as reduced serotonin (5HT) transporter binding in thalamus and hypothalamus (27). After recovery BN showed reduced midbrain but increased cingulate cortex 5HT transporter availability (28), reduced orbitofrontal 5HT2A (29), and increased 5HT1A receptor binding (10), most prominently in prefrontal, cingulate and parietal cortex regions. Altogether, those studies indicate brain alterations in BN in ill and recovered states, which may be related to altered food intake, mood states and anxiety, but their relationship to WM function is unclear. In this study we wanted to investigate whether we would find altered WM functionality in BN similar to results we previously reported in AN (13). Following on our AN results, we hypothesized that we would find reduced FA values in BN in the fornix area, fronto-occipital fasciculus and the cingulum, and those findings would not be due to WM volume alterations. We further hypothesized that lower FA would predict higher harm avoidance and trait anxiety. If BN were to have similar WM disturbances as the AN individuals, that might indicate a common vulnerability across eating disorder groups. Furthermore, we wanted to test whether BN specific behaviors such as binge/purge frequency would predict WM functionality, as it did predict brain reward response in BN in the past (8).